Seasonal Changes in Kidney Function in CKD of Uncertain Etiology.
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ABSTRACT:
SUBMITTER: Arora S
PROVIDER: S-EPMC8589687 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Epidemics of CKD of uncertain etiology (CKDu) are emerging around the world. Highlighting common risk factors for CKD of uncertain etiology across various regions and populations may be important for health policy and public health responses.We searched PubMed, Embase, Scopus and Web of Science databases to identify published studies on CKDu. The search was generated in January of 2015; no language or date limits were used. We used a vote-counting method to evaluate exposures across all studies.We identified 1607 articles, of which 26 met inclusion criteria. Eighteen (69%) were conducted in known CKDu-endemic countries: Sri Lanka (38%), Nicaragua (19%), and El Salvador (12%). The other studies were from India, Japan, Australia, Mexico, Sweden, Tunisia, Tanzania, and the United States. Heavy metals, heat stress, and dietary exposures were reported across all geographic regions. In south Asia, family history, agrochemical use, and heavy metal exposures were reported most frequently, whereas altitude and temperature were reported only in studies from Central America. Across all regions, CKDu was most frequently associated with a family history of CKDu, agricultural occupation, men, middle age, snake bite, and heavy metal exposure.Studies examining etiologies of CKDu have reported many exposures that are heterogeneous and vary by region. To identify etiologies of CKDu, designing consistent and comparative multisite studies across high-risk populations may help elucidate the importance of region-specific versus global risk factors.
| S-EPMC4791820 | biostudies-other
Project description:IntroductionAlthough the investigation of chronic kidney disease of uncertain etiology (CKDu) has identified many possible influencing factors in recent years, the exact pathomechanism of this disease remains unclear.MethodsIn this study, we collected 13 renal biopsies from patients with symptomatic CKDu (Sym-CKDu) from Sri Lanka with well-documented clinical and socioeconomic factors. We performed light microscopy and electron microscopic evaluation for ultrastructural analysis, which was compared with 100 biopsies from German patients with 20 different kidney diseases.ResultsOf the 13 Sri Lankan patients, 12 were men (92.3%), frequently employed in agriculture (50%), and experienced symptoms such as feeling feverish (83.3%), dysuria (83.3%), and arthralgia (66.6%). Light microscopic evaluation using activity and chronicity score revealed that cases represented early stages of CKDu except for 2 biopsies, which showed additional signs of diabetes. Most glomeruli showed only mild changes, such as podocyte foot process effacement on electron microscopy. We found a spectrum of early tubulointerstitial changes including partial loss of brush border in proximal tubules, detachment of tubular cells, enlarged vacuoles, and mitochondrial swelling associated with loss of cristae and dysmorphic lysosomes with electron-dense aggregates. None of these changes occurred exclusively in Sym-CKDu; however, they were significantly more frequent in these cases than in the control cohort.ConclusionIn conclusion, our findings confirm the predominant and early alterations of tubular structure in CKDu that can occur without significant glomerular changes. The ultrastructural changes do not provide concrete evidence of the cause of CKDu but were significantly more frequent in Sym-CKDu than in the controls.
| S-EPMC10014386 | biostudies-literature
Project description:Introduction:Chronic kidney disease of uncertain etiology (CKDu), an emerging chronic kidney disease (CKD) subtype, contributes to significant morbidity and mortality in certain tropical countries. Although several indicators of CKDu have been previously suggested, sensitive and specific tests to detect early disease or predict disease progression are currently unavailable. This study focused on evaluating 8 renal urinary markers, namely neutrophil gelatinase-associated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM1), cystatin C (CST3), beta 2 microglobulin (B2M), osteopontin (OPN), alpha 1 microglobulin (A1M), tissue inhibitor of metalloproteinase 1 (TIMP1), and retinol binding protein 4 (RBP4), with the hypothesis that these have distinct expression patterns in patients with CKDu. Methods:A cross-sectional study was conducted with 5 study groups comprising subjects from CKDu, endemic CKD, nonendemic CKD, and endemic healthy and nonendemic healthy controls. The urinary levels of the 8 selected renal biomarkers were quantified using multiplex biomarker assay, and the data were subjected to systematic analysis using logistic regression algorithm aiming to extract the best marker combination that could distinctly identify the disease groups noninvasively from the healthy controls. Results:A 3-marker signature panel comprising A1M, KIM1, and RBP4 was identified to represent the best minimum marker combination for differentiating all CKD categories, including CKDu, from healthy controls with an overall sensitivity of ?0.867 and specificity ?0.765. The marker combination comprising OPN, KIM1, and RBP4 showed high predictive performance for distinguishing patients with CKDu from patients with CKD with both sensitivity and specificity ?0.93, which was superior to any existing noninvasive indicator. Conclusion:In all, our systematic evaluation of urinary markers previously linked to CKD, in general, allowed identification of exclusive marker panel combination for early diagnosis and confirmation of CKDu.
| S-EPMC6829189 | biostudies-literature
Project description:BackgroundThe Kidney Disease: Improving Global Outcomes guidelines advocate the cause-glomerular filtration rate (GFR)-albuminuria (CGA) classification for predicting outcomes. However, there is a dearth of data supporting the use of the cause of chronic kidney disease. This study aimed to address how to incorporate a prior biopsy-proven diagnosis in outcome prediction.MethodsWe examined the association of biopsy-proven kidney disease diagnoses with kidney failure with replacement therapy (KFRT) and all-cause death before KFRT in patients with various biopsy-proven diagnoses (n = 778, analysis A) and patients with diabetes mellitus labeled with biopsy-proven diabetic nephropathy (DN), other biopsy-proven diseases and no biopsy (n = 1117, analysis B).ResultsIn analysis A, adding biopsy-proven diagnoses to the GFR-albuminuria (GA) classification improved the prediction of 8-year incidence of KFRT and all-cause death significantly regarding integrated discrimination improvement and net reclassification index. Fine-Gray (FG) models with KFRT as a competing event showed significantly higher subdistribution hazard ratios (SHRs) for all-cause death in nephrosclerosis {4.12 [95% confidence interval (CI) 1.11-15.2)], focal segmental glomerulosclerosis [3.77 (95% CI 1.09-13.1)]} and membranous nephropathy (MN) [2.91 (95% CI 1.02-8.30)] than in immunoglobulin A nephropathy (IgAN), while the Cox model failed to show significant associations. Crescentic glomerulonephritis had the highest risk of all-cause death [SHR 5.90 (95% CI 2.05-17.0)]. MN had a significantly lower risk of KFRT than IgAN [SHR 0.45 (95% CI 0.24-0.84)]. In analysis B, other biopsy-proven diseases had a lower risk of KFRT than biopsy-proven DN in the FG model, with death as a competing event [SHR 0.62 (95% CI 0.39-0.97)].ConclusionsThe CGA classification is of greater value in predicting outcomes than the GA classification.
| S-EPMC9923708 | biostudies-literature
Project description:IntroductionDespite much research on chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka and the Mesoamerican nephropathy, the etiology and pathogenesis of this disease remains elusive. The pathology has broadly been described as chronic tubulointerstitial nephritis and no specific signature lesions have been identified.MethodsA scoping review was conducted through MEDLINE and Google Scholar databases for peer-reviewed publications on biopsy studies related to CKDu - Sri Lanka and Mesoamerican nephropathy to develop a comparative and critical analysis of the renal pathology found in these patients.ResultsThirteen studies met the selection criteria. Interstitial fibrosis was the predominant lesion in all the studies. Tubulointerstitial and glomerular abnormalities showed a more variable distribution. No characteristic histopathological feature was reported other than a proximal tubular lysosomal inclusion body which was claimed to indicate a toxic etiology. Three main pathogenetic mechanisms were postulated: repeated acute insults leading to scarring, low-grade chronic insults leading to non-inflammatory fibrosis, and tubulointerstitial damage in combination with glomerular injury. The main limitations in the interpretation and comparative analysis of these studies were the heterogeneity in case selection and biopsy reporting.ConclusionsAlthough no characteristic histopathological feature could be found in CKDu-Sri Lanka or Mesoamerican nephropathy, there are noticeable differences between these two groups in the frequency and severity of the glomerular and tubulointerstitial changes which warrant more explorative studies preferably on kidneys in early stages of the disease. Future strategies should ensure that more uniform selection criteria and reporting methods are used.
| S-EPMC8207327 | biostudies-literature
Project description:Chronic Kidney Disease of uncertain etiology (CKDu) is an endemic, disease that mostly affects young agricultural workers in the rural dry zone of Sri Lanka. This study was designed to identify specific biochemical manifestations of CKDu cases. All (119) non-dialysis definite CKDu patients in Girandurukotte and Wilgamuwa were selected. Blood and urine samples were collected and measured biochemical parameters. All analyses were performed in IBM SPSS statistics version 23 (IBM Corp, USA). The median blood pressure was normal though nearly half of the patients (45.4%) who were in the advanced stages (Stage 3b, 4 and 5) of CKDu. Patients without a history of hypertension before the diagnosis of CKDu (100%) and minimal proteinuria (26%) are similar to the previous findings. Patients without a history of diabetes before the CKDu diagnosis had high percentages of diabetes (15.7%) and pre-diabetes (59.8%) and hence indicated the possibility of uremia induced impaired glucose intolerance in the rural areas of the country. There were 62.2% patients who had low vitamin D and only a minority had evidence of bone mineral diseases. Out of liver disease markers serum glutamic pyruvic transaminases (SGPT), serum glutamic oxaloacetic transaminases (SGOT), gamma-glutamyl transferase (GGT), and Lactic acid degydrogenase (LDH) had an inverse correlation with the advancement of the disease indicating subclinical liver disease. Osmolality in serum and urine showed a discrepancy despite > 50% of CKDu patients had increased their serum osmolality. The current study supports most of the previously described manifestations of CKDu. Moreover, some specific patterns have been identified which need to be validated in a larger group.
| S-EPMC7197770 | biostudies-literature
Project description:Background and objectivesThe kidney failure risk equation is a clinical tool commonly used for prediction of progression from CKD to kidney failure. The kidney failure risk equation's accuracy in advanced CKD and whether this varies by CKD etiology remains unknown. This study examined the kidney failure risk equation's discrimination and calibration at 2 and 5 years among a large tertiary care population with advanced CKD from heterogeneous etiologies.Design, setting, participants, & measurementsThis retrospective cohort study included 1293 patients with advanced CKD (median eGFR 15 ml/min per 1.73 m2) referred to the Ottawa Hospital Multi-Care Kidney Clinic between 2010 and 2016, with follow-up clinical data available through 2018. Four-variable kidney failure risk equation scores for 2- and 5-year risks of progression to kidney failure (defined as dialysis or kidney transplantation) were calculated upon initial referral and correlated with the subsequent observed kidney failure incidence within these time frames. Receiver operating characteristic curves and calibration plots were used to measure the discrimination and calibration of the kidney failure risk equation both in the overall advanced CKD population and by CKD etiology: diabetic kidney disease, hypertensive nephrosclerosis, GN, polycystic kidney disease, and other. Pairwise comparisons of the receiver operating characteristic curves by CKD etiology were performed to compare kidney failure risk equation discrimination.ResultsThe kidney failure risk equation provided adequate to excellent discrimination in identifying patients with CKD likely to progress to kidney failure at the 2- and 5-year time points both overall (2-year area under the curve, 0.83; 95% confidence interval, 0.81 to 0.85; 5-year area under the curve, 0.81; 95% confidence interval, 0.77 to 0.84) and across CKD etiologies. The kidney failure risk equation displayed adequate calibration at the 2- and 5-year time points both overall and across CKD etiologies (Hosmer-Lemeshow P≥0.05); however, the predicted risks of kidney failure were higher than the observed risks across CKD etiologies with the exception of polycystic kidney disease.ConclusionsThe kidney failure risk equation provides adequate discrimination and calibration in advanced CKD and across CKD etiologies.
| S-EPMC7536763 | biostudies-literature
Project description:Background and objectivesThe association between plant-based diets, incident CKD, and kidney function decline has not been examined in the general population. We prospectively investigated this relationship in a population-based study, and evaluated if risk varied by different types of plant-based diets.Design, setting, participants, & measurementsAnalyses were conducted in a sample of 14,686 middle-aged adults enrolled in the Atherosclerosis Risk in Communities study. Diets were characterized using four plant-based diet indices. In the overall plant-based diet index, all plant foods were positively scored; in the healthy plant-based diet index, only healthful plant foods were positively scored; in the provegetarian diet, selected plant foods were positively scored. In the less healthy plant-based diet index, only less healthful plant foods were positively scored. All indices negatively scored animal foods. We used Cox proportional hazards models to study the association with incident CKD and linear mixed models to examine decline in eGFR, adjusting for confounders.ResultsDuring a median follow-up of 24 years, 4343 incident CKD cases occurred. Higher adherence to a healthy plant-based diet (HR comparing quintile 5 versus quintile 1 [HRQ5 versus Q1], 0.86; 95% confidence interval [95% CI], 0.78 to 0.96; P for trend =0.001) and a provegetarian diet (HRQ5 versus Q1, 0.90; 95% CI, 0.82 to 0.99; P for trend =0.03) were associated with a lower risk of CKD, whereas higher adherence to a less healthy plant-based diet (HRQ5 versus Q1, 1.11; 95% CI, 1.01 to 1.21; P for trend =0.04) was associated with an elevated risk. Higher adherence to an overall plant-based diet and a healthy plant-based diet was associated with slower eGFR decline. The proportion of CKD attributable to lower adherence to healthy plant-based diets was 4.1% (95% CI, 0.6% to 8.3%).ConclusionsHigher adherence to healthy plant-based diets and a vegetarian diet was associated with favorable kidney disease outcomes.
| S-EPMC6500948 | biostudies-literature
Project description:Heart failure is a common consequence of CKD, and it portends high risk for mortality. However, among patients without known heart failure, the associations of different stages of estimated GFR (eGFR) with changes in cardiac structure and function are not well described. Here, we performed a cross-sectional analysis to study these associations among 3487 participants of the Chronic Renal Insufficiency Cohort Study. We estimated GFR using cystatin C. The prevalence of left ventricular hypertrophy (LVH) assessed by echocardiography was 32%, 48%, 57%, and 75% for eGFR categories ?60, 45-59, 30-44, and <30 ml/min per 1.73 m(2), respectively. In fully adjusted multivariable analyses, subjects with eGFR levels of <30 ml/min per 1.73 m(2) had twofold higher odds of LVH (OR=2.20, 95% CI=1.40-3.40; P<0.001) relative to subjects with eGFR?60 ml/min per 1.73 m(2). This reduction in kidney function also significantly associated with abnormal LV geometry but not diastolic or systolic dysfunction. An eGFR of 30-44 ml/min per 1.73 m(2) also significantly associated with LVH and abnormal LV geometry compared with eGFR?60 ml/min per 1.73 m(2). In summary, in this large CKD cohort, reduced kidney function associated with abnormal cardiac structure. We did not detect significant associations between kidney function and systolic or diastolic function after adjusting for potential confounding variables.
| S-EPMC3458463 | biostudies-other
Project description:Chronic kidney disease of uncertain etiology (CKDu) is an increasing problem in Sri Lanka especially among the farming community. The etiologies although uncertain, have been associated with occupational and environmental factors. The expression pattern of genes in blood of these CKDu patients in an endemic region of Sri Lanka was analyzed compared to healthy individuals from a non-endemic region to see any expression changes that could be associated to environmental factors. Pattern of expression changes could lead to either strengthen or weaken current hypotheses for the causes.
2018-12-30 | GSE62792 | GEO