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Identification of young adults at risk of an accelerated loss of kidney function in an area affected by Mesoamerican nephropathy.

ABSTRACT: BACKGROUND:After two-years of follow-up of 263 apparently healthy 18- to 30-year-old men in communities affected by Mesoamerican nephropathy (MeN), we identified three distinct case groups: a subgroup with (i) established renal dysfunction (case-group 1); individuals with (ii) a rapid decline in kidney function (case-group 2); and individuals with (iii) stable kidney function (non-cases). This paper investigates whether local tests are potentially useful for the timely identification of these case groups. METHODS:Creatinine levels were measured in local laboratories every six months for two years. Aliquots were sent to a centralized laboratory for measurements of cystatin C and creatinine levels. We investigated agreement between the locally and centrally measured creatinine-based Chronic Kidney disease Epidemiology Collaboration (CKD-EPI) equation for estimating the Glomerular Filtration Rate (eGFR). A logistic regression analysis was used to assess predictive factors for case groups 1 and 2 compared to non-cases. Predictive variables were locally measured eGFR, and urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels. The discrimination performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS:Considerable variation in local eGFR measurements was observed. The prediction model for case-group 1 included baseline kidney function and with or without uNGAL (AUC?=?0.98, 95% confidence interval (CI), 0.91-1.00). The prediction model for case-group 2 also required eGFRScr at six and twelve months after baseline, with or without uNGAL levels (AUC?=?0.88; 95% CI 0.80-0.99). CONCLUSIONS:Established renal dysfunction was detected at a single time point using local measurements and uNGAL. For the detection of a rapid decline in kidney function over time, at least 2 more measurements at six and twelve months are needed.

SUBMITTER: Gonzalez-Quiroz M

PROVIDER: S-EPMC6335797 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Identification of young adults at risk of an accelerated loss of kidney function in an area affected by Mesoamerican nephropathy.

Gonzalez-Quiroz Marvin M Smpokou Evangelia-Theano ET Pearce Neil N Caplin Ben B Nitsch Dorothea D

BMC nephrology 20190116 1

<h4>Background</h4>After two-years of follow-up of 263 apparently healthy 18- to 30-year-old men in communities affected by Mesoamerican nephropathy (MeN), we identified three distinct case groups: a subgroup with (i) established renal dysfunction (case-group 1); individuals with (ii) a rapid decline in kidney function (case-group 2); and individuals with (iii) stable kidney function (non-cases). This paper investigates whether local tests are potentially useful for the timely identification of ...[more]

PMID: 30651081

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Project description:BackgroundIdentifying potentially modifiable risk factors is critically important for reducing the burden of chronic kidney disease. We sought to examine the association of body mass index (BMI) with kidney function decline in a cohort of young adults with preserved glomerular filtration at baseline.Study designLongitudinal cohort.Setting & participants2,839 black and white young adults with cystatin C-based estimated glomerular filtration rate (eGFRcys)>90mL/min/1.73m(2) taking part in the year-10 examination (in 1995-1996) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study.PredictorBMI, categorized as 18.5-24.9 (reference), 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2).OutcomesTrajectory of kidney function decline, rapid decline (>3% per year), and incident eGFRcys <60mL/min/1.73m(2) over 10 years of follow-up.MeasurementsGFRcys estimated from the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation for calibrated cystatin C at CARDIA years 10, 15, and 20.ResultsAt year 10, participants had a mean age of 35.1 years, median eGFRcys of 114mL/min/1.73m(2), and 24.5% had BMI≥30.0kg/m(2). After age 30 years, average eGFRcys was progressively lower with each increment in BMI after adjustment for baseline age, race, sex, hyperlipidemia, smoking status, and physical activity. Higher BMI category was associated with successively higher odds of rapid decline (for 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2), adjusted ORs were 1.50 [95% CI, 1.21-1.87], 2.01 [95% CI, 1.57-2.87], and 2.57 [95% CI, 1.67-3.94], respectively). 18 participants (0.6%) had incident eGFRcys<60mL/min/1.73m(2). In unadjusted analysis, higher BMI category was associated with incident eGFRcys<60mL/min/1.73m(2) (for 25.0-29.9, 30.0-39.9, and ≥40.0kg/m(2), ORs were 5.17 [95% CI, 1.10-25.38], 7.44 [95% CI, 1.54-35.95], and 5.55 [95% CI, 0.50-61.81], respectively); adjusted associations were no longer significant.LimitationsInability to describe kidney function before differences by BMI category were already evident. Absence of data for measured GFR or GFR estimated from serum creatinine level.ConclusionsHigher BMI categories are associated with greater declines in kidney function in a cohort of young adults with preserved GFR at baseline. Clinicians should vigilantly monitor overweight and obese patients for evidence of early kidney function decline.

Project description:Rationale & objectivePrevious studies have suggested that microRNA-21 (miR-21) plays an important role in kidney fibrosis. We examined the relationship between intrarenal miR-21 level and rate of kidney function loss in immunoglobulin A nephropathy (IgAN).Study designProspective cohort study.Setting & participants40 patients with IgAN and 10 with hypertensive nephrosclerosis as controls.PredictorsmiR-21 levels in kidney biopsy specimen and urinary sediment, quantified as ratio to the housekeeping gene.OutcomesKidney event-free survival and rate of kidney function decline.Analytic approachTime-to-event and correlation analysis.ResultsThe IgAN group had significantly higher intrarenal miR-21 expression compared with the hypertensive nephrosclerosis group (1.71 [IQR, 0.99-2.77] vs 0.31 [IQR, 0.25-1.32]; P < 0.0001), but urinary miR-21 levels were similar. Intrarenal miR-21 expression had significant but modest correlation with severity of glomerulosclerosis (r = 0.293; P = 0.05) and tubulointerstitial fibrosis (r = 0.341; P = 0.03). Patients with high intrarenal miR-21 expression had significantly higher risk for developing kidney end points compared with those with low expression (log-rank test, P = 0.017). Univariate Cox analysis showed that intrarenal miR-21 expression significantly predicted the development of kidney end points (unadjusted HR, 1.586; 95% CI, 1.179-2.134; P = 0.002). However, the result was just short of statistical significance after adjusting for the severity of histologic damage (P = 0.06). There was also a significant correlation between intrarenal miR-21 expression and the slope of kidney function decline by univariate analysis (r = -0.399; P = 0.02).LimitationsSmall sample size; uncertain cellular origin of miR-21.ConclusionsWe found that intrarenal miR-21 expression is increased in patients with IgAN, modestly correlated with the severity of histologic damage, and predictive of subsequent kidney function loss.

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Dataset Information

Identification of young adults at risk of an accelerated loss of kidney function in an area affected by Mesoamerican nephropathy.

Publications

Identification of young adults at risk of an accelerated loss of kidney function in an area affected by Mesoamerican nephropathy.

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