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Li R, Jia Y, Yi X, Wang L, Huang Q. Evaluation of six GFR estimation equations in Chinese patients with chronic kidney disease. Clin Chim Acta 2025; 575:120374. [PMID: 40398556 DOI: 10.1016/j.cca.2025.120374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 05/06/2025] [Accepted: 05/16/2025] [Indexed: 05/23/2025]
Abstract
BACKGROUND Glomerular filtration rate (GFR) is recognized as the most reliable indicator of renal function and is usually estimated based on the serum creatinine equations. However, the reliability of these equations in specific regions needs to be properly quantified. We evaluated the applicability of the abbreviated MDRD equation (aGFR), the modified abbreviated MDRD equation (maGFR), the CKD-EPI creatinine equation (C-GFRcr), the CKD-EPI creatinine-cystatin C equation (C-GFRcr-cys), the EKFC creatinine equation (E-GFRcr), and the EKFC creatinine-cystatin C equation (E-GFRcr-cys) to chronic kidney disease (CKD) patients in Chongqing, China. METHODS A total of 234 adult patients with CKD were selected for the study. Their sex, age, and etiology of CKD were recorded, and serum creatinine and cystatin C were measured and traceable to primary reference materials. The technetium 99 m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) renal scintigraphy was used as the reference method for GFR measurement. Six GFR estimation equations were analyzed in the overall analysis and across various stages of CKD to evaluate differences, absolute differences, bias, precision, and accuracy. RESULTS In the validation dataset, the differences for maGFR were smaller compared to other equations, while those for C-GFRcr-cys and E-GFRcr-cys were larger. The bias for C-GFRcr-cys and E-GFRcr-cys was significantly higher than that of the other equations, although all six equations exhibited similar levels of precision. In CKD stages 1 through 3, the accuracy of C-GFRcr-cys and E-GFRcr-cys was significantly lower when compared to the other equations. Conversely, in CKD stages 4 and 5, maGFR and E-GFRcr-cys demonstrated significantly greater accuracy than the other equations. In CKD stage 1, maGFR misclassified only 5.21 % of patients, whereas C-GFRcr-cys and E-GFRcr-cys had significantly higher misclassification rates of 66.67 % and 68.75 %, respectively, compared to the other equations. CONCLUSIONS Overall, maGFR performed better than other equations and can be used as a confirmatory test in CKD patients in Chongqing, China.
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Affiliation(s)
- Ruoxu Li
- Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Yuhui Jia
- Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Xin Yi
- Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Lixin Wang
- Department of Laboratory Medicine, The Affiliated Rehabilitation Hospital of Chongqing Medical University, Chongqing 400050, China.
| | - Qing Huang
- Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China.
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Bouderlique E, Pszczolinski R, Prot-Bertoye C, Courbebaisse M. Glomerular filtration rate and sexual dimorphism: lessons from animal and human studies. Curr Opin Nephrol Hypertens 2025; 34:330-335. [PMID: 40265514 DOI: 10.1097/mnh.0000000000001079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025]
Abstract
PURPOSE OF REVIEW Integrating sex-based analyses is becoming a key point in the new recommendations, particularly in nephrology. RECENT FINDINGS Whereas single nephron glomerular filtration rate (GFR) is not different between men and women, male sex is associated, after multiple adjustments, with a higher number of nephrons. However, after indexation to body surface area, measured GFR (mGFR) in healthy potential kidney donors is not different between men and women between 20 and 50 years of age. After 50 years, mGFR decline seems faster in women than in men, which is concordant with the protective role of estrogens on renal function, as demonstrated in animal and some human studies. Conversely, testosterone has a detrimental effect on renal function. Of note, although testosterone has been shown to increase the kidney volume of the remnant kidney after a unilateral nephrectomy in animal models, this may generate deleterious hyperfiltration in the longer term. SUMMARY Taken together, these data highlight the impact of sex on GFR, notably through sexual hormones whose receptors are expressed in glomerular cells.
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Affiliation(s)
- Elise Bouderlique
- Service de Physiologie-Explorations Fonctionnelles, Hôpital Européen Georges-Pompidou, Assistance Publique - Hôpitaux de Paris
- Université Paris Cité (UPC)
- Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA)
- Centre de Référence des Maladies Rares du Calcium et du Phosphate
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, CNRS ERL 8228 - Laboratoire de Physiologie Rénale et Tubulopathies
| | - Romain Pszczolinski
- Service de Physiologie-Explorations Fonctionnelles, Hôpital Européen Georges-Pompidou, Assistance Publique - Hôpitaux de Paris
- Université Paris Cité (UPC)
- Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA)
- Centre de Référence des Maladies Rares du Calcium et du Phosphate
| | - Caroline Prot-Bertoye
- Service de Physiologie-Explorations Fonctionnelles, Hôpital Européen Georges-Pompidou, Assistance Publique - Hôpitaux de Paris
- Université Paris Cité (UPC)
- Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA)
- Centre de Référence des Maladies Rares du Calcium et du Phosphate
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, CNRS ERL 8228 - Laboratoire de Physiologie Rénale et Tubulopathies
| | - Marie Courbebaisse
- Service de Physiologie-Explorations Fonctionnelles, Hôpital Européen Georges-Pompidou, Assistance Publique - Hôpitaux de Paris
- Université Paris Cité (UPC)
- Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA)
- Centre de Référence des Maladies Rares du Calcium et du Phosphate
- INEM, INSERM U1151, Paris, France
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Delanaye P, Gama RM, Stehlé T. Impact of the choice of biomarkers and equations to estimate kidney function on the epidemiology of chronic kidney disease. Curr Opin Nephrol Hypertens 2025; 34:336-345. [PMID: 40387074 DOI: 10.1097/mnh.0000000000001085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2025]
Abstract
PURPOSE OF REVIEW The CKD-EPI equations were updated in 2021 to remove the race variable from eGFR estimation. In the same year, the creatinine-based EKFC equation was published, subsequently supplemented by the cystatin C-based EKFC equation. Recent findings suggest that the prevalence of chronic kidney disease (CKD) can vary depending on the equation, the biomarker, and the population studied. RECENT FINDINGS Using the CKD-EPI 2021 equation instead of the CKD-EPI 2009 equation results in an increased prevalence of CKD among Black individuals in the U.S. and a decreased prevalence among non-Blacks. The CKD-EPI equations may underestimate the prevalence of CKD in India and in some sub-Saharan African populations. This is corrected by using the EKFC equation and dedicated Q-values. In general, the prevalence of CKD is slightly higher with EKFC than with the CKD-EPI equations. The CKD-EPI cys equation generally leads to a higher CKD prevalence than the CKD-EPIcrea equations. Few epidemiological data are available for EKFC cys . SUMMARY The choice of biomarkers and equations has an impact on the prevalence of CKD, with implications that also depend on the characteristics of the population being studied.
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Affiliation(s)
- Pierre Delanaye
- Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium
- Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Nîmes, France
| | - Rouvick Mariano Gama
- Department of Inflammation Biology, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Thomas Stehlé
- Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Service de Néphrologie et Transplantation, Fédération Hospitalo-Universitaire « Innovative therapy for immune disorders », Créteil, France
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Gembillo G, Soraci L, Santoro D. Chronic kidney disease in geriatric patients: Estimating glomerular filtration rate in older patients with comorbidities. World J Nephrol 2025; 14:105803. [DOI: 10.5527/wjn.v14.i2.105803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/07/2025] [Accepted: 03/21/2025] [Indexed: 04/09/2025] Open
Abstract
Aging is an inevitable process that is usually measured by chronological age, with people aged 65 and over being defined as "older individuals". There is disagreement in the current scientific literature regarding the best methods to estimate glomerular filtration rate (eGFR) in older adults. Several studies suggest the use of an age-adjusted definition to improve accuracy and avoid overdiagnosis. In contrast, some researchers argue that such changes could complicate the classification of chronic kidney disease (CKD). Several formulas, including the Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration, and Cockcroft-Gault equations, are used to estimate eGFR. However, each of these formulas has significant limitations when applied to older adults, primarily due to sarcopenia and malnutrition, which greatly affect both muscle mass and creatinine levels. Alternative formulas, such as the Berlin Initiative Study and the Full Age Spectrum equations, provide more accurate estimates of values for older adults by accounting for age-related physiological changes. In frail older adults, the use of cystatin C leads to better eGFR calculations to assess renal function. Accurate eGFR measurements improve the health of older patients by enabling better medication dosing. A thorough approach that includes multiple calibrated diagnostic methods and a detailed geriatric assessment is necessary for the effective management of kidney disease and other age-related conditions in older adults.
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Affiliation(s)
- Guido Gembillo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina 98125, Sicilia, Italy
| | - Luca Soraci
- Unit of Geriatric Medicine, Italian National Research Center on Aging (IRCCS INRCA), Cosenza 87100, Calabria, Italy
| | - Domenico Santoro
- Unit of Nephrology and Dialysis, AOU "G. Martino", University of Messina, Messina 98125, Sicilia, Italy
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Astley ME, Chesnaye NC, Hallan S, Gambaro G, Ortiz A, Carrero JJ, Ebert N, Eriksen BO, Faucon AL, Ferraro PM, Indridason OS, Ittermann T, Jonsson AJ, Rise Langlo KA, Melsom T, Schaeffner E, Stracke S, Stel VS, Jager KJ. Age- and sex-specific reference values of estimated glomerular filtration rate for European adults. Kidney Int 2025; 107:1076-1087. [PMID: 40122341 DOI: 10.1016/j.kint.2025.02.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 02/04/2025] [Accepted: 02/17/2025] [Indexed: 03/25/2025]
Abstract
Kidney function, often assessed by estimated glomerular filtration rate (eGFR), declines naturally with age. However, there is a lack of eGFR reference values to describe normal and abnormal values for a specific age. The European Chronic Kidney Disease Burden Consortium is comprised of nine participating general population-based studies from seven European countries which provides European age- and sex-specific eGFR reference values in healthy adults using the European Kidney Function Consortium (EKFC) equation. Of 2,572,020 individuals, 1,535,253 (60%) were considered healthy, of which 45% were men. Ages ranged from 18 to 105 years old in men and 18 to 107 years old in women with a median age of 43 years in both sexes. At age 20 in men, the 5th, 50th and 95th eGFR percentiles were 78 ml/min per 1.73 m2, 99 ml/min per 1.73 m2, and 119 ml/min per 1.73 m2. In 20-year-old women this was 81 ml/min per 1.73 m2, 101 ml/min per 1.73 m2, and 121 ml/min per 1.73 m2. Consequently, in men aged 80 years old, the 5th, 50th and 95th eGFR percentiles were 49 ml/min per 1.73 m2, 66 ml/min per 1.73 m2, and 84 ml/min per 1.73 m2. In 80 year old women this was 46 ml/min per 1.73 m2, 63 ml/min per 1.73 m2, and 81 ml/min per 1.73 m2. Overall, our study shows that eGFR is not preserved with ageing in healthy individuals and these eGFR reference values can help determine abnormal and normal kidney function across the age range.
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Affiliation(s)
- Megan E Astley
- ERA Registry, Department of Medical Informatics, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands; Health Behaviours and Chronic Diseases and Methodology, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
| | - Nicholas C Chesnaye
- ERA Registry, Department of Medical Informatics, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands; Quality of Care, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Stein Hallan
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Nephrology, St. Olavs Hospital, Trondheim, Norway
| | - Giovanni Gambaro
- Department of Medicine, Division of Nephrology and Dialysis, University of Verona, Verona, Italy
| | - Alberto Ortiz
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain
| | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Danderyd, Sweden
| | - Natalie Ebert
- Institute of Public Health, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Bjørn Odvar Eriksen
- Section of Nephrology, Clinic of Internal Medicine, University Hospital of North Norway, Tromsø, Norway; Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway
| | - Anne-Laure Faucon
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Epidemiology, Centre for Research in Epidemiology and Population Health, INSERM U1018, Paris-Saclay University, Paris, France
| | - Pietro Manuel Ferraro
- Section of Nephrology, Department of Medicine, Università degli Studi di Verona, Verona, Italy
| | | | - Till Ittermann
- Institute for Community Medicine - SHIP Clinical Epidemiological Research, University Medicine Greifswald, Greifswald, Germany
| | - Arnar J Jonsson
- Internal Medicine Services, Landspitali University Hospital, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Knut Asbjørn Rise Langlo
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Nephrology, St. Olavs Hospital, Trondheim, Norway
| | - Toralf Melsom
- Section of Nephrology, Clinic of Internal Medicine, University Hospital of North Norway, Tromsø, Norway; Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway
| | - Elke Schaeffner
- Institute of Public Health, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Sylvia Stracke
- Division of Nephrology, Internal Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Vianda S Stel
- ERA Registry, Department of Medical Informatics, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands; Quality of Care, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Kitty J Jager
- Quality of Care, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Amsterdam UMC location University of Amsterdam, Medical Informatics, Amsterdam, the Netherlands
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Theodorakakou F, Fotiou D, Apostolakou F, Papassotiriou I, Spiliopoulou V, Ntanasis-Stathopoulos I, Malandrakis P, Migkou M, Kanellias N, Eleutherakis-Papaiakovou E, Psimenou E, Papanikolaou A, Gakiopoulou C, Marinaki S, Giannouli S, Gavriatopoulou M, Terpos E, Dimopoulos MA, Kastritis E. Cystatin C as Biomarker for the Evaluation of Renal Outcome in AL Amyloidosis. Am J Hematol 2025. [PMID: 40387384 DOI: 10.1002/ajh.27716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 04/23/2025] [Accepted: 04/29/2025] [Indexed: 05/20/2025]
Abstract
Cystatin C (CysC) has emerged as a novel and potentially more reliable biomarker for the estimation of glomerular filtration in the general population in patients with various conditions. In AL amyloidosis, the current renal staging system and renal response criteria are based on proteinuria and creatinine-based eGFR. We explored the prognostic role of CysC and of estimation of eGFR based on CysC-based equations in a cohort of 195 patients with newly diagnosed AL amyloidosis with renal involvement. Baseline CysC level was strongly and independently associated with progression to dialysis, and CysC levels ≥ 1.9 mg/L can be used in combination with the current renal staging system to identify patients with different risk of progression to dialysis among renal stages 2 and 3. eGFR based on CysC performed at least similarly to eGFR based on creatinine alone (by CKD-EPI race free formula) and the cutoff of 30 mL/min/1.73 m2 could better predict progression to dialysis at 2 years. At 6 months landmark, an increase in CysC by ≥ 1 mg/L was associated with higher risk of progression to dialysis (HR: 19.8, 95% CI 6.5-60.5, p < 0.001); a reduction of CysC based eGFR ≥ 30% was also associated with poor renal outcome, with a prognostic performance similar to current renal progression criteria. In conclusion, CysC provides prognostic information regarding the renal outcomes in patients with AL amyloidosis independently of the established biomarkers, but requires further validation.
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Affiliation(s)
- Foteini Theodorakakou
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Despina Fotiou
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Filia Apostolakou
- Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece
| | - Ioannis Papassotiriou
- First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Vasiliki Spiliopoulou
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Panagiotis Malandrakis
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Magdalini Migkou
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Nikolaos Kanellias
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Erasmia Psimenou
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Charikleia Gakiopoulou
- First Department of Pathology, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Smaragdi Marinaki
- Clinic of Nephrology and Renal Transplantation, National and Kapodistrian University of Athens, School of Medicine, Laikon Hospital, Athens, Greece
| | - Stavroula Giannouli
- Second Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Gavriatopoulou
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Terpos
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Meletios-Athanasios Dimopoulos
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
- Department of Medicine, Korea University, Seoul, South Korea
| | - Efstathios Kastritis
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
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7
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Chen J, Yan L, Hu L, Xiao S, Liao Y, Yao X, Yang R. Association Between the Serum Creatinine to Cystatin C Ratio and Cardiovascular Disease in Middle-Aged and Older Adults in China: A Nationwide Cohort Study. J Am Heart Assoc 2025; 14:e040050. [PMID: 40281656 DOI: 10.1161/jaha.124.040050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 03/24/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND The relationship between the serum creatinine to cystatin C ratio (sarcopenia index [SI]) and the risk of incident cardiovascular disease (CVD) remains unclear. Therefore, this study aims to explore the association between SI and the risk of incident CVD in middle-aged and older Chinese adults using nationally representative data. METHODS AND RESULTS We analyzed data from participants in CHARLS (China Health and Retirement Longitudinal Study) conducted in 2015 and 2018. The exposure variable was SI, calculated as the ratio of serum creatinine to cystatin C, multiplied by 100. The outcome variable was self-reported CVD (heart disease or stroke). A cross-sectional analysis was first performed using 2015 CHARLS data, which included 11 115 eligible participants (46.1% men; mean±SD age, 60.28±9.60 years). Logistic regression was used to estimate the association between SI and CVD. Longitudinal analysis was then conducted using the 2018 follow-up data, which included 8589 participants (46.4% men; mean±SD age, 59.57±9.42 years), with a median follow-up period of 3.0 years. Cox proportional hazard models were used to assess the relationship between SI and the risk of incident CVD, and a multivariate-adjusted restricted cubic spline model was used to explore the dose-response relationship. In the cross-sectional analysis, multivariate logistic regression revealed a significant negative association between SI and CVD. The longitudinal analysis identified 854 (9.94%) new CVD cases. Cox models showed that lower SI was significantly associated with an increased risk of incipient CVD. The multivariable adjusted hazard ratios for participants in the quartile 2 to quartile4 groups compared with those in the quartile 1 group were 0.94 (95% CI, 0.79-1.12), 0.63 (95% CI, 0.51-0.78), and 0.60 (95% CI, 0.47-0.75), respectively. Restricted cubic spline curves demonstrated a significant linear relationship between SI and CVD incidence (all P-nonlinear>0.05). CONCLUSIONS A lower SI was significantly associated with an increased risk of new-onset CVD in middle-aged and older Chinese adults. This suggests that SI has an important potential application as a serum marker of sarcopenia in predicting CVD.
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Affiliation(s)
- Jintao Chen
- Department of Cardiovascular Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang China
| | - Liying Yan
- Department of General Practice The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang China
| | - Longlong Hu
- Department of Cardiovascular Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang China
| | - Shucai Xiao
- Department of Cardiovascular Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang China
| | - Yanhui Liao
- Department of Cardiovascular Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang China
| | - Xiongda Yao
- Department of Cardiovascular Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang China
| | - Renqiang Yang
- Department of Cardiovascular Medicine The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang China
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8
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Madero M, Levin A, Ahmed SB, Carrero JJ, Foster B, Francis A, Hall RK, Herrington WG, Hill G, Inker LA, Kazancıoğlu R, Lamb E, Lin P, McIntyre N, Morrow K, Roberts G, Sabanayagam D, Shlipak M, Shroff R, Tangri N, Thanachayanont T, Ulasi I, Wong G, Yang CW, Zhang L, Robinson KA, Wilson LM, Wilson RF, Kasiske BL, Cheung M, Earley A, Stevens PE, Schaeffner E. Evaluation and Management of Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2024 Clinical Practice Guideline. Ann Intern Med 2025; 178:705-713. [PMID: 40063957 DOI: 10.7326/annals-24-01926] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/21/2025] Open
Abstract
DESCRIPTION The Kidney Disease: Improving Global Outcomes (KDIGO) organization updated its existing clinical practice guideline in 2024 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving kidney replacement therapy. METHODS The KDIGO CKD Guideline Work Group defined the scope of the guideline and determined topics for systematic review. An independent Evidence Review Team systematically reviewed the evidence and graded the certainty of evidence for each of the review topics. Latest searches of the English-language literature were done in July 2023. Final modification of the guideline was informed by a public review process during summer of 2023 involving registered stakeholders. RECOMMENDATIONS The full guideline included 28 recommendations and 141 practice points. This synopsis focuses on the recommendations that have the greatest evidence. Practice points reflect the expert opinion of the group where evidence is not that strong. Recommendations include greater emphasis on cystatin C for assessment of glomerular filtration rate, point-of-care testing in remote areas, a shift to an individualized risk-based approach to predict kidney failure, sodium-glucose cotransporter-2 inhibitors for some patients with CKD with and without diabetes, and statin use for adults older than 50 years and CKD. Together the recommendations and practice points provide guidance for how to evaluate and manage persons with CKD.
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Affiliation(s)
- Magdalena Madero
- Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, Mexico (M.M.)
| | - Adeera Levin
- University of British Columbia, Vancouver, British Columbia, Canada (A.L.)
| | - Sofia B Ahmed
- University of Alberta, Edmonton, Alberta, Canada (S.B.A.)
| | | | | | - Anna Francis
- Queensland Children's Hospital, Brisbane, Australia (A.F.)
| | | | - William G Herrington
- Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (W.G.H.)
| | - Guy Hill
- Patient partner, Manchester, United Kingdom (G.H.)
| | | | | | - Edmund Lamb
- East Kent Hospitals University NHS Foundation Trust, Canterbury, United Kingdom (E.L.)
| | - Peter Lin
- Canadian Heart Research Center, Toronto, Ontario, Canada (P.L.)
| | - Natasha McIntyre
- Western University, London Health Sciences Centre-Victoria Hospital, London, Ontario, Canada (N.M.)
| | - Kelly Morrow
- Bastyr University, Osher Center for Integrative Medicine, University of Washington, Kenmore, Washington (K.M.)
| | - Glenda Roberts
- UW Center for Dialysis Innovation & Kidney Research Institute, Seattle, Washington (G.R.)
| | | | - Michael Shlipak
- University of California, San Francisco, San Francisco, California (M.S.)
| | - Rukshana Shroff
- UCL Great Ormond Street Hospital Institute of Child Health, London, United Kingdom (R.S.)
| | - Navdeep Tangri
- University of Manitoba, Winnipeg, Manitoba, Canada (N.T.)
| | | | - Ifeoma Ulasi
- University of Nigeria, Ituku-Ozalla Campus, Enugu, Nigeria (I.U.)
| | - Germaine Wong
- University of Sydney, Sydney, Australia (D.S., G.W.)
| | - Chih-Wei Yang
- Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan (C.-W.Y.)
| | - Luxia Zhang
- Peking University First Hospital, Beijing, China (L.Z.)
| | - Karen A Robinson
- The Johns Hopkins University Evidence-based Practice Center, Johns Hopkins University, Baltimore, Maryland (K.A.R., L.M.W., R.F.W.)
| | - Lisa M Wilson
- The Johns Hopkins University Evidence-based Practice Center, Johns Hopkins University, Baltimore, Maryland (K.A.R., L.M.W., R.F.W.)
| | - Renee F Wilson
- The Johns Hopkins University Evidence-based Practice Center, Johns Hopkins University, Baltimore, Maryland (K.A.R., L.M.W., R.F.W.)
| | - Bertram L Kasiske
- Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota (B.L.K.)
| | | | | | - Paul E Stevens
- Kent Kidney Care Centre, East Kent Hospitals University NHS Foundation Trust, Canterbury, United Kingdom (P.E.S.)
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9
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Blum MF, Neuen BL, Grams ME. Risk-directed management of chronic kidney disease. Nat Rev Nephrol 2025; 21:287-298. [PMID: 39885336 DOI: 10.1038/s41581-025-00931-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2025] [Indexed: 02/01/2025]
Abstract
The timely and rational institution of therapy is a key step towards reducing the global burden of chronic kidney disease (CKD). CKD is a heterogeneous entity with varied aetiologies and diverse trajectories, which include risk of kidney failure but also cardiovascular events and death. Developments in the past decade include substantial progress in CKD risk prediction, driven in part by the accumulation of electronic health records data. In addition, large randomized clinical trials have demonstrated the effectiveness of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists in reducing adverse events in CKD, greatly expanding the options for effective therapy. Alongside angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, these classes of medication have been proposed to be the four pillars of CKD pharmacotherapy. However, all of these drug classes are underutilized, even in individuals at high risk. Leveraging prognostic estimates to guide therapy could help clinicians to prescribe CKD-related therapies to those who are most likely to benefit from their use. Risk-based CKD management thus aligns patient risk and care, allowing the prioritization of absolute benefit in determining therapeutic selection and timing. Here, we discuss CKD prognosis tools, evidence-based management and prognosis-guided therapies.
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Affiliation(s)
- Matthew F Blum
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Brendon L Neuen
- The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Morgan E Grams
- New York University Grossman School of Medicine, New York, NY, USA.
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10
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Jeong TD. Current Status of Standardization of Glomerular Filtration Rate Markers in Korea. Ann Lab Med 2025; 45:272-275. [PMID: 40097176 PMCID: PMC11996686 DOI: 10.3343/alm.2024.0702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 12/30/2024] [Accepted: 03/04/2025] [Indexed: 03/19/2025] Open
Affiliation(s)
- Tae-Dong Jeong
- Department of Laboratory Medicine, Ewha Womans University College of Medicine, Seoul, Korea
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11
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Ng DK, Patel A, Schwartz GJ, Seegmiller JC, Warady BA, Furth SL, Cox C. A comparison of neural networks and regression-based approaches for estimating kidney function in pediatric chronic kidney disease: Practical predictive epidemiology for clinical management of a progressive disease. Ann Epidemiol 2025; 105:75-79. [PMID: 40209838 DOI: 10.1016/j.annepidem.2025.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 04/06/2025] [Accepted: 04/07/2025] [Indexed: 04/12/2025]
Abstract
PURPOSE Clinical management of pediatric chronic kidney disease requires estimation of glomerular filtration rate (eGFR). Currently, eGFR is determined by two endogenous markers measured in blood: serum creatine (SCr) and cystatin C (CysC). Machine learning methods show promise to potentially improve eGFR, but it is unclear if they can outperform regression-based approaches under clinical constraining requiring real time measurement and only two predictors. We constructed a neural network for eGFR (NNeGFR) and compared it to the clinical standard Under 25 (U25eGFR) equations using the same data for training and validation. METHODS The U25eGFR data comprised 1683 training and 843 validation observations that included iohexol measured GFR (mGFR), SCr and CysC. Sex-stratified feed forward NNs included the same predictors as U25eGFR (i.e., age, height/SCr, CysC) with additional nonlinear transformations. Performance was evaluated by bias (for calibration), proportions within 10 % and 30 % of mGFR (P10 and P30, for accuracy), root mean square error (RMSE, for precision) and R2 (for discrimination). RESULTS NNeGFR performed comparably to the U25eGFR equations on all metrics. Biases were minimal, slightly favoring U25eGFR. NNeGFR and U25eGFR had similar P10 (>37 %), P30 (>86 %) and RMSE. CONCLUSIONS NNeGFR performed as well as established equations to estimate GFR. Without additional biomarkers related to kidney function, which are not currently clinically available in real time, NN methods are unlikely to substantially outperform regression derived GFR estimating equations. Implications for translation of these advanced epidemiologic methods to clinical practice are discussed.
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Affiliation(s)
- Derek K Ng
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
| | - Ankur Patel
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - George J Schwartz
- Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA
| | - Jesse C Seegmiller
- Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Bradley A Warady
- Division of Pediatric Nephrology, Children's Mercy Kansas City, Kansas City, MO, USA
| | - Susan L Furth
- Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Division of Nephrology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Christopher Cox
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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12
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Jia P, Luo Z, Ding X. Response by Jia et al to Letter Regarding Article, "Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial". Circulation 2025; 151:e959-e960. [PMID: 40258051 DOI: 10.1161/circulationaha.125.073969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/23/2025]
Affiliation(s)
- Ping Jia
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., X.D.)
| | - Zhe Luo
- Cardiac Intensive Care Center, Zhongshan Hospital, Fudan University, China (Z.L.)
| | - Xiaoqiang Ding
- Department of Nephrology, Zhongshan Hospital, Fudan University, and Shanghai Medical Center of Kidney, and Shanghai Key Laboratory of Kidney and Blood Purification, China (P.J., X.D.)
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13
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Ilori EO, Cai CR, Sahor F, Wilson B, Veeramachaneni T, Parikh SM, Hashim IA. Performance of the 2021 Estimated Glomerular Filtration Rate CKD-EPI Refit and the European Kidney Function Consortium (EKFC) Formulas. Diagnostics (Basel) 2025; 15:1047. [PMID: 40310408 PMCID: PMC12025858 DOI: 10.3390/diagnostics15081047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 04/14/2025] [Accepted: 04/15/2025] [Indexed: 05/02/2025] Open
Abstract
Background: The glomerular filtration rate (GFR) is a universal clinical measure central to assessing kidney function and to the management of kidney disorders. Several formulas for the estimation of GFR are in use. The European Kidney Function Consortium (EKFC) formula has been reported to more accurately estimate the GFR as compared to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and its recent version (REFIT equation) in European and African populations. However, validation of the EKFC equation in diverse U.S. populations, especially the Black subpopulation, is needed. Methods: Data from the electronic medical records of 75,442 individuals presenting to a large safety net county hospital with measurements of serum creatinine and/or iohexol clearance studies were used to calculate the estimated GFR (eGFR) and to determine CKD stage using the various reported eGFR formulas. The correlation between eGFR and measured GFR was determined for each equation. Results: The median eGFR for Black participants using the CKD-EPI, REFIT, and EKFC formulas was 130.6 mL/min/1.73 m2, 82.0 mL/min/1.73 m2, and 80.6 mL/min/1.73 m2 (p < 0.001), respectively. For White participants, the median eGFR using the CKD-EPI, REFIT, and EKFC formulas was 145.3 mL/min/1.73 m2, 105.6 mL/min/1.73 m2, and 99.2 mL/min/1.73 m2, respectively (p < 0.001). The REFIT equation underestimates the mGFR in Black individuals at eGFR < 80 mL/min per 1.73 m2 and in White individuals at eGFR > 20 mL/min per 1.73 m2. In comparison, the EKFC equation underestimates the mGFR at eGFR > 20 mL/min per 1.73 m2 in both Black and White individuals. The REFIT equation had the least absolute median bias as compared to EKFC and CKD-EPI in both Black and White participants (p < 0.0001). The P30 of the REFIT and EKFC equations was not statistically different for either Black or White participants (p = 0.16, p = 0.37). Conclusions: Although the accuracies (P30) of the EKFC and REFIT equations are not statistically significant (p = 0.16 and 0.37, Black and White individuals, respectively), adopting the EKFC formula in Americans requires the evaluation of each subpopulation. Both the EKFC and REFIT formulas underestimate the mGFR at a lower eGFR, which may have a direct impact on CKD classification for Black and White patients, with potentially significant implications for clinical management.
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Affiliation(s)
- Evelyn O. Ilori
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Department of Pathology, Parkland Health, Dallas, TX 75235, USA
| | - Casey R. Cai
- Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Fatou Sahor
- Department of Pathology, Parkland Health, Dallas, TX 75235, USA
| | - Brianna Wilson
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Tanooha Veeramachaneni
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Samir M. Parikh
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Ibrahim A. Hashim
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Department of Pathology, Parkland Health, Dallas, TX 75235, USA
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Hassan A, Carrot A, Kimbidima R, Colomban O, Herledan C, Glehen O, You B, Rioufol C, Ranchon F. Comparison of carboplatin doses according to several formulae in a cohort of patients treated for an ovarian cancer in real life. J Oncol Pharm Pract 2025:10781552251332600. [PMID: 40239094 DOI: 10.1177/10781552251332600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
IntroductionCarboplatin doses are calculated using several formulae, with the most recent being the Calvert formula with Glomerular Filtration Rate estimated using the CKD Epi cystatin C (Calvert CKD-Epi Cys) equation. The aim of this study was to compare the carboplatin doses estimated by this formula with the most commonly used formulas.Materials and methodsThe carboplatin doses prescribed for 84 patients with ovarian cancer were calculated according to Chatelut, Calvert with Glomerular Filtration Rate estimated using Cockcroft and Gault (Calvert CG), CKD-Epi (Calvert CKD-Epi) equation, modified Thomas and Calvert CKD-Epi Cys formulas. First, these 4 formulas were compared with the Calvert CKD-Epi Cys formula using a Wilcoxon test for pairwise comparison, and by assessing mean predictive error (MPE), mean absolute percentage error (MAPE), and absolute percentage error over 20% (P20). A subgroup analysis was then performed to determine the clinical and biological parameters responsible for the observed differences.ResultsThomas modified formulas showed low bias (MPE = 1.5%) and good precision (MAPE = 4.5%). Chatelut and Calvert CG were less precise with P20 values of32.1% and 13.5% respectively. Differences were mostly due to body weight, age and plasma cystatin C levels. The Calvert CKD-Epi formula showed good precision (MAPE = 8.1%) and low bias (MPE = 2.4%) except when plasma cystatin C levels were equal or above normal range (MPE = 14.9%).ConclusionAs proposed by White-Koning et al., we have chosen Calvert CKD-Epi Cys formula as a reference for carboplatin dosage calculations in our hospital. However, the limited doses differences with the Calvert CKD-Epi formula make it another reliable option in clinical practice.
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Affiliation(s)
- Ali Hassan
- Unité de Pharmacie Clinique Oncologique, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Aurore Carrot
- Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, Oullins, France
| | - Reine Kimbidima
- Unité de Pharmacie Clinique Oncologique, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Olivier Colomban
- Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, Oullins, France
| | - Chloé Herledan
- Unité de Pharmacie Clinique Oncologique, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre-Bénite, France
- Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, Oullins, France
| | - Olivier Glehen
- Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, Oullins, France
- Department of Surgical Oncology, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Benoît You
- Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, Oullins, France
- Unité d'Oncologie médicale, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Catherine Rioufol
- Unité de Pharmacie Clinique Oncologique, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre-Bénite, France
- Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, Oullins, France
| | - Florence Ranchon
- Unité de Pharmacie Clinique Oncologique, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre-Bénite, France
- Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, Oullins, France
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15
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Awdishu L, Maxson R, Gratt C, Rubenzik T, Battistella M. KDIGO 2024 clinical practice guideline on evaluation and management of chronic kidney disease: A primer on what pharmacists need to know. Am J Health Syst Pharm 2025:zxaf044. [PMID: 40197825 DOI: 10.1093/ajhp/zxaf044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2025] Open
Abstract
PURPOSE To review the key updates in the 2024 KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease (CKD) and highlight the essential role of pharmacists in implementing these recommendations. SUMMARY The updated guideline introduces significant changes in CKD management, including the use of validated equations for estimating glomerular filtration rate (GFR) for drug dosing, with incorporation of serum cystatin C into GFR estimates for specific patient populations, and an emphasis on a comprehensive approach to delay disease progression. The guideline recommends sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy for kidney disease with proteinuria, with or without diabetes, renin-angiotensin-aldosterone system inhibitors (RAASi) blood pressure control and proteinuria management, and statins to reduce the risk of atherosclerotic cardiovascular disease. New evidence supports the use of finerenone in patients with type 2 diabetes and CKD, and GLP-1 receptor agonists for their kidney-protective effects. The guidelines also emphasize the importance of nephrotoxin stewardship and prevention of acute kidney injury through patient education on sick day medication management. CONCLUSION Pharmacists play a crucial role in implementing these updated guidelines through comprehensive medication management, nephrotoxin stewardship, drug dosing adjustments, and patient education. Their involvement in interprofessional care teams is essential for optimizing health outcomes in patients with CKD.
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Affiliation(s)
- Linda Awdishu
- Division of Clinical Pharmacy, University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA
| | - Rebecca Maxson
- Harrison College of Pharmacy, Auburn University, Auburn, AL, USA
| | | | - Tamara Rubenzik
- Division of Nephrology, University of California, San Diego School of Medicine, La Jolla, CA, USA
| | - Marisa Battistella
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada, and University Health Network, Toronto, ON, Canada
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Hooper L, Heung M, Kenes M, Stringer KA, Mueller BA, Pai MP. The Kinetics of Cystatin C and Serum Creatinine in AKI. Clin J Am Soc Nephrol 2025; 20:477-484. [PMID: 39888675 PMCID: PMC12007825 DOI: 10.2215/cjn.0000000654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/28/2025] [Indexed: 02/02/2025]
Abstract
Key Points Modeling shows that serum cystatin C can detect AKI 6–48 hours earlier than serum creatinine, regardless of baseline kidney function. Absolute value diagnostic cutoffs are more effective than percentage-based thresholds for AKI detection across different CKD stages. Background AKI is a common condition affecting a significant portion of hospitalized and critically ill patients. Current AKI diagnosis relies on serum creatinine (sCr), which has several recognized limitations that affect the timely detection and response to AKI management. Serum cystatin C (sCys) has characteristics that can overcome the limitations of sCr, but head-to-head comparisons of these biomarkers are difficult to study prospectively. A quantitative assessment of the kinetics of sCys and sCr during AKI is necessary to support clinical workflow implementation for AKI diagnosis and management. Methods A quantitative systems pharmacology model was developed using Matrix Laboratories and Simbiology (The MathWorks, Natick, MA), to simulate the concentration–time profiles of sCr and sCys under varying degrees of AKI across a spectrum of baseline kidney function. The model incorporated parameters from existing literature and used a contemporary sCr and sCys GFR equation to assess the time to reach AKI diagnostic criteria for both biomarkers. Results The model demonstrated that sCys achieves steady-state concentration and meets AKI diagnostic thresholds significantly faster than sCr, with an advantage of 6–48 hours, depending on CKD stage. sCys exhibited greater sensitivity in detecting GFR reductions, with the ability to detect AKI within 12–24 hours after AKI, compared with 12–72 hours for sCr. The study also identified that for sCys, absolute value diagnostic cutoffs are more effective than percentage-based thresholds and can provide consistent detection across different CKD stages. Conclusions sCys has superior kinetics for early AKI detection compared with sCr, making it a valuable addition to AKI diagnostic protocols, particularly in high-risk populations. Daily monitoring of sCys in patients at risk of AKI would facilitate more timely detection and potentially improve clinical outcomes. Future research should focus on validating sCys diagnostic criteria and integrating it with other biomarkers to enhance AKI management.
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Affiliation(s)
- Levi Hooper
- Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan
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Abstract
Multimorbidity, i.e. the simultaneous presence of 2 or more diseases, is common in patients with chronic kidney disease (CKD). Cardiovascular diseases such as coronary heart disease, heart failure, stroke or vascular dementia are of particular importance. CKD and comorbidities influence each other, which is why the current KDIGO guidelines emphasize the need for personalized treatment approaches. This applies in particular to older patients, who are especially frequently affected by CKD. The diagnosis of CKD patients should not only include typical comorbidities, but also a comprehensive risk assessment and an evaluation to avoid polypharmacy.Recognising CKD is of particular importance for patients with chronic diseases in old age, as kidney disease can have a profound effect on or worsen the course of other diseases and the limitation of kidney function has a significant influence on the treatment approach. Particular attention must be paid to the correct assessment of kidney function in older people in terms of determining the estimated glomerular filtration rate (eGFR). Here, a measurement of serum creatinine is not always sufficient due to lower muscle mass and may need to be supplemented by additional parameters to estimate the glomerular filtration rate, such as cystatin C.Depending on the eGFR, kidney disease is categorized into the stages CKD G1-G5. In addition, if kidney disease is suspected, a test for proteinuria should also be performed, preferably as a measurement of albumin excretion in spontaneous urine (albumin-to-creatinine ratio, ACR). Geriatric screening and assessment are also crucial to recognize the multimorbidity, frailty and psychosocial aspects of older patients.The treatment of multimorbidity in CKD patients focusses on progression reduction and secondary and tertiary prevention, whereby a healthy lifestyle, regular exercise and a balanced diet are also important. The prevention of cardiovascular disease, particularly in the case of high blood pressure and diabetes mellitus, requires individualized therapy, in which the choice and dosage of medication must also be taken into account, particularly in the case of advanced renal impairment. If heart failure and/or atrial fibrillation are also present, close interdisciplinary collaboration between nephrologists, cardiologists and GPs is helpful in order to optimize treatment. In addition, CKD patients with dementia face particular challenges in terms of medication and the avoidance of delirium and mental symptoms.
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Delanaye P, Flamant M, Vidal-Petiot E, Björk J, Nyman U, Grubb A, Bakker SJ, de Borst MH, van Londen M, Derain-Dubourg L, Rule AD, Eriksen BO, Melsom T, Sundin PO, Ebert N, Schaeffner E, Hansson M, Littmann K, Larsson A, Stehlé T, Cavalier E, Bukabau JB, Sumaili EK, Yayo E, Mariat C, Moranne O, Christensson A, Lanot A, Pottel H. Discordant Results Between Creatinine- and Cystatin C-based Equations for Estimating GFR. Kidney Int Rep 2025; 10:1248-1259. [PMID: 40303200 PMCID: PMC12034923 DOI: 10.1016/j.ekir.2025.01.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 01/17/2025] [Accepted: 01/21/2025] [Indexed: 05/02/2025] Open
Abstract
Introduction Discordant results between cystatin C and creatinine in estimating glomerular filtration rate (GFR) are an important medical issue. However, the equation that should be used when GFR estimates are discordant remains unclear. Methods This cross-sectional analysis included 15,485 participants with GFR measured by the clearance of an exogenous marker, serum creatinine, and cystatin C. We studied the proportion of discordant results defined as an absolute (> 15 ml/min per 1.73 m2) or relative (> 20%) difference between creatinine-based estimated GFR (eGFR, eGFRcrea) and cystatin C-based eGFR (eGFRcys) using different equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], and reexpressed Lund-Malmö [r-LMR]). We also researched for the best estimating equations to be used in subjects with concordant or discordant results to estimate measured GFR (mGFR). Results In the total cohort, the proportion of subjects with discordant results (absolute or relative) was larger for CKD-EPI (35.1 and 40.6%) than for EKFC (21.9 and 31.7%) or r-LMR (22.8 and 32.8%) equations. Among discrepant results, the proportion of eGFRcys < eGFRcrea was significantly higher than the proportion of eGFRcrea < eGFRcys for the CKD-EPI equations, whereas the occurrence of discrepancy was similar in the 2 discrepant groups for EKFC or r-LMR. For the EKFC and r-LMR equations, but not for the CKD-EPI, the equation combining creatinine and cystatin C was consistently the closest to the mGFR in the discrepant groups. Conclusion Based on the lower discrepancy proportion, better balance between eGFRcrea and eGFRcys, and better concordance with mGFR, the EKFC, and r-LMR equations should be preferred over the CKD-EPI to estimate GFR.
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Affiliation(s)
- Pierre Delanaye
- Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium
- Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Université de Montpellier, Nîmes, France
| | - Martin Flamant
- Assistance Publique-Hôpitaux de Paris, Bichat Hospital, INSERM U1148, Université Paris Cité and Université Sorbonne Paris Nord, LVTS, Center, Paris, France
| | - Emmanuelle Vidal-Petiot
- Assistance Publique-Hôpitaux de Paris, Bichat Hospital, INSERM U1148, Université Paris Cité and Université Sorbonne Paris Nord, LVTS, Center, Paris, France
| | - Jonas Björk
- Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
- Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden
| | - Ulf Nyman
- Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö, Sweden
| | - Anders Grubb
- Department of Clinical Chemistry, Skåne University Hospital, Lund University, Lund, Sweden
| | - Stephan J.L. Bakker
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Martin H. de Borst
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Marco van Londen
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Laurence Derain-Dubourg
- Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Andrew D. Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
| | - Björn O. Eriksen
- Section of Nephrology, University Hospital of North Norway and Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway
| | - Toralf Melsom
- Section of Nephrology, University Hospital of North Norway and Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway
| | - Per-Ola Sundin
- Karla Healthcare Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Natalie Ebert
- Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany
| | - Elke Schaeffner
- Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany
| | - Magnus Hansson
- Function Area Clinical Chemistry, Karolinska University Laboratory, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden
| | - Karin Littmann
- Division of Medicine Huddinge (MedH), Karolinska Institute, Stockholm, Sweden
| | - Anders Larsson
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
| | - Thomas Stehlé
- Université Paris Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Service de Néphrologie et Transplantation, Fédération Hospitalo-Universitaire, Innovative therapy for immune disorders, Créteil, France
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CHU Sart Tilman, Liège, Belgium
| | - Justine B. Bukabau
- Renal Unit, Department of Internal Medicine, Kinshasa University Hospital, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
| | - Ernest K. Sumaili
- Renal Unit, Department of Internal Medicine, Kinshasa University Hospital, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
| | - Eric Yayo
- Département de Biochimie, UFR Sciences Pharmaceutiques et Biologiques, Université Felix Houphouët Boigny, Abidjan, Côte d’Ivoire
| | - Christophe Mariat
- Service de Néphrologie, Dialyse et Transplantation Rénale, Hôpital Nord, CHU de Saint-Etienne, France
| | - Olivier Moranne
- Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Université de Montpellier, Nîmes, France
| | - Anders Christensson
- Department of Nephrology, Skåne University Hospital, Lund University, Malmö, Sweden
| | - Antoine Lanot
- Normandie Université, Unicaen, CHU de Caen Normandie, Néphrologie, Côte de Nacre Caen, France
- Normandie Université, Unicaen, UFR de médecine, Caen, France
- ANTICIPE" U1086 INSERM-UCN, Center François Baclesse, Caen, France
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
| | - Hans Pottel
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
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19
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Budhiraja P, Butterfield R, Hommos M, Heilman RL, Cheungpasitporn W, Alajous S, Me HM, Chakkera HA, Corey RL, Abu Jawdeh BG, Khamash HA. Performance of Glomerular Filtration Rate Estimating Equations in Kidney Transplant Recipients of Various Races: A Retrospective Cohort Study. Transplant Proc 2025; 57:230-240. [PMID: 39837671 DOI: 10.1016/j.transproceed.2024.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 11/18/2024] [Accepted: 12/05/2024] [Indexed: 01/23/2025]
Abstract
BACKGROUND We assessed the accuracy of different GFR estimating equations in kidney transplant recipients across diverse racial backgrounds, addressing the previously identified validation gap in multiethnic populations predominantly studied in White cohorts. METHODS In this single-center study, eGFR was compared to the measured GFR (mGFR) one year following kidney transplantation. RESULTS The 1-year eGFR and mGFR data from 1145 participants (54% Whites, 23% Hispanics, 9% Blacks, 7% Native Americans, and 6% Asians) revealed varied correlations across racial groups. For Whites, the combined 2021 CKD-EPI creatinine-cystatin C formulas demonstrated a stronger correlation (r = 0.72, [0.65, 0.78]) compared to the 2021 CKD-EPI creatinine and EKFC cystatin C equation. This equation also achieved the highest accuracy (P30: 77.1%). In Black recipients, both the 2009 CKD-EPI (r = 0.56 [0.42, 0.68]) and the 2021 CKD-EPI creatinine (r = 0.56 [0.41, 0.68]) exhibited modest correlations. The 2021 CKD-EPI creatinine-cystatin C equation showed improved correlation (r = 0.63 (0.43, 0.77)] and an accuracy of 62.7% (P30), which was slightly lower than the EKFC cystatin C equation (P30: 64.7%). However, neither the EKFC (rescaled) cystatin C nor the race-free kidney-specific equations outperformed existing eGFR equations for Black participants In Hispanic patients, combined creatinine-cystatin C equations outperformed creatinine-only equations. Among Native Americans, the combined creatinine-cystatin, EKFC (rescaled) cystatin C, and race-free kidney-specific equations achieved an accuracy rate exceeding 85%. In Asians, the CKD-EPI creatinine-cystatin C equation showed the highest correlation, while the race-free kidney-specific equation had the most accuracy. CONCLUSION Our findings indicate that creatinine-cystatin C combined equations outperformed single-marker formulas across all racial groups, with negligible differences between the 2009 CKD EPI and the race-neutral 2021 CKD-EPI version.
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Affiliation(s)
- Pooja Budhiraja
- Division of Medicine, Mayo Clinic Arizona, Phoenix, Arizona.
| | | | - Musab Hommos
- Division of Medicine, Mayo Clinic Arizona, Phoenix, Arizona
| | | | | | - Salah Alajous
- Division of Medicine, Mayo Clinic Arizona, Phoenix, Arizona
| | - Hay Me Me
- Division of Medicine, Mayo Clinic Arizona, Phoenix, Arizona
| | | | - Rebecca L Corey
- Department of Pharmacy, Mayo Clinic Arizona, Phoenix, Arizona
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20
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Nguyen MK, Bandaru D. Importance of Creatinine Generation Rate in Estimating Glomerular Filtration Rate. Cureus 2025; 17:e80441. [PMID: 40225530 PMCID: PMC11990720 DOI: 10.7759/cureus.80441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/11/2025] [Indexed: 04/15/2025] Open
Abstract
Assessment of glomerular filtration rate (GFR) is commonly based on serum creatinine levels. It is well-established that, for a given GFR, the mean serum creatinine level is higher in Black individuals than in non-Black individuals. Failure to account for this difference in creatinine-based GFR estimation equations leads to inaccuracies in GFR estimates for Black individuals. This higher mean serum creatinine level in Black individuals has been attributed to greater muscle mass, though this explanation remains debated. In this article, we provide mathematical proof showing that the higher mean serum creatinine level in Black individuals reflects the "net" creatinine generation rate after accounting for renal tubular secretion of creatinine and extrarenal creatinine elimination. To accurately estimate GFR, this "net" creatinine generation rate must be considered. By rescaling serum creatinine to account for the differences in creatinine production rates between Black and non-Black populations, the population-specific creatinine-based European Kidney Function Consortium (EKFC) equation provides a more accurate GFR estimate than the current Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation.
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Affiliation(s)
- Minhtri K Nguyen
- Medicine, Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, USA
| | - Dhiresh Bandaru
- Medicine, Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, USA
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21
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Titan SM, Lieske JC, Meeusen JW, Thorson S, Lin Y, Nowakowski GS, Barreto JN, Barreto EF, Ruddy KJ, Leung N, Rule AD, Herrmann SM. Performance of Creatinine and Cystatin-Based Equations on Estimating Measured GFR in People with Hematological and Solid Cancers. Clin J Am Soc Nephrol 2025; 20:358-366. [PMID: 39874103 PMCID: PMC11905996 DOI: 10.2215/cjn.0000000616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 01/10/2025] [Indexed: 01/30/2025]
Abstract
Key Points Studies on GFR assessment in people with cancer are needed. In this study, the creatinine–cystatin C equations performed better than other equations, and this was observed in solid and hematological cancers. Our findings give support to the preferential use of creatinine and cystatin C–based equations in people with cancer. Background GFR assessment is important in clinical practice with implications for diagnosis, prognostication, and drug dosing. People with cancer are at risk of imprecision in GFR estimation. This cross-sectional study evaluated the performance of various creatinine and cystatin C–based equations in comparison with measured GFR (mGFR) in people with cancer. Methods We retrieved data for all adult patients who had mGFR by urinary iothalamate clearance between 2011 and 2023 at Mayo Clinic and use of an electronic health record diagnosis code for cancer within 2 years before mGFR. The CKD Epidemiology Collaboration (CKD-EPI), European Kidney Function Consortium, and Cockcroft–Gault equations were computed, along with performance metrics (bias, precision, and root mean square error [RMSE]. Confidence intervals were generated by bootstrapping, and analysis were stratified by solid and hematological cancers. Results From all adults with cancer and mGFR, 1145 had both creatinine and cystatin C available within 7 days of mGFR. Among all equations, the creatinine–cystatin C CKD-EPI equation provided the best performance, with small bias (median, 3.0; 95% confidence interval, 2.3 to 3.8) and higher precision (RMSE, 14.5) compared with creatinine-only or cystatin C–only equations (RMSE varying from 16.6 to 20), and this was also true in solid and hematological cancers. The creatinine–cystatin European Kidney Function Consortium equation had a similar performance to CKD-EPI, Cockcroft–Gault showed worst precision (30% of people with errors above 30%), and cystatin C CKD-EPI equation was the most biased, prone to underestimation of mGFR. Conclusions In our cohort of patients with mGFR and cancer, the CKD-EPI creatinine–cystatin C equation performed best for GFR assessment, and this was true for both solid and hematological cancers. Our findings give support for the preferential use of creatinine and cystatin C–based equations instead of creatinine-only or cystatin C–only equations in people with cancer.
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Affiliation(s)
- Silvia M. Titan
- Nephrology and Hypertension Division, Mayo Clinic, Rochester, Minnesota
| | - John C. Lieske
- Nephrology and Hypertension Division, Mayo Clinic, Rochester, Minnesota
| | | | - Stacy Thorson
- Biomedical Informatics, Center for Clinical and Translational Science, Mayo Clinic, Rochester, Minnesota
| | - Yi Lin
- Hematology Division, Mayo Clinic, Rochester, Minnesota
| | | | | | | | | | - Nelson Leung
- Nephrology and Hypertension Division, Mayo Clinic, Rochester, Minnesota
| | - Andrew D. Rule
- Nephrology and Hypertension Division, Mayo Clinic, Rochester, Minnesota
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22
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Eisinger F, Neumann M, Wörn M, Fritsche A, Heyne N, Peter A, Birkenfeld AL, von Schwartzenberg RJ, Artunc F. Comparison of GFR estimation in patients with diabetes mellitus using the EKFC and CKD-EPI equations. J Nephrol 2025; 38:707-716. [PMID: 39792299 PMCID: PMC11961541 DOI: 10.1007/s40620-024-02202-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 12/15/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND The estimation of glomerular filtration rate (eGFR) is essential in the early detection of diabetic nephropathy. We herein compare the performance of common eGFR formulas against a gold standard measurement of GFR in patients with diabetes mellitus. METHODS GFR was measured in 93 patients with diabetes mellitus using iohexol clearance as the reference standard. The performance of the creatinine- and cystatin C-based EKFC formulas (2021, 2023) and the CKD-EPI formulas (2009, 2012) was compared against measured GFR. RESULTS Sixty patients with type 2 diabetes mellitus and 33 patients with type 1 diabetes mellitus were included. The creatinine-based EKFC formula showed lower bias and higher accuracy than the CKD-EPI formula. No significant difference was observed between the cystatin C-based formulas. The combined creatinine- and cystatin C-based formulas had the highest accuracy and lowest bias. Body fat or diabetes type did not significantly influence the accuracy of the cystatin C-based formulas. CONCLUSIONS Our study demonstrated a slight advantage of the creatinine-based EKFC formula over the CKD-EPI formula in patients with diabetes. However, both for the CKD-EPI and the EKFC formula, the best performance was achieved by the combined creatinine- and cystatin C-based formulas.
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Affiliation(s)
- Felix Eisinger
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
| | - Mareike Neumann
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
| | - Matthias Wörn
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
| | - Andreas Fritsche
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
| | - Nils Heyne
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
| | - Andreas Peter
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
- Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital of Tuebingen, Tuebingen, Germany
| | - Andreas L Birkenfeld
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
| | - Reiner Jumpertz von Schwartzenberg
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
| | - Ferruh Artunc
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany.
- Southwest Clinic Network, Hospital Sindelfingen, Section Nephrology, Sindelfingen, Germany.
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23
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Delanaye P, Björk J, Vidal-Petiot E, Flamant M, Ebert N, Schaeffner E, Grubb A, Christensson A, Nyman U, Stehlé T, Pottel H. Diabetic status and the performances of creatinine- and cystatin C-based eGFR equations. Nephrol Dial Transplant 2025; 40:516-523. [PMID: 39013610 DOI: 10.1093/ndt/gfae161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Indexed: 07/18/2024] Open
Abstract
BACKGROUND The estimation of glomerular filtration rate (GFR) is one tool to detect renal disease. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equation is the most validated in Europe. More recently, cystatin C has been proposed as a biomarker. We studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status. METHODS Four cohorts from the EKFC dataset were retrospectively considered in which the diabetic status was available. GFR was measured by plasma clearances (mGFR; iohexol or chromium 51-ethylenediaminetetraacetic acid). The performance of the equations was assessed by calculating bias, precision [interquartile range (IQR)] and P30 (percentage of eGFR values within ±30% of mGFR). RESULTS In the whole population (N = 6158), the median age was 61 years (IQR 47-72) and 45.8% were women. The mean mGFR was 60 ml/min/1.73 m2 (IQR 39-82). Compared with non-diabetic individuals (n = 5124), diabetic patients (n = 1034) were older, more frequently male, heavier and had lower mGFR. The performance of the EKFCcys equation was similar to that of the EKFCcrea equation, but the EKFCcrea+cys equation had a better P30 than the single-biomarker equations. P30 values were substantially lower in diabetic patients than in non-diabetic patients, but according to a matched analysis, this is mainly explained by the difference in GFR levels between the two populations, not by diabetic status. CONCLUSION We showed that the equation combining creatinine and cystatin C performed better. If the accuracy of equations seems better in non-diabetic than in diabetic individuals, it is more likely due to differences in GFR levels rather than diabetic status.
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Affiliation(s)
- Pierre Delanaye
- Department of Nephrology, Dialysis, Transplantation, University of Liège, Centre Hospitalier Universitaire Sart Tilman, Liège, Belgium
- Department of Nephrology, Dialysis, Apheresis, Hôpital Universitaire Carémeau, Nîmes, France
| | - Jonas Björk
- Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
- Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden
| | - Emmanuelle Vidal-Petiot
- Assistance Publique-Hôpitaux de Paris, Bichat Hospital, and Université de Paris, UMR S1138, Cordeliers Research Center, Paris, France
| | - Martin Flamant
- Assistance Publique-Hôpitaux de Paris, Bichat Hospital, and Université de Paris, UMR S1138, Cordeliers Research Center, Paris, France
| | - Natalie Ebert
- Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany
| | - Elke Schaeffner
- Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany
| | - Anders Grubb
- Department of Clinical Chemistry, Skåne University Hospital, Lund University, Lund, Sweden
| | - Anders Christensson
- Department of Nephrology, Skåne University Hospital, Lund University, Malmö, Sweden
| | - Ulf Nyman
- Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö, Sweden
| | - Thomas Stehlé
- Université Paris Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Service de Néphrologie et Transplantation, Fédération Hospitalo-Universitaire Innovative Therapy for Immune Disorders, Créteil, France
| | - Hans Pottel
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
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24
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Cavalier E, Zima T, Datta P, Makris K, Schaeffner E, Langlois M, Plebani M, Delanaye P. Recommendations for European laboratories based on the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Clin Chem Lab Med 2025; 63:525-534. [PMID: 39584585 DOI: 10.1515/cclm-2024-1082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 11/01/2024] [Indexed: 11/26/2024]
Abstract
The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD) evaluation and management bring important updates, particularly for European laboratories. These guidelines emphasize the need for harmonization in CKD testing, promoting the use of regional equations. In Europe, the European Kidney Function Consortium (EKFC) equation is particularly suited for European populations, particularly compared to the CKD-EPI 2021 race-free equation. A significant focus is placed on the combined use of creatinine and cystatin C to estimate glomerular filtration rate (eGFRcr-cys), improving diagnostic accuracy. In situations where eGFR may be inaccurate or clinically insufficient, the guidelines encourage the use of measured GFR (mGFR) through exogenous markers like iohexol. These guidelines emphasize the need to standardize creatinine and cystatin C measurements, ensure traceability to international reference materials, and adopt harmonized reporting practices. The recommendations also highlight the importance of incorporating risk prediction models, such as the Kidney Failure Risk Equation (KFRE), into routine clinical practice to better tailor patient care. This article provides a European perspective on how these KDIGO updates should be implemented in clinical laboratories to enhance CKD diagnosis and management, ensuring consistency across the continent.
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Affiliation(s)
- Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CIRM, CHU de Liège, Liège, Belgium
| | - Tomáš Zima
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Pradip Datta
- Siemens Healthineers Diagnostics, Newark, DE, USA
| | - Konstantinos Makris
- Clinical Biochemistry Department, KAT General Hospital, Kifissia, Athens, Greece
| | - Elke Schaeffner
- Division of Nephrology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Michel Langlois
- Department of Laboratory Medicine, AZ St. Jan Hospital, Bruges, Belgium
| | - Mario Plebani
- Honorary Professor of Clinical Biochemistry and Clinical Molecular Biology, University of Padova, Padova, Italy
- Department of Pathology, University of Texas, Galveston, TX, USA
| | - Pierre Delanaye
- Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU de Liège, Belgium
- Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Nîmes, France
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25
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Jing S, Ge Y, Pan J, Chang P, Qiao X. The independent and interactive effects of heavy metal pollution and vitamin D deficiency on early kidney injury indicators: analysis of the National Health and Nutrition Examination Survey 2001-2004. BMC Public Health 2025; 25:719. [PMID: 39984925 PMCID: PMC11844014 DOI: 10.1186/s12889-025-21796-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 02/05/2025] [Indexed: 02/23/2025] Open
Abstract
BACKGROUND Heavy metals (e.g., cadmium, lead, mercury, etc.) can infiltrate the human body via diverse routes, with a propensity to accumulate in the kidney cortex, thereby precipitating kidney dysfunction. Vitamin D has been implicated in mitigating the oxidative stress and inflammatory reactions triggered by heavy metal exposure. However, the interplay between heavy metal toxicity and vitamin D deficiency in the context of incipient kidney injury remains an underexplored area of research. METHODS Utilizing data from the National Health and Nutrition Examination Survey spanning from 2001 to 2004, Our methodology leveraged spline smoothing within the framework of generalized additive models to more vividly elucidate the impact of heavy metal exposure and serum vitamin D levels on the trajectory of early kidney injury biomarkers (including albumin-to-creatinine ratio, β-2 microglobulin (B2M), cystatin C (CYST), and estimated glomerular filtration rate (eGFR) (serum creatinine(SCr)-based(eGFR), CYST-based eGFR, and SCr-CYST-based eGFR). Furthermore, we conducted an interaction analysis to assess the combined effects of heavy metal exposure and vitamin D deficiency on early kidney injury. RESULTS The cohort comprised 2,422 adults. Our results indicated that cadmium levels were positively correlated with B2M, CYST, and negatively correlated with eGFRc, eGFRs. Similarly, lead levels showed a positive correlation with ACR, B2M, and CYST, and negative correlation with eGFRc, eGFRc&s. In contrast, mercury levels were negatively correlated with B2M, CYST and positively correlated with eGFRc. In addition, there was an interaction between lead exposure and vitamin D deficiency in early kidney injury indicators (P for interaction: B2M: 0.028, CYST: 0.038, eGFRc&s: 0.011). CONCLUSIONS This study suggests a correlation between exposure to cadmium and lead and an increased risk of early kidney injury. It highlights the potential importance of targeted vitamin D supplementation and reduction in lead exposure in mitigating early kidney injury. However, these findings warrant validation through further prospective research.
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Affiliation(s)
- Shuhui Jing
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
- Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China
- Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Yuan Ge
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
- Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China
- Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Juan Pan
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
- Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China
- Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Pei Chang
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
- Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China
- Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Xi Qiao
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.
- Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China.
- Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China.
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26
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Iatridi F, Carrero JJ, Gall ECL, Kanbay M, Luyckx V, Shroff R, Ferro CJ. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease in Children and Adults: a commentary from the European Renal Best Practice (ERBP). Nephrol Dial Transplant 2025; 40:273-282. [PMID: 39299913 PMCID: PMC11792658 DOI: 10.1093/ndt/gfae209] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Indexed: 09/22/2024] Open
Abstract
The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Guideline for Identification and Management of Chronic Kidney Disease (CKD) is a welcome development, coming 12 years after the paradigm-changing 2012 guidelines. We are living in an unprecedented era in nephrology with novel therapies, including sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists, now being proven in multiple randomized controlled clinical trials to reduce both the progression of CKD and cardiovascular morbidity and mortality. The KDIGO 2024 CKD Guideline is aimed at a broad audience looking after children and adults with CKD and provide practical and actionable steps to improve care. This commentary reviews the guideline sections pertaining to the evaluation and risk assessment of individuals with CKD from a European perspective. We feel that despite the last guideline being published 12 years ago, and the fact that the assessment of CKD has been emphasized by many other national/international nephrology, cardiology and diabetology guidelines and societies, the diagnosis and treatment of CKD remains poor across Europe. As such, the KDIGO 2024 CKD Guideline should be seen as an urgent call to action to improve diagnosis and care of children and adults with CKD across Europe. We know what we need to do. We now need to get on and do it.
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Affiliation(s)
- Fotini Iatridi
- First Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Juan Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden
| | - Emilie Cornec-Le Gall
- University Brest, Inserm, UMR 1078, GGB, CHU Brest, Centre de Références Maladies Rénales Héréditaires de L'enfant et de L'adulte MARHEA, Brest, France
| | - Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koç University School of Medicine, Istanbul, Turkey
| | - Valerie Luyckx
- University Children's Hospital Zurich; Department of Public Health and Global Health, Epidemiology, Biostatistics and Prevention Institute, University of Zurich; Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Paediatrics and Child Health, University of Cape Town
| | - Rukshana Shroff
- Pediatric Nephrology Unit, University College London Great Ormond Street Hospital for Children and Institute of Child Health, London, UK
| | - Charles J Ferro
- Department of Renal Medicine University Hospitals Birmingham and Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
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27
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Ho FK, Mark PB, Lees JS, Pell JP, Strawbridge RJ, Kimenai DM, Mills NL, Woodward M, McMurray JJV, Sattar N, Welsh P. A Proteomics-Based Approach for Prediction of Different Cardiovascular Diseases and Dementia. Circulation 2025; 151:277-287. [PMID: 39540306 DOI: 10.1161/circulationaha.124.070454] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 09/27/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes. METHODS Among 51 859 UK Biobank participants (mean age, 56.7 years; 45.5% male) without cardiovascular disease and with proteomics measurements, we examined the primary composite outcome of fatal and nonfatal coronary heart disease, stroke, or heart failure (major adverse cardiovascular events), as well as additional secondary cardiovascular outcomes. An exposome-wide association study was conducted using relative protein concentrations, adjusted for a range of classic, demographic, and lifestyle risk factors. A prediction model using only age, sex, and protein markers (protein model) was developed using a least absolute shrinkage and selection operator-regularized approach (derivation: 80% of cohort) and validated using split-sample testing (20% of cohort). Their performance was assessed by comparing calibration, net reclassification index, and c statistic with the PREVENT (Predicting Risk of CVD Events) risk score. RESULTS Over a median 13.6 years of follow-up, 4857 participants experienced first major adverse cardiovascular events. After adjustment, the proteins most strongly associated with major adverse cardiovascular events included NT-proBNP (N-terminal pro B-type natriuretic peptide; hazard ratio [HR], 1.68 per SD increase), proADM (pro-adrenomedullin; HR, 1.60), GDF-15 (growth differentiation factor-15; HR, 1.47), WFDC2 (WAP four-disulfide core domain protein 2; HR, 1.46), and IGFBP4 (insulin-like growth factor-binding protein 4; HR, 1.41). In total, 222 separate proteins were predictors of all outcomes of interest in the protein model, and 86 were selected for the primary outcome specifically. In the validation cohort, compared with the PREVENT risk factor model, the protein model improved net reclassification (net reclassification index +0.09), and c statistic (+0.051) for major adverse cardiovascular events. The protein model also improved the prediction of other outcomes, including ASCVD (c statistic +0.035), myocardial infarction (+0.023), stroke (+0.024), aortic stenosis (+0.015), heart failure (+0.060), abdominal aortic aneurysm (+0.024), and dementia (+0.068). CONCLUSIONS Measurement of targeted protein biomarkers produced superior prediction of aggregated and disaggregated cardiovascular events. This study represents proof of concept for the application of targeted proteomics in predicting a range of cardiovascular outcomes.
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Affiliation(s)
- Frederick K Ho
- School of Health and Wellbeing (F.K.H., J.P.P., R.J.S.), University of Glasgow, UK
| | - Patrick B Mark
- School of Cardiovascular and Metabolic Health (P.B.M., J.S.L., J.J.V.M., N.S., P.W.), University of Glasgow, UK
| | - Jennifer S Lees
- School of Cardiovascular and Metabolic Health (P.B.M., J.S.L., J.J.V.M., N.S., P.W.), University of Glasgow, UK
- Glasgow Renal and Transplant Unit, NHS Greater Glasgow and Clyde, UK (J.S.L.)
| | - Jill P Pell
- School of Health and Wellbeing (F.K.H., J.P.P., R.J.S.), University of Glasgow, UK
| | - Rona J Strawbridge
- School of Health and Wellbeing (F.K.H., J.P.P., R.J.S.), University of Glasgow, UK
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden (R.J.S.)
- Health Data Research UK (HDR-UK), Glasgow, UK (R.J.S.)
| | - Dorien M Kimenai
- BHF Centre for Cardiovascular Science, University of Edinburgh, UK (D.M.K., N.L.M.)
| | - Nicholas L Mills
- BHF Centre for Cardiovascular Science, University of Edinburgh, UK (D.M.K., N.L.M.)
- Usher Institute, University of Edinburgh, UK (N.L.M.)
| | - Mark Woodward
- The George Institute for Global Health, School of Public Health, Imperial College London, UK (M.W.)
- The George Institute for Global Health, University of New South Wales, Sydney, Australia (M.W.)
| | - John J V McMurray
- School of Cardiovascular and Metabolic Health (P.B.M., J.S.L., J.J.V.M., N.S., P.W.), University of Glasgow, UK
| | - Naveed Sattar
- School of Cardiovascular and Metabolic Health (P.B.M., J.S.L., J.J.V.M., N.S., P.W.), University of Glasgow, UK
| | - Paul Welsh
- School of Cardiovascular and Metabolic Health (P.B.M., J.S.L., J.J.V.M., N.S., P.W.), University of Glasgow, UK
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Karger AB, Shlipak MG. Glomerular Filtration Rate (GFR) Estimation with Cystatin C-Past, Present, and Future. Clin Chem 2025:hvae226. [PMID: 39902788 DOI: 10.1093/clinchem/hvae226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 12/18/2024] [Indexed: 02/06/2025]
Abstract
BACKGROUND Cystatin C is a long-established filtration marker which can be used to assess kidney function, but it has been sparingly used for clinical care due to creatinine's role as the primary biomarker for kidney function assessment based on estimated glomerular filtration rate (eGFR). CONTENT This review summarizes the evolution of cystatin C's role in kidney disease assessment and highlights new guidelines promoting more widespread use. Specifically, the 2021 National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease report, and the 2024 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD), recommend increased use of cystatin C as an alternative and complementary biomarker for kidney function assessment, since it does not differ by race like creatinine, correlates better with adverse outcomes compared to creatinine, and provides a more accurate eGFR when used in combination with creatinine. SUMMARY While robust literature demonstrates improved accuracy with cystatin C-based eGFR (eGFRcys) in certain clinical subpopulations, future research is needed to better understand its performance relative to creatinine-based eGFR (eGFRcr) and measured glomerular filtration rate (mGFR) in additional diverse cohorts, and to achieve assay standardization to match the performance of creatinine assays. Additionally, cystatin C testing availability will need to be broadened from primarily reference laboratories to local laboratories, and partnerships will need to be developed between clinical stakeholders and the laboratory to promote cystatin C's clinical use, to achieve widespread adoption of guideline-recommended eGFR equations.
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Affiliation(s)
- Amy B Karger
- Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, United States
| | - Michael G Shlipak
- Kidney Health Research Collaborative, University of California San Francisco, San Francisco VA Healthcare System, San Francisco, CA, United States
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Yang H, Huang Y, Jiang G, Duan Z, Du R, Hao Y, Huang W, Liu X. Sex differences in the association between sarcopenia index and sarcopenia: a cross-sectional study from a Chinese community-based population. Eur Geriatr Med 2025; 16:55-65. [PMID: 39623162 PMCID: PMC11850426 DOI: 10.1007/s41999-024-01111-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 11/11/2024] [Indexed: 02/25/2025]
Abstract
PURPOSE The sarcopenia index (SI) is a convenient method to screen for sarcopenia, but few studies have analysed whether there are sex differences. The aim of this study was to analyse sex differences in the relationship between SI and sarcopenia in a Chinese community-based population. METHODS This cross-sectional study included participants from 2011 China Health and Retirement Longitudinal Study. The SI was defined as 100 × creatinine / cystatin C. Diagnosis of sarcopenia based on the Asian Working Group for Sarcopenia 2019 consensus. Logistic regression model, linear regression model, and natural spline model were used to analyze the association between SI and sarcopenia. RESULTS A total of 7,118 participants with a mean age of 60.6 ± 10.1 were included, 53.4% females. In males, the prevalence of sarcopenia decreased by 25% for every 10 increase in SI, and skeletal muscle mass index (SMI) increased by 0.04, odds ratio (OR), β, and 95% confidence interval (CI) were 0.75 (0.65-0.87), 0.04 (0.02-0.05), both P < 0.001. In females, the SI was not significantly associated with sarcopenia, OR and 95% CI were 0.99 (0.9 ~ 1.08), P = 0.775; for every 10 increase in SI, the SMI in females decreased by 0.03, β and 95% CI were -0.03 (-0.04 ~ -0.01), P = 0.001. CONCLUSION In the Chinese community, the SI is negatively associated with sarcopenia in males and has moderate diagnostic test performance. It was not associated with sarcopenia in females, and using the SI to screen for sarcopenia in females may not be a reliable method.
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Affiliation(s)
- Hong Yang
- Department of Geriatrics, The Third People's Hospital of Yunnan Province, 292 Beijing Road, Kunming, 650011, Yunnan, China
| | - Yunda Huang
- Department of Geriatrics, The Third People's Hospital of Yunnan Province, 292 Beijing Road, Kunming, 650011, Yunnan, China
| | - Guihua Jiang
- Department of Geriatrics, The Third People's Hospital of Yunnan Province, 292 Beijing Road, Kunming, 650011, Yunnan, China
| | - Zhiping Duan
- Department of Geriatrics, The Third People's Hospital of Yunnan Province, 292 Beijing Road, Kunming, 650011, Yunnan, China
| | - Runfen Du
- Department of Geriatrics, The Third People's Hospital of Yunnan Province, 292 Beijing Road, Kunming, 650011, Yunnan, China
| | - Yinan Hao
- Department of Geriatrics, The Third People's Hospital of Yunnan Province, 292 Beijing Road, Kunming, 650011, Yunnan, China
| | - Wei Huang
- Department of Geriatrics, The Third People's Hospital of Yunnan Province, 292 Beijing Road, Kunming, 650011, Yunnan, China.
| | - Xiaoling Liu
- Radiotherapy Department, Yunnan Cancer Hospital, No. 519 Kunzhou Road, Kunming, 650118, Yunnan, China.
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Navaneethan SD, Bansal N, Cavanaugh KL, Chang A, Crowley S, Delgado C, Estrella MM, Ghossein C, Ikizler TA, Koncicki H, St Peter W, Tuttle KR, William J. KDOQI US Commentary on the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD. Am J Kidney Dis 2025; 85:135-176. [PMID: 39556063 DOI: 10.1053/j.ajkd.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 08/04/2024] [Indexed: 11/19/2024]
Abstract
The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the 2024 KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the management of chronic kidney disease (CKD). The KDOQI Work Group reviewed the KDIGO guideline statements and practice points and provided perspective for implementation within the context of clinical practice in the United States. In general, the KDOQI Work Group concurs with several recommendations and practice points proposed by the KDIGO guidelines regarding CKD evaluation, risk assessment, and management options (both lifestyle and medications) for slowing CKD progression, addressing CKD-related complications, and improving cardiovascular outcomes. The KDOQI Work Group acknowledges the growing evidence base to support the use of several novel agents such as sodium/glucose cotransporter 2 inhibitors for several CKD etiologies, and glucagon-like peptide 1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists for type 2 CKD in setting of diabetes. Further, KDIGO guidelines emphasize the importance of team-based care which was also recognized by the work group as a key factor to address the growing CKD burden. In this commentary, the Work Group has also assessed and discussed various barriers and potential opportunities for implementing the recommendations put forth in the 2024 KDIGO guidelines while the scientific community continues to focus on enhancing early identification of CKD and discovering newer therapies for managing kidney disease.
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Affiliation(s)
- Sankar D Navaneethan
- Section of Nephrology, Department of Medicine, Selzman Institute for Kidney Health and Institute of Clinical and Translational Research, Baylor College of Medicine, Houston, Texas; Section of Nephrology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
| | - Nisha Bansal
- Cardiovascular Health Research Unit, Department of Medicine, Washington
| | - Kerri L Cavanaugh
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Alexander Chang
- Department of Population Health Sciences, Geisinger, Danville, Pennsylvania
| | - Susan Crowley
- Section of Nephrology, Department of Medicine, School of Medicine, Yale University, New Haven, Connecticut; Kidney Medicine Section, Medical Services, VA Connecticut Healthcare System, West Haven, Connecticut
| | - Cynthia Delgado
- Nephrology Section, San Francisco Veterans Affairs Health Care System, San Francisco, California; Division of Nephrology, University of California-San Francisco, San Francisco, California
| | - Michelle M Estrella
- Nephrology Section, San Francisco Veterans Affairs Health Care System, San Francisco, California; Division of Nephrology, University of California-San Francisco, San Francisco, California
| | - Cybele Ghossein
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - T Alp Ikizler
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Holly Koncicki
- Division of Nephrology, Mount Sinai Health System, New York, New York
| | - Wendy St Peter
- College of Pharmacy, University of Minnesota, Minneapolis, Minnesota
| | - Katherine R Tuttle
- Institute of Translational Health Sciences, Kidney Research Institute, and Nephrology Division, Washington; School of Medicine, University of Washington, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington
| | - Jeffrey William
- Division of Nephrology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
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Villain C, Ebert N, Glassock RJ, Mielke N, Bothe T, Barghouth MH, Pöhlmann A, Fietz AK, Gill JS, Schaeffner E. Medical Suitability and Willingness for Living Kidney Donation Among Older Adults. Am J Kidney Dis 2025; 85:205-214.e1. [PMID: 39362396 DOI: 10.1053/j.ajkd.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 07/04/2024] [Accepted: 07/17/2024] [Indexed: 10/05/2024]
Abstract
RATIONALE & OBJECTIVE The benefits of kidney transplantation compared with treatment with dialysis, including in older adults, are primarily limited by the number of donated kidneys. We studied the potential to expand the use of older living kidney donors. STUDY DESIGN Secondary analysis of the Berlin Initiative Study, a population-based cohort. SETTING & PARTICIPANTS 2,069 adults aged≥70 years in Germany. EXPOSURE Age and sex. OUTCOME Suitability for living donation assessed by the absence of kidney-related exclusions for donation including albuminuria and low estimated glomerular filtration rate (eGFR) as well as absence of other medical exclusions. Willingness for living and deceased kidney donation assessed by participant survey. ANALYTICAL APPROACH Descriptive analysis. RESULTS Among the 2,069 participants (median age 80 years, 53% women, median eGFR 63mL/min/1.73m2), 93% had≥1 medical contraindication for living donation at study entry unrelated to eGFR or albuminuria. Using 2 published eGFR and albuminuria thresholds for donor acceptance, 38% to 54% of participants had kidney-related exclusions for donation. Among the 5% to 6% of participants with neither medical nor kidney-related exclusions for living donation at baseline, 11% to 12% remained suitable for donation during 8 years of follow-up. Willingness for living or deceased donation was high (73% and 60%, respectively). LIMITATIONS GFR was not measured, and medical exclusions unrelated to eGFR and albuminuria were assessed using a cohort database complemented by claims data. CONCLUSIONS One in 20 older adults were potentially suitable for living kidney donation, and willingness for living donation was high. Further studies are warranted to define the feasibility of expanding living kidney donation among older adults. PLAIN-LANGUAGE SUMMARY Although potentially beneficial, kidney transplantation remains infrequent among older adults aged≥70 years with kidney failure. Study evaluated the potential to increase living kidney donation among older adults, including their medical suitability as well as willingness to donate. Among 2,069 community-dwelling older adults (median age 80 years), 5% to 6% had no exclusion to donation. Among these individuals, 11% to 12% remained suitable for donation during 8 years of follow-up. Most exclusions were not related to eGFR and albuminuria. Willingness to living donation was high (73%). These findings highlight the potential benefits from expanding the pool of transplantable kidneys through the use of living donation in older adults.
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Affiliation(s)
- Cédric Villain
- Institute of Public Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Geriatric Medicine, Centre Hospitalier Universitaire de Caen Normandie, Normandie University, UNICAEN, INSERM U1075, COMETE, Caen, France
| | - Natalie Ebert
- Institute of Public Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Richard J Glassock
- Department of Medicine, Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California
| | - Nina Mielke
- Institute of Public Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Tim Bothe
- Institute of Public Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Muhammad Helmi Barghouth
- Institute of Public Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Anna Pöhlmann
- Institute of Public Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Anne-Katrin Fietz
- Institute of Public Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - John S Gill
- Division of Nephrology, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
| | - Elke Schaeffner
- Institute of Public Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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Mommaerts K, Monzel AS, Zagare A, Nickels SL, Diederich NJ, Longhino L, Mathieson W, Antony PMA, Betsou F, Schwamborn JC. Cystatin C Secretion in Blood Derivatives and Cellular Models of Idiopathic Parkinson's Disease. PARKINSON'S DISEASE 2025; 2025:5149071. [PMID: 39958955 PMCID: PMC11824396 DOI: 10.1155/padi/5149071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 09/26/2024] [Accepted: 12/05/2024] [Indexed: 02/18/2025]
Abstract
Parkinson's disease is an age-related progressive neurodegenerative disorder. A large majority of Parkinson's disease patients have an unknown etiology, which is classified as idiopathic Parkinson's disease. Generating disease models directly from idiopathic Parkinson's disease patients may improve the understanding of the disease pathology. Both neuroprotective and neurodegenerative roles have been suggested for cystatin C in neurodegenerative disease. In Parkinson's disease, investigations assessing cystatin C levels in different types of biospecimens such as blood, cerebrospinal fluid, and in vitro models have had conflicting results. We present a study assessing cystatin C levels in different biospecimen types originating from the same subjects. Using a sandwich ELISA, we compared cystatin C concentration in blood derivatives (plasma and serum) and culture media of derived models (stem cells, neuroepithelial stem cells, and midbrain organoids) of three idiopathic Parkinson's disease and three age-matched healthy control subjects with the same CST3 genotype. Genotyping analyses confirmed that all subjects were homozygous AA. The identity of the derived models was confirmed using immunohistochemical staining. Secreted cystatin C concentration was measured in each biospecimen tested. No statistically significant differences in cystatin C concentrations were found between the subjects in any of the biospecimen types. As a personalized marker, a higher cystatin C concentration was shown for some individual patients in the culture medium of midbrain organoids, suggesting a potential involvement in Parkinson's disease physiopathology. This proof of concept demonstrates that cystatin C is secreted by various idiopathic Parkinson's disease cell models, including midbrain organoids, which in turn suggests that cystatin C secretion by midbrain organoids might be pertinent in neurodegenerative disease research.
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Affiliation(s)
- Kathleen Mommaerts
- Integrated Biobank of Luxembourg, Luxembourg Institute of Health, Dudelange, Luxembourg
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Anna S. Monzel
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Alise Zagare
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Sarah L. Nickels
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Nico J. Diederich
- Department of Neurosciences, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg
| | - Laura Longhino
- Department of Neurosciences, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg
| | - William Mathieson
- Integrated Biobank of Luxembourg, Luxembourg Institute of Health, Dudelange, Luxembourg
| | - Paul M. A. Antony
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Fay Betsou
- Centre de Ressources Biologiques de l'Institut Pasteur, Institut Pasteur, Paris, France
| | - Jens C. Schwamborn
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
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Ye Z, Wang H, Xie E, Zhou Z, Dou K. The Superiority of European Kidney Function Consortium Cystatin C-Based Formula for Risk Stratification of All-Cause and Cardiovascular Deaths in US Adults. Am J Nephrol 2025; 56:267-278. [PMID: 39827845 DOI: 10.1159/000542912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 11/28/2024] [Indexed: 01/22/2025]
Abstract
INTRODUCTION We intended to compare the predictive value for all-cause and cardiovascular deaths between estimated glomerular filtration rate (eGFR) derived from the European Kidney Function Consortium (EKFC) cystatin C-based formula, the EKFC creatinine-based formula, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C- or creatinine-based formulas. METHODS Overall, 4,132 participants from the National Health and Nutrition Examination Survey between 1999 and 2002 were included, and death information was obtained through the National Death Index. To compare predictive accuracy between EKFC eGFRcys (EKFC cystatin C-based formula), CKD-EPI eGFRcys (CKD-EPI cystatin C-based formula), EKFC eGFRcr (EKFC creatinine-based formula), and CKD-EPI eGFRcr (CKD-EPI creatinine-based formula), we conducted time-dependent receiver operator characteristic (ROC) curves and reclassification analysis. RESULTS During a median follow-up of 17.4 years, a total of 1,987 all-cause and 530 cardiovascular deaths were confirmed. Restricted cubic splines analyses showed that reduced EKFC eGFRcys was linearly related to higher risks of all-cause and cardiovascular deaths (p for nonlinearity > 0.05). Time-dependent ROC curves suggested that EKFC eGFRcys exhibited higher predictive ability than CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr at 5-year and 10-year follow-ups. For 10-year all-cause deaths, EKFC eGFRcys yielded significant improvement over CKD-EPI eGFRcr (integrated discrimination improvement [IDI], 9.4%; net reclassification improvement [NRI], 39.7%). Similar improvement was observed in 10-year cardiovascular deaths when comparing EKFC eGFRcys to CKD-EPI eGFRcr (IDI, 6.7%; NRI, 45.1%). CONCLUSION The EKFC eGFRcys outperformed CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr in predicting all-cause and cardiovascular deaths, providing the possibility to utilize EKFC eGFRcys in the stratification of death risk among the general US population.
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Affiliation(s)
- Zixiang Ye
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haixu Wang
- National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, China
| | - Enmin Xie
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zeming Zhou
- National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, China
| | - Kefei Dou
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, China
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Morales-Betanzos C, Berasi SP, Federspiel JD, Neubert H, Fernandez Ocana M. Development of a Multiplexed LC-MS/MS Assay for the Quantitation of Podocyte Injury Biomarkers Nephrin, Podocalyxin, and Podocin in Human Urine. J Proteome Res 2025; 24:282-288. [PMID: 39651829 PMCID: PMC11705212 DOI: 10.1021/acs.jproteome.4c00751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/11/2024] [Accepted: 11/26/2024] [Indexed: 01/04/2025]
Abstract
CKD is frequently diagnosed only after a significant progression. GFR is the most common indicator of kidney function but is limited in detecting early CKD cases and distinguishing glomerular, tubular, and global CKD. Aiming to provide a glomeruli specific biomarker assay, we developed a peptide immunoaffinity targeted mass spectrometry method for the quantitation of three podocyte specific proteins in human urine: nephrin, podocalyxin, and podocin. Proteins in urine were precipitated, stable isotope labeled peptide standards incorporated, and digested with trypsin. Target peptides were enriched using an online antibody column prior to LC-MS/MS. The performance metrics for nephrin, podocalyxin, and podocin were evaluated: The lower limits of quantitation were 3.8, 22.0, and 5.4 pM, respectively. The intraplate relative error (RE) was within ±10.6%, ± 10.4%, and ±16.1%, and coefficient of variation (CV) was ≤27.2%, ≤ 14.1%, and ≤20.7% accordingly. The interplate RE was within ±7.0%, ± 3.8%, and ±3.0%, and CV was ≤17.2%, ≤ 12.1%, and ≤20.0% for the three analytes. The urinary nephrin, podocalyxin, and podocin concentrations in 60 healthy volunteers and 20 disease samples was measured, thereby establishing the basal levels of these protein and enabling future evaluation of their roles as noninvasive biomarkers of glomerular injury in the clinic.
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Izzedine H, Jhaveri KD, Courbebaisse M. More on Selpercatinib and Pseudo-Decreases in Kidney Function. Reply. N Engl J Med 2025; 392:104. [PMID: 39752314 DOI: 10.1056/nejmc2413668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/10/2025]
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Schaeffner E. [Chronic Kidney Disease: epidemiology, implications for clinical practice and equations for diagnosis]. Dtsch Med Wochenschr 2025; 150:77-82. [PMID: 39809430 DOI: 10.1055/a-2265-9422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
The article is based, among other things, on the updated KDIGO guideline for the evaluation and management of chronic kidney disease, which was published in Kidney International in March 2024. Chronic kidney disease is one of the most common chronic diseases, with a prevalence of around 10%, not least due to demographic ageing. The incidence of chronic kidney disease is approximately twice that of diabetes and approximately 20 times higher than that of cancer. Chronic kidney disease is classified using glomerular filtration rate and albuminuria. The definition of CKD may also include markers other than GFR and ACR. Patients with diabetes or hypertension should have GFR and ACR tested regularly. The individual risk of kidney failure requiring dialysis can be determined using a prediction equation. A better understanding of age- and gender-specific differences means that personalized therapy approaches are becoming increasingly important. Clinicians should be aware of the limitations of the endogenous biomarkers creatinine and cystatin C for determining GFR. For Germany, the equations of the European Kidney Function Consortium (EKFC) are recommended for estimating GFR.
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Puhr HC, Winkler EC, Preusser M. Ethnic origin in cancer clinical trials: overrated or understated? A comprehensive analysis of cancer clinical trials leading to FDA and EMA approvals between 2020 and 2022. ESMO Open 2025; 10:104093. [PMID: 39754982 PMCID: PMC11758121 DOI: 10.1016/j.esmoop.2024.104093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 11/11/2024] [Accepted: 11/25/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Ethnic diversity in cancer clinical trials is essential to ensure that therapeutic advances are equitable and broadly applicable in multicultural societies. Yet, missing consensus on the documentation of ethnic origin, partially based on the complexity of the terminology and fear of discrimination, leads to suboptimal patient management of minority populations. Additionally, eligibility criteria, such as stringent laboratory cut-offs, often fail to account for variations across ethnic groups, potentially excluding patients without evidence-based justification. PATIENTS AND METHODS This analysis addresses this issue by investigating ethnic diversity in clinical trials that led to European Medicines Agency (EMA) and Food and Drug Administration (FDA) approvals between 2020 and 2022. Trials were identified from FDA and EMA databases, and available protocols and full-text publications were reviewed for documentation of ethnic background and eligibility criteria for organ function (bone marrow, liver, and renal). Descriptive statistics were applied to summarize the findings. RESULTS Of the 56 trials analyzed, only two-thirds of primary result publications included information on ethnic origin. Caucasian and Asian groups were documented in most of those trials and also had the highest percentages of participants across trials, while other ethnic subgroups were less frequently documented and only made up a small proportion of trial participants. Eligibility criteria often set strict organ function cut-offs that did not consider variations among ethnic groups, potentially excluding minorities. The Cockcroft-Gault formula was frequently used to assess kidney function, despite its known limitations for multiethnic cohorts. CONCLUSIONS Ethnic homogenous participants and eligibility criteria that favor majority groups limit the applicability of findings in diverse populations, leading to inadequate patient management. While United States guidelines encourage inclusivity, similar recommendations are lacking in Europe. Thus European regulatory authorities, research organizations, and patient advocates should establish guidelines to improve ethnic diversity in cancer clinical trials, aligning research practices with the increasingly multicultural composition of European societies.
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Affiliation(s)
- H C Puhr
- Division of Oncology, Department of Medicine I, Medical University Vienna, Vienna, Austria. https://twitter.com/Hannah_C_Puhr
| | - E C Winkler
- Section for Translational Medical Ethics, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | - M Preusser
- Division of Oncology, Department of Medicine I, Medical University Vienna, Vienna, Austria.
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Huang T, Luo Y, Wu Y, Niu L, Xiao Y, Wu T, Chen X, Liu Y, Lu J, Zhu D, Liu T. Population pharmacokinetics of colistin sulfate in patients on continuous veno-venous hemodiafiltration. Sci Prog 2025; 108:368504251325334. [PMID: 40033936 PMCID: PMC11877486 DOI: 10.1177/00368504251325334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
OBJECTIVE The aim of this study is to establish a population pharmacokinetic (PK) model for patients undergoing continuous veno-venous hemodiafiltration (CVVHDF) and optimize the dosing regimen of colistin sulfate. METHODS A prospective observational study in a single center was conducted on patients who were administrated with colistin sulfate and CVVHDF for at least 48 h. Blood samples were obtained prior to dosing and four to six blood samples (primarily C0.5h, C1h, C2h, C4h, and C6h) after dosing. The blood concentration of colistin sulfate was determined by ultra-high performance liquid chromatography-tandem mass spectrometry assay. The NONMEM program was used to establish the population PK model and perform Monte Carlo simulations. The predictability and stability of the model were internally evaluated by the goodness of fit plots, visual prediction check, and bootstraps. RESULTS A total of 86 plasma concentrations from 20 patients were used for population PK modeling. A two-compartment model with first-order linear elimination best described the population PK characteristics of colistin sulfate. Cystatin C (CysC) and body weight (WT) were identified as covariates for clearance (CL). Internal evaluation results showed that the final model had good stability and prediction performance. Monte Carlo simulations showed that only when the body WT was 50 kg with CysC ≥3.07 mg/l, and when the body WT was 65 kg with CysC = 5.11 mg/l, and minimum inhibitory concentration (MIC) = 0.25 mg/l, the target attainment probability (PTA) of the daily dose of 1.5 million U regimen was ≥90%. All treatment regimens fail to achieve the target PTA when MIC = 1 mg/l. CONCLUSIONS With the decrease of CysC levels and the increase of WT, the dose of colistin sulfate may need to be increased. It may be prudent for colistin sulfate to consider an initial dose doubling and subsequent maintenance dosing regimen of 200-225 million unit daily, administered in 2-3 divided doses, to attain PTA standard. This study was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR2300072191).
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Affiliation(s)
- Tianmin Huang
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yilin Luo
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yun Wu
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Lulu Niu
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yang Xiao
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Tingqing Wu
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xin Chen
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yongjun Liu
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jiejiu Lu
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Donglan Zhu
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Taotao Liu
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Åkesson A, Malmgren L, Leion F, Nyman U, Christensson A, Björk J, Grubb A. Different ways of diagnosing selective glomerular hypofiltration syndromes such as shrunken pore syndrome and the associated increase in mortality. J Intern Med 2025; 297:79-92. [PMID: 39560353 PMCID: PMC11636450 DOI: 10.1111/joim.20035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2024]
Abstract
BACKGROUND In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed "Shrunken pore syndrome." Numerous studies have thereafter found an association between this syndrome (defined by a low eGFRcystatin C to eGFRcreatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFRcystatin C and eGFRcreatinine to describe a similar disorder, and this investigation compares the two measures. METHODS Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFRdifference and the eGFRratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated. RESULTS Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 "healthy" individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria. CONCLUSION The eGFRdifference is not superior to the eGFRratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification.
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Affiliation(s)
- Anna Åkesson
- Division of Occupational and Environmental MedicineLund UniversityLundSweden
- Clinical Studies SwedenForum SouthSkåne University HospitalLundSweden
| | - Linnea Malmgren
- Department of Clinical Sciences MalmöClinical and Molecular Osteoporosis Research UnitLund UniversityMalmöSweden
- Department of GeriatricsSkåne University HospitalMalmöSweden
| | - Felicia Leion
- Department of Clinical ChemistrySkåne University HospitalLund UniversityLundSweden
| | - Ulf Nyman
- Department of Translational MedicineDivision of Medical RadiologyUniversity of LundMalmöSweden
| | | | - Jonas Björk
- Division of Occupational and Environmental MedicineLund UniversityLundSweden
- Clinical Studies SwedenForum SouthSkåne University HospitalLundSweden
| | - Anders Grubb
- Department of Clinical ChemistrySkåne University HospitalLund UniversityLundSweden
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Lin Y, Huang J. Hypertension Risk and Kidney Function Following Kidney Donation. JAMA 2024; 332:2036. [PMID: 39565599 DOI: 10.1001/jama.2024.21427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Affiliation(s)
- Yifei Lin
- Department of Urology, West China Hospital of Sichuan University, Chengdu, China
| | - Jin Huang
- Lab of Health Data Science, West China Hospital of Sichuan University, Chengdu, China
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Peruzzo S, Ottaviani S, Tagliafico L, Muzyka M, Ponzano M, Marelli C, Signori A, Nencioni A, Monacelli F. Renal function assessment in older people: comparative analysis of estimation equation with serum creatinine. Front Med (Lausanne) 2024; 11:1477500. [PMID: 39697206 PMCID: PMC11652175 DOI: 10.3389/fmed.2024.1477500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 11/21/2024] [Indexed: 12/20/2024] Open
Abstract
Introduction Age-related changes occurring in the kidney can lead to a reduction in Glomerular Filtration Rate (GFR); especially in older adults with multimorbidity and/or frailty, an accurate evaluation of kidney function is critical. For the estimation of GFR in patients over 70 years, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) is often used. However, validated equations exist for old-age populations like BIS1 (Berlin Initiative Study 1) and FAS (Full Age Spectrum). Here we aimed to compare the performance of CKD-EPI, MDRD (Modification of Diet in Renal Disease), BIS1, and FAS in assessing eGFR in a population of patients over 70, to evaluate which equations show the most accurate performance in our setting. Materials and methods A total of 499 older adults were consecutively recruited in the Orthogeriatric ward and Oncogeriatrics clinic of IRCCS Polyclinic San Martino in Genoa Italy. eGFR was calculated using CKD-EPI, MDRD, BIS1, and FAS, calculating mean, median, standard deviation, and interquartile range. Bland-Altman graphs were used to evaluate how each equation performs with respect to the others and the concordance of the attribution of the KDIGO CKD stage was performed with Cohen's K constant and chi-squared test. Results Patients' mean age was 82.6 years (± 7.44), and the mean creatinine value was 0.97 (± 0.71) mg/dl. The mean value of eGFR was 70 mL/min with CKD-EPI (± 20.6) and MDRD (± 25.7), 57 mL/min with BIS1 (± 16.7) and FAS (± 19.0), respectively. BIS1 and FAS estimated lower eGFR values than CKD-EPI and MDRD. As age increases, a steady decrease in filtrate value is observed with BIS1 and FAS. MDRD and CDK-EPI do not show the same trend. The performance of the equations at a fixed eGFR value of 30 mL/min is more linear for BIS1 and FAS compared with CKD-EPI and MDRD. Upon evaluation with chi-square, the attribution of KDIGO stage was statistically different among the various equations. Discussion An appropriate assessment of renal function is of key clinical relevance to prevent adverse outcomes and risk of drug accumulation in older adults. Our study originally showed that in persons aged more than 70 years old BIS1 is the most accurate formula in calculating eGFR values when only serum creatinine is available.
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Affiliation(s)
- Stefania Peruzzo
- Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
- Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Silvia Ottaviani
- Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
- Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Luca Tagliafico
- Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
- Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Mariya Muzyka
- Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
- Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Marta Ponzano
- Department of Health Sciences – Section of Biostatistics, University of Genoa, Genoa, Italy
| | - Cristina Marelli
- Department of Health Sciences – Section of Biostatistics, University of Genoa, Genoa, Italy
| | - Alessio Signori
- Department of Health Sciences – Section of Biostatistics, University of Genoa, Genoa, Italy
| | - Alessio Nencioni
- Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
- Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Fiammetta Monacelli
- Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
- Ospedale Policlinico San Martino IRCCS, Genoa, Italy
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Yadav AK, Kaur J, Kaur P, Kamboj K, Yasuda Y, Horio M, Pal A, Shafiq N, Sahni N, Kohli HS, Matsuo S, Kumar V, Jha V. Evaluation of Race-Neutral Glomerular Filtration Rate Estimating Equations in an Indian Population. Kidney Int Rep 2024; 9:3414-3426. [PMID: 39698357 PMCID: PMC11652306 DOI: 10.1016/j.ekir.2024.09.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 09/26/2024] [Accepted: 09/30/2024] [Indexed: 12/20/2024] Open
Abstract
Introduction Glomerular filtration rate (GFR) estimation equations have not been extensively validated in the Indian population. Preliminary data showed that the widely used creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr) 2009 significantly overestimated GFR in Indians. Newer estimated GFR (eGFR) equations based on creatinine and cystatin C, omitting the race, have been recently proposed. We investigated the performance of race-free eGFR equations in the Indian population. Methods Patients with chronic kidney disease (CKD) and potential kidney donors attending the outpatient clinic at the Postgraduate Institute of Medical Education and Research Chandigarh, India, were screened for enrolment. GFR was measured by urinary clearance of inulin and plasma clearance of iohexol. Performance of eGFR equations (CKD-EPICr(2021), CKD-EPICr-Cys(2021), CKD-EPICr(2009), CKD-EPICr-Cys(2012), CKD-EPICys, 2020Csy-B2M-BTP and 2020Cr-Csy-B2M-BTP, EKFCcr, EKFCcys, and EKFCcr-cys) were assessed against measured GFR (mGFR) using bias, precision, and accuracy (root mean square error [RMSE], mean absolute error [MAE] and P30 [% with eGFR within 30% of mGFR]). Results A total of 412 subjects (55% with CKD), average age 47 ± 11 years with an equal distribution of males and females were enrolled. The mean mGFR in the study population was 54.2 ± 30.2 ml/min per 1.73 m2. The average mGFR in the potential kidney donor's subgroup was 79.5 ± 23.2 ml/min per 1.73 m2. Bias was highest for creatinine-based eGFR equations (CKD-EPIcr(2021): -19.2 [-21.3 to -17.0] ml/min per 1.73 m2and CKD-EPIcr(2009): -17.0 [-19.1 to -15.0] ml/min per 1.73 m2). Cystatin C- (either alone or with other markers) based equations were slightly better but still did not reach P30 ≥ 80%. Conclusions Race-neutral CKD-EPICr(2021) equation did not significantly improve performance as compared to CKD-EPICr(2009) equation. These observations emphasize the need for developing new eGFR equations for Indians and to standardize the mGFR for easy access to care providers for individualized patient care.
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Affiliation(s)
- Ashok Kumar Yadav
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jaskiran Kaur
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Prabhjot Kaur
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Kajal Kamboj
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yoshinari Yasuda
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Department of CKD Initiatives, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masaru Horio
- Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Arnab Pal
- Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nusrat Shafiq
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nancy Sahni
- Department of Dietetics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Harbir Singh Kohli
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Seiichi Matsuo
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Vivek Kumar
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vivekanand Jha
- The George Institute for Global Health, New Delhi
- School of Public Health, Imperial College, London, UK
- Manipal Academy of Higher Education, Manipal, India
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Engole Mompango Y, Bukabau Busanga J, Makulo Rissassy JR, Nlandu Mayamba Y, Makanzu B, Nkodila A, Tshiswaka T, Mokoli Momeme V, Longo Luzayadio A, Mboliasa Ingole MF, Kajingulu Musungayi F, Fwana S, Ilunga Kabemba C, Nkondi Nsenga C, Zinga Vuvu C, Nseka Mangani N, Sumaili Kiswaya E. Prevalence and associated factors of glomerular hyperfiltration among adult stable sickle cells in Kinshasa, DR Congo. Ren Fail 2024; 46:2407888. [PMID: 39329176 PMCID: PMC11441020 DOI: 10.1080/0886022x.2024.2407888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 09/18/2024] [Accepted: 09/18/2024] [Indexed: 09/28/2024] Open
Abstract
INTRODUCTION Glomerular hyperfiltration is highly frequent, theoretically dependent on cardiac output, low systemic vascular resistance and hemolysis markers. In sickle cell disease (SCD), hyperfiltration is an extremely common phenomenon and occurred in young and early adult patients. Despite the fact that the glomerular hyperfiltration is known as the early manifestations of sickle cell nephropathy, its burden among adult sickle cell disease in sub-Saharan is poor studied. This study aimed to determine the prevalence and associated factors of hyperfiltration. METHODS This was an analytical multicentric cross-sectional study involving stable adult sickle cell patients in Kinshasa, recruited between March and October 2023. Parameters of interest encompasses demographic, clinical, biological, echocardiographic and pulse wave measurement data. Hyperfiltration was defined using the CDK-EPI equation based on cystatin C; eGFR >130 for women and >140 ml/min/1.73m2 for men. We used multivariate logistic regression analysis to search determinants of glomerular hyperfiltration. RESULTS Two hundred and fourty six (246) patients with SCD were enrolled. The prevalence of hyperfiltration was 20.7%. In multiple logistic regression analysis, hyperfiltration status was independently associated with age (< 25 years) [3.57 (1.78-7.49); p = 0.027)], female sex [4.36 (2.55-5.62); p = 0.031), CRP (< 6 mg/l) [0.77 (0.61-0.97); p = 0.028)], central systolic pressure (< 100 mmHg) and central diastolic pressure (< 60 mmHg) [0.86(0.74-0.98), p = 0.028)], [(0.83 (0.71-0.98); p = 0.032)]. CONCLUSION One out of five SS adults exhibits hyperfiltration, which is associated with young age and female sex, whereas low CRP and blood pressure were negative risk factors.
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Affiliation(s)
- Yannick Engole Mompango
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
- Specialized Clinics in Kinshasa, Kinshasa, Democratic Republic of the Congo
| | - Justine Bukabau Busanga
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | | | - Yannick Nlandu Mayamba
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
- Specialized Clinics in Kinshasa, Kinshasa, Democratic Republic of the Congo
| | - Brady Makanzu
- Specialized Clinics in Kinshasa, Kinshasa, Democratic Republic of the Congo
- Cardiology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | - Aliocha Nkodila
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | - Tresor Tshiswaka
- Cardiology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | - Vieux Mokoli Momeme
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | | | | | | | - Shekinah Fwana
- Specialized Clinics in Kinshasa, Kinshasa, Democratic Republic of the Congo
| | - Cedric Ilunga Kabemba
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | - Clarisse Nkondi Nsenga
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | - Chantal Zinga Vuvu
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | - Nazaire Nseka Mangani
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
| | - Ernest Sumaili Kiswaya
- Nephrology Unit, Kinshasa University Hospital, Kinshasa, XI, Democratic Republic of the Congo
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Zheng G, Cheng Y, Wang C, Wang B, Zou X, Zhou J, Peng L, Zeng T. Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis. Ren Fail 2024; 46:2367028. [PMID: 39010723 PMCID: PMC11265307 DOI: 10.1080/0886022x.2024.2367028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 06/06/2024] [Indexed: 07/17/2024] Open
Abstract
BACKGROUND Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous. METHODS Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999-2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells' mediating roles in the FI-CKD relationship. RESULT Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD. CONCLUSION Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population.
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Affiliation(s)
- Guanghao Zheng
- Department of Medicine, Graduate School of Nanchang University, Nanchang, China
| | - Yu Cheng
- Department of Medicine, Graduate School of Nanchang University, Nanchang, China
| | - Chenlong Wang
- Department of Central Laboratory, The Affiliated Huaian No.1 Peopele’s Hospital, Nanjing Medical University, Huai’an, China
| | - Bin Wang
- Department of Medicine, Graduate School of Nanchang University, Nanchang, China
| | - Xinchang Zou
- Department of Medicine, Graduate School of Nanchang University, Nanchang, China
| | - Jie Zhou
- Department of Medicine, Graduate School of Nanchang University, Nanchang, China
| | - Lifen Peng
- Molecular Experiment Center, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, China
| | - Tao Zeng
- Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Steinbrenner I, Kotsis F, Kosch R, Meiselbach H, Bärthlein B, Stockmann H, Lipovsek J, Zacharias HU, Altenbuchinger M, Dienemann T, Wytopil M, Bächle H, Sommerer C, Titze S, Weigel A, Weissensteiner H, Schönherr S, Forer L, Kurz NS, Menne J, Schlieper G, Schneider MP, Schaeffner E, Kielstein JT, Sitter T, Floege J, Wanner C, Kronenberg F, Köttgen A, Busch M, Krane V, Schmid M, Eckardt KU, Schultheiss UT. Interactive exploration of adverse events and multimorbidity in CKD. Nephrol Dial Transplant 2024; 39:2016-2024. [PMID: 38664006 PMCID: PMC11596092 DOI: 10.1093/ndt/gfae092] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Persons with chronic kidney disease (CKD) are at increased risk of adverse events, early mortality and multimorbidity. A detailed overview of adverse event types and rates from a large CKD cohort under regular nephrological care is missing. We generated an interactive tool to enable exploration of adverse events and their combinations in the prospective, observational German CKD (GCKD) study. METHODS The GCKD study enrolled 5217 participants under regular nephrological care with an estimated glomerular filtration rate of 30-60 or >60 mL/min/1.73 m2 and an overt proteinuria. Cardiovascular, cerebrovascular and peripheral vascular, kidney, infection, and cancer events, as well as deaths were adjudicated following a standard operation procedure. We summarized these time-to-event data points for exploration in interactive graphs within an R shiny app. Multivariable adjusted Cox models for time to first event were fitted. Cumulative incidence functions, Kaplan-Meier curves and intersection plots were used to display main adverse events and their combinations by sex and CKD etiology. RESULTS Over a median of 6.5 years, 10 271 events occurred in 2947 participants (56.5%), of which 680 participants (13.0%) died. The new publicly available interactive platform enables readers to scrutinize adverse events and their combinations as well as mortality trends as a gateway to better understand multimorbidity in CKD: incident rates per 1000 patient-years varied by event type, CKD etiology and baseline characteristics. Incidence rates for the most frequent events and their recurrence were 113.6 (cardiovascular), 75.0 (kidney) and 66.0 (infection). Participants with presumed diabetic kidney disease and men were more prone to experiencing events. CONCLUSION This comprehensive explorative tool to visualize adverse events (https://www.gckd.org/studienhintergrund/previous-study-results/event-analysis/), their combination, mortality and multimorbidity among persons with CKD may serve as a valuable resourec for patient care, identification of high-risk groups, health services and public health policy planning.
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Affiliation(s)
- Inga Steinbrenner
- Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
| | - Fruzsina Kotsis
- Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
- Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
| | - Robin Kosch
- Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover Medical School, Hannover, Germany
- Department of Medical Bioinformatics, University Medical Center Göttingen, Göttingen, Germany
| | - Heike Meiselbach
- Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Barbara Bärthlein
- Medical Centre for Information and Communication Technology, University Hospital Erlangen, Erlangen, Germany
| | - Helena Stockmann
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Department of Nephrology, University Medical Center Regensburg, Regensburg, Germany
| | - Jan Lipovsek
- Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
| | - Helena U Zacharias
- Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover Medical School, Hannover, Germany
| | - Michael Altenbuchinger
- Department of Medical Bioinformatics, University Medical Center Göttingen, Göttingen, Germany
| | - Thomas Dienemann
- Department of Operative Intensive Care, University Hospital Regensburg, Regensburg, Germany
| | - Monika Wytopil
- Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Helena Bächle
- Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
| | - Claudia Sommerer
- Department of Nephrology, University Hospital Heidelberg, Renal Center, Heidelberg, Germany
| | - Stephanie Titze
- Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Anke Weigel
- Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Hansi Weissensteiner
- Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Sebastian Schönherr
- Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Lukas Forer
- Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Nadine S Kurz
- Department of Medical Bioinformatics, University Medical Center Göttingen, Göttingen, Germany
| | - Jan Menne
- Department of Nephrology, Rheumatology and Vascular Medicine, KRH Klinikum Siloah, Hannover, Germany
| | - Georg Schlieper
- Zentrum für Nieren-, Hochdruck- und Stoffwechselerkrankungen, Hannover, Germany
- Division of Nephrology and Clinical Immunology, University Hospital RWTH Aachen, Aachen, Germany
| | - Markus P Schneider
- Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Elke Schaeffner
- Institute of Public Health, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Jan T Kielstein
- Medical Clinic V Nephrology, Rheumatology, Blood Purification – Academic Teaching Hospital Braunschweig, Braunschweig, Germany
| | - Thomas Sitter
- Department of Nephrology and Hypertension, Ludwig-Maximilians University, Munich, Germany
| | - Jürgen Floege
- Division of Nephrology and Clinical Immunology, University Hospital RWTH Aachen, Aachen, Germany
| | - Christoph Wanner
- Department of Clinical Research and Epidemiology, German Heart Failure Center, University Hospital Würzburg, Würzburg, Germany
| | - Florian Kronenberg
- Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Anna Köttgen
- Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
| | - Martin Busch
- Department of Internal Medicine III, Nephrology, University Hospital Jena – Friedrich Schiller University Jena, Jena, Germany
| | - Vera Krane
- Department of Clinical Research and Epidemiology, German Heart Failure Center, University Hospital Würzburg, Würzburg, Germany
- Department of Medicine I, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany
| | - Matthias Schmid
- Department of Medical Biometry, Informatics, and Epidemiology, University Hospital Bonn, Bonn, Germany
| | - Kai-Uwe Eckardt
- Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Ulla T Schultheiss
- Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
- Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany
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46
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Xin G, Li Q, Sheng C, Zha Y, Cheng K. Comparation of two cystatin C-based eGFR equations in assessing risk of all-cause mortality and incident cardiovascular disease. Nutr Metab (Lond) 2024; 21:94. [PMID: 39563329 PMCID: PMC11577579 DOI: 10.1186/s12986-024-00870-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 11/07/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 and European Kidney Function Consortium (EKFC) 2023 both recently updated the equations to estimate the glomerular filtration rate (eGFR) using cystatin C; however, little is known about the benefits of using the equations for the risk stratification of health outcomes. We conducted this longitudinal study to compare the cystatin C CKD-EPI and EKFC equations to track the risks of cardiovascular disease and all-cause mortality among Chinese adults. METHODS We used data from China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Adjusted logistic regression models and restricted cubic spline functions were used to evaluate the relationships of cystatin C-based eGFR values with incidence of cardiovascular disease and mortality. RESULTS A total of 6 496 participants were finally included in this study. The mean age of the participants was 59.6 (± 9.5) years, including 2996 (46.1%) males. There were 473 deaths and 1996 cases of cardiovascular disease observed during a maximum follow-up of 7.0 years. Using cystatin C-based CKD-EPI equation, people of eGFR < 60 mL/min/1.73 m2 had an increased risk of mortality (risk ratio [RR], 1.527; 95% CI, 1.068-2.178) and incident cardiovascular disease (RR, 1.363; 95% CI, 1.006-1.844), compared to those of eGFR ≥ 90 mL/min/1.73 m2. On the contrary, we did not observe significant associations of eGFR levels by EKFC equation with mortality nor cardiovascular disease. CONCLUSIONS The findings indicated that cystatin C-based eGFR using CKD-EPI equation is more closely associated with all-cause mortality and cardiovascular disease compared to EKFC equation among Chinese adults. The cystatin C-based eGFR by CKD-EPI equation should be monitored in health practice, which needs further validation in other populations.
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Affiliation(s)
- Guangda Xin
- Department of Radiology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China
| | - Qianyu Li
- Department of Radiology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China
| | - Chen Sheng
- Harvard T H Chan School of Public Health, Boston, USA
| | - Yining Zha
- Harvard T H Chan School of Public Health, Boston, USA
| | - Kailiang Cheng
- Department of Radiology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China.
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Svigelj R, de Marco A. Biological and technical factors affecting the point-of-care diagnostics in not-oncological chronic diseases. Biosens Bioelectron 2024; 264:116669. [PMID: 39146770 DOI: 10.1016/j.bios.2024.116669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/05/2024] [Accepted: 08/12/2024] [Indexed: 08/17/2024]
Abstract
Inexpensive point-of-care (POC) analytical solutions have the potential to allow the implementation of large-scale screening campaigns aimed at identifying the initial stages of pathologies in the population, reducing morbidity, mortality and, indirectly, also the costs for the healthcare system. At global level, the most common preventive screening schemes address some cancer pathologies or are used to monitor the spread of some infective diseases. However, systematic testing might become decisive to improve the care response even in the case of chronic pathologies and, in this review, we analyzed the state-of-the-art of the POC diagnostics for Chronic Kidney Disease, Chronic Obstructive Pulmonary Disease and Multiple Sclerosis. The different technological options used to manufacture the biosensors and evaluate the produced data have been described and this information has been integrated with the present knowledge relatively to the biomarkers that have been proposed to monitor such diseases, namely their availability and reliability. Finally, the nature of the macromolecules used to capture the biomarkers has been discussed in relation to the biomarker nature.
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Affiliation(s)
- Rossella Svigelj
- Department of Agrifood, Environmental and Animal Sciences, University of Udine, Via Cotonificio 108, 33100, Udine, Italy
| | - Ario de Marco
- Lab of Environmental and Life Sciences, University of Nova Gorica, Vipavska Cesta 13, 5000, Nova Gorica, Slovenia.
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48
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Nakano FK, Åkesson A, de Boer J, Dedja K, D'hondt R, Haredasht FN, Björk J, Courbebaisse M, Couzi L, Ebert N, Eriksen BO, Dalton RN, Derain-Dubourg L, Gaillard F, Garrouste C, Grubb A, Jacquemont L, Hansson M, Kamar N, Legendre C, Littmann K, Mariat C, Melsom T, Rostaing L, Rule AD, Schaeffner E, Sundin PO, Bökenkamp A, Berg U, Åsling-Monemi K, Selistre L, Larsson A, Nyman U, Lanot A, Pottel H, Delanaye P, Vens C. Comparison between the EKFC-equation and machine learning models to predict Glomerular Filtration Rate. Sci Rep 2024; 14:26383. [PMID: 39487227 PMCID: PMC11530427 DOI: 10.1038/s41598-024-77618-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 10/23/2024] [Indexed: 11/04/2024] Open
Abstract
In clinical practice, the glomerular filtration rate (GFR), a measurement of kidney functioning, is normally calculated using equations, such as the European Kidney Function Consortium (EKFC) equation. Despite being the most general equation, EKFC, just like previously proposed approaches, can still struggle to achieve satisfactory performance, limiting its clinical applicability. As a possible solution, recently machine learning (ML) has been investigated to improve GFR prediction, nonetheless the literature still lacks a general and multi-center study. Using a dataset with 19,629 patients from 13 cohorts, we investigate if ML can improve GFR prediction in comparison to EKFC. More specifically, we compare diverse ML methods, which were allowed to use age, sex, serum creatinine, cystatin C, height, weight and BMI as features, in internal and external cohorts against EKFC. The results show that the most performing ML method, random forest (RF), and EKFC are very competitive where RF and EKFC achieved respectively P10 and P30 values of 0.45 (95% CI 0.44;0.46) and 0.89 (95% CI 0.88;0.90), whereas EKFC yielded 0.44 (95% CI 0.43; 0.44) and 0.89 (95% CI 0.88; 0.90), considering the entire cohort. Small differences were, however, observed in patients younger than 12 years where RF slightly outperformed EKFC.
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Affiliation(s)
- Felipe Kenji Nakano
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
- Itec, Imec Research Group at KU Leuven, Kortrijk, Belgium.
| | - Anna Åkesson
- Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
- Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden
| | - Jasper de Boer
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- Itec, Imec Research Group at KU Leuven, Kortrijk, Belgium
| | - Klest Dedja
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- Itec, Imec Research Group at KU Leuven, Kortrijk, Belgium
| | - Robbe D'hondt
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- Itec, Imec Research Group at KU Leuven, Kortrijk, Belgium
| | - Fateme Nateghi Haredasht
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- Itec, Imec Research Group at KU Leuven, Kortrijk, Belgium
| | - Jonas Björk
- Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
- Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden
| | - Marie Courbebaisse
- Physiology Department, Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris, INSERM U1151-CNRS UMR8253, Paris Descartes University, Paris, France
| | - Lionel Couzi
- CNRS-UMR 5164 Immuno ConcEpT, CHU de Bordeaux, Nephrologie-Transplantation-Dialyse, Université de Bordeaux, Bordeaux, France
| | - Natalie Ebert
- Institute of Public Health, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Björn O Eriksen
- Metabolic and Renal Research Group, UiT the Arctic University of Norway, Tromsö, Norway
| | - R Neil Dalton
- The Wellchild Laboratory, Evelina London Children's Hospital, London, UK
| | - Laurence Derain-Dubourg
- Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon, France
| | - Francois Gaillard
- Renal Transplantation Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Cyril Garrouste
- Department of Nephrology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Anders Grubb
- Department of Clinical Chemistry, Skåne University Hospital, Lund University, Lund, Sweden
| | - Lola Jacquemont
- Renal Transplantation Department, CHU Nantes, Nantes University, Nantes, France
| | - Magnus Hansson
- Function Area Clinical Chemistry, Karolinska University Laboratory, Karolinska Institute, Karolinska University Hospital Huddinge and Department of Laboratory Medicine, Stockholm, Sweden
| | - Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR-BMT, University Paul Sabatier, Toulouse, France
| | | | - Karin Littmann
- Institute om Medicine Huddinge (Med H), Karolinska Institute, Solna, Sweden
| | - Christophe Mariat
- Service de Néphrologie, Dialyse et Transplantation Rénale, Hôpital Nord, CHU de Saint-Etienne, Saint-Priest-en-Jarez, France
| | - Toralf Melsom
- Metabolic and Renal Research Group, UiT the Arctic University of Norway, Tromsö, Norway
| | - Lionel Rostaing
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Hôpital Michallon, CHU Grenoble-Alpes, Tronche, France
| | - Andrew D Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Elke Schaeffner
- Institute of Public Health, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Per-Ola Sundin
- Karla Healthcare Centre, Faculty of Medicine and Health, Örebro University, 70182, Örebro, SE, Sweden
| | - Arend Bökenkamp
- Department of Paediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Ulla Berg
- Department of Clinical Science, Intervention and Technology, Division of Pediatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Kajsa Åsling-Monemi
- Department of Clinical Science, Intervention and Technology, Division of Pediatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Luciano Selistre
- Mestrado Em Ciências da Saúde-Universidade Caxias do Sul Foundation CAPES, Caxias Do Sul, Brazil
| | - Anders Larsson
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
| | - Ulf Nyman
- Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö, Sweden
| | - Antoine Lanot
- Normandie Université, Unicaen, CHU de Caen Normandie, Néphrologie, Caen, France
- Normandie Université, Unicaen, UFR de Médecine, 2 Rue Des Rochambelles, Caen, France
- ANTICIPE U1086 INSERM-UCN, Centre François Baclesse, Caen, France
| | - Hans Pottel
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
| | - Pierre Delanaye
- Department of Nephrology-Dialysis-Transplantation, University of Liège (ULg CHU), CHU Sart Tilman, Liège, Belgium
- Department of Nephrology-Dialysis-Apheresis, Hopital Universitaire Caremeau, Nimes, France
| | - Celine Vens
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
- Itec, Imec Research Group at KU Leuven, Kortrijk, Belgium
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Zhang C, Zhang H, Zhang B, Lindenberg J, Amat MJ, Rice MB, Mukamal KJ. Marijuana Use and Hemoglobin Concentrations in NHANES 2009-2018: Implications for Subclinical Hypoxemia. Ann Am Thorac Soc 2024; 21:1488-1495. [PMID: 38985494 DOI: 10.1513/annalsats.202404-357oc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 07/10/2024] [Indexed: 07/11/2024] Open
Abstract
Rationale: Cannabis use is rapidly growing in the United States, but its health implications are poorly understood, particularly when compared with cigarette smoking. Previous research conducted on animal models or nonrepresentative populations with small sample sizes has yielded mixed results on the impact of marijuana use on hemoglobin concentrations, which might reflect subclinical hypoxemia and/or carbon monoxide exposure. Objectives: We evaluated the association between marijuana use and hemoglobin concentrations in a nationally representative sample of U.S. adults. Methods: This cross-sectional study included 16,038 individuals 18-59 years of age enrolled in National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We related current and former marijuana use with measured hemoglobin concentrations, with adjustment for demographics, education, housing, and cigarette smoking status in multivariable analyses that incorporated complex survey weights. As candidate positive and negative control exposures, we used similar methods to relate cigarette smoking and benzodiazepine use, respectively, with hemoglobin concentrations. Results: Current marijuana use was associated with significantly higher hemoglobin concentrations. After multivariable adjustment, compared with never use, current marijuana use was associated with a 0.111 (95% confidence interval, 0.021 to 0.201) g/dl higher hemoglobin concentration, whereas former use was associated with a 0.047 (95% confidence interval, -0.018 to 0.113) g/dl higher concentration (linear trend P = 0.01). As hypothesized, cigarette smoking was also associated with higher hemoglobin concentrations, whereas benzodiazepine use was not. Conclusions: Among American adults, current marijuana use was associated with higher hemoglobin concentrations, as is cigarette smoking but not benzodiazepine use. These results suggest the possibility that marijuana smoking induces subclinical hypoxemia stimulating hemoglobin production. Further confirmation of this observational finding is needed in light of the increasing medical and recreational use of smoked marijuana products.
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Affiliation(s)
| | - Hui Zhang
- Division of Biostatistics, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and
| | - Bo Zhang
- Department of Neurology and
- Institutional Centers of Clinical and Translational Research Biostatistics and Research Design Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
| | | | | | - Mary B Rice
- Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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50
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Weidmann L, Laux C, Castrezana Lopez K, Harmacek D, George B, von Moos S, Schachtner T. Immunosuppression and transplantation-related characteristics affect the difference between eGFR equations based on creatinine compared to cystatin C in kidney transplant recipients. Clin Kidney J 2024; 17:sfae253. [PMID: 39502371 PMCID: PMC11536772 DOI: 10.1093/ckj/sfae253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Indexed: 11/08/2024] Open
Abstract
Introduction Previous studies show heterogeneity when applying estimated glomerular filtration (eGFR) equations to kidney transplant recipients (KTRs). However, research on the impact of transplantation-related characteristics on eGFR equations using creatinine (eGFRcr) compared to cystatin C (eGFRcys) is scarce. Methods We conducted a comprehensive analysis with three eGFRcr equations (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009, European Kidney Function Consortium (EKFC) 2021, kidney recipient specific-glomerular filtration rate KRS-GFR) 2023), comparing them to two eGFRcys (CKD-EPI 2012 and EKFC 2023) in 596 KTRs. Bland-Altman plots demonstrated relative differences according to different eGFR-stages. Multivariable logistic regression identified transplantation-related characteristics independently associated with smaller or greater differences between eGFRcr and eGFRcys equations. Results 94.3% of the cohort were White individuals. Median eGFR differed as much as 9 ml/min/1.73 m2 between equations. The median relative differences (Q2) were greater (more negative) when comparing the eGFRcr equations to eGFRcys CKD-EPI 2012, than when comparing them to eGFRcys EKFC 2023 (P < .001). Better average eGFR was associated with smaller mean relative differences in all comparisons but eGFRcr CKD-EPI 2009 with eGFR EKFC 2023 and eGFRcr EKFC 2021 with eGFRcys EKFC 2023. Living kidney donation and belatacept use were independent factors associated with a smaller difference (≥Q3) between eGFRcr and eGFRcys equations, while prednisone use or higher HbA1c were independently associated with a greater difference (≤Q1) between equations. Conclusion Different eGFR-stages, donor, or recipient characteristics, along with immunosuppression such as belatacept or prednisone, contribute to differences between eGFRcr and eGFRcys. These effects need to be considered in the clinical management of KTRs.
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Affiliation(s)
- Lukas Weidmann
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | - Catherine Laux
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | | | - Dusan Harmacek
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | - Britta George
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | - Seraina von Moos
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
- Department of Nephrology, Cantonal Hospital of Lucerne, Lucerne, Switzerland
| | - Thomas Schachtner
- Department of Nephrology, University Hospital of Zurich, Zurich, Switzerland
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