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Santos S, Lousa I, Carvalho M, Sameiro-Faria M, Santos-Silva A, Belo L. Anemia in Elderly Patients: Contribution of Renal Aging and Chronic Kidney Disease. Geriatrics (Basel) 2025; 10:43. [PMID: 40126293 PMCID: PMC11932280 DOI: 10.3390/geriatrics10020043] [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: 02/17/2025] [Revised: 03/09/2025] [Accepted: 03/12/2025] [Indexed: 03/25/2025] Open
Abstract
Renal aging is a physiological process characterized by structural and functional changes in the kidneys. The presence of disorders or pathologies can exacerbate these age-related changes, potentially leading to organ dysfunction. Chronic kidney disease (CKD), a significant global public health issue, is particularly prevalent in the elderly and is often associated with the age-related decline in kidney function. Anemia is one of the most frequent complications of CKD and is also highly prevalent in the elderly. Mild anemia, often multifactorial, is the most common presentation. Understanding the mechanisms driving anemia in this population is crucial to ensure appropriate treatment. The primary etiologies include nutritional deficiency, anemia of unknown cause, and anemia of chronic diseases, including CKD. This review provides an in-depth exploration of the complex pathophysiological mechanisms underlying anemia in elderly patients with CKD.
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Affiliation(s)
- Simone Santos
- UCIBIO i4HB, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; (S.S.); (I.L.); (M.S.-F.); (A.S.-S.)
| | - Irina Lousa
- UCIBIO i4HB, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; (S.S.); (I.L.); (M.S.-F.); (A.S.-S.)
| | - Márcia Carvalho
- FP-I3ID, FP-BHS, Universidade Fernando Pessoa, Praça de 9 de Abril 349, 4249-004 Porto, Portugal;
- LAQV/REQUIMTE, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- RISE-Health, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Fundação Ensino e Cultura Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal
| | - Maria Sameiro-Faria
- UCIBIO i4HB, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; (S.S.); (I.L.); (M.S.-F.); (A.S.-S.)
- Centro Hospitalar Universitário do Porto, Centro Materno-Infantil do Norte, Serviço de Pediatria, Unidade de Nefrologia Pediátrica, 4050-651 Porto, Portugal
| | - Alice Santos-Silva
- UCIBIO i4HB, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; (S.S.); (I.L.); (M.S.-F.); (A.S.-S.)
| | - Luís Belo
- UCIBIO i4HB, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; (S.S.); (I.L.); (M.S.-F.); (A.S.-S.)
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Wang X, Mu J, Ma K, Ma Y. Challenges of Serum Creatinine Level in GFR Assessment and Drug Dosing Decisions in Kidney Injury. Adv Pharm Bull 2024; 14:745-758. [PMID: 40190670 PMCID: PMC11970497 DOI: 10.34172/apb.42345] [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: 10/12/2023] [Revised: 11/23/2024] [Accepted: 12/03/2024] [Indexed: 04/09/2025] Open
Abstract
Serum creatinine (SCr) is widely regarded as a standard biomarker for assessing glomerular filtration rate (GFR) and is commonly used to guide dose adjustments for renally eliminated drugs. However, the application of SCr as a marker for evaluating GFR and drug dosing in kidney injury has significant limitations that are often overlooked in clinical practice. This oversight can result in subtherapeutic drug concentrations or adverse drug reactions due to inappropriate dosing adjustments based on SCr levels alone. This review aimed to highlight the factors affecting serum creatinine (SCr) and the challenges associated with using SCr as a biomarker for assessing GFR and adjusting drug doses with regard to its limitations and variability. The findings of this review underscore the complexity of SCr regulation, which is affected by its synthesis, metabolism, and excretion processes (glomerular filtration, tubular secretion, tubular reabsorption and extra-renal elimination), and disease states (such as trauma-induced hyperfiltration and HIV) and the use of medications (drug-creatinine interactions) lead to altered renal excretion of creatinine, either increasing or decreasing its levels. Additionally, the renal excretion pathways for drugs and creatinine are not entirely the same, making it difficult to use creatinine to evaluate drug renal excretion. In conclusion, SCr is an imperfect index of GFR and adjusting drug dosing, and the development of multi-biomarker panels, incorporating biomarkers from different excretory pathways-particularly those involving tubular transport-holds promise for improving the evaluation of renal excretory function and ensuring safer and more effective drug dosing.
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Affiliation(s)
- Xinyi Wang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Jing Mu
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Kexin Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Yanrong Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
- Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, China
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de Moura ELB, Pereira RW. Crossing Age Boundaries: The Unifying Potential of Presepsin in Sepsis Diagnosis Across Diverse Age Groups. J Clin Med 2024; 13:7038. [PMID: 39685497 DOI: 10.3390/jcm13237038] [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: 09/20/2024] [Revised: 10/29/2024] [Accepted: 10/31/2024] [Indexed: 12/18/2024] Open
Abstract
Sepsis is a pervasive condition that affects individuals of all ages, with significant social and economic consequences. The early diagnosis of sepsis is fundamental for establishing appropriate treatment and is based on warning scores and clinical characteristics, with positive microbiological cultures being the gold standard. Research has yet to identify a single biomarker to meet this diagnostic demand. Presepsin is a molecule that has the potential as a biomarker for diagnosing sepsis. In this paper, we present a narrative review of the diagnostic and prognostic performance of presepsin in different age groups. Given its particularities, it is identified that presepsin is a potential biomarker for sepsis at all stages of life.
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Affiliation(s)
- Edmilson Leal Bastos de Moura
- Health Sciences Doctoral Program, University of Brasília (UnB), Brasilia 70910-900, Distrito Federal, Brazil
- School of Health Sciences, Distrito Federal University (UnDF), Brasilia 70710-907, Distrito Federal, Brazil
| | - Rinaldo Wellerson Pereira
- Health Sciences Doctoral Program, University of Brasília (UnB), Brasilia 70910-900, Distrito Federal, Brazil
- Genomic Sciences and Biotechnology Graduate Program, Catholic University of Brasilia, Brasilia 71966-700, Distrito Federal, Brazil
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Jeon J, Shin DW, Park SH, Jung JH, Lee K, Lee JE, Huh W, Han K, Jang HR. Kidney and Cardiovascular Outcomes in Older Population with Mildly to Moderately Decreased Kidney Function: A Nationwide Cohort Study. Am J Nephrol 2024; 56:123-135. [PMID: 39462486 DOI: 10.1159/000541832] [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: 07/24/2024] [Accepted: 10/02/2024] [Indexed: 10/29/2024]
Abstract
INTRODUCTION Although the prevalence of chronic kidney disease (CKD) is increasing in the aging population, the clinical relevance of the CKD definition (glomerular filtration rate [GFR] <60 mL/min/1.73 m2) in older populations remains debatable. We investigated the clinical outcomes in older populations with mildly to moderately decreased GFR (45-59 mL/min/1.73 m2, CKD stage 3A). METHODS A total of 7,789,242 participants aged ≥40 years with estimated GFR (eGFR) ≥45 mL/min/1.73 m2 in national health screening examination from 2012 to 2017 were included in this retrospective cohort study using the Korean National Health Insurance Service database. The main outcomes included kidney failure, cardiovascular disease (CVD), and all-cause death. Cox regression hazard models were used to estimate the hazard ratios. RESULTS The proportion of participants with eGFR 45-59 mL/min/1.73 m2 was 10.0% and 16.3% in the old (65-74 years) and very old (75≥ years) groups, respectively. Mildly to moderately decreased eGFR was associated with a higher risk of kidney failure, CVD, and all-cause death compared with eGFR 60-89 mL/min/1.73 m2 in the old and very old groups, regardless of proteinuria (adjusted hazard ratio [95% confidence interval] in the very old group without proteinuria: kidney failure 3.048 [2.495-3.722], CVD 1.103 [1.066-1.142], and all-cause death 1.172 [1.144-1.201]). CONCLUSION Mildly to moderately decreased eGFR was associated with an increased risk of kidney failure, CVD, and all-cause death in the older population, regardless of proteinuria, suggesting the importance of appropriate monitoring and management in this population.
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Affiliation(s)
- Junseok Jeon
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea,
| | - Dong Wook Shin
- Department of Family Medicine/Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Park
- Department of Family Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jin-Hyung Jung
- Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Kyungho Lee
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jung Eun Lee
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Wooseong Huh
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Hye Ryoun Jang
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Kato A, Fuwa M, Asano M, Mori I, Iida S, Okada H, Uno Y, Fujioka K, Morita H. Development and validation of a predictive scoring system for hypoglycaemic agents for optimal control of blood glucose during glucocorticoid therapy. Intern Med J 2024. [PMID: 39440721 DOI: 10.1111/imj.16547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 09/24/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Glucocorticoid (GC) treatments are often used. There is limited information on the prediction of hyperglycaemia after GC administration. AIMS This study aimed to identify the risk factors for hyperglycaemia after glucocorticoid (GC) administration and the need for hypoglycaemic agents to correct it and to develop and validate a novel scoring system for predicting GC-induced hyperglycaemia. METHODS In a development set, 508 adults receiving prednisolone (PSL) for the first time were divided into two groups based on treatment with or without hypoglycaemic agents. Clinical and laboratory parameters were compared, and risk factors were identified using logistic regression analysis after performing univariate analyses between the two groups. A point-addition scoring system with several categories and coefficients for each risk factor was constructed to predict the need for hypoglycaemic agents. The scoring system was then applied and validated on two validation sets: A and B. RESULTS Older age, higher glycated haemoglobin percentage, body mass index and initial PSL dosage were identified as risk factors. The sensitivity, specificity and accuracy of the scoring system were 70.6%, 81.9% and 77.1% in the development set; 75.8%, 78.4% and 77.4% in validation set A; and 79.4%, 73.9% and 75.3% in validation set B respectively. By fitting the total score in the development set and the probability of hyperglycaemia to a logistic curve, a figure was created to show the probability of GC-induced hyperglycaemia in patients scheduled to receive GC. CONCLUSION This scoring system is a novel, valid and reliable tool for predicting GC-induced hyperglycaemia and the need for hypoglycaemic agents to correct it.
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Affiliation(s)
- Ayaka Kato
- Department of General Medicine and General Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Masayuki Fuwa
- Department of General Medicine and General Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Motochika Asano
- Department of General Medicine and General Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Ichiro Mori
- Department of General Medicine and General Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Saori Iida
- Department of General Internal Medicine, Gifu Prefectural General Medical Center, Gifu, Japan
| | - Hideyuki Okada
- Department of General Internal Medicine, Gifu Prefectural General Medical Center, Gifu, Japan
| | - Yoshihiro Uno
- Department of General Internal Medicine, Gifu Prefectural General Medical Center, Gifu, Japan
| | - Kei Fujioka
- Center of General Internal Medicine and Rheumatology, Gifu Municipal Hospital, Gifu, Japan
| | - Hiroyuki Morita
- Department of General Medicine and General Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
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Liu HX, Tang BH, van den Anker J, Hao GX, Zhao W, Zheng Y. Population pharmacokinetics of antibacterial agents in the older population: a literature review. Expert Rev Clin Pharmacol 2024; 17:19-31. [PMID: 38131668 DOI: 10.1080/17512433.2023.2295009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 12/11/2023] [Indexed: 12/23/2023]
Abstract
INTRODUCTION Older individuals face an elevated risk of developing bacterial infections. The optimal use of antibacterial agents in this population is challenging because of age-related physiological alterations, changes in pharmacokinetics (PK) and pharmacodynamics (PD), and the presence of multiple underlying diseases. Therefore, population pharmacokinetics (PPK) studies are of great importance for optimizing individual treatments and prompt identification of potential risk factors. AREA COVERED Our search involved keywords such as 'elderly,' 'old people,' and 'geriatric,' combined with 'population pharmacokinetics' and 'antibacterial agents.' This comprehensive search yielded 11 categories encompassing 28 antibacterial drugs, including vancomycin, ceftriaxone, meropenem, and linezolid. Out of 127 studies identified, 26 (20.5%) were associated with vancomycin, 14 (11%) with meropenem, and 14 (11%) with piperacillin. Other antibacterial agents were administered less frequently. EXPERT OPINION PPK studies are invaluable for elucidating the characteristics and relevant factors affecting the PK of antibacterial agents in the older population. Further research is warranted to develop and validate PPK models for antibacterial agents in this vulnerable population.
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Affiliation(s)
- Hui-Xin Liu
- Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Bo-Hao Tang
- Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - John van den Anker
- Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA
- Departments of Pediatrics, Pharmacology & Physiology, Genomics and Precision Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA
- Department of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland
| | - Guo-Xiang Hao
- Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Wei Zhao
- Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Clinical Pharmacy, Clinical Trial Center, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China
| | - Yi Zheng
- Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
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Abudahab S, Slattum PW, Price ET, McClay JL. Epigenetic regulation of drug metabolism in aging: utilizing epigenetics to optimize geriatric pharmacotherapy. Pharmacogenomics 2024; 25:41-54. [PMID: 38126340 PMCID: PMC10794944 DOI: 10.2217/pgs-2023-0199] [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: 10/19/2023] [Accepted: 12/06/2023] [Indexed: 12/23/2023] Open
Abstract
We explore the relationship between epigenetic aging and drug metabolism. We review current evidence for changes in drug metabolism in normal aging, followed by a description of how epigenetic modifications associated with age can regulate the expression and functionality of genes. In particular, we focus on the role of epigenome-wide studies of human and mouse liver in understanding these age-related processes with respect to xenobiotic processing. We highlight genes encoding drug metabolizing enzymes and transporters revealed to be affected by epigenetic aging in these studies. We conclude that substantial evidence exists for epigenetic aging impacting drug metabolism and transport genes, but more work is needed. We further highlight the promise of pharmacoepigenetics applied to enhancing drug safety in older adults.
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Affiliation(s)
- Sara Abudahab
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA
| | - Patricia W Slattum
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA
- Virginia Center on Aging, Virginia Commonwealth University, Richmond, VA 23298, USA
| | - Elvin T Price
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA
| | - Joseph L McClay
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA
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Shankland SJ, Rule AD, Kutz JN, Pippin JW, Wessely O. Podocyte Senescence and Aging. KIDNEY360 2023; 4:1784-1793. [PMID: 37950369 PMCID: PMC10758523 DOI: 10.34067/kid.0000000000000284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 10/11/2023] [Indexed: 11/12/2023]
Abstract
As the population in many industrial countries is aging, the risk, incidence, and prevalence of CKD increases. In the kidney, advancing age results in a progressive decrease in nephron number and an increase in glomerulosclerosis. In this review, we focus on the effect of aging on glomerular podocytes, the post-mitotic epithelial cells critical for the normal integrity and function of the glomerular filtration barrier. The podocytes undergo senescence and transition to a senescence-associated secretory phenotype typified by the production and secretion of inflammatory cytokines that can influence neighboring glomerular cells by paracrine signaling. In addition to senescence, the aging podocyte phenotype is characterized by ultrastructural and functional changes; hypertrophy; cellular, oxidative, and endoplasmic reticulum stress; reduced autophagy; and increased expression of aging genes. This results in a reduced podocyte health span and a shortened life span. Importantly, these changes in the pathways/processes characteristic of healthy podocyte aging are also often similar to pathways in the disease-induced injured podocyte. Finally, the better understanding of podocyte aging and senescence opens therapeutic options to slow the rate of podocyte aging and promote kidney health.
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Affiliation(s)
- Stuart J. Shankland
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
| | - Andrew D. Rule
- Division of Nephrology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - J. Nathan Kutz
- Department of Applied Mathematics, University of Washington, Seattle, Washington
| | - Jeffrey W. Pippin
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington
| | - Oliver Wessely
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio
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Rodriguez-Sanchez N, Galloway SDR. A randomised trial to assess fluid and electrolyte balance responses following ingestion of different beverages in young and older men. Eur J Appl Physiol 2023; 123:2331-2340. [PMID: 37294517 PMCID: PMC10492686 DOI: 10.1007/s00421-023-05241-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 05/23/2023] [Indexed: 06/10/2023]
Abstract
BACKGROUND Older adults are susceptible to dehydration and fluid overload due to a reduced ability to maintain homeostatic control of fluid and electrolyte balance. PURPOSE To assess fluid and electrolyte balance responses in young and older men following ingestion of commonly consumed beverages differing in composition. METHODS 12 young and 11 older men were recruited. Euhydrated body mass was recorded. Participants consumed 1L (250 ml every 15 min) of water, fruit juice, a sports drink or low-fat milk in a randomized cross-over design. Urine and blood samples were obtained before and after the drinking period and every hour thereafter for 3-h. Samples were used to determine osmolality, electrolytes (Na+ and K+), water clearance, and glomerular filtration rate. RESULTS Free water clearance was significantly higher in Young than Older at 1 and 2 h after the ingestion of W and S (p < 0.05). Net Na+ and K+ balance were not different between Young and Older (p = 0.91 and p = 0.65) adults, respectively. At 3 h Na+ balance was negative after ingesting water and fruit juice, but neutral after sport drink and milk. Net K+ balance was neutral at 3 h after ingesting milk, but negative after water, fruit juice and sport drink. CONCLUSIONS Milk was retained longer than other beverages in Young, but not in Older, despite similar net electrolyte balance responses. Older had higher fluid retention in the first 2 h after the ingestion of all beverages, except for milk when compared to Young, indicating an age-related loss of ability to regulate fluid balance under current study conditions.
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Affiliation(s)
- Nidia Rodriguez-Sanchez
- Physiology, Exercise and Nutrition Research Group, Faculty of Health Sciences and Sport, University of Stirling, Stirling, FK9 4LA, UK.
| | - Stuart D R Galloway
- Physiology, Exercise and Nutrition Research Group, Faculty of Health Sciences and Sport, University of Stirling, Stirling, FK9 4LA, UK
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Liu T, Zhuang XX, Gao JR. Identifying Aging-Related Biomarkers and Immune Infiltration Features in Diabetic Nephropathy Using Integrative Bioinformatics Approaches and Machine-Learning Strategies. Biomedicines 2023; 11:2454. [PMID: 37760894 PMCID: PMC10525809 DOI: 10.3390/biomedicines11092454] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/16/2023] [Accepted: 08/25/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Aging plays an essential role in the development of diabetic nephropathy (DN). This study aimed to identify and verify potential aging-related genes associated with DN using bioinformatics analysis. METHODS To begin with, we combined the datasets from GEO microarrays (GSE104954 and GSE30528) to find the genes that were differentially expressed (DEGs) across samples from DN and healthy patient populations. By overlapping DEGs, weighted co-expression network analysis (WGCNA), and 1357 aging-related genes (ARGs), differentially expressed ARGs (DEARGs) were discovered. We next performed functional analysis to determine DEARGs' possible roles. Moreover, protein-protein interactions were examined using STRING. The hub DEARGs were identified using the CytoHubba, MCODE, and LASSO algorithms. We next used two validation datasets and Receiver Operating Characteristic (ROC) curves to determine the diagnostic significance of the hub DEARGs. RT-qPCR, meanwhile, was used to confirm the hub DEARGs' expression levels in vitro. In addition, we investigated the relationships between immune cells and hub DEARGs. Next, Gene Set Enrichment Analysis (GSEA) was used to identify each biomarker's biological role. The hub DEARGs' subcellular location and cell subpopulations were both identified and predicted using the HPA and COMPARTMENTS databases, respectively. Finally, drug-protein interactions were predicted and validated using STITCH and AutoDock Vina. RESULTS A total of 57 DEARGs were identified, and functional analysis reveals that they play a major role in inflammatory processes and immunomodulation in DN. In particular, aging and the AGE-RAGE signaling pathway in diabetic complications are significantly enriched. Four hub DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) were further screened using the interaction network, CytoHubba, MCODE, and LASSO algorithms. The results above were further supported by validation sets, ROC curves, and RT-qPCR. According to an evaluation of immune infiltration, DN had significantly more resting mast cells and delta gamma T cells but fewer regulatory T cells and active mast cells. Four DEARGs have statistical correlations with them as well. Further investigation revealed that four DEARGs were implicated in immune cell abnormalities and regulated a wide range of immunological and inflammatory responses. Furthermore, the drug-protein interactions included four possible therapeutic medicines that target four DEARGs, and molecular docking could make this association practical. CONCLUSIONS This study identified four DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) associated with DN, which might play a key role in the development of DN and could be potential biomarkers in DN.
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Affiliation(s)
- Tao Liu
- Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230012, China;
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230011, China
| | - Xing-Xing Zhuang
- Department of Pharmacy, Chaohu Hospital of Anhui Medical University, Chaohu 238000, China;
| | - Jia-Rong Gao
- Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230012, China;
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230011, China
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Lee J, Lee SH, Yoon KH, Cho JH, Han K, Yang Y. Risk of developing chronic kidney disease in young-onset Type 2 diabetes in Korea. Sci Rep 2023; 13:10100. [PMID: 37344516 DOI: 10.1038/s41598-023-36711-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 06/08/2023] [Indexed: 06/23/2023] Open
Abstract
We investigated the risk of developing chronic kidney disease (CKD) in patients with young-onset Type 2 diabetes (YOD, diagnosed age < 40 years). We enrolled 84,384 patients aged 20-64 who started anti-diabetic medication between 2010 and 2011 from the Korea National Health Insurance Sharing Service; patients with Type 1 diabetes or a history of CKD were excluded. Multivariate logistic regression analyses were performed to adjust for YOD-distinct variables and compare the incidence of CKD between YOD and late-onset diabetes (LOD, diagnosed age ≥ 40 years). During the median observation period of 5.16 years (interquartile range: 4.58-5.77 years), 1480 out of 77,039 LOD patients and 34 out of 7345 YOD patients developed CKD. Patients with YOD had distinct baseline characteristics compared with the patients with LOD. The odds ratio of developing CKD in patients with YOD over LOD was 1.70 (95% CI 1.15-2.51) after adjusting clinically distinct variables. The increased CKD odds in YOD compared with LOD was greater in the non-smoking group (OR 2.03, 95% CI 1.26-3.26) than in the smoking group (OR 1.49, 95% CI 0.74-2.98, p = 0.0393 for interaction). Among YOD patients, hypertension (34.76% vs. 64.71%, p = 0.0003), dyslipidemia (46.87% vs. 73.53%, p = 0.0019), and sulfonylurea use (35.54% vs. 52.94%, p = 0.0345) were associated with CKD development. YOD patients have a greater risk of developing CKD than LOD patients after adjusting clinically distinct variables.
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Affiliation(s)
- Joonyub Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung-Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, 222, Banpo-Daero, Seocho-Gu, Seoul, 06591, Republic of Korea
| | - Kun-Ho Yoon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, 222, Banpo-Daero, Seocho-Gu, Seoul, 06591, Republic of Korea
| | - Jae Hyoung Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, 222, Banpo-Daero, Seocho-Gu, Seoul, 06591, Republic of Korea
- Catholic Smart Health Care Center, The Catholic University of Korea, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul, 06978, Korea.
| | - Yeoree Yang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
- Catholic Smart Health Care Center, The Catholic University of Korea, Seoul, Korea.
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12
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McAdam J, Bell EM. Determinants of maternal and neonatal PFAS concentrations: a review. Environ Health 2023; 22:41. [PMID: 37161484 PMCID: PMC10170754 DOI: 10.1186/s12940-023-00992-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/19/2023] [Indexed: 05/11/2023]
Abstract
Per- and polyfluoroalkyl substances (PFAS) are used for their properties such as stain and water resistance. The substances have been associated with adverse health outcomes in both pregnant mothers and infants, including pre-eclampsia and low birthweight. A growing body of research suggests that PFAS are transferred from mother to fetus through the placenta, leading to in utero exposure. A systematic review was performed using the PubMed database to search for studies evaluating determinants of PFAS concentrations in blood matrices of pregnant mothers and neonates shortly after birth. Studies were included in this review if an observational study design was utilized, exposure to at least one PFAS analyte was measured, PFAS were measured in maternal or neonatal matrices, at least one determinant of PFAS concentrations was assessed, and results such as beta estimates were provided. We identified 35 studies for inclusion in the review and evaluated the PFAS and determinant relationships among the factors collected in these studies. Parity, breastfeeding history, maternal race and country of origin, and household income had the strongest and most consistent evidence to support their roles as determinants of certain PFAS concentrations in pregnant mothers. Reported study findings on smoking status, alcohol consumption, and pre-pregnancy body mass index (BMI) suggest that these factors are not important determinants of PFAS concentrations in pregnant mothers or neonates. Further study into informative factors such as consumer product use, detailed dietary information, and consumed water sources as potential determinants of maternal or neonatal PFAS concentrations is needed. Research on determinants of maternal or neonatal PFAS concentrations is critical to estimate past PFAS exposure, build improved exposure models, and further our understanding on dose-response relationships, which can influence epidemiological studies and risk assessment evaluations. Given the potential for adverse outcomes in pregnant mothers and neonates exposed to PFAS, it is important to identify and understand determinants of maternal and neonatal PFAS concentrations to better implement public health interventions in these populations.
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Affiliation(s)
- Jordan McAdam
- Department of Environmental Health Sciences, University at Albany, Rensselaer, NY, USA
| | - Erin M Bell
- Department of Environmental Health Sciences, University at Albany, Rensselaer, NY, USA.
- Department of Epidemiology and Biostatistics, University at Albany, Rensselaer, NY, USA.
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13
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Soraci L, Cherubini A, Paoletti L, Filippelli G, Luciani F, Laganà P, Gambuzza ME, Filicetti E, Corsonello A, Lattanzio F. Safety and Tolerability of Antimicrobial Agents in the Older Patient. Drugs Aging 2023; 40:499-526. [PMID: 36976501 PMCID: PMC10043546 DOI: 10.1007/s40266-023-01019-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2023] [Indexed: 03/29/2023]
Abstract
Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug-drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing.
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Affiliation(s)
- Luca Soraci
- Unit of Geriatric Medicine, IRCCS INRCA, 87100, Cosenza, Italy
| | - Antonio Cherubini
- Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamento, IRCCS INRCA, Ancona, Italy
| | - Luca Paoletti
- Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamento, IRCCS INRCA, Ancona, Italy
| | | | - Filippo Luciani
- Infectious Diseases Unit of Annunziata Hospital, Cosenza, Italy
| | - Pasqualina Laganà
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
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14
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Jaques DA, Vollenweider P, Bochud M, Ponte B. Aging and hypertension in kidney function decline: A 10 year population-based study. Front Cardiovasc Med 2022; 9:1035313. [PMID: 36277793 PMCID: PMC9582457 DOI: 10.3389/fcvm.2022.1035313] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 09/20/2022] [Indexed: 11/13/2022] Open
Abstract
Background Aging is associated with a physiological decline in kidney function (KFD). In this study, we aimed to describe the impact of age on the rate of KFD and its interplay with risk factors for chronic kidney disease (CKD), considering mainly hypertension (HT), in the general population. Materials and methods Participants of European descent, aged 35-75, were recruited from a populational cohort in Lausanne, Switzerland. Participants with a 10 year follow-up were selected. KFD was defined as the difference in estimated glomerular filtration rate (eGFR) between baseline and follow-up, divided by the observation period. Multivariate linear regressions were used with KFD as the outcome and age as the main predictor. HT was tested as a modifying factor. Results We included 4,163 participants with mean age 52.2 ± 10.4, 44.7% men, 31.9% HT, and 5.0% diabetics. Mean baseline eGFR was 85.9 ± 14.6 ml/min/1.73 m2. Mean KFD was -0.49 ± 1.08 ml/min/1.73 m2 per year with 70% of participants decreasing their eGFR during follow-up. The relationship between age and KFD was non-linear and age was divided in tertiles. Old participants had faster rates of KFD as compared to young and middle-age participants (p < 0.001). A significant interaction was found between age and HT on KFD prediction (p < 0.001). In HT participants, KFD was significantly different across tertiles of age (p < 0.001). On contrary, KFD was not different across tertiles of age in non-HT participants. Conclusion A physiological KFD is present over time in the general population. Age contributes non-linearly to the rate of this decline with older subjects declining the fastest. The presence of HT is a major contributing factor in this setting as KFD worsened with age only in hypertensive participants. Thus, HT represents an important pathological factor aggravating the age-related physiological decline in eGFR in the general population.
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Affiliation(s)
- David A. Jaques
- Division of Nephrology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland,*Correspondence: David A. Jaques,
| | - Peter Vollenweider
- Department of Internal Medicine, University Hospital of Lausanne, Lausanne, Switzerland
| | - Murielle Bochud
- Department of Epidemiology and Health Systems, University Center of General Medicine and Public Health, Lausanne, Switzerland
| | - Belen Ponte
- Division of Nephrology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland,Department of Epidemiology and Health Systems, University Center of General Medicine and Public Health, Lausanne, Switzerland,Belen Ponte,
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15
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Ofori E, Gyan KF, Gyabaah S, Nguah SB, Sarfo FS. Predictors of rapid progression of estimated glomerular filtration rate among persons living with diabetes and/or hypertension in Ghana: Findings from a multicentre study. J Clin Hypertens (Greenwich) 2022; 24:1358-1369. [PMID: 36067082 PMCID: PMC9581086 DOI: 10.1111/jch.14568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 08/10/2022] [Accepted: 08/12/2022] [Indexed: 11/23/2022]
Abstract
In Ghana, the prevalence of chronic kidney disease (CKD) is 28.5% in diabetic hypertensive patients, 26.3% in hypertensives, and 16.1% in those with diabetes only. Trajectories of estimated glomerular filtration rate (eGFR) among patients with hypertension and diabetes are important for monitoring and instituting prompt interventions to prevent the development of CKD, especially in the face of limited access to renal replacement therapy. In this prospective multi‐center study conducted at five hospitals in Ghana, we assessed predictors of rapid eGFR progression among adults with hypertension and/or diabetes. Serum creatinine at baseline and 18 months were taken and eGFR determined using the CKD‐EPI formula. eGFR trajectory was defined as fast when the decline of GFR was ≥ 5 ml/min/1.73 m2 per year. A multivariable logistic regression model was fitted to identify predictors of the fast progression of eGFR. Total 13% of 1261 participants met the criteria for rapid decline in eGFR. The adjusted odds ratio, aOR (95%CI), of four factors adversely associated with fast progression of eGFR were: increasing age 1.20 (1.03–1.14), partial health insurance coverage for medications 1.48 (1.05–2.08), history of smoking 1.91 (1.11–3.27), angiotensin‐receptor blockade use 1.55 (1.06–2.25) while metformin use was protective .56 (.35–.90). Proportion with eGFR <60 ml/min increased from 14% at baseline to 19% at month 18. Effective health insurance policies to improve medication access and avoidance of smoking are interventions that may mitigate the rising burden of CKD in individuals with diabetes mellitus and/or hypertension.
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Affiliation(s)
- Emmanuel Ofori
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Kwadwo Faka Gyan
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Solomon Gyabaah
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Samuel Blay Nguah
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.,Department of Medicine, Kwame Nkrumah University of Science & Technology, Kumasi, Ghana
| | - Fred Stephen Sarfo
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.,Department of Medicine, Kwame Nkrumah University of Science & Technology, Kumasi, Ghana
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16
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Sertsu A, Worku T, Fekadu G, Tura AK. Prevalence of chronic kidney disease and associated factors among patients visiting renal unit of St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia: A cross-sectional study design. SAGE Open Med 2022; 10:20503121221116942. [PMID: 35966210 PMCID: PMC9373155 DOI: 10.1177/20503121221116942] [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: 02/06/2022] [Accepted: 07/14/2022] [Indexed: 11/17/2022] Open
Abstract
Objective: This study aimed to assess the magnitude of chronic kidney disease among
patients attending the renal unit of St. Paul’s Hospital Millennium Medical
College, Addis Ababa, Ethiopia. Methods: Institution-based cross-sectional study was conducted among 620 randomly
selected patients who visited St. Paul’s Hospital Millennium Medical College
renal unit from 1 January to 31 December, 2019. Data on sociodemographic
characteristics, clinical conditions, behavioral risk factors, electrolytes,
and renal function tests were extracted from patients’ medical records. To
enter and analyze data, EpiData 3.1 and SPSS 22 were used, respectively.
Bivariable and multivariable logistic regression analyses were conducted to
see the association between predictor variables and chronic kidney disease.
Adjusted odds ratio at 95% confidence interval was used to describe
significant association. A p-value <0.05 was considered
to declare an association between chronic kidney disease and independent
variables. Results: Of 620 patients, 139 (22.4%; 95% confidence interval: 19.2, 25.6) and 61
(9.8%; 95% confidence interval: 7.4, 12.3) had chronic kidney disease using
cut-off value of 90 and 60 ml/min/1.73 m2, respectively. Having
urinary tract obstruction (adjusted odds ratio = 2.32; 95% confidence
interval: 1.32, 4.06), hypertension (adjusted odds ratio = 4.06; 95%
confidence interval: 2.50, 6.59), diabetes mellitus (adjusted odds
ratio = 2.80; 95% confidence interval: 1.62, 4.85), cardiovascular disease
(adjusted odds ratio = 2.54; 95% confidence interval: 1.60, 4.01), and age
(adjusted odds ratio = 1.83; 95% confidence interval: 1.44, 3.57), family
history of chronic kidney disease (adjusted odds ratio = 2.26; 95%
confidence interval: 1.36, 3.75) were factors positively associated with
having chronic kidney disease. Conclusion: Nearly, one out of five and one out of ten patients who visited the renal
unit had chronic kidney disease using the two thresholds as a cut value.
Patients with concomitant urinary tract obstruction, age, hypertension,
diabetes mellitus, cardiovascular disease, and a family history of chronic
kidney disease were more likely to develop chronic kidney disease. Regular
screening for chronic kidney disease, optimal blood sugar, and blood
pressure management should be practiced.
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Affiliation(s)
- Addisu Sertsu
- Department of Nursing, School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Teshager Worku
- Department of Nursing, School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Gelana Fekadu
- Department of Nursing, School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Abera Kenay Tura
- Department of Nursing, School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.,Department of Obstetrics and Gynecology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
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17
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Alouidor R, Siu M, Roh S, Perez Coulter AM, Kamine TH, Kramer KZ, Winston ES, Ryb G, Putnam AT, Kelly E. Impact of Modified Geriatric Trauma Activation Criteria on patient outcomes at a level 1 trauma center. TRAUMA-ENGLAND 2022. [DOI: 10.1177/14604086221110972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background The American College of Surgeons Trauma Quality Improvement Program recommends a lower threshold for trauma activation on geriatric patients. We implemented the Modified Geriatric Trauma Activation Criteria (MGTAC) and assessed the clinical impact on geriatric trauma patients. Methods Geriatric trauma patients aged 65 years and over presenting between 1/1/2014 and 12/31/2020 were identified through the Trauma Registry. MGTAC were implemented on 3/1/2017, where patients aged 65 and above were rendered as Highest Level activations when presenting with no prior work-up. Those presenting from 1/1/2014 to 2/28/2017 were grouped as Standard Activation Criteria (SAC), and those presenting between 3/1/2017 and 12/31/2020 were grouped as MGTAC. Patient demographics, mechanism of injury, level of activation, operative intervention, intensive care unit (ICU) admission, length of stay, survival, and undertriage rates were reviewed. Chi square, ANOVA, and unpaired t-test were used for analysis to compare SAC and MGTAC patient outcomes. Results 2582 patients were identified: 1293 (50.1%) in SAC and 1289 (49.9%) in MGTAC. Highest Level trauma activations for SAC vs. MGTAC were 9.3% vs. 30.4%, p < .01. Between SAC and MGTAC, ICU admission was 24.1% vs. 16.5%, p<0.01; operative intervention was 10.3% vs. 12.9%, p = .04; undertriage rates were 6.1% vs. 3.8%, p = .01; and average length of stay was 7 days for SAC vs. 6.4 days for MGTAC, p = .54. Overall mortality was 9% for SAC and 9.5% for MGTAC, p = .66. Conclusion Implementation of MGTAC did not improve geriatric trauma patient mortality. However, it decreased ICU admission and undertriage, and increased operative intervention during the first 24 hours.
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Affiliation(s)
- Reginald Alouidor
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Margaret Siu
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Sandy Roh
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Aixa M. Perez Coulter
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Tovy H. Kamine
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Kristina Z. Kramer
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Eleanor S. Winston
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Gabriel Ryb
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Adin T. Putnam
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
| | - Edward Kelly
- Department of Trauma, Critical Care & Acute Care Surgery, University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA, USA
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18
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Lee SE, Park JH, Kim KA, Choi HS. Discordance in Bone Mineral Density between the Lumbar Spine and Femoral Neck Is Associated with Renal Dysfunction. Yonsei Med J 2022; 63:133-140. [PMID: 35083898 PMCID: PMC8819412 DOI: 10.3349/ymj.2022.63.2.133] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 09/12/2021] [Accepted: 10/23/2021] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Bone mineral density (BMD) determined by dual-energy X-ray absorptiometry is considered a gold standard for diagnosing osteoporosis. Some people show discordance in BMD values measured at the femur and that at the lumbar spine (LS). The aim of the present study was to investigate whether differences in BMD T-scores between the LS and femur neck (FN) are associated with renal dysfunction in the general population of Korea. MATERIALS AND METHODS We analyzed national data for 17306 adults from the Korean National Health and Nutrition Examination Survey conducted between 2008 and 2011. BMD T-score differences between LS and FN (termed BMD offset) were calculated by subtracting FN T-scores from LS T-scores. Diminished renal function was defined as estimated glomerular filtration rates (eGFR) less than 60 mL/min/1.73 m². RESULTS Among those aged ≥50 years, BMD offset was negatively associated with eGFR levels. Additionally, eGFR levels decreased linearly across increasing BMD offset quartiles. Men and women with an offset of >1.5 showed a 4.79-times and 2.51-times higher risk of renal dysfunction, respectively, compared to individuals with an offset of ≤0, after adjusting for age, body mass index, educational level, current smoking, and physical activity. In contrast, there was little evidence of an association between renal dysfunction and BMD offset in subjects aged <50 years. CONCLUSION Discordance between LS and FN BMDs was significantly associated with renal dysfunction in subjects aged ≥50 years. When assessing bone health in older chronic kidney disease patients, physicians should consider the possibility of BMD discordance between LS and FN.
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Affiliation(s)
- Seung Eun Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Ju-Hyun Park
- Department of Statistics, Dongguk University, Seoul, Korea
| | - Kyoung-Ah Kim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Han Seok Choi
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea.
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19
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van der Burgh AC, Rizopoulos D, Ikram MA, Hoorn EJ, Chaker L. Determinants of the Evolution of Kidney Function With Age. Kidney Int Rep 2021; 6:3054-3063. [PMID: 34901574 PMCID: PMC8640542 DOI: 10.1016/j.ekir.2021.10.006] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 09/23/2021] [Accepted: 10/04/2021] [Indexed: 12/23/2022] Open
Abstract
Introduction Kidney function declines with age, but its determinants in the general population remain incompletely understood. We investigated the rate and determinants of kidney function decline in the general population. Methods Participants with information on kidney function were selected from a population-based cohort study. Joint models were used to investigate the evolution of the estimated glomerular filtration rate (eGFR, expressed in ml/min per 1.73 m2 per year) and the urine albumin-to-creatinine ratio (ACR, expressed in mg/g per year) with age. We stratified for 8 potential determinants of kidney function decline, including sex, cardiovascular risk factors, and cardiovascular disease. Results We included 12,062 participants with 85,922 eGFR assessments (mean age 67.0 years, 58.7% women) and 3522 participants with 5995 ACR measurements. The annual eGFR decline was 0.82 and the ACR increase was 0.05. All determinants appeared detrimental for eGFR and ACR, except for prediabetes and higher body mass index which proved only detrimental for ACR. In participants without the determinants, eGFR decline was 0.75 and ACR increase was 0.002. Higher baseline eGFR but faster eGFR decline with age was detected in men (0.92 vs. 0.75), smokers (0.90 vs. 0.75), and participants with diabetes (1.07 vs. 0.78). Conclusion We identify prediabetes, smoking, and blood pressure as modifiable risk factors for kidney function decline. As with diabetes, hyperfiltration seems important in accelerated kidney function decline in men and smokers. The interpretation of kidney function decline may require adjustment for age and sex to prevent overdiagnosis of chronic kidney disease in aging populations.
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Affiliation(s)
- Anna C van der Burgh
- Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.,Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Dimitris Rizopoulos
- Department of Biostatistics, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ewout J Hoorn
- Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Layal Chaker
- Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.,Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
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20
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Shih CC, Chen SH, Chen GD, Chang CC, Shih YL. Development of a Longitudinal Diagnosis and Prognosis in Patients with Chronic Kidney Disease: Intelligent Clinical Decision-Making Scheme. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182312807. [PMID: 34886533 PMCID: PMC8657318 DOI: 10.3390/ijerph182312807] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/01/2021] [Accepted: 12/02/2021] [Indexed: 01/08/2023]
Abstract
Previous studies on CKD patients have mostly been retrospective, cross-sectional studies. Few studies have assessed the longitudinal assessment of patients over an extended period. In consideration of the heterogeneity of CKD progression. It’s critical to develop a longitudinal diagnosis and prognosis for CKD patients. We proposed an auto Machine Learning (ML) scheme in this study. It consists of four main parts: classification pipeline, cross-validation (CV), Taguchi method and improve strategies. This study includes datasets from 50,174 patients, data were collected from 32 chain clinics and three special physical examination centers, between 2015 and 2019. The proposed auto-ML scheme can auto-select the level of each strategy to associate with a classifier which finally shows an acceptable testing accuracy of 86.17%, balanced accuracy of 84.08%, sensitivity of 90.90% and specificity of 77.26%, precision of 88.27%, and F1 score of 89.57%. In addition, the experimental results showed that age, creatinine, high blood pressure, smoking are important risk factors, and has been proven in previous studies. Our auto-ML scheme light on the possibility of evaluation for the effectiveness of one or a combination of those risk factors. This methodology may provide essential information and longitudinal change for personalized treatment in the future.
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Affiliation(s)
- Chin-Chuan Shih
- Dean of the Lian-An Clinic, Taipei 24200, Taiwan;
- Deputy Chairman, Taiwan Association of Family Medicine, Taipei 24200, Taiwan
| | - Ssu-Han Chen
- Department of Industrial Engineering and Management, Ming Chi University of Technology, New Taipei City 243303, Taiwan;
- Center for Artificial Intelligence & Data Science, Ming Chi University of Technology, New Taipei City 243303, Taiwan
| | - Gin-Den Chen
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
| | - Chi-Chang Chang
- Department of Medical Informatics, Chung Shan Medical University & IT Office, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Department of Information Management, Ming Chuan University, Taoyuan 33300, Taiwan
- Correspondence: ; Tel.: +886-4-24730022
| | - Yu-Lin Shih
- Department of Otolaryngology-Head and Neck Surgery, Chang-Gung Memorial Hospital, Linkou Branch, Taoyuan City 33305, Taiwan;
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21
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Sateesh J, Guha K, Dutta A, Sengupta P, Rao KS. Design and Modeling of Bioreactor Utilizing Electrophoresis and Di-electrophoresis Techniques for Regenerating Reabsorption Function of Human Kidney PCT in Microfluidics Environment. IEEE Trans Nanobioscience 2021; 21:529-541. [PMID: 34847037 DOI: 10.1109/tnb.2021.3131351] [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: 11/10/2022]
Abstract
The need for innovation in medical device technology is immense; especially to replace the dialysis techniques the necessity is extremely high. The available techniques that promised to replace dialysis have not yet geared up to the marketization level. The utilization of live kidney cells makes these devices costly, delicate, and unreliable. This paper aims to design a bioreactor to mimic the reabsorption function of the kidney that is fully artificial and highly controllable, which can be one step forward to the emerging Kidney-on-Chip (KOC) technology. The additional benefit of the proposed design is that it utilizes size-dependent reabsorption along with charge-dependent reabsorption phenomena to make it more compatible with human kidney function. The electrophoresis (EP), and di-electrophoresis (DEP) techniques are utilized to mimic the reabsorption function in this report. The structure utilized in the present design exactly replicates the proximal convoluted tubule (PCT) dimensions and functions as well. The whole setup is implemented in the COMSOL Multiphysics FEM benchmark tool for simulation, and analysis with appropriate boundary conditions. The device when excited by an electric field, Electrophoresis has produced a maximum velocity of 1.07 m/s for DC excitation and di-electrophoresis has produced a maximum flow velocity of 1.23 m/s, where both the offset voltages are the same (0.7 V). The flow velocity obtained utilizing both EP and DEP produced a reabsorption rate of 50-58% depending on the voltage applied and dimensions considered which is close to 60% reabsorption rate of the normal human kidney PCT. In accordance with the outcomes produced, the di-electrophoresis technique proved to be more efficient in realizing bioreactor as compared to electrophoresis. The novelty of the present work lies in the creation of a simulation environment, rigorous analysis, and optimization of the bioreactor supported by compact mathematical model.
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22
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Drew R, Hagen TG, Champness D, Sellier A. Half-lives of several polyfluoroalkyl substances (PFAS) in cattle serum and tissues. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2021; 39:320-340. [PMID: 34732107 DOI: 10.1080/19440049.2021.1991004] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Cattle that were at steady-state serum polyfluoroalkyl substances (PFAS) concentrations due to several years of exposure to water contaminated by residues of Aqueous Film-Forming (AFFF) firefighting foam had perfluorooctane sulphonate (PFOS) isomers, perfluoroheptane sulphonate (PFHpS), perfluorohexane sulphonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in serum. Elimination serum half-lives were determined in five heifers from serial blood sampling over 215 days. Eleven additional animals that had blood sampled on day 19 (d19) were euthanised on d63. PFAS half-life estimates from the serial blood sampling and from d19/d63 data were not significantly different. The combined (n = 16) serum half-lives (in days) were: total PFOS (tPFOS, 74.1 ± 13.4), PFHpS (45.7 ± 9.4), PFHxS (9.3 ± 1.3), PFNA (12.3 ± 3.2) and PFDA (60.4 ± 10.4). The half-lives of linear PFOS (L-PFOS, 69.4 ± 11.6) and mono branched PFOS isomers (m-PFOS, 83.6 ± 19) were not significantly different from tPFOS, but for the di-branched isomers (di-PFOS), the serum half-life was significantly lower (29.9 ± 5.8). Animal age (1.4-12.3 years old) and serum concentration at the start of depuration did not influence half-lives, and there was no difference between steers and heifers. Consideration of serum and tissue PFAS concentrations at d63 and d215 indicated there was no difference in tPFOS depuration from serum or muscle, but elimination from liver and kidney may be slightly longer. Depuration of PFHpS is essentially the same in serum, kidney and liver, and it is expected depletion from muscle would be comparable. The short half-life of di-PFOS, PFHxS and PFNA did not allow an assessment of clearance from tissues because they were not measurable at d215 but based on the results for PFOS and PFHpS, elimination of PFHxS from tissues is expected to mirror that from serum. Human health risk assessment implications are discussed.
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Affiliation(s)
- Roger Drew
- ToxConsult Pty Ltd, Malvern East, Australia
| | | | - David Champness
- Department of Economic Development, Jobs, Transport and Resources (now known as the Department of Jobs, Precincts and Regions), Agriculture Victoria, Hamilton, Australia
| | - Amelie Sellier
- Wellington - Laboratory, AsureQuality, Auckland, New Zealand
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Lockwood MB, Steel JL, Doorenbos AZ, Contreras BN, Fischer MJ. Emerging Patient-Centered Concepts in Pain Among Adults With Chronic Kidney Disease, Maintenance Dialysis, and Kidney Transplant. Semin Nephrol 2021; 41:550-562. [PMID: 34973699 PMCID: PMC8740641 DOI: 10.1016/j.semnephrol.2021.10.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Patient reports of moderate to severe pain are common across the spectrum of chronic kidney disease. The synergistic effects of comorbid depression and anxiety can lead to maladaptive coping responses to pain, namely pain catastrophizing and illness-related post-traumatic stress disorder. If underlying depression and anxiety and associated maladaptive coping responses are not treated, patients can experience an increased perception of pain, worsened disability, decreased quality of life, withdrawal from social activities, and increased morbidity and mortality. Meanwhile, interest in nonpharmacologic treatments for pain that targets coping as well as comorbid anxiety and depression has been increasing, particularly given the significant societal damage that has resulted from the opioid epidemic. Evidence-based, nonpharmacologic treatments have shown promise in treating pain in areas outside of nephrology. Currently, little is known about the effects of these treatments among adults with CKD, and particularly end-stage kidney disease, when chronic pain can become debilitating. In this review, we examine patient-centered concepts related to pain that have received little attention in the nephrology literature. We also describe emerging areas of research, including omics technologies for biomarker discovery and advanced symptom clustering methods for symptom phenotyping, which may be useful to future kidney disease research and treatment.
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Affiliation(s)
- Mark B Lockwood
- Department of Behavioral Nursing Science, University of Illinois Chicago, College of Nursing, Chicago, IL.
| | - Jennifer L Steel
- Center for Excellence in Behavioral Medicine, Department of Surgery, University of Pittsburg, Pittsburg, PA
| | - Ardith Z Doorenbos
- Department of Biobehavioral Nursing Science, University of Illinois Chicago, College of Nursing, Chicago, IL
| | - Blanca N Contreras
- Section of Nephrology, Department of Medicine, University of Illinois at Chicago, Chicago, IL
| | - Michael J Fischer
- Department of Internal Medicine, University of Illinois Hospital and Health Sciences Center, Chicago, IL; Renal Section, Medical Service, Jesse Brown VA Medical Center, Chicago, IL; Center of Innovation for Complex Chronic Health Care, Edward Hines, Jr. VA Hospital, Hines, IL
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24
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Shankland SJ, Wang Y, Shaw AS, Vaughan JC, Pippin JW, Wessely O. Podocyte Aging: Why and How Getting Old Matters. J Am Soc Nephrol 2021; 32:2697-2713. [PMID: 34716239 PMCID: PMC8806106 DOI: 10.1681/asn.2021050614] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/26/2021] [Indexed: 02/04/2023] Open
Abstract
The effects of healthy aging on the kidney, and how these effects intersect with superimposed diseases, are highly relevant in the context of the population's increasing longevity. Age-associated changes to podocytes, which are terminally differentiated glomerular epithelial cells, adversely affect kidney health. This review discusses the molecular and cellular mechanisms underlying podocyte aging, how these mechanisms might be augmented by disease in the aged kidney, and approaches to mitigate progressive damage to podocytes. Furthermore, we address how biologic pathways such as those associated with cellular growth confound aging in humans and rodents.
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Affiliation(s)
- Stuart J. Shankland
- Division of Nephrology, University of Washington, Seattle, Washington
- Institute for Stem Cell & Regenerative Medicine, University of Washington, Seattle, Washington
| | - Yuliang Wang
- Institute for Stem Cell & Regenerative Medicine, University of Washington, Seattle, Washington
- Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, Washington
| | - Andrey S. Shaw
- Department of Research Biology, Genentech, South San Francisco, California
| | - Joshua C. Vaughan
- Department of Chemistry, University of Washington, Seattle, Washington
- Department of Physiology and Biophysics, University of Washington, Seattle, Washington
| | - Jeffrey W. Pippin
- Division of Nephrology, University of Washington, Seattle, Washington
| | - Oliver Wessely
- Lerner Research Institute, Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic Foundation, Cleveland, Ohio
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25
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de Lima CS, Ferreira KRG, Borin-Crivellenti S, Maia SR, Santana AE, Crivellenti LZ. Renal Magnesium Handling: A Comparison Between Dogs With Chronic Kidney Disease and Healthy Elderly Dogs. Top Companion Anim Med 2021; 46:100588. [PMID: 34610438 DOI: 10.1016/j.tcam.2021.100588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 09/22/2021] [Accepted: 09/30/2021] [Indexed: 11/19/2022]
Abstract
Chronic kidney disease (CKD) and aging are known to possibly cause a progressive reduction in glomerular filtration rate, which may be associated with an increase in fractional excretion of electrolytes due to an adaptive response of the remaining functioning nephrons. However, the behavior of magnesium excretion has not been studied in CKD and healthy elderly dogs. The objective was to evaluate the fractional excretion of magnesium (FEMg) in dogs with (CKD) compared to healthy elderly dogs. Sixteen healthy elderly dogs and 43 dogs with CKD were divided into 3 groups (CKD 2 [n = 14], CKD 3 [n = 17], CKD 4 [n = 12]), in accordance with the current International Renal Interest Society (IRIS) criteria that were used in this study. Blood samples were obtained by jugular venipuncture and urine samples were obtained by cystocentesis. The FEMg was evaluated at a single time point in both urine and blood samples. FEMg was significantly higher in dogs with CKD compared to healthy elderly dogs, especially in advanced stages. This preliminary study demonstrates that FEMg may be altered in dogs with CKD. Further research is warranted to elucidate magnesium's potential role in cardiovascular and arterial calcification in dogs with CKD as observed in humans with CKD.
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Affiliation(s)
- Charles Silva de Lima
- Veterinary Teaching Hospital/Animal Science Graduate Program, Franca University (UNIFRAN), Franca, São Paulo, Brazil
| | | | - Sofia Borin-Crivellenti
- Graduate Program in Veterinary Science (PPGCV)/College of Veterinary Medicine (FAMEV), Federal University of Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil
| | - Suellen Rodrigues Maia
- Veterinary Medicine Graduate Program/School of Veterinary Medicine and Animal Science (FMVZ), Paulista State University (UNESP), Botucatu, São Paulo, Brazil
| | | | - Leandro Zuccolotto Crivellenti
- Graduate Program in Veterinary Science (PPGCV)/College of Veterinary Medicine (FAMEV), Federal University of Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil.
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McKinley JM, Mueller U, Atkinson PM, Ofterdinger U, Cox SF, Doherty R, Fogarty D, Egozcue JJ, Pawlowsky-Glahn V. Chronic kidney disease of unknown origin is associated with environmental urbanisation in Belfast, UK. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2021; 43:2597-2614. [PMID: 32583129 PMCID: PMC8275563 DOI: 10.1007/s10653-020-00618-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 06/08/2020] [Indexed: 05/02/2023]
Abstract
Chronic kidney disease (CKD), a collective term for many causes of progressive renal failure, is increasing worldwide due to ageing, obesity and diabetes. However, these factors cannot explain the many environmental clusters of renal disease that are known to occur globally. This study uses data from the UK Renal Registry (UKRR) including CKD of uncertain aetiology (CKDu) to investigate environmental factors in Belfast, UK. Urbanisation has been reported to have an increasing impact on soils. Using an urban soil geochemistry database of elemental concentrations of potentially toxic elements (PTEs), we investigated the association of the standardised incidence rates (SIRs) of both CKD and CKD of uncertain aetiology (CKDu) with environmental factors (PTEs), controlling for social deprivation. A compositional data analysis approach was used through balances (a special class of log contrasts) to identify elemental balances associated with CKDu. A statistically significant relationship was observed between CKD with the social deprivation measures of employment, income and education (significance levels of 0.001, 0.01 and 0.001, respectively), which have been used as a proxy for socio-economic factors such as smoking. Using three alternative regression methods (linear, generalised linear and Tweedie models), the elemental balances of Cr/Ni and As/Mo were found to produce the largest correlation with CKDu. Geogenic and atmospheric pollution deposition, traffic and brake wear emissions have been cited as sources for these PTEs which have been linked to kidney damage. This research, thus, sheds light on the increasing global burden of CKD and, in particular, the environmental and anthropogenic factors that may be linked to CKDu, particularly environmental PTEs linked to urbanisation.
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Affiliation(s)
- Jennifer M McKinley
- School of Natural and Built Environment, Queen's University Belfast, Belfast, Northern Ireland.
| | - Ute Mueller
- School of Science, Edith Cowan University, Perth, WA, Australia
| | - Peter M Atkinson
- School of Natural and Built Environment, Queen's University Belfast, Belfast, Northern Ireland
- Lancaster Environment Centre, Lancaster University, Lancaster, UK
| | - Ulrich Ofterdinger
- School of Natural and Built Environment, Queen's University Belfast, Belfast, Northern Ireland
| | - Siobhan F Cox
- School of Natural and Built Environment, Queen's University Belfast, Belfast, Northern Ireland
| | - Rory Doherty
- School of Natural and Built Environment, Queen's University Belfast, Belfast, Northern Ireland
| | | | - J J Egozcue
- Department of Civil and Environmental Engineering, U. Politécnica de Cataluña (UPC), Barcelona, Spain
| | - V Pawlowsky-Glahn
- Department of Computer Sciences, Applied Mathematics, and Statistics, University of Girona, Girona, Spain
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Ebefors K, Lassén E, Anandakrishnan N, Azeloglu EU, Daehn IS. Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk. Front Physiol 2021; 12:689083. [PMID: 34149462 PMCID: PMC8206562 DOI: 10.3389/fphys.2021.689083] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/05/2021] [Indexed: 12/11/2022] Open
Abstract
The glomerulus is a compact cluster of capillaries responsible for blood filtration and initiating urine production in the renal nephrons. A trilaminar structure in the capillary wall forms the glomerular filtration barrier (GFB), composed of glycocalyx-enriched and fenestrated endothelial cells adhering to the glomerular basement membrane and specialized visceral epithelial cells, podocytes, forming the outermost layer with a molecular slit diaphragm between their interdigitating foot processes. The unique dynamic and selective nature of blood filtration to produce urine requires the functionality of each of the GFB components, and hence, mimicking the glomerular filter in vitro has been challenging, though critical for various research applications and drug screening. Research efforts in the past few years have transformed our understanding of the structure and multifaceted roles of the cells and their intricate crosstalk in development and disease pathogenesis. In this review, we present a new wave of technologies that include glomerulus-on-a-chip, three-dimensional microfluidic models, and organoids all promising to improve our understanding of glomerular biology and to enable the development of GFB-targeted therapies. Here, we also outline the challenges and the opportunities of these emerging biomimetic systems that aim to recapitulate the complex glomerular filter, and the evolving perspectives on the sophisticated repertoire of cellular signaling that comprise the glomerular milieu.
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Affiliation(s)
- Kerstin Ebefors
- Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Emelie Lassén
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Nanditha Anandakrishnan
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Evren U Azeloglu
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Ilse S Daehn
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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Microbiota and Metabolite Modifications after Dietary Exclusion of Dairy Products and Reduced Consumption of Fermented Food in Young and Older Men. Nutrients 2021; 13:nu13061905. [PMID: 34205926 PMCID: PMC8228243 DOI: 10.3390/nu13061905] [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: 04/14/2021] [Revised: 05/19/2021] [Accepted: 05/21/2021] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota adapts to age-related changes in host physiology but is also affected by environmental stimuli, like diet. As a source of both pre- and probiotics, dairy and fermented foods modulate the gut microbiota composition, which makes them interesting food groups to use for the investigation of interactions between diet and ageing. Here we present the effects of excluding dairy products and limiting fermented food consumption for 19 days on gut microbiota composition and circulating metabolites of 28 healthy, young (YA) and older (OA) adult men. The intervention affected gut microbial composition in both groups, with significant increases in Akkermansia muciniphila and decreases in bacteria of the Clostridiales order. Lower fasting levels of glucose and insulin, as well as dairy-associated metabolites like lactose and pentadecanoic acid, were observed after the intervention, with no effect of age. The intervention also decreased HDL and LDL cholesterol levels. Dairy fat intake was positively associated with the HDL cholesterol changes but not with the LDL/HDL ratio. In conclusion, restricting the intake of dairy and fermented foods in men modified their gut microbiota and blood metabolites, while the impact of the dietary restrictions on these outcomes was more marked than the effect of age.
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29
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Stader F, Kinvig H, Penny MA, Battegay M, Siccardi M, Marzolini C. Physiologically Based Pharmacokinetic Modelling to Identify Pharmacokinetic Parameters Driving Drug Exposure Changes in the Elderly. Clin Pharmacokinet 2021; 59:383-401. [PMID: 31583609 DOI: 10.1007/s40262-019-00822-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Medication use is highly prevalent with advanced age, but clinical studies are rarely conducted in the elderly, leading to limited knowledge regarding age-related pharmacokinetic changes. OBJECTIVE The objective of this study was to investigate which pharmacokinetic parameters determine drug exposure changes in the elderly by conducting virtual clinical trials for ten drugs (midazolam, metoprolol, lisinopril, amlodipine, rivaroxaban, repaglinide, atorvastatin, rosuvastatin, clarithromycin and rifampicin) using our physiologically based pharmacokinetic (PBPK) framework. METHODS PBPK models for all ten drugs were developed in young adults (20-50 years) following the best practice approach, before predicting pharmacokinetics in the elderly (≥ 65 years) without any modification of drug parameters. A descriptive relationship between age and each investigated pharmacokinetic parameter (peak concentration [Cmax], time to Cmax [tmax], area under the curve [AUC], clearance, volume of distribution, elimination-half-life) was derived using the final PBPK models, and verified with independent clinically observed data from 52 drugs. RESULTS The age-related changes in drug exposure were successfully simulated for all ten drugs. Pharmacokinetic parameters were predicted within 1.25-fold (70%), 1.5-fold (86%) and 2-fold (100%) of clinical data. AUC increased progressively by 0.9% per year throughout adulthood from the age of 20 years, which was explained by decreased clearance, while Cmax, tmax and volume of distribution were not affected by human aging. Additional clinical data of 52 drugs were contained within the estimated variability of the established age-dependent correlations for each pharmacokinetic parameter. CONCLUSION The progressive decrease in hepatic and renal blood flow, as well as glomerular filtration, rate led to a reduced clearance driving exposure changes in the healthy elderly, independent of the drug.
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Affiliation(s)
- Felix Stader
- Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland. .,Infectious Disease Modelling Unit, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. .,University of Basel, Basel, Switzerland.
| | - Hannah Kinvig
- Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Melissa A Penny
- Infectious Disease Modelling Unit, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Manuel Battegay
- Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Marco Siccardi
- Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Catia Marzolini
- Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.,University of Basel, Basel, Switzerland
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IVUS-Guided Zero-Contrast PCI in CKD Patients: Safety and Short-Term Outcome in Patients with Complex Demographics and/or Lesion Characteristics. J Interv Cardiol 2021. [DOI: 10.1155/2021/6626749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background. Percutaneous coronary intervention (PCI) in patients with significant renal dysfunction is challenging because of the lesion characteristics and the risk of contrast-induced acute kidney injury (CI-AKI). With the advent of intravascular ultrasound- (IVUS-) guided zero-contrast PCI, outcomes have improved considerably. Objective. To assess the safety and short-term outcomes of IVUS-guided zero-contrast PCI in chronic kidney disease (CKD) patients with complex demographics or lesion morphology. Methods. Patients who underwent IVUS-guided zero-contrast PCI at a tertiary center, from November 2019 to May 2020, were included in this prospective analysis. Clinical characteristics, procedural data, and follow-up data were collected and analyzed. Results. A total of 15 patients (27 vessels), all men (mean age, 70.0 ± 11.0 years), underwent zero-contrast PCI. The mean estimated glomerular filtration rate (eGFR) and serum creatinine were 30.8 ± 7.3 mL/min/1.73 m2 and 2.6 ± 1.3 mg/dL, respectively. The mean BMC2 risk for dialysis was 2.1 ± 1.1%, mean SYNTAX score was 20.3 ± 10.3, and mean left ventricular ejection fraction (LVEF) was 42.4 ± 11.6%. Four patients (26.6%) underwent left main coronary artery (LMCA) PCI including one LMCA bifurcation. One patient underwent chronic total occlusion PCI. Technical and procedural success were 100% without any periprocedural complications. No major adverse cardiovascular events (MACE) were reported, and no patient required dialysis within three months of follow-up. Conclusion. Zero-contrast PCI guided by IVUS is safe in coronary artery disease (CAD) patients with moderate-to-severe CKD. High procedural success without complications can be achieved even in cases with complex clinical characteristics and lesion morphology.
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Santos B, Sanz M, Muñoz Ramos P, Gilabert N, Costa R, Otero S, Carles P, Ruano P, Quiroga B. [Baseline characteristics of nonagenarians hospitalised due to acute kidney injury compared to other age groups]. Rev Esp Geriatr Gerontol 2020; 55:326-331. [PMID: 32718579 DOI: 10.1016/j.regg.2020.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 06/07/2020] [Accepted: 06/29/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND The increase in life expectancy leads to higher hospitalisation rates in elderly patients. The aim of this work is to study the characteristics of the population over 90 years of age that are admitted due to acute kidney injury (AKI). MATERIAL AND METHODS A cross-sectional study was conducted that included all patients admitted to hospital with AKI in the years 2013 and 2014. Epidemiological characteristics, comorbidity, medication and baseline analytical data were collected, and a comparison was made between patients with age over 90 years-old and the others. RESULTS A total of 1733 patients were included, of whom 264 (15%) were over 90 years-old. A significantly higher proportion of these patients were women. The most frequent cause of AKI in patients older than 90 years was functional (81%) (p < 0.001 compared to other age groups). The main cause of hospital admission was infection. In the group of over 90 years of age, a higher prevalence was found for arterial hypertension (p = 0.005), chronic kidney disease (p = 0.014), congestive heart failure (p = 0.006), and cognitive impairment (p < 0.0001). The baseline glomerular filtration rate by CKD-EPI was lower in the group of patients older than 90 years (p < 0.0001). Patients under 90 years admitted to hospital due to AKI, had a higher prevalence of diabetes mellitus (p < 0.001), dyslipidaemia (p < 0.001), history of neoplasia (p < 0.001), and a higher Barthel index (p < 0.0001). CONCLUSIONS Nonagenarians admitted due to AKI have functional aetiology as the most common factor. These patients have a higher prevalence of hypertension, heart failure, chronic kidney disease, low functional status, and more cognitive impairment.
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Affiliation(s)
- Begoña Santos
- Servicio de Nefrología, Hospital Universitario de La Princesa, Madrid, España
| | - Marta Sanz
- Servicio de Nefrología, Hospital Universitario de La Princesa, Madrid, España
| | | | - Noemi Gilabert
- Servicio de Medicina Interna, Hospital Universitario de La Princesa, Madrid, España
| | - Ramón Costa
- Servicio de Medicina Interna, Hospital Universitario de La Princesa, Madrid, España
| | - Silvia Otero
- Servicio de Medicina Interna, Hospital Universitario de La Princesa, Madrid, España
| | - Patricia Carles
- Servicio de Medicina Interna, Hospital Universitario de La Princesa, Madrid, España
| | - Pablo Ruano
- Servicio de Medicina Interna, Hospital Universitario de La Princesa, Madrid, España
| | - Borja Quiroga
- Servicio de Nefrología, Hospital Universitario de La Princesa, Madrid, España.
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Clinical characteristics and cost of hospital stay of octogenarians and nonagenarians in intensive care nephrology unit. Int Urol Nephrol 2020; 53:147-153. [PMID: 32949335 DOI: 10.1007/s11255-020-02647-z] [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: 04/30/2020] [Accepted: 09/07/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE As the population gets older, the elderly and very elderly patients are increasingly been treated in nephrology intensive care units (ICU). In this study we evaluated the characteristics and outcomes of the octogenarians (80-89 years old), nonagenarians (≥ 90 years old) and compared them with elderly (65-79 years old) patients treated in nephrology ICU. METHODS Eighteen nonagenarians, 70 octogenarians and 88 elderly patients were included in the study. Indication for hospitalization, presence of comorbid diseases, and requirement for acute dialysis treatment were investigated. Need for mechanical ventilation, vasopressors, central venous catheterization, urinary catheterization, anticoagulation, and transfusion of blood products were evaluated. Mortality rate and hospital cost were calculated. Data about survival at 1 month after discharge was collected. RESULTS Causes of hospitalization, need for dialysis treatment, mechanical ventilation, vasopressors, central venous catheterization, urinary catheterization, anticoagulation, and transfusion of blood products were not different between age groups. Diabetes mellitus and malignancy were more frequent in elderly, whereas dementia/Alzheimer's disease was more common in nonagenarians. Although, mortality in ICU was increased as the age increased, it was statistically insignificant. However, 1 month mortality rate after discharge from hospital was increased especially in nonagenarians. In nonagenarians infection, whereas in octogenarians need for dialysis treatment, were related with mortality. Length of intensive care stay and hospital cost did not differ between age groups. CONCLUSION Length of nephrology intensive care stay, mortality rate and hospital cost did not differ for very elderly age groups, but mortality risk was higher for nonagenarians after discharge from hospital.
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Guo J, Zheng HJ, Zhang W, Lou W, Xia C, Han XT, Huang WJ, Zhang F, Wang Y, Liu WJ. Accelerated Kidney Aging in Diabetes Mellitus. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:1234059. [PMID: 32774664 PMCID: PMC7407029 DOI: 10.1155/2020/1234059] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 05/25/2020] [Accepted: 06/25/2020] [Indexed: 02/07/2023]
Abstract
With aging, the kidney undergoes inexorable and progressive changes in structural and functional performance. These aging-related alterations are more obvious and serious in diabetes mellitus (DM). Renal accelerated aging under DM conditions is associated with multiple stresses such as accumulation of advanced glycation end products (AGEs), hypertension, oxidative stress, and inflammation. The main hallmarks of cellular senescence in diabetic kidneys include cyclin-dependent kinase inhibitors, telomere shortening, and diabetic nephropathy-associated secretory phenotype. Lysosome-dependent autophagy and antiaging proteins Klotho and Sirt1 play a fundamental role in the accelerated aging of kidneys in DM, among which the autophagy-lysosome system is the convergent mechanism of the multiple antiaging pathways involved in renal aging under DM conditions. Metformin and the inhibitor of sodium-glucose cotransporter 2 are recommended due to their antiaging effects independent of antihyperglycemia, besides angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Additionally, diet intervention including low protein and low AGEs with antioxidants are suggested for patients with diabetic nephropathy (DN). However, their long-term benefits still need further study. Exploring the interactive relationships among antiaging protein Klotho, Sirt1, and autophagy-lysosome system may provide insight into better satisfying the urgent medical needs of elderly patients with aging-related DN.
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Affiliation(s)
- Jing Guo
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Hui Juan Zheng
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Wenting Zhang
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Wenjiao Lou
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Chenhui Xia
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xue Ting Han
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Wei Jun Huang
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Fan Zhang
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Yaoxian Wang
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Wei Jing Liu
- Renal Research Institution; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
- Institute of Nephrology, and Zhanjiang Key Laboratory of Prevention and Management of Chronic Kidney Disease, Guangdong Medical University, No. 57th South Renmin Road, Zhanjiang, Guangdong 524001, China
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Early Renal Function Alterations in Renal Branches vs. Renal Fenestrations - A Dynamic Scintigraphy Based Prospective Study. Eur J Vasc Endovasc Surg 2020; 60:395-401. [PMID: 32665199 DOI: 10.1016/j.ejvs.2020.05.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 04/24/2020] [Accepted: 05/14/2020] [Indexed: 11/21/2022]
Abstract
OBJECTIVE The objective of this prospective single centre study was to assess whether branches and fenestrations have different outcomes on renal function in the early phase. METHODS From March 2018 to June 2019, 67 patients who underwent elective fenestrated and branched endovascular aneurysm repair (F/BEVAR) procedures were enrolled in this study. The patients were divided into two groups according to the renal bridging component configuration (fenestration vs. branch). All of them underwent dynamic renal scintigraphy with 99mTc diethylenetriaminepentaacetic acid (DTPA), two weeks pre-operatively, and three months and one year post-operatively. The primary end points were peri-procedural technical success, 30 day major adverse events, differences in glomerular filtration rate (GFR) between the branch and fenestration configurations, and variations between the pre-operative and the post-operative dynamic renal scintigraphy. RESULTS Overall, 135 kidneys were analysed: 63 in the 32 patients treated with fenestrations, and 72 in the 35 patients treated with branches; the mean GFR on baseline scintigraphy was 58.4 ± 30.9 mL/min in the fenestration group, and 65.1 ± 29.2 mL/min in the branch group. Only kidneys associated with a patent fenestration/branch were included in the split GFR final analysis. The mean total GFR at three month scintigraphy decreased by 6.0 ± 2.9 mL/min in the fenestration group and by 23.4 ± 6.4 mL/min in the branch group. The split GFR decreased by 3.5 ± 0.6 mL/min in the fenestration group, and by 15.4 ± 5.4 mL/min in the branch group. The GFR decrease remained stable at one year. CONCLUSION In this study, the use of branches for renal arteries during F/BEVAR resulted in a greater decrease in the GFR than in those patients who were treated with fenestrations alone. The scintigraphic alterations were evident at an early phase.
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Stader F, Siccardi M, Battegay M, Kinvig H, Penny MA, Marzolini C. Repository Describing an Aging Population to Inform Physiologically Based Pharmacokinetic Models Considering Anatomical, Physiological, and Biological Age-Dependent Changes. Clin Pharmacokinet 2020; 58:483-501. [PMID: 30128967 DOI: 10.1007/s40262-018-0709-7] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Aging is characterized by anatomical, physiological, and biological changes that can impact drug kinetics. The elderly are often excluded from clinical trials and knowledge about drug kinetics and drug-drug interaction magnitudes is sparse. Physiologically based pharmacokinetic modeling can overcome this clinical limitation but detailed descriptions of the population characteristics are essential to adequately inform models. OBJECTIVE The objective of this study was to develop and verify a population database for aging Caucasians considering anatomical, physiological, and biological system parameters required to inform a physiologically based pharmacokinetic model that included population variability. METHODS A structured literature search was performed to analyze age-dependent changes of system parameters. All collated data were carefully analyzed, and descriptive mathematical equations were derived. RESULTS A total of 362 studies were found of which 318 studies were included in the analysis as they reported rich data for anthropometric parameters and specific organs (e.g., liver). Continuous functions could be derived for most system parameters describing a Caucasian population from 20 to 99 years of age with variability. Areas with sparse data were identified such as tissue composition, but knowledge gaps were filled with plausible qualified assumptions. The developed population was implemented in Matlab® and estimated system parameters from 1000 virtual individuals were in accordance with independent observed data showing the robustness of the developed population. CONCLUSIONS The developed repository for aging subjects provides a singular specific source for key system parameters needed for physiologically based pharmacokinetic modeling and can in turn be used to investigate drug kinetics and drug-drug interaction magnitudes in the elderly.
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Affiliation(s)
- Felix Stader
- Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland. .,Infectious Disease Modelling Unit, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. .,University of Basel, Basel, Switzerland.
| | - Marco Siccardi
- Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Manuel Battegay
- Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Hannah Kinvig
- Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Melissa A Penny
- Infectious Disease Modelling Unit, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Catia Marzolini
- Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.,University of Basel, Basel, Switzerland
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Trace Level Detection of Bisphenol A Analogues and Parabens by LC-MS/MS in Human Plasma from Malaysians. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2581287. [PMID: 32420332 PMCID: PMC7210526 DOI: 10.1155/2020/2581287] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 01/14/2020] [Accepted: 03/13/2020] [Indexed: 12/17/2022]
Abstract
In this study, a novel LC-MS/MS method was designed using a simple extraction procedure that was scientifically developed to capture the most relevant bisphenol A (BPA) analogues (BPB, BPF, BPS, and BPAF) and parabens (propylparaben, ethylparaben, butylparaben, and methylparaben) in human plasma. The LC-MS/MS method was validated using US FDA guidelines, and all validation requirements were satisfactory. This is the method that allows for the detection of plasma bisphenols and parabens in one run and is also the fastest BPA analogue and paraben detection technique for human plasma. The method was used to analyze samples from 150 healthy volunteers from Malaysia who enrolled in the study. No BPB was detected in any of the volunteers; however, 99.3% were positive for BPF. Only 24% and 10.7% of volunteers were positive for BPAF and BPS, respectively. A high percentage of volunteers were negative for propylparaben, ethylparaben, butylparaben, and methylparaben (56%, 68%, 86.7%, and 83.3%, respectively). These results suggest that persons in Malaysia are exposed to different BPA analogues and parabens, from both the daily use of products (cosmetic and plastic products) and the environment.
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Brennan M, Murray O, O'Shea PM, Mulkerrin EC. Increased rates of hypernatraemia during modest heatwaves in temperate climates. QJM 2020; 113:266-270. [PMID: 31665466 DOI: 10.1093/qjmed/hcz280] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 09/25/2019] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Hypernatraemia is associated with morbidity and mortality, particularly in the older person. Last summer, Ireland experienced prolonged periods of excessive heat. The Irish meteorological service defines a heatwave as temperatures exceeding 25°C for five consecutive days. AIM This study sought to compare the frequency of hypernatraemia (sodium (Na+) >145 mmol/l) observed during a modest heatwave with that during average ambient temperature in the temperate Irish climate. DESIGN Retrospective cross-sectional analysis with nested case-control study. METHODS The 10-day period from 24 June to 3 July in 2017 and 2018 were chosen as the control and heatwave periods, respectively. Patients aged >65 with at least one Na+ value recorded on the laboratory information system were included. Local meteorological data, age, gender and Na+ levels were evaluated. RESULTS Maximum air temperatures were significantly higher during the heatwave period (mean 27°C vs. 16.8°C, P < 0.0001). Hypernatraemia was present in 3.6% (66/1840) of samples collected during the heatwave compared to 1.4% (23/1593) in the control period. The mean age of affected patients was similar in both groups, 75 years ±7 (P = 1.000). Almost half of participants (49.5%) were male. The frequency of hypernatraemia observed was not influenced by gender, P = 0.33. The median sodium concentrations were similar in both groups, P = 1.00. CONCLUSION Hypernatraemia was 2.5 times more frequent in samples drawn during the heatwave compared to the control period. In this study, neither age nor gender impacted the profile of patients diagnosed with hypernatraemia. A modest rise in temperatures increases hypernatraemia rates in temperate climates.
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Affiliation(s)
- M Brennan
- Department of Geriatric Medicine, Saolta University Health Care Group (SUHCG), University Hospital Galway, Newcastle Road, Galway, Ireland
| | - O Murray
- Department of Pharmacology & Therapeutics, National University of Ireland, Newcastle Road, Galway, Ireland
| | - P M O'Shea
- Department of Clinical Biochemistry, Saolta University Health Care Group (SUHCG), University Hospital Galway, Newcastle Road, Galway, Ireland
| | - E C Mulkerrin
- Department of Geriatric Medicine, Saolta University Health Care Group (SUHCG), University Hospital Galway, Newcastle Road, Galway, Ireland
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Chen YS, Chou CY, Chen AL. Early prediction of acquiring acute kidney injury for older inpatients using most effective laboratory test results. BMC Med Inform Decis Mak 2020; 20:36. [PMID: 32079533 PMCID: PMC7032003 DOI: 10.1186/s12911-020-1050-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 02/13/2020] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Acute Kidney Injury (AKI) is common among inpatients. Severe AKI increases all-cause mortality especially in critically ill patients. Older patients are more at risk of AKI because of the declined renal function, increased comorbidities, aggressive medical treatments, and nephrotoxic drugs. Early prediction of AKI for older inpatients is therefore crucial. METHODS We use 80 different laboratory tests from the electronic health records and two types of representations for each laboratory test, that is, we consider 160 (laboratory test, type) pairs one by one to do the prediction. By proposing new similarity measures and employing the classification technique of the K nearest neighbors, we are able to identify the most effective (laboratory test, type) pairs for the prediction. Furthermore, in order to know how early and accurately can AKI be predicted to make our method clinically useful, we evaluate the prediction performance of up to 5 days prior to the AKI event. RESULTS We compare our method with two existing works and it shows our method outperforms the others. In addition, we implemented an existing method using our dataset, which also shows our method has a better performance. The most effective (laboratory test, type) pairs found for different prediction times are slightly different. However, Blood Urea Nitrogen (BUN) is found the most effective (laboratory test, type) pair for most prediction times. CONCLUSION Our study is first to consider the last value and the trend of the sequence for each laboratory test. In addition, we define the exclusion criteria to identify the inpatients who develop AKI during hospitalization and we set the length of the data collection window to ensure the laboratory data we collect is close to the AKI time. Furthermore, we individually select the most effective (laboratory test, type) pairs to do the prediction for different days of early prediction. In the future, we will extend this approach and develop a system for early prediction of major diseases to help better disease management for inpatients.
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Affiliation(s)
- Yi-Shian Chen
- Department of Computer Science, National Tsing Hua University, Hsinchu, Taiwan
| | - Che-Yi Chou
- Division of Nephrology, Asia University Hospital, Taichung, Taiwan
- Department of Post-baccalaureate Veterinary Medicine, Asia University, Taichung, Taiwan
- Kidney Institute and Division of Nephrology, China Medical University Hospital, Taichung, Taiwan
| | - Arbee L.P. Chen
- Department of Computer Science and Information Engineering, Asia University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
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Xu J, Yu J, Xu X, Shen B, Wang Y, Jiang W, Lv W, Fang Y, Luo Z, Wang C, Teng J, Ding X. Preoperative hidden renal dysfunction add an age dependent risk of progressive chronic kidney disease after cardiac surgery. J Cardiothorac Surg 2019; 14:151. [PMID: 31438993 PMCID: PMC6704689 DOI: 10.1186/s13019-019-0977-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 08/15/2019] [Indexed: 01/08/2023] Open
Abstract
Background To study different value of estimated glomerular filtration rate with normal serum creatinine whether is a risk factor for hidden renal function of cardiac surgery outcomes. Methods A total of 1744 cardiac surgery patients with serum creatinine ≤1.2 mg/dL (female)/1.5 mg/dL (male) were divided into 3 groups: estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 (no renal dysfunction, n = 829), 60 ≤ estimated glomerular filtration rate < 90 mL/min/1.73 m2 (hidden renal dysfunction, n = 857), estimated glomerular filtration rate < 60 mL/min/1.73 m2 (known renal dysfunction, n = 58) and followed up for 3 years. Multivariate regression analyses for risk factors of postoperative acute kidney injury. Results The proportion of preoperative hidden renal dysfunction was 67.1% among patients ≥ 65 years old and 44.1% among patients < 65 years old. Multivariate Cox regression analyses showed that for patients < 65 years, known renal dysfunction was a risk factor for postoperative acute kidney injury (P < 0.01) and progressive chronic kidney disease (P = 0.018), while hidden renal dysfunction was a risk factor for progressive chronic kidney disease (P = 0.024). For patients ≥ 65 years, only known renal dysfunction was a risk factors for 3-year mortality (P = 0.022) and progressive chronic kidney disease (P < 0.01). Conclusion Hidden renal dysfunction was common in patients with normal serum creatinine for cardiac surgery, with a prevalence of 49.1%. For patients < 65 years old, hidden renal dysfunction was an independent risk factor for progressive chronic kidney disease.
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Affiliation(s)
- Jiarui Xu
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Jiawei Yu
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Xialian Xu
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Bo Shen
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Yimei Wang
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Wuhua Jiang
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Wenlv Lv
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Yi Fang
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China.,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China.,Hemodialysis Quality of Control Center of Shanghai, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Zhe Luo
- Department of Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Chunsheng Wang
- Department of Cardiovascular Surgery, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China
| | - Jie Teng
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China. .,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China. .,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China. .,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China. .,Hemodialysis Quality of Control Center of Shanghai, No. 180 Fenglin Road, Shanghai, 200032, China. .,Department of Nephrology, Xiamen Branch, Zhongshan Hospital, Fudan University, No. 668 Jinhu Road, Xiamen, 361015, Fujian, China.
| | - Xiaoqiang Ding
- Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China. .,Shanghai Medical Center of Kidney, No. 180 Fenglin Road, Shanghai, 200032, China. .,Shanghai Institute for Kidney and Dialysis, No. 180 Fenglin Road, Shanghai, 200032, China. .,Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai, 200032, China. .,Hemodialysis Quality of Control Center of Shanghai, No. 180 Fenglin Road, Shanghai, 200032, China. .,Department of Nephrology, Xiamen Branch, Zhongshan Hospital, Fudan University, No. 668 Jinhu Road, Xiamen, 361015, Fujian, China.
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Neghab M, Mirzaei A, Jalilian H, Jahangiri M, Zahedi J, Yousefinejad S. Effects of Low-level Occupational Exposure to Ammonia on Hematological Parameters and Kidney Function. THE INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE 2019; 10:80-88. [PMID: 31041925 PMCID: PMC6524738 DOI: 10.15171/ijoem.2019.1527] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Accepted: 03/29/2019] [Indexed: 01/06/2023]
Abstract
Background: Many workers, particularly those working in manufacture of fertilizers, explosives, rubber, pesticides, textiles, and employees of petrochemical industries are exposed to ammonia in their workplaces. Toxic responses of hematopoietic system and kidney following occupational exposure to this chemical have not been thoroughly investigated. Objective: To determine the relationship between long-term occupational exposure to low levels of ammonia and hematological parameters and kidney function. Methods: In this cross-sectional study, 119 randomly selected, male petrochemical workers and 131 office employees (comparison group) were examined. Urine and blood samples were taken from all participants for urinalysis, complete blood count (CBC), serum calcium level, and blood urea nitrogen (BUN) and plasma creatinine. Personal, environmental, and peak ammonia exposure were also measured. Results: The median personal, environmental, and peak occupational exposure to ammonia were 0.23, 0.16, and 65.50 mg/m3, respectively, among the exposed group. No significant difference was observed between the exposed and unexposed participants in terms of hematological parameters and urinalysis. Conversely, calcium and BUN, while within the normal range, were significantly higher in the exposed than in the comparison group. Conclusion: Occupational exposure to low atmospheric concentrations of ammonia was associated with subtle, sub-clinical, pre-pathologic changes in kidney function. Possible longterm consequences and ramifications of these effects require further investigation.
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Affiliation(s)
- Masoud Neghab
- Department of Occupational Health Engineering, Research Center for Health Sciences, Institute of Health, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ahmad Mirzaei
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Hamed Jalilian
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Jahangiri
- Department of Occupational Health Engineering, Research Center for Health Sciences, Institute of Health, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jafar Zahedi
- Petrochemical Complex, South Pars District, Iran
| | - Saeed Yousefinejad
- Department of Occupational Health Engineering, Research Center for Health Sciences, Institute of Health, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran
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Sesan OO, Ojo AR, Samuel IO, Christian IE, Quadri AK. Proteinuria in relation to age-dependent changes in the plasma and urine concentrations of some electrolytes and hematological indices in Wistar rats. Vet Anim Sci 2019; 7:100048. [PMID: 32734070 PMCID: PMC7386671 DOI: 10.1016/j.vas.2019.100048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 01/19/2019] [Accepted: 01/22/2019] [Indexed: 01/13/2023] Open
Abstract
The study was carried out to determine the influence of proteinuria on plasma and urine concentrations of electrolytes and hematological indices in Wistar rats of different age groups. Eighty Wistar rats of both sexes were used for this study. Groups 1 and 2 each consisted of 8 one month old male and female rats; 3 and 4 had 8 three month old rats; 5 and 6 had 8 six month old rats; 7 and 8 had 8 nine month old rats; 9 and 10 had 8 twelve month old rats. The plasma sodium, potassium and calcium concentrations of 3 month old rats were significantly lower when compared with 1, 6, 9 and 12 months of age. Similarly, rats aged 3 months had significantly lower urine concentrations of sodium, potassium and calcium than rats of other age groups. A strong correlation was observed between the urine protein and urine sodium of the female rats at ages 3, 9 and 12 months but it was only significant at age 12 months (p = 0.105 and p = 0.021, respectively). Also, the female rats aged 3 and 12 months had a strong correlation between their urine protein and urine calcium (p = 0.002 and p = 0.131, respectively). The red blood cells, lymphocyte and monocyte counts of the rats increased gradually and peaked at age 9 months with a subsequent decline at 12 months of age. It was concluded that the influence of proteinuria on electrolytes was least observed in the rats aged 3 months, since they had reduced and consistent plasma and urine concentrations of electrolytes measured when compared with other age groups. This implies that long-term renal studies involving the use of rats must be carefully interpreted because of the changes in plasma and urine concentrations of electrolytes as the rats age.
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Affiliation(s)
- Olukiran Olaoluwa Sesan
- Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Akomolafe Rufus Ojo
- Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Ilesanmi Olutosin Samuel
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Imafidon Eseigbe Christian
- Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
- Department of Physiology, Faculty of Basic Medical and Health Sciences, Bowen University, Iwo, Osun State, Nigeria
| | - Alabi Kunle Quadri
- Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
- Department of Physiology, Faculty of Basic Medical Sciences, Adeleke University, Ede, Osun State, Nigeria
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Djukanović L, Ležaić V, Bukvić D, Mirković D, Marić I. Increased Glomerular Filtration Rate in Early Stage of Balkan Endemic Nephropathy. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:E155. [PMID: 31108979 PMCID: PMC6572402 DOI: 10.3390/medicina55050155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 03/01/2019] [Accepted: 05/15/2019] [Indexed: 12/21/2022]
Abstract
Background: A previous study indicated that Balkan endemic nephropathy (BEN) patients in the early stage of the disease had significantly higher creatinine clearance (Ccr) than healthy persons. The aim of the study was to assess whether tubular creatinine secretion affects Ccr in early stages of BEN and to check the applicability of serum creatinine-based glomerular filtration rate (GFR) equations in these patients. Methods: The study involved 21 BEN patients with estimated GFR (eGFR) above 60 mL/min/1.73 m2, excluding any conditions that could affect GFR or tubular creatinine secretion, and 15 healthy controls. In all participants Ccr with and without cimetidine and iohexol clearance (mGFR) were measured and eGFR calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease Study (MDRD) equations. Glomerular hyperfiltration cutoff (GFR-HF) was calculated. Results: There was no significant difference between the groups in Ccr before and after cimetidine or for eGFR, but mGFR was significantly higher in BEN patients than in controls (122.02 ± 28.03 mL/min/1.73 m2 vs. 101.15 ± 27.32 mL/min/1.73 m2; p = 0.032). Cimetidine administration reduced Ccr by 10% in both groups. The ratio of Ccr to mGFR was significantly above one in seven BEN patients and five controls and their mGFR values were similar. Seven other patients and eight controls had this ratio equal to one, while values below one were recorded for seven more patients and two controls. mGFR of all these 14 patients was significantly higher than that of healthy controls (129.88 ± 27.52 mL/min/1.73 m2 vs. 107.43 ± 19.51 mL/min/1.73 m2; p = 0.009). Mean GFR-HF was significantly higher than mGFR in controls, but these two values were similar in BEN patients. eGFR underestimated mGFR in both BEN patients and controls. Conclusion: The ratio of Ccr to mGFR and mGFR to GFR-HF indicated that elevated mGFR in early stages of BEN could be explained by increased glomerular filtration, but tubular creatinine secretion augmented Ccr in a smaller proportion of patients, who did not differ from healthy subjects.
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Affiliation(s)
| | - Višnja Ležaić
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Department of Nephrology, Clinical Centre of Serbia, 11000 Belgrade, Serbia.
| | - Danica Bukvić
- Special Hospital for Endemic Nephropathy, 11550 Lazarevac, Serbia.
| | - Dušan Mirković
- Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
- Centre for Medical Biochemistry, Clinical Centre of Serbia, 11000 Belgrade, Serbia.
| | - Ivko Marić
- Special Hospital for Endemic Nephropathy, 11550 Lazarevac, Serbia.
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Aucella F, Corsonello A, Leosco D, Brunori G, Gesualdo L, Antonelli-Incalzi R. Beyond chronic kidney disease: the diagnosis of Renal Disease in the Elderly as an unmet need. A position paper endorsed by Italian Society of Nephrology (SIN) and Italian Society of Geriatrics and Gerontology (SIGG). J Nephrol 2019; 32:165-176. [PMID: 30659521 PMCID: PMC6423311 DOI: 10.1007/s40620-019-00584-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 12/27/2018] [Indexed: 12/21/2022]
Abstract
The dramatic increase in prevalence of chronic kidney disease (CKD) with ageing makes the recognition and correct referral of these patients of paramount relevance in order to implement interventions preventing or delaying the development of CKD complications and end-stage renal disease. Nevertheless, several issues make the diagnosis of CKD in the elderly cumbersome. Among these are age related changes in structures and functions of the kidney, which may be difficult to distinguish from CKD, and multimorbidity. Thus, symptoms, clinical findings and laboratory abnormalities should be considered as potential clues to suspect CKD and to suggest screening. Comprehensive geriatric assessment is essential to define the clinical impact of CKD on functional status and to plan treatment. Correct patient referral is very important: patients with stage 4-5 CKD, as well as those with worsening proteinuria or progressive nephropathy (i.e. eGFR reduction > 5 ml/year) should be referred to nephrologist. Renal biopsy not unfrequently may be the key diagnostic exam and should not be denied simply on the basis of age. Indeed, identifying the cause(s) of CKD is highly desirable to perform a targeted therapy against the pathogenetic mechanisms of CKD, which complement and may outperform in efficacy the general measures for CKD.
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Affiliation(s)
- Filippo Aucella
- Department of Nephrology and Dialysis, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013, San Giovanni Rotondo, FG, Italy.
| | | | - Dario Leosco
- Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy
| | - Giuliano Brunori
- Department of Nephrology and Dialysis, Santa Chiara Hospital, Azienda Provinciale Servizi Sanitari, Trento, Italy
| | - Loreto Gesualdo
- Division of Nephrology, University "Aldo Moro", Piazza G. Cesare n. 11, 70124, Bari, Italy
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Li H, Cao W, Zhang X, Sun B, Jiang S, Li J, Liu C, Yin W, Wu Y, Liu T, Yao D, Luo C. BOLD-fMRI reveals the association between renal oxygenation and functional connectivity in the aging brain. Neuroimage 2019; 186:510-517. [DOI: 10.1016/j.neuroimage.2018.11.030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 11/19/2018] [Accepted: 11/20/2018] [Indexed: 01/23/2023] Open
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Abstract
We begin this chapter by describing normal characteristics of several pertinent connective tissue components, and some of the basic changes they undergo with ageing. These alterations are not necessarily tied to any specific disease or disorders, but rather an essential part of the normal ageing process. The general features of age-induced changes, such as skin wrinkles, in selected organs with high content of connective or soft tissues are discussed in the next part of the chapter. This is followed by a section dealing with age-related changes in specific diseases that fall into at least two categories. The first category encompasses common diseases with high prevalence among mostly ageing populations where both genetic and environmental factors play roles. They include but may not be limited to atherosclerosis and coronary heart disease, type II diabetes, osteopenia and osteoporosis, osteoarthritis, tendon dysfunction and injury, age-related disorders of spine and joints. Disorders where genetics plays the primary role in pathogenesis and progression include certain types of progeria, such as Werner syndrome and Hutchinson-Gilford progeria belong to the second category discussed in this chapter. These disorders are characterized by accelerated signs and symptoms of ageing. Other hereditary diseases or syndromes that arise from mutations of genes encoding for components of connective tissue and are less common than diseases included in the first group will be discussed briefly as well, though they may not be directly associated with ageing, but their connective tissue undergoes some changes compatible with ageing. Marfan and Ehlers-Danlos syndromes are primary examples of such disorders. We will probe the role of specific components of connective tissue and extracellular matrix if not in each of the diseases, then at least in the main representatives of these disorders.
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Affiliation(s)
- Carolyn Ann Sarbacher
- Department of Pathology, College of Veterinary Medicine, The University of Georgia and AU/UGA Medical Partnership, Athens, GA, USA
| | - Jaroslava T Halper
- Department of Pathology, College of Veterinary Medicine, The University of Georgia and AU/UGA Medical Partnership, Athens, GA, USA.
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Alshelleh SA, Oweis AO, Alzoubi KH. Acute kidney injury among nonagenarians in Jordan: a retrospective case-control study. Int J Nephrol Renovasc Dis 2018; 11:337-342. [PMID: 30555251 PMCID: PMC6280911 DOI: 10.2147/ijnrd.s186121] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Improvements in health care systems worldwide have had notable effects on the life expectancy of older individuals. As a result, nonagenarians are emerging as a separate age group with distinct health care needs. The aim of this study was to evaluate the incidence of acute kidney injury (AKI), the mortality rates, and length of in-hospital stay among nonagenarians. Methods This is a retrospective case–control chart review of patients of age 90 years and above who were admitted to hospital. Patients with Stage I, II, or III chronic kidney disease were included in the analysis. The incidence of AKI was determined using data from the Acute Kidney Injury Network (AKIN) classification. Primary outcome variables included length of in-hospital stay and mortality rates. Results Of the 253 patients who were included in the study, the mean age was 91.5 years, 61 of the patients (25.9%) developed AKI, and 41 patients (66.1%) were in Stage I AKI according to AKIN criteria. Fifty-seven patients died during the study period; 57.9% of those patients had AKI. Hospital stay was longer in patients with AKI with a mean length of stay of 8.1 days. Congestive heart failure, cancer, and use of non-steroidal anti-inflammatory drugs were the main risk factors for AKI among those patients. Conclusion AKI is common in nonagenarians. It was associated with increased length of hospital stays and increased risk for mortality.
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Affiliation(s)
- Sameeha A Alshelleh
- Division of Nephrology, Department of Medicine, The University of Jordan, Amman, Jordan,
| | - Ashraf O Oweis
- Division of Nephrology, Department of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Karem H Alzoubi
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
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Jang IA, Kim EN, Lim JH, Kim MY, Ban TH, Yoon HE, Park CW, Chang YS, Choi BS. Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney. Nutrients 2018; 10:E1741. [PMID: 30424556 PMCID: PMC6267480 DOI: 10.3390/nu10111741] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 11/02/2018] [Accepted: 11/09/2018] [Indexed: 02/07/2023] Open
Abstract
The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2'-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation.
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Affiliation(s)
- In-Ae Jang
- Department of Internal medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
| | - Eun Nim Kim
- Division of Medical Cell Biology, Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
| | - Ji Hee Lim
- Division of Medical Cell Biology, Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
| | - Min Young Kim
- Division of Medical Cell Biology, Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
| | - Tae Hyun Ban
- Department of Internal medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul 06591, Korea.
| | - Hye Eun Yoon
- Department of Internal medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
- Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon 21431, Korea.
| | - Cheol Whee Park
- Department of Internal medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul 06591, Korea.
| | - Yoon Sik Chang
- Department of Internal medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
- Division of Nephrology, Department of Internal Medicine, Yeouido St. Mary's Hospital, Seoul 07345, Korea.
| | - Bum Soon Choi
- Department of Internal medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
- Division of Nephrology, Department of Internal Medicine, St. Paul's Hospital, Seoul 02559, Korea.
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Ratelle M, Li X, Laird BD. Cadmium exposure in First Nations communities of the Northwest Territories, Canada: smoking is a greater contributor than consumption of cadmium-accumulating organ meats. ENVIRONMENTAL SCIENCE. PROCESSES & IMPACTS 2018; 20:1441-1453. [PMID: 30221302 DOI: 10.1039/c8em00232k] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Traditional food consumption among northern populations is associated with improved nutrition but occasionally can also increase contaminant exposure. High levels of cadmium in the organs of moose from certain regions of the Northwest Territories, Canada, led to the release of consumption notices. These notices recommended that individuals limit their consumption of kidney and liver from moose harvested from the Southern Mackenzie Mountain. A human biomonitoring project was designed to better characterize exposure and risks from contaminants, including cadmium, among Dene/Métis communities of the Northwest Territories Mackenzie Valley, Canada. The project included a dietary assessment (food frequency questionnaire) to estimate moose and caribou organ (kidney and liver) consumption, as well as urine and blood sampling for the measurement of cadmium concentration using mass spectrometry. For a subset of the samples, urine cotinine was also quantified. The results from this biomonitoring research show that cadmium levels in urine (GM = 0.32 μg L-1) and blood (GM = 0.58 μg L-1) are similar to those observed in other populations in Canada. For the 38% of participants reporting eating game organs, current traditional food consumption patterns were not associated with cadmium biomarker levels. Instead, smoking appeared to be the main determinant of cadmium exposure. These results are supporting ongoing efforts at the community and territorial level to identify health priorities and design follow up plans in response to environmental monitoring data.
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Affiliation(s)
- Mylene Ratelle
- School of Public Health and Health Systems, Faculty of Applied Health Sciences, University of Waterloo. 200 University Avenue West, Lyle Hallman North, Room LHN-1727, Waterloo, Ontario, CanadaN2L 3G1.
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Talenfeld AD, Gennarelli RL, Elkin EB, Atoria CL, Durack JC, Huang WC, Kwan SW. Percutaneous Ablation Versus Partial and Radical Nephrectomy for T1a Renal Cancer: A Population-Based Analysis. Ann Intern Med 2018; 169:69-77. [PMID: 29946703 PMCID: PMC8243237 DOI: 10.7326/m17-0585] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Background Stage T1a renal cell carcinoma (RCC) (tumors <4 cm) is usually curable. Nephron-sparing partial nephrectomy (PN) has replaced radical nephrectomy (RN) as the standard of care for these tumors. Radical nephrectomy remains the first alternative treatment option, whereas percutaneous ablation (PA), a newer, nonsurgical treatment, is recommended less strongly because of the relative paucity of comparative PA data. Objective To compare PA, PN, and RN outcomes. Design Observational cohort analysis using inverse probability of treatment-weighted propensity scores. Setting Population-based SEER (Surveillance, Epidemiology, and End Results) cancer registry data linked to Medicare claims. Patients Persons aged 66 years or older who received treatment for T1a RCC between 2006 and 2011. Interventions PA versus PN and RN. Measurements RCC-specific and overall survival, 30- and 365-day postintervention complications. Results 4310 patients were followed for a median of 52 months for overall survival and 42 months for RCC-specific survival. After PA versus PN, the 5-year RCC-specific survival rate was 95% (95% CI, 93% to 98%) versus 98% (CI, 96% to 99%); after PA versus RN, 96% (CI, 94% to 98%) versus 95% (CI, 93% to 96%). After PA versus PN, the 5-year overall survival rate was 77% (CI, 74% to 81%) versus 86% (CI, 84% to 88%); after PA versus RN, 74% (CI, 71% to 78%) versus 75% (CI, 73% to 77%). Cumulative rates of renal insufficiency 31 to 365 days after PA, PN, and RN were 11% (CI, 8% to 14%), 9% (CI, 8% to 10%), and 18% (CI, 17% to 20%), respectively. Rates of nonurologic complications within 30 days after PA, PN, and RN were 6% (CI, 4% to 9%), 29% (CI, 27% to 30%), and 30% (CI, 28% to 32%), respectively. Ten percent of patients in the PN group had intraoperative conversion to RN. Seven percent of patients in the PA group received additional PA within 1 year of treatment. Limitations Analysis of observational data may have been affected by residual confounding by provider or from selection bias toward younger, healthier patients in the PN group. Findings from this older study population are probably less applicable to younger patients. Use of SEER-Medicare linked files prevented analysis of patients who received treatment after 2011, possibly reducing generalizability to the newest PA, PN, and RN techniques. Conclusion For well-selected older adults with T1a RCC, PA may result in oncologic outcomes similar to those of RN, but with less long-term renal insufficiency and markedly fewer periprocedural complications. Compared with PN, PA may be associated with slightly shorter RCC-specific survival but fewer periprocedural complications. Primary Funding Source Association of University Radiologists GE Radiology Research Academic Fellowship and Society of Interventional Radiology Foundation.
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Affiliation(s)
| | - Renee L Gennarelli
- Memorial Sloan Kettering Cancer Center, New York, New York (R.L.G., E.B.E., C.L.A., J.C.D.)
| | - Elena B Elkin
- Memorial Sloan Kettering Cancer Center, New York, New York (R.L.G., E.B.E., C.L.A., J.C.D.)
| | - Coral L Atoria
- Memorial Sloan Kettering Cancer Center, New York, New York (R.L.G., E.B.E., C.L.A., J.C.D.)
| | - Jeremy C Durack
- Memorial Sloan Kettering Cancer Center, New York, New York (R.L.G., E.B.E., C.L.A., J.C.D.)
| | - William C Huang
- New York University Langone Medical Center, New York, New York (W.C.H.)
| | - Sharon W Kwan
- University of Washington, Seattle, Washington (S.W.K.)
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