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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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Gao C, Mumtaz S, McCall S, O'Sullivan K, McGilchrist M, Morales DR, Hall C, Wilde K, Mayor C, Linksted P, Harrison K, Cole C, Jefferson E. A pipeline for harmonising NHS Scotland laboratory data to enable national-level analyses. J Biomed Inform 2025; 162:104771. [PMID: 39755323 DOI: 10.1016/j.jbi.2024.104771] [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: 04/04/2024] [Revised: 12/23/2024] [Accepted: 12/30/2024] [Indexed: 01/06/2025]
Abstract
OBJECTIVE Medical laboratory data together with prescribing and hospitalisation records are three of the most used electronic health records (EHRs) for data-driven health research. In Scotland, hospitalisation, prescribing and the death register data are available nationally whereas laboratory data is captured, stored and reported from local health board systems with significant heterogeneity. For researchers or other users of this regionally curated data, working on laboratory datasets across regional cohorts requires effort and time. As part of this study, the Scottish Safe Haven Network have developed an open-source software pipeline to generate a harmonised laboratory dataset. METHODS We obtained sample laboratory data from the four regional Safe Havens in Scotland covering people within the SHARE consented cohort. We compared the variables collected by each regional Safe Haven and mapped these to 11 FHIR and 2 Scottish-specific standardised terms (i.e., one to indicate the regional health board and a second to describe the source clinical code description). RESULTS We compared the laboratory data and found that 180 test codes covered 98.7 % of test records performed across Scotland. Focusing on the 180 test codes, we developed a set of transformations to convert test results captured in different units to the same unit. We included both Read Codes and SNOMED CT to encode the tests within the pipeline. CONCLUSION We validated our harmonisation pipeline by comparing the results across the different regional datasets. The pipeline can be reused by researchers and/or Safe Havens to generate clean, harmonised laboratory data at a national level with minimal effort.
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Affiliation(s)
- Chuang Gao
- Health Informatics Centre, School of Medicine, University of Dundee, UK; Population Health and Genomics, School of Medicine, University of Dundee, UK
| | - Shahzad Mumtaz
- School of Natural & Computing Sciences, University of Aberdeen, UK
| | - Sophie McCall
- Research Data Scotland, UK; DataLoch, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Katherine O'Sullivan
- Grampian Data Safe Haven (DaSH), Aberdeen Centre for Health Data Science, University of Aberdeen, Aberdeen, UK
| | - Mark McGilchrist
- Health Informatics Centre, School of Medicine, University of Dundee, UK
| | - Daniel R Morales
- Population Health and Genomics, School of Medicine, University of Dundee, UK
| | - Christopher Hall
- Health Informatics Centre, School of Medicine, University of Dundee, UK
| | - Katie Wilde
- Grampian Data Safe Haven (DaSH), Aberdeen Centre for Health Data Science, University of Aberdeen, Aberdeen, UK
| | - Charlie Mayor
- West of Scotland Safe Haven, Research and Innovation Division of NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Pamela Linksted
- DataLoch, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Kathy Harrison
- DataLoch, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Christian Cole
- Health Informatics Centre, School of Medicine, University of Dundee, UK; Population Health and Genomics, School of Medicine, University of Dundee, UK.
| | - Emily Jefferson
- Health Informatics Centre, School of Medicine, University of Dundee, UK; Health Data Research UK, London, UK.
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Sun M, Liang M, Kong R, Guo L, Xia L, Qu F. FRET-Based Dual-Color Carbon Dot Ratiometric Fluorescent Sensor Enables the Smartphone-Integrated Device for Noninvasive and Portable Diagnosis of Chronic Kidney Disease. Anal Chem 2024; 96:17907-17913. [PMID: 39444302 DOI: 10.1021/acs.analchem.4c04813] [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: 10/25/2024]
Abstract
Cystatin C (Cys C), a crucial renal disease marker for chronic kidney disease (CKD), plays a vital role in early diagnosis and treatment guidance. However, most current methods for detecting Cys C rely on a single signal and find it difficult to perform noninvasive and portable diagnosis. Here, we developed a ratiometric fluorescent carbon dot (CD) detection system for point-of-care testing (POCT) of Cys C through fluorescence resonance energy transfer (FRET). The detection is based on the hydrolysis effect of papain on a bovine serum albumin (BSA) scaffold and the specific inhibitory effect of Cys C on papain, endowing high-resolution color variance. Moreover, a low-cost, portable, yet reliable smartphone-assisted miniaturized device for real-time quantitative POCT of Cys C has been developed with a limit of detection (LOD) as low as 0.4 μg/mL. This sensing platform can effectively differentiate patients from healthy volunteers, which facilitates self-screening for healthy individuals and home monitoring for CKD patients.
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Affiliation(s)
- Mengyu Sun
- Chemistry and Chemical Engineering College, Qufu Normal University, Qufu, Shandong 273165, P. R. China
| | - Maosheng Liang
- Chemistry and Chemical Engineering College, Qufu Normal University, Qufu, Shandong 273165, P. R. China
| | - Rongmei Kong
- Chemistry and Chemical Engineering College, Qufu Normal University, Qufu, Shandong 273165, P. R. China
| | - Lan Guo
- Chemistry and Chemical Engineering College, Qufu Normal University, Qufu, Shandong 273165, P. R. China
| | - Lian Xia
- Chemistry and Chemical Engineering College, Qufu Normal University, Qufu, Shandong 273165, P. R. China
| | - Fengli Qu
- Department of Pathology, Cancer Hospital of Zhejiang Province, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P. R. China
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese, Academy of Sciences, Hangzhou 310024, P. R. China
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Cipriano A, Kapil RP, Zhou M, Shet MS, Whiteside GT, Willsie SK, Harris SC. Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-Ascending Doses of Sunobinop in Healthy Participants. Clin Pharmacol Drug Dev 2024; 13:790-800. [PMID: 38476082 DOI: 10.1002/cpdd.1394] [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: 11/21/2023] [Accepted: 02/02/2024] [Indexed: 03/14/2024]
Abstract
Sunobinop is an investigational, potent, selective partial agonist at the nociceptin/orphanin FQ peptide receptor in vitro. Three phase 1 studies were conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating single- and multiple-dose administration of sunobinop in healthy participants. Study 1 was a randomized, double-blind, placebo-controlled, single-ascending dose study. Study 2 was a randomized, double-blind, placebo-controlled, multiple-ascending dose study. Study 3 was a randomized, open-label, single-dose, 4-way crossover study of oral and sublingual sunobinop comparing morning (AM) and bedtime (PM) administration. Seventy participants were included. Systemic exposure (peak plasma concentration [Cmax], area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration [AUC0-t], and area under the plasma concentration-time curve from time 0 extrapolated to infinity [AUCinf]) of sunobinop was characterized by dose proportionality from 0.6 to 2 mg and increased less than proportionally from 3 to 30 mg. The PKs of sunobinop were similar, regardless of AM or PM administration, for both the oral and sublingual formulations. The majority of absorbed sunobinop was excreted unchanged in the urine within 8 hours of dosing, thereby showing rapid elimination with no appreciable accumulation following 14 consecutive days of once-daily dosing and suggesting exclusive renal elimination. Most treatment-emergent adverse events (TEAEs) were mild in severity; 1 severe TEAE occurred and all TEAEs resolved by the end of the studies. Sunobinop was generally well-tolerated and safe across the range of doses evaluated and presents a clinical profile suitable for continued development.
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Chirico V, Lacquaniti A, Tripodi F, Conti G, Marseglia L, Monardo P, Gitto E, Chimenz R. Acute Kidney Injury in Neonatal Intensive Care Unit: Epidemiology, Diagnosis and Risk Factors. J Clin Med 2024; 13:3446. [PMID: 38929977 PMCID: PMC11205241 DOI: 10.3390/jcm13123446] [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: 04/22/2024] [Revised: 06/02/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease.
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Affiliation(s)
- Valeria Chirico
- Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, 98124 Messina, Italy (F.T.)
| | - Antonio Lacquaniti
- Nephrology and Dialysis Unit, Papardo Hospital, 98158 Messina, Italy (P.M.)
| | - Filippo Tripodi
- Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, 98124 Messina, Italy (F.T.)
| | - Giovanni Conti
- Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, 98124 Messina, Italy (F.T.)
| | - Lucia Marseglia
- Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, 98124 Messina, Italy; (L.M.)
| | - Paolo Monardo
- Nephrology and Dialysis Unit, Papardo Hospital, 98158 Messina, Italy (P.M.)
| | - Eloisa Gitto
- Neonatal and Pediatric Intensive Care Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, 98124 Messina, Italy; (L.M.)
| | - Roberto Chimenz
- Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, 98124 Messina, Italy (F.T.)
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Nguyen HH, Thi Nguyen L, Van Nguyen T, Van Le M, Tran BLT, Hoang Ngo T, Tran AV, Nguyen KT. Estimating eGFR using serum creatinine or cystatin C in healthy Vietnamese population. Medicine (Baltimore) 2024; 103:e37997. [PMID: 38701272 PMCID: PMC11062701 DOI: 10.1097/md.0000000000037997] [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: 03/12/2024] [Accepted: 04/03/2024] [Indexed: 05/05/2024] Open
Abstract
Very few studies worldwide have assessed the estimated glomerular filtration rate (eGFR) using serum cystatin C (ScysC) in comparison to the gold standard measured glomerular filtration rate (mGFR) with a gamma camera technique using 99m-Technetium-Diethylene Triaminepentoacetic Acid (99mTc-DTPA). To determine the eGFR formula with the most accurate estimate of glomerular filtration rate when compared with mGFR in a healthy population in Vietnam. We conducted a cross-sectional descriptive study of more than 100 adults without hypertension. The study subjects were examined for general characteristics and blood biochemistry tests to assess eGFR, and the glomerular filtration rate was measured using 99mTc-DTPA with the Gates technique to record mGFR. The estimated values of the eGFR formula were evaluated and compared with the actual mGFR using 99mTechnetium-DTPA. Serum creatinine (Scr) concentration showed a significant difference between males and females: 0.9 ± 0.1 versus 0.8 ± 0.1 (P < .001), while ScysC concentration did not show this difference. The mGFR in the age groups < 40, 40 to 59, and ≥ 60: 105.0 ± 9.9, 94.8 ± 8.6, and 93.4 ± 10.6, respectively (P < .001). The eGFR-CKD-EPI-cystatin C 2012 formula showed the highest positive correlation with mGFR (ΔGFR = -1.6, R = 0.68, P < .001). eGFR calculated using cystatin C does not require sex adjustment, whereas, for creatinine, sex adjustment is necessary. The eGFR-CKD-Epi-CysC formula showed the lowest difference and a strong correlation with mGFR.
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Affiliation(s)
- Ha Hong Nguyen
- Can Tho University of Medicine and Pharmacy, Can Tho City, Vietnam
| | - Le Thi Nguyen
- University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh, Vietnam
| | | | - Minh Van Le
- Can Tho University of Medicine and Pharmacy, Can Tho City, Vietnam
| | | | - Toan Hoang Ngo
- Can Tho University of Medicine and Pharmacy, Can Tho City, Vietnam
| | - An Viet Tran
- Can Tho University of Medicine and Pharmacy, Can Tho City, Vietnam
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Corrêa-Castro G, Silva-Freitas ML, de Paula L, Soares Pereira L, Dutra MRT, Albuquerque HG, Cota G, de Azevedo Martins C, Da-Cruz AM, Gomes-Silva A, Santos-Oliveira JR. A link between circulating immune complexes and acute kidney injury in human visceral leishmaniasis. Sci Rep 2024; 14:9870. [PMID: 38684845 PMCID: PMC11059367 DOI: 10.1038/s41598-024-60209-0] [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: 08/22/2023] [Accepted: 04/19/2024] [Indexed: 05/02/2024] Open
Abstract
Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum. Clinically, VL evolves with systemic impairment, immunosuppression and hyperactivation with hypergammaglobulinemia. Although renal involvement has been recognized, a dearth of understanding about the underlying mechanisms driving acute kidney injury (AKI) in VL remains. We aimed to evaluate the involvement of immunoglobulins (Igs) and immune complexes (CIC) in the occurrence of AKI in VL patients. Fourteen VL patients were evaluated between early treatment and 12 months post-treatment (mpt). Anti-Leishmania Igs, CIC, cystatin C, C3a and C5a were assessed and correlated with AKI markers. Interestingly, high levels of CIC were observed in VL patients up to 6 mpt. Concomitantly, twelve patients met the criteria for AKI, while high levels of cystatin C were observed up to 6 mpt. Plasmatic cystatin C was positively correlated with CIC and Igs. Moreover, C5a was correlated with cystatin C, CIC and Igs. We did not identify any correlation between amphotericin B use and kidney function markers in VL patients, although this association needs to be further explored in subsequent studies. Our data reinforce the presence of an important renal function impairment during VL, suggesting the involvement of Igs, CIC, and C5a in this clinical condition.
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Affiliation(s)
- Gabriela Corrêa-Castro
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
- Núcleo de Ciências Biomédicas Aplicadas, Instituto Federal de Educação, Ciência e Tecnologia, IFRJ, Rio de Janeiro, Brazil
| | | | - Ludmila de Paula
- Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Minas Gerais, Brazil
| | - Leonardo Soares Pereira
- Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Minas Gerais, Brazil
| | | | | | - Glaucia Cota
- Instituto René Rachou, FIOCRUZ, Minas Gerais, Brazil
| | | | - Alda Maria Da-Cruz
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
- Disciplina de Parasitologia, DMIP, Faculdade de Ciências Médicas, UERJ, Rio de Janeiro, Brazil
- Rede de Pesquisas em Saúde do Estado do Rio de Janeiro, FAPERJ, Rio de Janeiro, Brazil
- Instituto Nacional de Neuroimunomodulação, INCT-NIM-CNPq, Rio de Janeiro, Brazil
| | - Adriano Gomes-Silva
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
- Laboratório de Pesquisa Clínica em Micobacterioses, Instituto Nacional de Infectologia Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil
| | - Joanna Reis Santos-Oliveira
- Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
- Núcleo de Ciências Biomédicas Aplicadas, Instituto Federal de Educação, Ciência e Tecnologia, IFRJ, Rio de Janeiro, Brazil.
- Instituto Nacional de Neuroimunomodulação, INCT-NIM-CNPq, Rio de Janeiro, Brazil.
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Trivic T, Roklicer R, Zenic N, Modric T, Milovancev A, Lukic-Sarkanovic M, Maksimovic N, Bianco A, Carraro A, Drid P. Rapid weight loss can increase the risk of acute kidney injury in wrestlers. BMJ Open Sport Exerc Med 2023; 9:e001617. [PMID: 37397266 PMCID: PMC10314685 DOI: 10.1136/bmjsem-2023-001617] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2023] [Indexed: 07/04/2023] Open
Abstract
Objective Restrictive diets, forced starvation or voluntary weight loss are attracting more and more attention from scientists. Overall trends show that about 80% of combat sports athletes use specific methods of reducing body mass. Rapid weight loss could be a risk factor for kidney-related adverse outcomes. This study aimed to examine the impact of high-intensity specific training combined with rapid weight loss in the first and without rapid weight loss in the second phases on body composition and biochemical markers of kidney function. Methods The study was conducted on 12 male wrestlers. Kidney function markers were measured, including blood urea nitrogen, serum creatinine, uric acid and serum Cystatin-C. Alterations in analysed markers were noted in both phases of the research. Results According to the data, a significant increase was noted in blood urea nitrogen (p=0.002), uric acid (p=0.000) and serum creatinine (p=0.006) during the first phase in comparison with the second phase. The levels of serum Cystatin-C were slightly elevated after both phases compared with the initial measurement. Conclusion It is evident that high-intensity specific training combined with rapid weight loss significantly affects the increase in kidney function markers compared with identical training without rapid weight loss. The findings in this study suggest that rapid body mass reduction is associated with an increased risk of acute kidney injury in wrestlers.
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Affiliation(s)
- Tatjana Trivic
- Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad, Serbia
| | - Roberto Roklicer
- Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad, Serbia
- Faculty of Education, Free University of Bozen-Bolzano, Bolzano, Italy
| | - Natasa Zenic
- Faculty of Kinesiology, University of Split, Split, Croatia
| | - Toni Modric
- Faculty of Kinesiology, University of Split, Split, Croatia
| | - Aleksandra Milovancev
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
- Institute of Cardiovascular Diseases of Vojvodina, Sremska Kamenica, Serbia
| | - Mirka Lukic-Sarkanovic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
- Intensive Therapy and Pain Therapy, Clinical Center of Vojvodina, Novi Sad, Serbia
| | - Nemanja Maksimovic
- Sport and Exercise Sciences Research Unit, University of Palermo, Palermo, Italy
| | - Antonino Bianco
- Sport and Exercise Sciences Research Unit, University of Palermo, Palermo, Italy
| | - Attilio Carraro
- Faculty of Education, Free University of Bozen-Bolzano, Bolzano, Italy
| | - Patrik Drid
- Faculty of Sport and Physical Education, University of Novi Sad, Novi Sad, Serbia
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Gama RM, Griffiths K, Vincent RP, Peters AM, Bramham K. Performance and pitfalls of the tools for measuring glomerular filtration rate to guide chronic kidney disease diagnosis and assessment. J Clin Pathol 2023:jcp-2023-208887. [PMID: 37164629 DOI: 10.1136/jcp-2023-208887] [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: 03/15/2023] [Accepted: 04/28/2023] [Indexed: 05/12/2023]
Abstract
Accurate diagnosis, classification and risk stratification for chronic kidney disease (CKD) allow for early recognition and delivering optimal care. Creatinine-based glomerular filtration rate (GFR), urinary albumin: creatinine ratio (UACR) and the kidney failure risk equation (KFRE) are important tools to achieve this, but understanding their limitations is important for optimal implementation.When accurate GFR is required (eg, chemotherapy dosing), GFR is measured using an exogenous filtration marker. In routine clinical practice, in contrast, estimated GFR (eGFR) from serum creatinine (SCr), calculated using the enzymatic method±UACR, is recommended. Limitations of SCr include non-GFR determinants such as muscle mass, diet and tubular handling. An alternative or additional endogenous filtration marker is cystatin C, which can be used alongside SCr for confirmatory testing of CKD. However, its role in the UK is more limited due to concerns regarding false positive results.The recommended creatinine-based eGFR equation in the UK is the CKD Epidemiology Collaboration 2009 equation. This was recently updated to a race-neutral 2021 version and demonstrated reduced bias in people of Black ethnicity, but has not been validated in the UK. Limitations are extremes of age, inaccuracy at greater GFRs and reduced generalisability to under-represented ethnicity groups.The KFRE (based on age, sex, SCr and UACR) has recently been developed to help determine 2-year and 5-year risk of progression to end-stage kidney disease. It has been validated in over 30 countries and provides meaningful quantitative information to patients. However, supporting evidence for their performance in ethnic minority groups and kidney diseases such as glomerulonephritis remains modest.In conclusion, early identification, risk stratification of kidney disease and timely intervention are important to impact kidney disease progression. However, clinician awareness of the limitations and variability of creatinine, cystatin C and the eGFR equations, is key to appropriate interpretation of results.
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Affiliation(s)
- Rouvick M Gama
- Department of Inflammation Biology, Faculty of Life Sciences and Medicine, King's College London, London, UK
- King's Kidney Care, King's College Hospital, London, UK
| | - Kathryn Griffiths
- King's Kidney Care, King's College Hospital, London, UK
- Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Royce P Vincent
- Department of Clinical Biochemistry (Synnovis), King's College Hospital, London, UK
- Department of Nutrition and Dietetics, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Adrien Michael Peters
- Department of Nuclear Medicine, King's College Hospital NHS Foundation Trust, London, UK
| | - Kate Bramham
- King's Kidney Care, King's College Hospital, London, UK
- Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
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Eggertsen PP, Hansen J, Andersen ML, Nielsen JF, Olsen RKJ, Palmfeldt J. Simultaneous measurement of kynurenine metabolites and explorative metabolomics using liquid chromatography-mass spectrometry: A novel accurate method applied to serum and plasma samples from a large healthy cohort. J Pharm Biomed Anal 2023; 227:115304. [PMID: 36827735 DOI: 10.1016/j.jpba.2023.115304] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/14/2023] [Accepted: 02/15/2023] [Indexed: 02/18/2023]
Abstract
Kynurenine metabolites are emerging as promising clinical biomarkers in several diseases, especially within psychiatry. Unfortunately, they are difficult to detect, particularly the challenging neurotoxic metabolite quinolinic acid (QUIN). The aim of this study was twofold: First, to develop a liquid chromatography-mass spectrometry method (LC-MS) for simultaneous targeted quantification of key kynurenine metabolites together with untargeted metabolomics, and second, to demonstrate the feasibility of the method by exploring serum/plasma and gender differences in 120 healthy young adults between 18 and 30 years of age. A range of analytical columns (C18 and biphenyl columns) and mobile phases (acidic and alkaline) were systematically evaluated. The optimized LC-MS method was based on a biphenyl column, a water-methanol gradient with 0.2% formic acid, and authentic isotope-labeled standards for each kynurenine metabolite. Precision and accuracy of targeted quantification of the key kynurenine metabolites tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and QUIN were excellent, far exceeding the acceptance criteria specified by international guidelines. Median inter- and intra-day precision were < 6% in serum and plasma; the median accuracy was 2.4% in serum and 8% in plasma. Serum concentrations were ≤ 10% different from the corresponding concentrations in plasma for all kynurenine metabolites in healthy young adults. Men had higher levels (8-18%) of TRP, KYN, and KYNA than women (p ≤ 0.009), while no differences were observed for 3-HK and QUIN (p > 0.70). Incurred sample reanalysis of 10% of the samples yielded a median difference < 5% from the initial measurement, demonstrating the robustness of the method. Besides the targeted quantification of key kynurenine metabolites, our method was found to be suitable for simultaneous untargeted metabolomics analyses of hundreds of metabolites. A range of compound classes could be detected including amino acids, nucleic acids, dipeptides, antioxidants, and acylcarnitines, making explorative studies highly feasible. For example, we identified an additional kynurenine metabolite, 2-Quinolinecarboxylic acid, which was 47% higher in males than females (adjusted p-value = 0.001). In conclusion, in this study, we present a reliable and robust LC-MS method for simultaneous targeted and untargeted metabolomics ready for both research and clinical use. We show that both serum and plasma can be used for kynurenine studies, and the reported gender differences are in accordance with the literature. Future studies should consider using biphenyl-based LC-MS columns to successfully detect QUIN.
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Affiliation(s)
- Peter Preben Eggertsen
- Department of Clinical Medicine, Aarhus University, Denmark; Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Denmark; Hammel Neurorehabilitation Centre and University Research Clinic, Denmark.
| | - Jakob Hansen
- Department of Forensic Medicine, Aarhus University, Denmark
| | - Malene Lundfold Andersen
- Department of Clinical Medicine, Aarhus University, Denmark; Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Denmark
| | - Jørgen Feldbæk Nielsen
- Department of Clinical Medicine, Aarhus University, Denmark; Hammel Neurorehabilitation Centre and University Research Clinic, Denmark
| | - Rikke Katrine Jentoft Olsen
- Department of Clinical Medicine, Aarhus University, Denmark; Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Denmark
| | - Johan Palmfeldt
- Department of Clinical Medicine, Aarhus University, Denmark; Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Denmark.
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Mikami R, Hayakawa M, Imai S, Sugawara M, Takekuma Y. Onset timing and duration of augmented renal clearance in a mixed intensive care unit. J Intensive Care 2023; 11:13. [PMID: 36959656 PMCID: PMC10035487 DOI: 10.1186/s40560-023-00660-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 03/10/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND Augmented renal clearance (ARC) is associated with lower blood plasma concentrations of renally excreted drugs; however, its time course is unknown. The current study aimed to determine the onset timing/duration of ARC, its risk factors, and its association with clinical outcomes by continuous monitoring of urinary creatinine clearance (CrCl) in critically ill patients. METHODS Data were retrospectively obtained from the medical records of 2592 critically ill patients admitted to the intensive care unit (ICU) from January 2019 to June 2022 at a tertiary emergency hospital. Among these, patients with continuously measured urinary CrCl were selected and observed over time. We evaluated the onset timing and duration of ARC by plotting Kaplan-Meier curves. Furthermore, by multivariate analyses, factors associated with the onset and persistence of ARC were analyzed, and the association between the ARC time course and clinical outcomes was evaluated. RESULTS The prevalence of ARC was 33.4% (245/734). ARC onset was within 3 days of admission in approximately half of the cases, and within 1 week in most of the other cases. In contrast, the persistence duration of ARC varied widely (median, 5 days), and lasted for more than a month in some cases. Multivariate analysis identified younger age, male sex, lower serum creatinine at admission, admission with central nervous system disease, no medical history, use of mechanically assisted ventilation, and vasopressor use as onset factors for ARC. Furthermore, factors associated with ARC persistence such as younger age and higher urinary CrCl on ARC day 1 were detected. The onset of ARC was significantly associated with reduced mortality, but persistent of ARC was significantly associated with fewer ICU-free days. CONCLUSIONS Despite the early onset of ARC, its duration varied widely and ARC persisted longer in younger patients with higher urinary CrCl. Since the duration of ARC was associated with fewer ICU-free days, it may be necessary to consider a long-term increased-dose regimen of renally excreted drugs beginning early in patients who are predicted to have a persistent ARC.
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Affiliation(s)
- Ryusei Mikami
- Department of Pharmacy, Hokkaido University Hospital, Sapporo, 060-8648, Japan
| | - Mineji Hayakawa
- Department of Emergency Medicine, Hokkaido University Hospital, Sapporo, 060-8648, Japan
| | - Shungo Imai
- Faculty of Pharmacy, Keio University, Tokyo, 105-8512, Japan
- Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan
| | - Mitsuru Sugawara
- Department of Pharmacy, Hokkaido University Hospital, Sapporo, 060-8648, Japan
- Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan
| | - Yoh Takekuma
- Department of Pharmacy, Hokkaido University Hospital, Sapporo, 060-8648, Japan.
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12
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Defilippi CR, Alemayehu WG, Voors AA, Kaye D, Blaustein RO, Butler J, Ezekowitz JA, Hernandez AF, Lam CSP, Roessig L, Seliger S, Shah P, Westerhout CM, Armstrong PW, O'Connor CM. Assessment of Biomarkers of Myocardial injury, Inflammation, and Renal Function in Heart Failure With Reduced Ejection Fraction: The VICTORIA Biomarker Substudy. J Card Fail 2023; 29:448-458. [PMID: 36634811 DOI: 10.1016/j.cardfail.2022.12.013] [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: 09/02/2022] [Revised: 12/12/2022] [Accepted: 12/12/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND Circulating biomarkers may be useful in understanding prognosis and treatment efficacy in heart failure with reduced ejection fraction. In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, vericiguat, a soluble guanylate cyclase stimulator, decreased the primary outcome of cardiovascular death or heart failure hospitalization in heart failure with reduced ejection fraction. We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations with outcomes and vericiguat treatment effect. METHODS AND RESULTS High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C were measured at baseline and 16 weeks. Associations of biomarkers with the primary outcome and its components were estimated. Interaction with study treatment was tested. Changes in biomarkers over time were examined by study treatment. One or more biomarkers were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16 weeks. After adjustment, higher values of hs-cTnT, growth differentiation factor-15, and interleukin-6 were associated with the primary outcome, independent of N-terminal pro-B-type natriuretic peptide. Higher hs-cTnT values were associated with a hazard ratio per log standard deviation of 1.21 (95% confidence interval 1.14-1.27). A treatment interaction with vericiguat was evident with hs-cTnT and cardiovascular death (P = .04), but not HF hospitalization (P = .38). All biomarkers except cystatin C decreased over 16 weeks and no relationship between treatment assignment and changes in biomarker levels was observed. CONCLUSIONS hs-cTnT, growth differentiation factor-15, and interleukin-6 levels were associated with risk of the primary outcome in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). Uniquely, lower hs-cTnT was associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with vericiguat.
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Affiliation(s)
| | | | - Adriaan A Voors
- University of Groningen, University Medical Center of Groningen, Groningen, the Netherlands
| | - David Kaye
- Baker Heart & Diabetes Institute, Melbourne, Australia
| | | | - Javed Butler
- Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
| | - Justin A Ezekowitz
- Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
| | - Adrian F Hernandez
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Carolyn S P Lam
- National Heart Centre Singapore and Duke-National University of Singapore, Singapore
| | | | - Stephen Seliger
- University of Maryland School of Medicine, Baltimore, Maryland
| | - Palak Shah
- Inova Heart and Vascular Institute, Falls Church, Virginia
| | | | - Paul W Armstrong
- Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
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13
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Kure Y, Okai T, Izumiya Y, Yoshida H, Mizutani K, Yamaguchi T, Ogawa M, Shibata A, Ito A, Takahashi Y, Shibata T, Fukuda D. Impact of cystatin C-derived glomerular filtration rate in patients undergoing transcatheter aortic valve implantation. Front Cardiovasc Med 2023; 10:1035736. [PMID: 37187794 PMCID: PMC10176087 DOI: 10.3389/fcvm.2023.1035736] [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: 09/03/2022] [Accepted: 03/27/2023] [Indexed: 05/17/2023] Open
Abstract
Background Chronic kidney disease (CKD) impacts prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). While estimated glomerular filtration rate (eGFR) calculated from serum creatinine [eGFR (creatinine)] is affected by body muscle mass which reflects frailty, eGFR calculated from serum cystatin C [eGFR (cystatin C)] is independent of body composition, resulting in better renal function assessment. Methods This study included 390 consecutive patients with symptomatic severe aortic stenosis (AS) who underwent TAVI, and measured cystatin C-based eGFR at discharge. Patients were divided into two groups, with or without CKD estimated with eGFR (cystatin C). The primary endpoint of this study was the 3-year all-cause mortality after TAVI. Results The median patient age was 84 years, and 32.8% patients were men. Multivariate Cox regression analysis indicated that eGFR (cystatin C), diabetes mellitus, and liver disease were independently associated with 3-year all-cause mortality. In the receiver-operating characteristic (ROC) curve, the predictive value of eGFR (cystatin C) was significantly higher than that of eGFR (creatinine). Furthermore, Kaplan-Meier estimates revealed that 3-year all-cause mortality was higher in the CKD (cystatin C) group than that in the non-CKD (cystatin C) group with log-rank p = 0.009. In contrast, there was no significant difference between the CKD (creatinine) and non-CKD (creatinine) groups with log-rank p = 0.94. Conclusions eGFR (cystatin C) was associated with 3-year all-cause mortality in patients who underwent TAVI, and it was superior to eGFR (creatinine) as a prognostic biomarker.
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Affiliation(s)
- Yusuke Kure
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Tsukasa Okai
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
- Correspondence: Tsukasa Okai
| | - Yasuhiro Izumiya
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hisako Yoshida
- Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Kazuki Mizutani
- Division of Cardiology, Department of Medicine, Kindai University Faculty of Medicine, Osaka, Japan
| | - Tomohiro Yamaguchi
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Mana Ogawa
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Atsushi Shibata
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Asahiro Ito
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yosuke Takahashi
- Department of Cardiovascular Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Toshihiko Shibata
- Department of Cardiovascular Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Daiju Fukuda
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
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14
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Saleh MA, Elmaaty AA, El Saeed HS, Saleh MM, Salah M, Ezz Eldin RR. Structure based design and synthesis of 3-(7-nitro-3-oxo-3,4-dihydroquinoxalin-2-yl)propanehydrazide derivatives as novel bacterial DNA-gyrase inhibitors: In-vitro, In-vivo, In-silico and SAR studies. Bioorg Chem 2022; 129:106186. [PMID: 36215786 DOI: 10.1016/j.bioorg.2022.106186] [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: 07/12/2022] [Revised: 09/26/2022] [Accepted: 09/28/2022] [Indexed: 11/02/2022]
Abstract
Antimicrobial resistance (AMR) is one of the critical challenges that have been encountered over the past years. On the other hand, bacterial DNA gyrase is regarded as one of the most outstanding biological targets that quinolones can extensively inhibit, improving AMR. Hence, a novel series of 3-(7-nitro-3-oxo-3,4-dihydroquinoxalin-2-yl)propanehydrazide derivatives (3-6j) were designed and synthesized employing the quinoxaline-2-one scaffold and relying on the pharmacophoric features experienced by the quinolone antibiotic; ciprofloxacin. The antibacterial activity of the synthesized compounds was assessed via in-vitro approaches using eight different Gram-positive and Gram-negative bacterial species. Most of the synthesized compounds revealed eligible antibacterial activities. In particular, compounds 6d and 6e displayed promising antibacterial activity among the investigated compounds. For example, compounds 6d and 6e displayed MIC values of 9.40 and 9.00 µM, respectively, regarding S. aureus, and 4.70 and 4.50 µM, respectively, regarding S. pneumonia in comparison to ciprofloxacin (12.07 µM). The cytotoxicity of compounds 6d and 6e were performed on normal human WI-38 cell lines with IC50 values of 288.69 and 227.64 μM, respectively assuring their safety and selectivity. Besides, DNA gyrase inhibition assay of compounds 6d and 6e was carried out in comparison to ciprofloxacin, and interestingly, compounds 6d and 6e disclosed promising IC50 values of 0.242 and 0.177 μM, respectively, whereas ciprofloxacin displayed an IC50 value of 0.768 μM, assuring the proposed mechanism of action for the afforded compounds. Consequently, compounds 6d and 6e were further assessed via in-vivo approaches by evaluating blood counts, liver and kidney functions, and histopathological examination. Both compounds were found to be safer on the liver and kidney than the reference ciprofloxacin. Moreover, in-silico molecular docking studies were established and revealed reasonable binding affinities for all afforded compounds, particularly compound 6d which exhibited a binding score of -7.51 kcal/mol, surpassing the reference ciprofloxacin (-7.29 kcal/mol) with better anticipated stability at the DNA gyrase binding pocket. Moreover, ADME studies were conducted, disclosing an eligible bioavailability score of >0.55 for all afforded compounds, and reasonable GIT absorption without passing the blood brain barrier was attained for most investigated compounds, ensuring their efficacy and safety. Lastly, a structure activity relationship study for the synthesized compounds was established and unveiled that not only the main pharmacophores required for DNA gyrase inhibition are enough for exerting promising antimicrobial activities, but also derivatization with diverse aryl/hetero aryl aldehydes is essential for their enhanced antimicrobial potential.
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Affiliation(s)
- Marwa A Saleh
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
| | - Ayman Abo Elmaaty
- Medicinal Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt.
| | - Hoda S El Saeed
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
| | - Moustafa M Saleh
- Microbiology and Immunology Department, Faculty of Pharmacy, Port Said University, Egypt
| | - Mohammed Salah
- Microbiology and Immunology Department, Faculty of Pharmacy, Port Said University, Egypt
| | - Rogy R Ezz Eldin
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said, Egypt.
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15
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Sharma A, Sahasrabudhe V, Musib L, Zhang S, Younis I, Kanodia J. Time to Rethink the Current Paradigm for Assessing Kidney Function in Drug Development and Beyond. Clin Pharmacol Ther 2022; 112:946-958. [PMID: 34800044 PMCID: PMC9786617 DOI: 10.1002/cpt.2489] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 11/11/2021] [Indexed: 12/30/2022]
Abstract
Chronic kidney disease (CKD) is an important health issue that affects ~ 9.1% of the world adult population. Serum creatinine is the most commonly used biomarker for assessing kidney function and is utilized in different equations for estimating creatinine clearance or glomerular filtration rate (GFR). The Cockcroft-Gault formula for adults and "original" Schwartz formula for children have been the most commonly used equations for estimating kidney function during the last 3-4 decades. Introduction of standardized serum creatinine bioanalytical methodology has reduced interlaboratory variability but is not intended to be used with Cockcroft-Gault or original Schwartz equations. More accurate equations (for instance, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for adults and bedside Schwartz or Chronic Kidney Disease in Children Schwartz equation for children) based on standardized serum creatinine values (and another biomarker-cystatin C) have been introduced and validated in recent years. Recently, the CKD-EPI equation refitted without a race variable was introduced. Clinical practice guidance in nephrology advocates a shift to these equations for managing health care of patients with CKD. The guidance also recommends use of albuminuria in addition to GFR for CKD diagnosis and management. Significant research with large data sets would be necessary to evaluate whether this paradigm would also be valuable in drug dose adjustments. This article attempts to highlight some important advancements in the field from a clinical pharmacology perspective and is a call to action to industry, regulators, and academia to rethink the current paradigm for assessing kidney function to enable dose recommendation in patients with CKD.
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Affiliation(s)
- Ashish Sharma
- Boehringer Ingelheim PharmaceuticalsRidgefieldConnecticutUSA
| | | | - Luna Musib
- Gilead Sciences IncFoster CityCaliforniaUSA
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16
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Liu S, Yang R, Yang Q, He G, Chen B, Dong R. The independent and interactive effects of phthalates exposure and hypertension on the indicators of early renal injury in US adults: Evidence from NHANES 2001-2004. ENVIRONMENTAL RESEARCH 2022; 213:113733. [PMID: 35750123 DOI: 10.1016/j.envres.2022.113733] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 05/04/2022] [Accepted: 06/17/2022] [Indexed: 05/26/2023]
Abstract
The association between phthalates and early renal injury is largely unknown in adults. We aim to explore the associations of phthalates and hypertension with early renal injury, and the interactive effects of phthalate and hypertension on the early renal injury. This study enrolled 3283 U.S. adults from NHANES 2001-2004. We detected nine phthalate metabolites in spot urine. We also measured the multiple indicators of early renal injury, including albumin-to-creatinine (Cr) ratio (ACR), β2-microglobulin (B2M), cystatin C (CYST), and calculated the estimated glomerular filtration rate (eGFR), including Cr-based eGFR, CYST-based eGFR, and Cr-CYST-based eGFR. Multiple linear regression and multivariable logistic regression were used to explore the associations among urinary phthalate metabolites, hypertension, and the indicators of early renal injury. The results showed that monobenzyl phthalate (MBzP), mono (3-carboxypropyl) phthalate (MCPP), and mono (2-ethylhexyl) phthalate (MEHP) were positively associated with ACR, B2M, CYST and negatively associated with three eGFR. Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was positively associated with ACR, with a β value of 0.099 (95% CI: 0.046, 0.152). Meanwhile, MEHP was associated with a higher risk of ACR abnormality, with an OR value of 1.258 (95% CI: 1.067, 1.482). MBzP, MCPP, and MEOHP increased the risks of ACR, B2M, CYST, and eGFR abnormality. Hypertension was positively associated with ACR, with a β value of 0.460 (95% CI: 0.360, 0.561). We also found interactive effects of monoethyl phthalate (MEP), MCPP, MBzP, monobutyl phthalate (MnBP), and hypertension on B2M, CYST, and three kinds of eGFR. Our results indicated that certain phthalate metabolites might contribute to increased risks of early renal injury. The hypertension population may be more sensitive to the early renal injury caused by phthalates exposure than the non-hypertension population.
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Affiliation(s)
- Shaojie Liu
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Ruoru Yang
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Qifan Yang
- Chemical Laboratory, Jing'an District Center for Disease Control and Prevention, Shanghai, 200041, China
| | - Gengsheng He
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Bo Chen
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China
| | - Ruihua Dong
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China.
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17
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Dahlén E, Björkhem-Bergman L. Comparison of Creatinine and Cystatin C to Estimate Renal Function in Geriatric and Frail Patients. Life (Basel) 2022; 12:life12060846. [PMID: 35743877 PMCID: PMC9227422 DOI: 10.3390/life12060846] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/04/2022] [Accepted: 06/06/2022] [Indexed: 01/10/2023] Open
Abstract
The aim of this study was to compare estimated glomerular filtration rate (eGFR) with creatinine (eGFRcrea) and cystatin C (eGFRcys) in geriatric and frail patients. A retrospective, cross-sectional study was performed at a geriatric clinic in Stockholm (n = 95). The revised Lund−Malmö equation was used to calculate eGFRcrea and the Caucasian-Asian-Pediatric-Adult (CAPA) equation was used for eGFRcys. The absolute mean percentage difference between eGFRcrea and eGFRcys was used as a surrogate measure for accuracy in eGFR. Other outcome measures were consistency expressed in Lin’s concordance correlation coefficient and the proportion of consistent staging of renal failure. Subgroup analyses were performed with regard to frailty (according to Clinical Frailty Scale) and age. eGFRcys estimated lower GFR than eGFRcrea across the entire study population as well as in all subgroups (p < 0.05). Difference between the estimates increased with increasing frailty (r2 = 0.15, p < 0.01), but was not significantly affected by age (r2 = 0.004, p = 0.55). In conclusion, eGFRcys was significantly lower compared to eGFRcrea in geriatric and frail patients. Moreover, frailty had greater impact than age on the accuracy of eGFR. However, this study cannot determine if any of the estimates are preferable over the other in this patient group.
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Affiliation(s)
- Erik Dahlén
- Jakobsberg Geriatric Clinic, Jakobsberg’s Hospital, Järfälla, 177 31 Stockholm, Sweden
- Correspondence:
| | - Linda Björkhem-Bergman
- Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Blickagången 16, Neo Floor 7, Huddinge, 141 83 Stockholm, Sweden;
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18
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Wongpraphairot S, Thongrueang A, Bhurayanontachai R. Glomerular filtration rate correlation and agreement between common predictive equations and standard 24-hour urinary creatinine clearance in medical critically ill patients. PeerJ 2022; 10:e13556. [PMID: 35669965 PMCID: PMC9165591 DOI: 10.7717/peerj.13556] [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: 03/02/2022] [Accepted: 05/17/2022] [Indexed: 01/17/2023] Open
Abstract
Background Determining kidney function in critically ill patients is paramount for the dose adjustment of several medications. When assessing kidney function, the glomerular filtration rate (GFR) is generally estimated either by calculating urine creatinine clearance (UCrCl) or using a predictive equation. Unfortunately, all predictive equations have been derived for medical outpatients. Therefore, the validity of predictive equations is of concern when compared with that of the UCrCl method, particularly in medical critically ill patients. Therefore, we conducted this study to assess the agreement of the estimated GFR (eGFR) using common predictive equations and UCrCl in medical critical care setting. Methods This was the secondary analysis of a nutrition therapy study. Urine was collected from participating patients over 24 h for urine creatinine, urine nitrogen, urine volume, and serum creatinine measurements on days 1, 3, 5, and 14 of the study. Subsequently, we calculated UCrCl and eGFR using four predictive equations, the Cockcroft-Gault (CG) formula, the four and six-variable Modification of Diet in Renal Disease Study (MDRD-4 and MDRD-6) equations, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The correlation and agreement between eGFR and UCrCl were determined using the Spearman rank correlation coefficient and Bland-Altman plot with multiple measurements per subject, respectively. The performance of each predictive equation for estimating GFR was reported as bias, precision, and absolute percentage error (APE). Results A total of 49 patients with 170 urine samples were included in the final analysis. Of 49 patients, the median age was 74 (21-92) years-old and 49% was male. All patients were hemodynamically stable with mean arterial blood pressure of 82 (65-108) mmHg. Baseline serum creatinine was 0.93 (0.3-4.84) mg/dL and baseline UCrCl was 46.69 (3.40-165.53) mL/min. The eGFR from all the predictive equations showed modest correlation with UCrCl (r: 0.692 to 0.759). However, the performance of all the predictive equations in estimating GFR compared to that of UCrCl was poor, demonstrating bias ranged from -8.36 to -31.95 mL/min, precision ranged from 92.02 to 166.43 mL/min, and an unacceptable APE (23.01% to 47.18%). Nevertheless, the CG formula showed the best performance in estimating GFR, with a small bias (-2.30 (-9.46 to 4.86) mL/min) and an acceptable APE (14.72% (10.87% to 23.80%)), especially in patients with normal UCrCl. Conclusion From our finding, CG formula was the best eGFR formula in the medical critically ill patients, which demonstrated the least bias and acceptable APE, especially in normal UCrCl patients. However, the predictive equation commonly used to estimate GFR in critically ill patients must be cautiously applied due to its large bias, wide precision, and unacceptable error, particularly in renal function impairment.
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Affiliation(s)
- Suwikran Wongpraphairot
- Nephrology Unit, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Attamon Thongrueang
- Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Rungsun Bhurayanontachai
- Critical Care Medicine Unit, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
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Wang N, Lu Z, Zhang W, Bai Y, Pei D, Li L. Serum Cystatin C Trajectory Is a Marker Associated With Diabetic Kidney Disease. Front Endocrinol (Lausanne) 2022; 13:824279. [PMID: 35634510 PMCID: PMC9130469 DOI: 10.3389/fendo.2022.824279] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 04/04/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To explore the association of the trajectory of serum Cystatin C (Cysc) with diabetic kidney disease (DKD), a retrospective cohort study of Chinese subjects was carried out. Method A review of 2,928 diabetes mellitus (DM) patients admitted to the clinic and ward of the Endocrinology Department, Shengjing Hospital of China Medical University from January 1, 2014 to December 31, 2014 was performed. Subsequent visits to the hospital were followed until December 31, 2020. The primary endpoint was the incidence of DKD as diagnosed by urinary albumin/creatinine ratio ≥30 mg/g and/or estimated glomerular filtration rate <60 ml/min per 1.73 m2. Healthy control subjects were identified from a health checkup database in Shengjing Hospital from 2016 to 2019. The latent class growth mixed modeling (LCGMM) method was used to analyze latent classes of serum Cysc in healthy and DM subjects. Finally, the hazard ratios (HRs) of latent classes of Cysc in DM subjects were analyzed by Cox regression analysis. Results A total of 805 type 2 diabetes mellitus (T2DM) and 349 healthy subjects were included in the trial. The HRs of quartiles of baseline Cysc in T2DM subjects were 7.15 [95% confidence interval (CI), 2.79 to 25.57], 2.30 (95% CI, 1.25 to 4.24), and 2.05 (95% CI, 1.14 to 3.70), respectively, for quartile 4 (Q4), Q3, and Q2 when compared with Q1. Through LCGMM, a 1-class linear model was selected for the Cysc latent class in healthy subjects. In contrast, a 3-class linear model was selected for that in DM subjects. The slopes of the three latent classes in T2DM subjects were larger than the slope in healthy subjects. The HRs of incident DKD were 3.43 (95% CI, 1.93 to 6.11) for the high-increasing class and 1.80 (95% CI, 1.17 to 2.77) for the middle-increasing class after adjusting for confounding variables. Conclusions Patients with T2DM had a higher velocity of increase in Cysc than healthy subjects. Patients with high baseline Cysc values and high latent increasing velocity of Cysc had a higher risk of developing DKD in later life. More attention should be paid to patients with these high-risk factors.
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Affiliation(s)
- Nana Wang
- Endocrinology Department, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhenyu Lu
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wei Zhang
- Endocrinology Department, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu Bai
- Endocrinology Department, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dongmei Pei
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ling Li
- Endocrinology Department, Shengjing Hospital of China Medical University, Shenyang, China
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20
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Lima C, Gorab DL, Fernandes CR, Macedo E. Role of proenkephalin in the diagnosis of severe and subclinical acute kidney injury during the perioperative period of liver transplantation. Pract Lab Med 2022; 31:e00278. [PMID: 35733419 PMCID: PMC9207138 DOI: 10.1016/j.plabm.2022.e00278] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/11/2022] [Accepted: 04/25/2022] [Indexed: 12/13/2022] Open
Abstract
In recent decades, clinical research on early biomarkers of renal injury has been frequent and intensive, with proenkephalin (PENK) being indicated as a promising filtration biomarker (BM). From a cohort of 57 patients, blood samples were collected preoperatively and 48 h after liver transplantation (LT). The following BMs were analyzed: PENK, cystatin-C (CYS-C), and serum creatinine (Scr). Diagnosis of AKI was based on the KDIGO criteria. Of the 57 patients undergoing LT, 50 (88%) developed acute kidney injury (AKI) and were categorized as follows: no-AKI/mild-AKI - 21 (36.8%) and severe-AKI 36 (63.2%). During the preoperative period, only PENK was significantly higher in patients with severe AKI, with an AUC of 0.69 (CI 0.54–0.83), a cutoff of 55.30 pmol/l, a sensitivity of 0.86, a specificity of 0.52, and an accuracy of 0.75. In addition, subclinical AKI was determined preoperatively in 32 patients. Forty-eight hours after LT, PENK maintained its performance in determining severe AKI, with an AUC of 0.83 (CI 0.72–0.94), a cutoff of 119.05 pmol/l, a sensitivity of 0.81, a specificity of 0.90, and an accuracy of 0.84. PENK detected AKI 48 h earlier than serum creatinine. In a multivariate linear regression analysis, PENK was an independent predictor of severe AKI. This small study suggests that the filtration biomarker PENK shows promise for detecting AKI in patients undergoing LT, revealing greater accuracy and an earlier rise in patients with severe AKI. The combination of kidney functional and filtration BMs may aid in the management and prevention of AKI progression.
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21
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Effect of age, sex, and breed on serum cystatin C and creatinine concentrations in dogs. Vet Res Commun 2022; 46:183-188. [DOI: 10.1007/s11259-021-09844-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 09/30/2021] [Indexed: 10/19/2022]
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22
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Lin L, Chen X, Chen J, Pan X, Xia P, Lin H, Du H. The predictive value of serum level of cystatin C for COVID-19 severity. Sci Rep 2021; 11:21964. [PMID: 34754069 PMCID: PMC8578213 DOI: 10.1038/s41598-021-01570-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 10/29/2021] [Indexed: 02/07/2023] Open
Abstract
To investigate the potential prognostic value of Serum cystatin C (sCys C) in patients with COVID-19 and determine the association of sCys C with severe COVID-19 illness. We performed a retrospective review of medical records of 162 (61.7 ± 13.5 years) patients with COVID-19. We assessed the predictive accuracy of sCys C for COVID-19 severity by the receiver operating characteristic (ROC) curve analysis. The participants were divided into two groups based on the sCys C cut-off value. We evaluated the association between high sCys C level and the development of severe COVID-19 disease, using a COX proportional hazards regression model. The area under the ROC curve was 0.708 (95% CI 0.594-0.822), the cut-off value was 1.245 (mg/L), and the sensitivity and specificity was 79.1% and 60.7%, respectively. A multivariable Cox analysis showed that a higher level of sCys C (adjusted HR 2.78 95% CI 1.25-6.18, p = 0.012) was significantly associated with an increased risk of developing a severe COVID-19 illness. Patients with a higher sCys C level have an increased risk of severe COVID-19 disease. Our findings suggest that early assessing sCys C could help to identify potential severe COVID-19 patients.
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Affiliation(s)
- Luanfeng Lin
- Department of Infectious Disease, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Xiaoling Chen
- Department of Infectious Disease, Fujian Medical University Union Hospital, Fuzhou, China
| | - Junnian Chen
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaobin Pan
- Department of Critical Care Medicine, Fujian Provincial Hospital South Branch, Fuzhou, China
| | - Pincang Xia
- Fujian Center for Disease Control and Prevention, Fuzhou, China
| | - Hailong Lin
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Houwei Du
- Department of Neurology, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, 350001, China.
- Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China.
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23
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Yang Q, Zhang M, Sun P, Li Y, Xu H, Wang K, Shen H, Ban B, Liu F. Cre/CysC ratio may predict muscle composition and is associated with glucose disposal ability and macrovascular disease in patients with type 2 diabetes. BMJ Open Diabetes Res Care 2021; 9:9/2/e002430. [PMID: 34732398 PMCID: PMC8572382 DOI: 10.1136/bmjdrc-2021-002430] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 10/07/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Since the ratio of creatinine to cystatin C (Cre/CysC) can reflect muscle volume, it has been proven to be a predictor of sarcopenia in patients with or without diabetes. Here, we investigated the predictive value of Cre/CysC for the skeletal muscle composition and its correlations with glucose disposal ability and diabetic complications in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS The skeletal muscle index (SMI) and mean skeletal muscle attenuation (MMA) values of 193 patients with type 2 diabetes were obtained through analyses of CT images at the lumbar 3 level. RESULTS Serum Cre/CysC was significantly correlated with both the SMI (r=0.375, p<0.001) and MMA (r=0.378, p<0.001). Multiple stepwise linear regression analysis demonstrated that Cre/CysC was the only biochemical predictor of the SMI (β=0.48 (95% CI 0.02 to 0.94)) and MMA (β=0.57 (95% CI 0.14 to 1.01)). Furthermore, the fat mass index (FMI) was significantly associated with the MMA (r=-0.481, p<0.001) but not the SMI (r=0.101, p=0.164). In the diabetic complications analysis, Cre/CysC was significantly lower in patients with cardiovascular disease (95% CI (-1.47 to -0.22), p=0.008) and lower extremity arterial disease (95% CI (-1.44 to -0.29), p=0.004). Moreover, in the 100 g steamed bun test, Cre/CysC was significantly correlated with glucose levels at 60 min (r=-0.162, p=0.045), 120 min (r=-0.287, p<0.001) and 180 min (r=-0.313, p<0.001). CONCLUSIONS Cre/CysC may be a valuable predictor of skeletal muscle composition in type 2 diabetes. Patients with a higher Cre/CysC may have a better ability to dispose of postprandial glucose and are at a lower risk of macrovascular disease.
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Affiliation(s)
- Qing Yang
- Department of Nutrition, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Mei Zhang
- Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Peng Sun
- Department of Nutrition, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Yanying Li
- Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Huichao Xu
- Department of Nutrition, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Kejun Wang
- Department of Nutrition, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Hongshan Shen
- Department of Nutrition, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Bo Ban
- Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Fupeng Liu
- Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
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24
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Screever EM, Kootstra-Ros JE, Doorn J, Nieuwenhuis JA, Meulenbelt HEJ, Meijers WC, de Boer RA. Kidney Function in Patients With Neuromuscular Disease: Creatinine Versus Cystatin C. Front Neurol 2021; 12:688246. [PMID: 34630276 PMCID: PMC8498206 DOI: 10.3389/fneur.2021.688246] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 08/26/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Accurate measurement of kidney function in patients with neuromuscular disorders is challenging. Cystatin C, a marker not influenced by skeletal muscle degradation, might be of clinical value in these patients. Methods: We consecutively enrolled 39 patients with neuromuscular disorders. We investigated the association of the eGFR, based on plasma creatinine and Cystatin C, with clinical and biochemical variables associated with kidney function, namely age and galectin-3. Results: Creatinine-based eGFR was 242 (±80) and Cystatin C-based eGFR was 110 (±23) mL/min/1.73 m2. Cystatin C-based eGFR was associated with age (β −0.63 p < 0.0001) and galectin-3 levels (β −0.43 p < 0.01), while creatinine-based eGFR was not (β −0.22 p = 0.20; β −0.28 p = 0.10). Sensitivity analyses in Duchenne and Becker patients revealed the same results: Cystatin C-based eGFR was associated with age (β −0.61 p < 0.01) and galectin-3 levels (β −0.43 p = 0.05), while creatinine-based eGFR was not (β −0.32 p = 0.13; β −0.34 p = 0.14). Conclusions: These data indicate that estimation of renal function in patients with neuromuscular disorders cannot reliably be achieved with creatinine, while Cystatin C appears a reasonable alternative. Since a large proportion of patients with neuromuscular disorders develops heart failure, and requires heart failure medication, adequate monitoring of renal function is warranted.
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Affiliation(s)
- Elles M Screever
- Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands
| | - Jenny E Kootstra-Ros
- Department of Laboratory Medicine, University Medical Center Groningen, Groningen, Netherlands
| | - Joyce Doorn
- Department of Laboratory Medicine, University Medical Center Groningen, Groningen, Netherlands
| | - Jellie A Nieuwenhuis
- Department of Pulmonary Disease, University Medical Center Groningen, Groningen, Netherlands
| | - Henk E J Meulenbelt
- Department of Rehabilitation Medicine, University Medical Center Groningen, Groningen, Netherlands
| | - Wouter C Meijers
- Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands
| | - Rudolf A de Boer
- Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands
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25
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Al-Amodi HS, Abdelsattar S, Kasemy ZA, Bedair HM, Elbarbary HS, Kamel HFM. Potential Value of TNF-α (-376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients. Front Mol Biosci 2021; 8:751299. [PMID: 34692772 PMCID: PMC8526786 DOI: 10.3389/fmolb.2021.751299] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 09/20/2021] [Indexed: 12/29/2022] Open
Abstract
Sepsis Associated Kidney Injury represents a major health concern as it is frequently associated with increased risk of mortality and morbidity. We aimed to evaluate the potential value of TNF-α (-376 G/A) and cystatin C in the diagnosis of S-AKI and prediction of mortality in critically ill patients. This study included 200 critically ill patients and 200 healthy controls. Patients were categorized into 116 with acute septic shock and 84 with sepsis, from which 142 (71%) developed S-AKI. Genotyping of TNF-α (-376 G/A) was performed by RT-PCR and serum CysC was assessed by Enzyme Linked Immunosorbent Assay. Our results showed a highly significant difference in the genotype frequencies of TNF-α (-376 G/A) SNP between S-AKI and non-AKI patients (p < 0.001). Additionally, sCysC levels were significantly higher in the S-AKI group (p = 0.011). The combination of both sCysC and TNF-α (-376 G/A) together had a better diagnostic ability for S-AKI than sCysC alone (AUC = 0.610, 0.838, respectively). Both GA and AA genotypes were independent predictors of S-AKI (p= < 0.001, p = 0.002 respectively). Additionally, sCysC was significantly associated with the risk of S-AKI development (Odds Ratio = 1.111). Both genotypes and sCysC were significant predictors of non-survival (p < 0.001), suggesting their potential role in the diagnosis of S-AKI and prediction of mortality.
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Affiliation(s)
- Hiba S Al-Amodi
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt
| | - Zeinab A. Kasemy
- Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt
| | - Hanan M. Bedair
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt
| | - Hany S. Elbarbary
- Department of Internal Medicine, Renal Unit, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt
- Department of Internal Medicine, Renal Unit, Faculty of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Hala F. M. Kamel
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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26
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Wainberg M, Kloiber S, Diniz B, McIntyre RS, Felsky D, Tripathy SJ. Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank. Transl Psychiatry 2021; 11:380. [PMID: 34234104 PMCID: PMC8263616 DOI: 10.1038/s41398-021-01505-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 06/16/2021] [Accepted: 06/24/2021] [Indexed: 11/23/2022] Open
Abstract
Prevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.
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Affiliation(s)
- Michael Wainberg
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Stefan Kloiber
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Breno Diniz
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Roger S McIntyre
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada
| | - Daniel Felsky
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Shreejoy J Tripathy
- Centre for Addiction and Mental Health, Toronto, ON, Canada.
- Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada.
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
- Department of Physiology, University of Toronto, Toronto, ON, Canada.
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27
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Natarajan S, DeRosa MC, Shah MI, Jayaraj J. Development and Evaluation of a Quantitative Fluorescent Lateral Flow Immunoassay for Cystatin-C, a Renal Dysfunction Biomarker. SENSORS (BASEL, SWITZERLAND) 2021; 21:3178. [PMID: 34063596 PMCID: PMC8125764 DOI: 10.3390/s21093178] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/18/2021] [Accepted: 04/28/2021] [Indexed: 01/09/2023]
Abstract
The diagnosis, prognosis, and control of chronic kidney disease rely on an understanding of the glomerular filtration rate (GFR). The renal clearance of the cystatin-C is closely associated with the GFR. Cystatin-C is a more suitable GFR marker than the commonly used creatinine. General techniques for cystatin-C calculation, such as particle-enhanced turbidimetric and nephelometric assay, are time-consuming and tedious. Here, we propose a rapid, quantitative immunoassay for the detection of cystatin-C. A fluorescence-based lateral-flow kit was developed in a sandwich format by using a monoclonal antibody. A Linear calibration was obtained over the clinical diagnostic range of 0.023-32 µg/mL and the limit of detection (LOD) was 0.023 µg/mL and the limit of quantification (LOQ) was 0.029 µg/mL. Average recoveries from spiked urine samples ranged from 96-100% and the coefficient of variation was less than 4% for both intra and inter-day assays with excellent repeatability. With the comparison with an ELISA kit, the developed kit is highly sensitive, performs well over the detection range, provides repeatable results in a short time, and can easily be used at point-of-care (POC), making it an ideal candidate for rapid testing in early detection, community screening for renal function disorders.
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Affiliation(s)
- Satheesh Natarajan
- Healthcare Technology Innovation Centre, Indian Institute of Technology Madras, Chennai 600113, India;
| | - Maria C. DeRosa
- Department of Chemistry, Carleton University, Ottawa, ON K1S 5B6, Canada;
| | - Malay Ilesh Shah
- Healthcare Technology Innovation Centre, Indian Institute of Technology Madras, Chennai 600113, India;
| | - Joseph Jayaraj
- Department of Electrical Engineering, Indian Institute of Technology, Madras, Chennai 600113, India
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28
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Jeraiby M. Assessment of renal function using cystatin C and creatinine in Saudi patients after transplantation. Ann Afr Med 2021; 20:59-63. [PMID: 33727514 PMCID: PMC8102893 DOI: 10.4103/aam.aam_67_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background: Rapid and accurate assessment of kidney function in patients after transplantation is of utmost importance. The aim of this study was to compare the relationships of serum creatinine and serum cystatin C with an estimated glomerular filtration rate (eGFR) in kidney transplants Saudi patients after a certain period of transplantation. Materials and Methods: In this prospective study, 127 patients were categorized into three groups based on their length of survival after kidney transplantation; <1 year, from 1 to 5 years, and above 5 years after transplantation. Results of cystatin C and creatinine levels were compared by eGFR derived from estimation equation chronic kidney disease epidemiology collaboration. Results: In the three assessed periods, the mean (standard deviation) cystatin C level was 1.72 (0.57), 1.59 (0.64), and 1.82 (0.82), respectively, being highest after 5 years of transplantation, normal in 9.40%, and elevated in 90.60% of the participants, while creatinine level, decreased from 1.57 (0.53) to 1.52 (0.64) in 1–5 years, then it became the highest at 1.75 (0.69) in more than 5 years. The mean was normal in 21.30% and elevated in 78.70% of the patients. Both serum creatinine and cystatin C levels were negatively correlated with posttransplantation time in kidney transplant patients. Conclusion: The cystatin C level was statistically significantly higher after 5 years of transplantation. It is a better parameter to rule out renal dysfunction after transplantation.
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Affiliation(s)
- M Jeraiby
- Department of Biochemistry, Faculty of Medicine, Jazan University, Jizan, Saudi Arabia
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29
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Shahwan M, Hassan N, Shaheen RA, Gaili A, Jairoun AA, Shahwan M, Najjar O, Jamshed S. Diabetes Mellitus and Renal Function: Current Medical Research and Opinion. Curr Diabetes Rev 2021; 17:e011121190176. [PMID: 33430750 DOI: 10.2174/1573399817999210111205532] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 11/22/2022]
Abstract
Diabetes mellitus (DM), which is defined as high blood glucose level, is a major public health issue worldwide. An enormous amount of data has been gathered regarding DM as populations have been living with it for more than a decade; however, continually updating our knowledge of DM remains important. Comorbidities are among the major challenges associated with DM. Poorly controlled DM, especially type 2 DM (T2DM), is considered a risk factor for many diseases, including but not limited to chronic kidney disease (CKD). Complications might appear over time as the aging process changes body functions; moreover, a significant number of antidiabetic medications are eventually cleared by the kidneys, thereby increasing the burden on kidney function and placing diabetic patients at risk. The significantly high number of patients with uncontrolled diabetes resulting from kidney disease shows the impact of this condition on the quality of life of patients. This review presents an overview of the pathophysiology, etiology, and prevalence of CKD and abnormal renal parameters correlated with poorly controlled T2DM, with an emphasis on clinical studies involving the association between vitamin D insufficiency/deficiency and CKD among patients with T2DM.
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Affiliation(s)
- Moyad Shahwan
- Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates
| | - Nageeb Hassan
- Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates
| | - Rima Ahd Shaheen
- Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates
| | - Ahmed Gaili
- Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates
| | | | - Monzer Shahwan
- Diabetes Clinic, Al-Swity Center for Dermatology and Chronic Diseases, Palestinian Territory, Occupied
| | - Osama Najjar
- General Directorate of Allied Health Professions, Ministry of Health, Palestinian Territory, Occupied
| | - Shazia Jamshed
- Department of Clinical Pharmacy and Practice, Faculty of Pharmacy, Universiti Sultan Zainal Abidin (UniSZA) Besut Campus, Kuala terraenganu, Malaysia
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Serum Cystatin C and Coronavirus Disease 2019: A Potential Inflammatory Biomarker in Predicting Critical Illness and Mortality for Adult Patients. Mediators Inflamm 2020; 2020:3764515. [PMID: 33061826 PMCID: PMC7545455 DOI: 10.1155/2020/3764515] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/10/2020] [Accepted: 08/01/2020] [Indexed: 12/28/2022] Open
Abstract
This study aimed at determining the relationship between baseline cystatin C levels and coronavirus disease 2019 (COVID-19) and investigating the potential prognostic value of serum cystatin C in adult patients with COVID-19. 481 patients with COVID-19 were consecutively included in this study from January 2, 2020, and followed up to April 15, 2020. All clinical and laboratory data of COVID-19 patients with definite outcomes were reviewed. For every measure, COVID-19 patients were grouped into quartiles according to the baseline levels of serum cystatin C. The highest cystatin C level was significantly related to more severe inflammatory conditions, worse organ dysfunction, and worse outcomes among patients with COVID-19 (P values < 0.05). In the adjusted logistic regression analyses, the highest cystatin C level and ln-transformed cystatin C levels were independently associated with the risks of developing critically ill COVID-19 and all-cause death either in overall patients or in patients without chronic kidney disease (P values < 0.05). As a potential inflammatory marker, increasing baseline levels of serum cystatin C might independently predict adverse outcomes for COVID-19 patients. Serum cystatin C could be routinely monitored during hospitalization, which showed clinical importance in prognosticating for adult patients with COVID-19.
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Microfluidic electrochemical immunosensor for the determination of cystatin C in human serum. Mikrochim Acta 2020; 187:585. [DOI: 10.1007/s00604-020-04503-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 08/18/2020] [Indexed: 01/02/2023]
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Hansson M, Gustafsson R, Jacquet C, Chebaane N, Satchell S, Thunberg T, Ahlm C, Fors Connolly AM. Cystatin C and α-1-Microglobulin Predict Severe Acute Kidney Injury in Patients with Hemorrhagic Fever with Renal Syndrome. Pathogens 2020; 9:pathogens9080666. [PMID: 32824680 PMCID: PMC7460112 DOI: 10.3390/pathogens9080666] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 12/29/2022] Open
Abstract
Puumala orthohantavirus causes hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury (AKI), an abrupt decrease in renal function. Creatinine is routinely used to detect and quantify AKI; however, early AKI may not be reflected in increased creatinine levels. Therefore, kidney injury markers that can predict AKI are needed. The potential of the kidney injury markers urea, cystatin C, α1-microglobulin (A1M) and neutrophil gelatinase-associated lipocalin (NGAL) to detect early AKI during HFRS was studied by quantifying the levels of these markers in consecutively obtained plasma (P) and urine samples (U) for 44 HFRS patients. P-cystatin C and U-A1M levels were significantly increased during early HFRS compared to follow-up. In a receiver operating characteristic (ROC) curve analysis, P-cystatin C, U-A1M and P-urea predicted severe AKI with area under the curve 0.72, 0.73 and 0.71, respectively, whereas the traditional kidney injury biomarkers creatinine and U-albumin did not predict AKI. Nearly half of the HFRS patients (41%) fulfilled the criteria for shrunken pore syndrome, which was associated with the level of inflammation as measured by P-CRP. P-cystatin C and U-A1M are more sensitive and earlier markers compared to creatinine in predicting kidney injury during HFRS.
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Affiliation(s)
- Magnus Hansson
- Clinical Chemistry, Karolinska University Hospital, 17176 Stockholm, Sweden;
- Department of Laboratory Medicine, Karolinska Institutet, 17177 Stockholm, Sweden
| | - Rasmus Gustafsson
- Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden;
| | - Chloé Jacquet
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
- Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden
| | - Nedia Chebaane
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
| | - Simon Satchell
- Bristol Renal, Bristol Medical School, University of Bristol, Bristol BS1 3NY, UK;
| | - Therese Thunberg
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
| | - Clas Ahlm
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
| | - Anne-Marie Fors Connolly
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
- Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden
- Correspondence:
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Kang E, Han SS, Kim J, Park SK, Chung W, Oh YK, Chae DW, Kim YS, Ahn C, Oh KH. Discrepant glomerular filtration rate trends from creatinine and cystatin C in patients with chronic kidney disease: results from the KNOW-CKD cohort. BMC Nephrol 2020; 21:280. [PMID: 32677901 PMCID: PMC7364655 DOI: 10.1186/s12882-020-01932-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 07/06/2020] [Indexed: 11/21/2022] Open
Abstract
Background Serum creatinine (Cr) and cystatin C (CysC) can both be used to estimate glomerular filtration rate (eGFRCr and eGFRCysC). However, certain conditions may cause discrepancies between eGFR trends from Cr and CysC, and these remain undetermined in patients with chronic kidney disease (CKD). Methods A total of 1069 patients from the Korean CKD cohort (KNOW-CKD), which enrolls pre-dialytic CKD patients, whose Cr and CysC had been followed for more than 4 years were included in the sample. We performed trajectory analysis using latent class mixed modeling and identified members of the discrepancy group when patient trends between eGFRCr and eGFRCysC differed. Multivariate logistic analyses with Firth’s penalized likelihood regression models were performed to identify conditions related to the discrepancy. Results Trajectory patterns of eGFRCr were classified into three groups: two groups with stable eGFRCr (stable with high eGFRCr and stable with low eGFRCr) and one group with decreasing eGFRCr. Trajectory analysis of eGFRCysC also showed similar patterns, comprising two groups with stable eGFRCysC and one group with decreasing eGFRCysC. Patients in the discrepancy group (decreasing eGFRCr but stable & low eGFRCysC; n = 55) were younger and had greater proteinuria values than the agreement group (stable & low eGFRCr and eGFRCysC; n = 706), differences that remained consistent irrespective of the measurement period (4 or 5 years). Conclusions In the present study, we identify conditions related to discrepant trends of eGFRCr and eGFRCysC. Clinicians should remain aware of such potential discrepancies when tracing both Cr and CysC.
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Affiliation(s)
- Eunjeong Kang
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Seung Seok Han
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Jayoun Kim
- Medical Research Collaborating Center, Seoul National University College of Medicine, Seoul, South Korea
| | - Sue Kyung Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Wookyung Chung
- Department of Internal Medicine, Gachon University, Gil Medical Center, Incheon, South Korea
| | - Yun Kyu Oh
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea
| | - Dong-Wan Chae
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Yong-Soo Kim
- Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Kook-Hwan Oh
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
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Kemmler W, von Stengel S, Kohl M, Rohleder N, Bertsch T, Sieber CC, Freiberger E, Kob R. Safety of a Combined WB-EMS and High-Protein Diet Intervention in Sarcopenic Obese Elderly Men. Clin Interv Aging 2020; 15:953-967. [PMID: 32612355 PMCID: PMC7322975 DOI: 10.2147/cia.s248868] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 05/20/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose Whole-body electromyostimulation (WB-EMS) especially in combination with a high-protein supplementation has been established as an efficient treatment against sarcopenia. However, there are several case reports of rhabdomyolysis after WB-EMS application. Thus, we asked if this training could potentially lead to deteriorations of the cardiac as well as the renal function. Materials and Methods One hundred sarcopenic obese men aged 70 years and older were randomly balanced (1-1-1) and allocated to one of the three study arms. During 16 weeks of intervention, these groups either performed WB-EMS and took a protein supplement (WB-EMS&P), solely received the protein supplement (Protein) or served as control group (CG). WB-EMS consisted of 1.5×20 min (85 Hz, 350 μs, 4 s of strain to 4 s of rest) applied with moderate-to-high intensity while moving. We further generated a daily protein intake of 1.7-1.8 g/kg/body mass per day. At baseline and 8-10 days after completion of the intervention, blood was drawn and biomarkers of muscle, cardiac and renal health were assessed. Results Hereby, we found slight but significant elevations of creatine kinase (CK) levels in the WB-EMS group pointing to minor damages of the skeletal muscle (140 U/l [81-210], p < 0.001). This was accompanied by a significant, low-grade increase of creatine kinase-muscle brain (CK-MB, 0.43 ng/mL [-0.29-0.96], p < 0.01) and high-sensitivity troponin T (hsTnT, 0.001 ng/mL. [0.000-0.003], p < 0.001) but without a higher risk of developing heart failure according to N-terminal prohormone of brain natriuretic peptide (NT-proBNP, -5.7 pg/mL [-38.8-24.6], p = 0.17). Estimated glomerular filtration rate (eGFR) was impaired neither by the high-protein supplementation alone nor in combination with WB-EMS (CG 76.0 mL/min/1.73 m2 [71.9-82.2] vs Protein 73.2 mL/min/1.73 m2 [63.0-78.9] vs WB-EMS&P 74.6 mL/min/1.73 m2 [62.8-84.1], p = 0.478). Conclusion In conclusion, even in the vulnerable group of sarcopenic obese seniors, the combination of WB-EMS with a high-protein intake revealed no short-term, negative impact on the eGFR, but potential consequences for the cardiovascular system need to be addressed in future studies.
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Affiliation(s)
- Wolfgang Kemmler
- Institute of Medical Physics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Simon von Stengel
- Institute of Medical Physics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Matthias Kohl
- Faculty of Medical and Life Science, University of Furtwangen, Schwenningen, Germany
| | - Nicolas Rohleder
- Institute of Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Thomas Bertsch
- Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, General Hospital Nuremberg, Paracelsus Medical University, Nuremberg, Germany
| | - Cornel C Sieber
- Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nuremberg, Germany
| | - Ellen Freiberger
- Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nuremberg, Germany
| | - Robert Kob
- Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nuremberg, Germany
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Shen R, Zhang W, Ming S, Li L, Peng Y, Gao X. Gender-related differences in the performance of sequential organ failure assessment (SOFA) to predict septic shock after percutaneous nephrolithotomy. Urolithiasis 2020; 49:65-72. [PMID: 32372319 DOI: 10.1007/s00240-020-01190-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 04/24/2020] [Indexed: 12/15/2022]
Abstract
The study aims to identify whether gender differences exist in the sequential organ failure assessment (SOFA) score to the extent of affecting its predictive accuracy for septic shock after percutaneous nephrolithotomy (PCNL). A retrospective study of 612 patients undergoing PCNL was performed. The SOFA scores of male and female groups were compared to identify any gender differences. The ROC curve was used to find differences between the original and adjusted SOFA scores. Postoperative septic shock developed in 21 (3.43%) cases. A marginally significant discrepancy in median SOFA scores between genders was discovered in a subgroup of patients < 40 years old (p = 0.048). A gender difference existed in the SOFA score after PCNL, with greater proportion of high scores in female patients (p = 0.011). Male patients had a higher proportion of ≥ 2 sub-score in hepatic and renal systems than female patients, caused by their higher preoperative bilirubin and creatinine (p < 0.05). An adjusted SOFA score was created to replace the original postoperative SOFA score with the perioperative changed values of bilirubin and creatinine. Performance of the adjusted SOFA score for predicting septic shock was comparable with the original SOFA score (AUC 0.987 vs. 0.985, p = 0.932). Under the premise of ensuring 100% sensitivity, the adjusted SOFA score reduced the 43.7% (31/71) false-positive rate for predicting septic shock compared with the original SOFA score. In conclusion, the gender should not be neglected when applying SOFA score for patients after PCNL. The adjusted SOFA score eliminates negative effects caused by gender differences in predicting septic shock.
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Affiliation(s)
- Rong Shen
- Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China
| | - Wei Zhang
- Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China
| | - Shaoxiong Ming
- Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China
| | - Ling Li
- Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China
| | - Yonghan Peng
- Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
| | - Xiaofeng Gao
- Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Rd, Shanghai, 200433, China.
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AKDAĞ İ, ERSOY A. Serum Cystatin C Measurement in Lupus Nephritis Patients: Its Correlation with Clinical and Histopathological Findings. TURKISH JOURNAL OF INTERNAL MEDICINE 2020. [DOI: 10.46310/tjim.710052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Mueangkhiao P, Siviroj P, Sapbamrer R, Khacha-Ananda S, Lungkaphin A, Seesen M, Jaikwang P, Wunnapuk K. Biological variation in kidney injury and kidney function biomarkers among farmers in Lamphun province, Thailand. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:12386-12394. [PMID: 31989504 DOI: 10.1007/s11356-020-07661-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 01/07/2020] [Indexed: 06/10/2023]
Abstract
Frequent and long-term exposure to pesticides can induce acute kidney injury and subsequent chronic kidney diseases. In this study, we aimed to investigate the correlation between kidney injury, kidney function biomarkers, and pesticide use in farmers from the Pasang district, Lamphun province, Thailand. A cross-sectional study was performed in 59 farmers occupationally exposed to various types of pesticides. The levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum creatinine (sCr), urinary microalbumin-to-creatinine ratio (ACR), serum cystatin C (sCys-C), estimated glomerular filtration rate (eGFR), and exposure intensity index (EII) were evaluated. Spearman's correlation and a linear regression analysis were carried out to investigate the association between age, pesticide use, EII, kidney injury markers, and kidney function biomarkers. The most common pesticide used in this study area was glyphosate, followed by paraquat and iprodione. Urinary NGAL levels showed a significant correlation with sCys-C levels, EII, and eGFR Cr-Cys. In addition, the sCr levels were associated with glyphosate use (B = 0.08) and EII (B = 0.01). In conclusion, occupation exposure to pesticides is likely to be linked to kidney injury and dysfunction. Pesticide mix status, pesticide application method, equipment repair status, and personal protective equipment (PPE) use are all involved in changes in kidney markers.
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Affiliation(s)
- Patthawee Mueangkhiao
- Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Penprapa Siviroj
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Ratana Sapbamrer
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Supakit Khacha-Ananda
- Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Anusorn Lungkaphin
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Mathuramat Seesen
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pittaya Jaikwang
- Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Klintean Wunnapuk
- Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
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Ferreira PAB, Araujo MCM, Prado CM, de Lima RA, Rodríguez BAG, Dutra RF. An ultrasensitive Cystatin C renal failure immunosensor based on a PPy/CNT electrochemical capacitor grafted on interdigitated electrode. Colloids Surf B Biointerfaces 2020; 189:110834. [PMID: 32066088 DOI: 10.1016/j.colsurfb.2020.110834] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 01/18/2020] [Accepted: 01/29/2020] [Indexed: 12/18/2022]
Abstract
An interdigitated immunosensor for Cystatin C detection based on polypyrrole/carbon nanotube electrochemical capacitor is described. Cystatin C (CysC) is powerful biomarker for early acute renal failure and one predictive for cardiovascular risk, sepsis, cancer and death. Recently, electrochemical immunosensors based on interdigitated electrodes (IDE) have been successfully focused on development of point-of-care testing, due to their miniaturization facilities and higher sensitivity as compared with the screen-printed electrochemical sensing. Herein, a polypyrrole/carbon nanotube nanoyhibrid film was grafted on two gold fingers by electropolymerization obtaining a supercapacitor. Anti-CysC antibodies were immobilized on the IDE by covalent entrapment via ethylenediamine bifunctional agent, followed by glycine blocking in acid and alkaline medium. Under low frequency, capacitive effect of antigen-antibody interaction were observed by double layer capacitance, and analytical responses of this IDE immunosensor to CysC serum were obtained by changes on phase angle a linear range up to 300 ng/mL. The cutoff was calculated for serum samples showing a total reducing of non-specific binding at approximately 28 ng/mL CysC. This immunosensor based on interdigitated electrode (IDE) is a potential tools as portable device,with possibility to use as a practical and rapid test for CysC diagnostic in samples of serum.
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Affiliation(s)
- Paula A B Ferreira
- Biomedical Engineering Laboratory, Department of Biomedical Engineering, Federal University of Pernambuco, Recife, Brazil
| | - Maria C M Araujo
- Biomedical Engineering Laboratory, Department of Biomedical Engineering, Federal University of Pernambuco, Recife, Brazil
| | - Cecília M Prado
- Biomedical Engineering Laboratory, Department of Biomedical Engineering, Federal University of Pernambuco, Recife, Brazil
| | - Ricardo A de Lima
- Electrical Engineering Department, Pernambuco State University, Recife, Brazil
| | - Blanca A G Rodríguez
- Biomedical Engineering Laboratory, Department of Biomedical Engineering, Federal University of Pernambuco, Recife, Brazil
| | - Rosa F Dutra
- Biomedical Engineering Laboratory, Department of Biomedical Engineering, Federal University of Pernambuco, Recife, Brazil.
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Kooshki H, Abbaszadeh R, Heidari R, Akbariqomi M, Mazloumi M, Shafei S, Absalan M, Tavoosidana G. Developing a DNA aptamer-based approach for biosensing cystatin-c in serum: An alternative to antibody-based methods. Anal Biochem 2019; 584:113386. [DOI: 10.1016/j.ab.2019.113386] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 07/22/2019] [Accepted: 08/03/2019] [Indexed: 12/28/2022]
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Valverde S, Gessoni G, Garelli E, Valle L, Gessoni F, Iacoviello M, Zatta M, Valle R. Valutazione di un approccio basato sul dosaggio di multipli biomarcatori nella diagnosi di scompenso cardiaco in soggetti in età geriatrica. LA RIVISTA ITALIANA DELLA MEDICINA DI LABORATORIO 2019; 15. [DOI: 10.23736/s1825-859x.19.00014-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/20/2025]
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Ayoola OO, Bolarinwa RA, Onakpoya UU, Onwuka CC, Adedeji TA, Afolabi BI, Onigbinde SO, Arogundade FA. Doppler ultrasonographic evaluation of celiac and mesenteric arteries in subjects with sickle cell disease. JOURNAL OF CLINICAL ULTRASOUND : JCU 2019; 47:501-507. [PMID: 31063231 DOI: 10.1002/jcu.22729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 04/11/2019] [Accepted: 04/21/2019] [Indexed: 06/09/2023]
Abstract
Vasculopathy, as occurring in sickle cell disease (SCD), can affect celiac and mesenteric arteries and result in stenosis, with elevated peak systolic velocity (PSV) on Doppler ultrasonography. In six subjects with confirmed SCD in steady state, routine Doppler ultrasonographic examination discovered features of celiac artery (CA) or superior mesenteric artery (SMA) stenosis with CA PSV >200 cm/s (median = 222.8 cm/s; range = 201.5-427.1 cm/s) and/or SMA PSV >275 cm/s (median 183.2 cm/s; range = 87.8-289.3 cm/s). Among the six subjects, five had elevated soluble P-selectin values (median 72.55 ng/mL), while all six (100%) had elevated cystatin C levels (median 4.15 mg/L). Peripheral oxygen saturation was suboptimal in five subjects. All subjects had low hemoglobin concentration levels (median 8.5 g/dL) while four had elevated white blood cell count. Although vaso-occlusive crises result from microvessel occlusion, these findings at the macrovascular level suggest that SCD patients may also be vulnerable to mesenteric ischemic injury, especially in the setting of anemic heart failure from hemolysis.
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Affiliation(s)
- Oluwagbemiga O Ayoola
- Department of Radiology, Faculty of Clinical Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
- Department of Radiology, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - Rahman A Bolarinwa
- Department of Hematology and Blood Transfusion, Faculty of Basic Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Uvie U Onakpoya
- Department of Surgery, Faculty of Clinical Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Chidiogo C Onwuka
- Department of Radiology, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - Tewogbade A Adedeji
- Department of Chemical Pathology, Faculty of Basic Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Babalola I Afolabi
- Department of Radiology, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - Stephen O Onigbinde
- Department of Radiology, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - Fatiu A Arogundade
- Department of Internal Medicine, Faculty of Clinical Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
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Liu C, Wen J, Xiang J, Ouyang X, Yang Y, Lu W, Wang J, Huang J, Min X. Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0-18 years old). J Int Med Res 2019; 47:3151-3159. [PMID: 31187682 PMCID: PMC6683897 DOI: 10.1177/0300060519855575] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 05/16/2019] [Indexed: 11/18/2022] Open
Abstract
Objective This study aimed to investigate serum levels of the cystatin C (CysC)/creatinine (Cr) ratio and renal serum markers (CysC, Cr, urea, and uric acid [UA]) for different ages and by sex. We also aimed to establish pediatric reference intervals for the serum CysC/Cr ratio. Methods Serum samples were collected from 4765 healthy children (0–18 years old). Serum markers of renal function were measured, and the CysC/Cr ratio of each participant was calculated and statistically analyzed. Results The renal marker CysC did not substantially change after 1 year old. Cr, urea, and UA levels generally increased with age. However, the serum CysC/Cr ratio steadily decreased with age. The CysC/Cr ratio showed significant differences in age among all age groups and varied with sex, except for in the 1 to 6-year-old groups. The overall serum CysC/Cr ratio in girls was higher than that in boys. Conclusion Reference intervals of the serum CysC/Cr ratio in the pediatric population were established. These intervals need to be partitioned by age and sex.
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Affiliation(s)
- Changjin Liu
- Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Jing Wen
- Department of Medical Imaging, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Jialin Xiang
- Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Xuhong Ouyang
- Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Yan Yang
- Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Wei Lu
- Department of Child Care, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Jianwei Wang
- Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China
| | - Jian Huang
- Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Xun Min
- Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Guizhou, China
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Sinna MM, Altaf FMN, Mosa OF. Serum and Urinary NGAL and Cystatin C Levels as Diagnostic Tools for Acute Kidney Injury and Chronic Kidney Disease: A Histobiochemical Comparative Study. Curr Pharm Des 2019; 25:1122-1133. [PMID: 31096894 DOI: 10.2174/1381612825666190516080920] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 05/02/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND High global incidence of acute kidney injury (AKI) is an observable complication in critically ill patients. Long-term disease and medication complexity contribute to devastating chronic kidney disease (CKD), diminishing quality of life. OBJECTIVES To establish new biomarkers to guide patient care and facilitate novel therapeutics development. METHODS Serum and urinary levels of creatinine, CysC, and NGAL were estimated in 86 renal patients and compared with healthy controls for AKI and CKD categorization. Creatinine and CysC measurements were used to estimate GFR. Kidney biopsies were prepared for light microscopy for further characterization. Patients' demographic data were used in group association studies. RESULTS Thirty-six patients met the criteria for AKI and 50 for CKD. Both mean serum and urine creatinine levels were significantly elevated by 2.8 and 2.6, respectively, from baseline in 48 h in the AKI group but not CKD group. Mean serum Cystatin C (CysC) values were higher than controls but similar in both disease states, while urine levels were slightly higher in CKD patients, and remained steady by the end of the follow-up (EF-Up). Further, a significant 2.9-fold and 5.5-fold (p=0.001) increase in serum NGAL in AKI and CKD, respectively, and a dramatic 7.1-factor reduction in AKI group, but no appreciable change in the CKD group from admission to EF-Up were observed. Similarly, urine NGAL level for AKI and CKD increased 3.2-fold and 6-fold respectively, on admission, which decreased moderately with the AKI group (2.5-fold) but increased by a factor of 1-8 (10.7- fold; p=0.001) at EF-Up. ROC assessment curve revealed relatively higher NGAL performance at good predictive values than CysC (p < 0.009). CONCLUSION Our data demonstrated creatinine elevation by a factor > 2 in 48 h in AKI group but not CKD group, which returned close to normal levels by the EF-Up, an indication of abrupt renal injury in AKI, compared with a persistent effect in the CKD group. Both serum and urine NGAL sensitivity and specificity provided powerful discriminative tool between AKI and CKD by reduction in the AKI group and an increase in the CKD group by the EF-UP, thus, contributing in establishing the basis for AKI and CKD classification. CysC, however, displayed less sensitivity than NGAL, indicating effects by enigmatic non-specific factors.
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Affiliation(s)
- Mustafa M Sinna
- Anatomy Department, College of Medicine, Umm Al Qura University, El-Abidia, Makkah, Saudi Arabia
| | - Faris M N Altaf
- Anatomy Department, College of Medicine, Umm Al Qura University, El-Abidia, Makkah, Saudi Arabia
| | - Osama F Mosa
- Public Health Department, Health Sciences College at Leith, Umm Al Qura University, Al-Lieth, Makkah, Saudi Arabia
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Pelander L, Häggström J, Larsson A, Syme H, Elliott J, Heiene R, Ljungvall I. Comparison of the diagnostic value of symmetric dimethylarginine, cystatin C, and creatinine for detection of decreased glomerular filtration rate in dogs. J Vet Intern Med 2019; 33:630-639. [PMID: 30791142 PMCID: PMC6430914 DOI: 10.1111/jvim.15445] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 01/23/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Early detection of decreased glomerular filtration rate (GFR) in dogs is challenging. Current methods are insensitive and new biomarkers are required. OBJECTIVE To compare overall diagnostic performance of serum symmetric dimethylarginine (SDMA) and serum cystatin C to serum creatinine, for detection of decreased GFR in clinically stable dogs, with or without chronic kidney disease (CKD). ANIMALS Ninety-seven client-owned dogs: 67 dogs with a diagnosis or suspicion of CKD and 30 healthy dogs were prospectively included. METHODS Prospective diagnostic accuracy study. All dogs underwent physical examination, systemic arterial blood pressure measurement, urinalysis, hematology and blood biochemistry analysis, cardiac and urinary ultrasound examinations, and scintigraphy for estimation of glomerular filtration rate (mGFR). Frozen serum was used for batch analysis of SDMA and cystatin C. RESULTS The area under the curve of creatinine, SDMA, and cystatin C for detection of an mGFR <30.8 mL/min/L was 0.98 (95% confidence interval [CI], 0.93-1.0), 0.96 (95% CI, 0.91-0.99), and 0.87 (95% CI, 0.79-0.93), respectively. The sensitivity of both creatinine and SDMA at their prespecified cutoffs (115 μmol/L [1.3 mg/dL] and 14 μg/dL) for detection of an abnormal mGFR was 90%. The specificity was 90% for creatinine and 87% for SDMA. When adjusting the cutoff for cystatin C to correspond to a diagnostic sensitivity of 90% (0.49 mg/L), specificity was lower (72%) than that of creatinine and SDMA. CONCLUSIONS AND CLINICAL IMPORTANCE Overall diagnostic performance of creatinine and SDMA for detection of decreased mGFR was similar. Overall diagnostic performance of cystatin C was inferior to both creatinine and SDMA.
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Affiliation(s)
- Lena Pelander
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Jens Häggström
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Anders Larsson
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Harriet Syme
- Department of Clinical Science and Services, The Royal Veterinary College, Hertfordshire, United Kingdom
| | - Jonathan Elliott
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, United Kingdom
| | - Reidun Heiene
- ABC Dyreklinikk Lillehammer AS, Hamarvegen 68A, 26 13 Lillehammer, Norway
| | - Ingrid Ljungvall
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
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Elsayed MS, El Badawy A, Ahmed A, Omar R, Mohamed A. Serum cystatin C as an indicator for early detection of diabetic nephropathy in type 2 diabetes mellitus. Diabetes Metab Syndr 2019; 13:374-381. [PMID: 30641728 DOI: 10.1016/j.dsx.2018.08.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 08/21/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. The metabolic dysregulations associated with DM causes secondary pathophysiological changes in multiple organ systems which result in various complications, responsible for the morbidity and mortality associated with the disease. METHODS The present study was carried out on 40 patients with type 2 diabetes mellitus, who were recruited from those attending outpatient clinic and inpatient of Internal Medicine Department at The National Institute of Diabetes and Endocrinology from January 2017 to june 2017. RESULTS The mean Cystatin C values in Group I were 0.74, group II were 1.07. and in Group III were 3.25, The results show that the Cystatin C values were raised even in the patients with Normoalbuminuria with GFR ≥90 whom clinical albuminuria had not yet started. CONCLUSIONS serum Cystatin C may be considered as an early marker, than microalbuminuria and serum creatinine, the commonly used marker for nephropathy, for declining renal function, in diabetic subjects. Further studies in larger population are needed to confirm this result.
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Affiliation(s)
- Mohamed Shawky Elsayed
- Internal Medicine Department, Head of Endocrinology Unit, Faculty of Medicine, Benha University, Egypt
| | | | | | - Rasha Omar
- Faculty of Medicine, Benha University, Egypt
| | - Amr Mohamed
- Faculty of Medicine, Benha University, Egypt.
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Zazuli Z, Vijverberg S, Slob E, Liu G, Carleton B, Veltman J, Baas P, Masereeuw R, Maitland-van der Zee AH. Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review. Front Pharmacol 2018; 9:1111. [PMID: 30319427 PMCID: PMC6171472 DOI: 10.3389/fphar.2018.01111] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 09/10/2018] [Indexed: 12/29/2022] Open
Abstract
Background: Nephrotoxicity is a notable adverse effect in cisplatin treated patients characterized by tubular injury and/or increased serum creatinine (SCr) with incidence varying from 20 to 70%. Pharmacogenomics has been shown to identify strongly predictive genetic markers to help determine which patients are more likely to experience, for example, a serious adverse drug reaction or receive optimal benefit through enhanced efficacy. Genetic variations have been reported to influence the risk of cisplatin nephrotoxicity; however, a comprehensive overview is lacking. Methods: A systematic review was performed using Pubmed, Embase and Web of Science on clinical studies that used cisplatin-based chemotherapy as treatment, had available genotyping data, and evaluated nephrotoxicity as an outcome. The quality of reporting was assessed using the STrengthening the REporting of Genetic Association Studies (STREGA) checklist. Results: Twenty-eight eligible studies were included; all were candidate gene studies. Over 300 SNPs across 135 genes were studied; 29 SNPs in 14 genes were significantly associated with cisplatin-induced nephrotoxicity. A variation in SLC22A2 rs316019, a gene involved in platinum uptake by the kidney, was associated with different measures of nephrotoxicity in four independent studies. Further, variants of ERCC1 (rs11615 and rs3212986) and ERCC2 (rs13181), two genes involved in DNA repair, were found to be positively associated with increased risks of nephrotoxicity in two independent studies. Conclusion: Three genes consistently associated with cisplatin-induced nephrotoxicity. Further research is needed to assess the biological mechanism and the clinical value of modifying treatment based on SLCC22A2 and ERCC1/2 genotypes.
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Affiliation(s)
- Zulfan Zazuli
- Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Department of Pharmacology-Clinical Pharmacy, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia
| | - Susanne Vijverberg
- Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Elise Slob
- Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Geoffrey Liu
- Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Hospital-University Health Network and University of Toronto, Toronto, ON, Canada
- Division of Epidemiology, Dalla Lana School of Public Health, Toronto, ON, Canada
| | - Bruce Carleton
- Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada
- Pharmaceutical Outcomes Programme, British Columbia Children's Hospital, Vancouver, BC, Canada
| | - Joris Veltman
- Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Paul Baas
- Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Rosalinde Masereeuw
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, Netherlands
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Pan W, Peng W, Ning F, Zhang Y, Zhang Y, Wang Y, Xie W, Zhang J, Xin H, Li C, Zhang X. Non-invasive detection of the early phase of kidney injury by photoacoustic/computed tomography imaging. NANOTECHNOLOGY 2018; 29:265101. [PMID: 29718825 DOI: 10.1088/1361-6528/aabcee] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
The early diagnosis of kidney diseases, which can remarkably impair the quality of life and are costly, has encountered great difficulties. Therefore, the development of methods for early diagnosis has great clinical significance. In this study, we used an emerging technique of photoacoustic (PA) imaging, which has relatively high spatial resolution and good imaging depth. Two kinds of PA gold nanoparticle (GNP)-based bioprobes were developed based on their superior photo detectability, size controllability and biocompatibility. The kidney injury mouse model was developed by unilateral ureteral obstruction for 96 h and the release of obstruction model). Giving 3.5 and 5.5 nm bioprobes by tail vein injection, we found that the 5.5 nm probe could be detected in the bladder in the model group, but not in the control group. These results were confirmed by computed tomography imaging. Furthermore, the model group did not show changes in the blood biochemical indices (BUN and Scr) and histologic examination. The 5.5 nm GNPs were found to be the critical point for early diagnosis of kidney injury. This new method was faster and more sensitive and accurate for the detection of renal injury, compared with conventional methods, and can be used for the development of a PA GNP-based bioprobe for diagnosing renal injury.
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Affiliation(s)
- Wanma Pan
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China
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Li J, Wei J, Xu P, Yan M, Li J, Chen Z, Jin T. Impact of diabetes-related gene polymorphisms on the clinical characteristics of type 2 diabetes Chinese Han population. Oncotarget 2018; 7:85464-85471. [PMID: 27863428 PMCID: PMC5356749 DOI: 10.18632/oncotarget.13399] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 10/19/2016] [Indexed: 12/30/2022] Open
Abstract
We investigated the correlation between type 2 diabetes (T2D)-related genes and the clinical characteristics of T2D in the Chinese Han population. Our study included 319 patients and 387 controls. Age, gender, clinical features, medications intake and biochemical blood profiles were analyzed. Genotyping was performed on a total of 18 single nucleotide polymorphisms previously reported to be associated with T2D. Our analyses revealed that the CT genotype of ARHGAP22 rs4838605 is associated with T2D risk. Upon analyzing the subjects’ clinical characteristics, we found that for rs2811893, the TT genotype correlated with high creatinine levels, while the AA genotype of rs17045754 and the TT genotype of rs4838605 correlated with elevated triglyceride levels. In addition, the AA genotype of rs17376456 and the TT genotype of rs6214 (p = 0.006) correlated with elevated hemoglobin A1c levels. Lastly, those carrying the TT genotype of rs7772697 and the CA genotype of rs3918227 exhibited higher mean body mass index and Cystatin C than controls. Our results showing that the ARHGAP22 gene is associated with an increased risk of T2D, and that seven SNPs in MYSM1, PLXDC2, ARHGAP22 and HS6ST3 promote T2D progression and could help predict the clinical course of T2D in patients at risk.
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Affiliation(s)
- Jing Li
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China
| | - Jiachen Wei
- Department of Endocrinology, Xi'an NO.1 Hospital, Xi'an 710002, China
| | - Pengcheng Xu
- Inner Mongolia Medical University, Inner Mongolia, Hohhot 010010, China
| | - Mengdan Yan
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China.,Xi'an Tiangen Precision Medical Institute, Xi'an, Shaanxi, 710075, China
| | - Jingjie Li
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China.,Xi'an Tiangen Precision Medical Institute, Xi'an, Shaanxi, 710075, China
| | - Zhengshuai Chen
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China.,Xi'an Tiangen Precision Medical Institute, Xi'an, Shaanxi, 710075, China
| | - Tianbo Jin
- Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China.,Xi'an Tiangen Precision Medical Institute, Xi'an, Shaanxi, 710075, China
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Domingueti CP, Fóscolo RB, Dusse LMS, Reis JS, Carvalho MDG, Gomes KB, Fernandes AP. Association of different biomarkers of renal function with D-dimer levels in patients with type 1 diabetes mellitus (renal biomarkers and D-dimer in diabetes). ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2018; 62:27-33. [PMID: 29694626 PMCID: PMC10118683 DOI: 10.20945/2359-3997000000003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 11/11/2016] [Indexed: 11/23/2022]
Abstract
Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8-25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2-12.9), 8.4 (2.5-25.4), 9.1 (2.6-31.4) and 3.5 (1.4-8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies.
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Medeiros T, do Rosário NF, Gama NA, Mérida LAD, Storch AS, Ferraz L, de Fátima Lopes P, da Silva AA, Almeida JR. Metabolic syndrome components and estimated glomerular filtration rate based on creatinine and/or cystatin C in young adults: A gender issue? Diabetes Metab Syndr 2017; 11 Suppl 1:S351-S357. [PMID: 28284908 DOI: 10.1016/j.dsx.2017.03.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 03/03/2017] [Indexed: 10/20/2022]
Abstract
AIMS This work aims to identify correlations between estimated glomerular filtration rate (eGFR) based on creatinine and/or cystatin C (Cr, CysC) with metabolic syndrome (MS) components in young adults, according to gender. MATERIAL AND METHODS This is a cross sectional study, where young adults aged between 18 and 30 were matched by gender, age and body mass index. All subjects underwent clinical evaluation and blood sampling for laboratory measurements. MS was determined according to the JIS criteria. The eGFR was estimated using CKD-EPI equations (eGFRCr; eGFRCysC; eGFRCr-CysC). RESULTS We evaluated 78 subjects with a mean age of 24.5 years. 10.2% had MS, with higher incidence among males (15.4% ♂ vs. 5.1% ♀). Elevated waist circumference was the MS component most observed. Significant correlations (Pearson; p<0.05) between eGFR and metabolic markers were observed only in males. In addition, we observed a significant association between the increase of MS components and the decay of eGFRCr and eGFRCr-CysC (zero vs. two or more components, ANOVA, p<0.05) only among males. CONCLUSION eGFR decay associated with components of MS and insulin resistance in young male adults could represent a worrying specific risk and indicate that further studies are needed to better understand these findings.
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Affiliation(s)
- Thalia Medeiros
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
| | - Natalia Fonseca do Rosário
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
| | - Nycole Abreu Gama
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
| | - Lyris Anunciata Demétrio Mérida
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
| | - Amanda Sampaio Storch
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
| | - Leda Ferraz
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
| | - Patricia de Fátima Lopes
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil; Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
| | - Andrea Alice da Silva
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil; Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
| | - Jorge Reis Almeida
- Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil; Serviço de Nefrologia, Departamento de Medicina Clínica, Faculdade de Medicina, UFF, Rio de Janeiro, Brazil.
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