Dataset Information

Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease.

ABSTRACT: Sickle cell disease (SCD) nephropathy and lower estimated glomerular filtration rate (eGFR) are risk factors for early mortality. Furthermore, rate of eGFR decline predicts progression to end-stage renal disease in many clinical settings. However, factors predicting renal function decline in SCD are poorly documented. Using clinical, laboratory, genetic, and metabolomic data, we evaluated predictors of renal function decline in a longitudinal cohort of 288 adults (mean age 33.0 years). In 193 subjects with 5-year follow-up data, mean rate of eGFR decline was 2.35?mL/min/1.73?m2 /year, nearly twice that of African American adults overall. Hyperfiltration was prevalent at baseline (61.1%), and 36.8% of subjects experienced rapid eGFR decline (?3 mL/min/1.73?m2 /year). Severe Hb genotype; proteinuria; higher platelet and reticulocyte counts, and systolic BP; and lower Hb level and BMI were associated with rapid decline. A risk scoring system was created using these 7 variables and was highly predictive of rapid eGFR decline, with odds of rapid decline increasing 1.635-fold for every point increment (P < 0.0001). Rapid eGFR decline was also associated with higher organ system severity score and peak creatinine. Additionally, two metabolites (asymmetric dimethylarginine and quinolinic acid) were associated with rapid decline. Further investigation into longitudinal SCD nephropathy (SCDN) trajectory, early markers of SCDN, and tools for risk stratification should inform interventional studies targeted to slowing GFR decline and improving SCD outcomes.

SUBMITTER: Xu JZ

PROVIDER: S-EPMC6397774 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease.

Xu Julia Z JZ Garrett Melanie E ME Soldano Karen L KL Chen Sean T ST Clish Clary B CB Ashley-Koch Allison E AE Telen Marilyn J MJ

American journal of hematology 20180927 12

Sickle cell disease (SCD) nephropathy and lower estimated glomerular filtration rate (eGFR) are risk factors for early mortality. Furthermore, rate of eGFR decline predicts progression to end-stage renal disease in many clinical settings. However, factors predicting renal function decline in SCD are poorly documented. Using clinical, laboratory, genetic, and metabolomic data, we evaluated predictors of renal function decline in a longitudinal cohort of 288 adults (mean age 33.0 years). In 193 su ...[more]

PMID: 30144150

Similar Datasets

Project description:♦ BACKGROUND: The aim of the study was to assess risk factors for residual renal function (RRF) decline in children during the first/second year of chronic peritoneal dialysis (PD). ♦ METHODS: The study group included 56 children with end-stage renal disease (ESRD) (age 10.13 ± 4.86 years), including 18 on continuous ambulatory PD (CAPD) and 38 on automated PD (APD), in whom we evaluated RRF (daily diuresis [mL/m2/24 h], residual glomerular filtration rate (rGFR) [mL/min/1.73 m2]), etiology of ESRD, PD fluid volume (mL/m2/24 h), glucose load (g/m2/24 h), ultrafiltration (mL/m2/24 h), peritoneal permeability (D/PCrea 4h, D/D0 Glu 4h), dialysis adequacy (twKt/V, twCCr [L/week/1.73 m2]), blood pressure (BP), biochemical parameters, and medications used. Duration of follow-up was 24 months. ♦ RESULTS: Mean diuresis before initiation of PD was 1,394.93 ± 698.37 (mL/m2/24 h), and mean rGFR was 7.41 ± 3.96 (mL/min/1.73 m2). The rate of daily diuresis decline was -529.34 ± 546.28 in the first year and -107.10 ± 291.54 (mL/m2/24 h) in the second year (p = 0.005), and the rate of rGFR decline was -3.35 ± 3.73 in the first year and -1.63 ± 1.85 (mL/min/1.73 m2) in the second year (p = 0.118). Eleven (19.64%) patients became anuric. In univariate analysis, the rate of daily diuresis decline in the first year was related to baseline diuresis (r = -0.29, p = 0.031), proteinuria (r = -0.43, p = 0.001), and systolic BP (r = -0.31, p = 0.020); 12-month changes (Δ0 - 12) in PD fluid volume (r = -0.37, p = 0.004), glucose load (r = -0.28, p = 0.035), and ultrafiltration (r = -0.38, p = 0.004); serum calcium-phosphorus product (r = -0.41, p = 0.002); and Δ0 - 12 body mass index (BMI) Z-score (r = 0.30, p = 0.024); while the rate of rGFR decline in the first year was related only to baseline rGFR (r = -0.57, p < 0.001). In multivariate analysis, significant predictors of the rate of daily diuresis decline in the first year were baseline diuresis (β = -0.386, p < 0.001) and proteinuria (β = -0.278, p = 0.017), mean systolic BP Z-score (β = -0.237, p = 0.027), and age at the onset of PD (β = -0.224, p = 0.037), while predictors of the rate of rGFR decline were baseline rGFR (β = -0.607, p < 0.001) and baseline proteinuria (β = -0.225, p = 0.046). In the second year, the only predictors of the rate of rGFR decline were D/D0 Glu 4h (r = 0.44, p = 0.033, univariate analysis) and rGFR at 12 months (β = -0.499, p = 0.044). ♦ CONCLUSION: The most important risk factors for rapid RRF decline in children during the first year of chronic PD include higher baseline daily diuresis and proteinuria, and additional factors are systolic BP and age at the onset of PD; while high baseline GFR and low peritoneal transport status may be the only important factors during the second year.

Project description:BackgroundRacial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. Greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population.Study designProspective cohort study.Setting & participants3,653 African American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from 2 of 3 examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation.PredictorsDemographics, socioeconomic status, lifestyle, and clinical risk factors for kidney failure.OutcomesRapid decline was defined as a ≥30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models.MeasurementsClinical (systolic blood pressure and albuminuria [albumin-creatinine ratio]) and modifiable risk factors.ResultsMean age was 54±12 (SD) years, 37% were men, average body mass index was 31.8±7.1kg/m(2), 19% had diabetes mellitus (DM), and mean eGFR was 96.0±20mL/min/1.73m(2) with an annual rate of decline of 1.27mL/min/1.73m(2). Those with rapid decline (11.5%) were older, were more likely to be of low/middle income, and had higher systolic blood pressures and greater DM than those with nonrapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71), cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17mmHg greater, 1.22; 95% CI, 1.06-1.41), DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein level, and physical activity with rapid decline.LimitationsNo midstudy creatinine measurement at examination 2 (2005-2008).ConclusionsRapid decline heterogeneity exists among African Americans in JHS. Interventions targeting potentially modifiable factors may help reduce the incidence of kidney failure.

Dataset Information

Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease.

Publications

Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets