Abstract
BackgroundFew investigations have evaluated the incremental usefulness of multiple biomarkers representing varying physiological pathways for predicting risk of renal outcomes in African Americans.Design, setting, participants, and measurementsWe related a multi-marker panel to incident chronic kidney disease (CKD) and rapid kidney function decline (RKFD) in 2813 Jackson Heart Study participants without prevalent CKD at exam 1 (2000–2004) and with complete assays at exam 1 for 9 biomarkers: adiponectin, aldosterone, B-natriuretic peptide [BNP], cortisol, high sensitivity C-reactive protein (hsCRP), endothelin, homocysteine, plasma renin activity and mass. Incident CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at exam 3 while RKFD was defined as eGFR ≥30% loss between exams 1 and 3 (8.2 median years). We employed multiple logistic regression model to describe association between the panel and incident CKD and RKFD and used backward elimination strategy to estimate the most parsimonious biomarker model while controlling for conventional risk factors.ResultsThe multi-marker panel predicted the risk for both incident CKD (odds ratios [OR], 2.72; 95% confidence intervals [CI], 1.63, 4.56; P = 0.001) and RKFD (2.61; 95% CI, 1.67, 4.08; P < 0.001). Per standard deviation increase in log biomarker concentrations were significantly (multivariable adjusted odds ratios, [95% confidence interval], p-value) associated with incident CKD: plasma adiponectin (1.24 [1.07, 1.44], p = 0.005) and leptin (1.3 [1.06, 1.61], p = 0.011), and with RKFD: plasma adiponectin (1.22 [1.06, 1.40], p = 0.006); hsCRP (1.17 [1.01, 1.36], p = 0.031) and aldosterone (0.85 [0.74, 0.96], p = 0.012). Moderate levels (3rd quartile) of aldosterone were inversely associated with incident CKD (0.54 [0.35, 0.82], p = 0.004) while leptin was associated with RKFD (1.64 [1.10, 2.44], p = 0.015). Biomarkers improved CKD risk prediction (P = 0.003) but not RKFD risk prediction (P = 0.10).ConclusionIn this community-based sample of African Americans, a multi-marker panel added only moderate predictive improvement compared to conventional risk factors.
Highlights
Few investigations have evaluated the incremental usefulness of multiple biomarkers representing varying physiological pathways for predicting risk of renal outcomes in African Americans
Per standard deviation increase in log biomarker concentrations were significantly associated with incident chronic kidney disease (CKD): plasma adiponectin (1.24 [1.07, 1.44], p = 0.005) and leptin (1.3 [1.06, 1.61], p = 0.011), and with rapid kidney function decline (RKFD): plasma adiponectin (1.22 [1.06, 1.40], p = 0.006); high sensitivity C-reactive protein (hsCRP) (1.17 [1.01, 1.36], p = 0.031) and aldosterone (0.85 [0.74, 0.96], p = 0.012)
Moderate levels (3rd quartile) of aldosterone were inversely associated with incident CKD (0.54 [0.35, 0.82], p = 0.004) while leptin was associated with RKFD (1.64 [1.10, 2.44], p = 0.015)
Summary
Few investigations have evaluated the incremental usefulness of multiple biomarkers representing varying physiological pathways for predicting risk of renal outcomes in African Americans. Established CKD risk factors explain only 34% of renal disease progression among whites and 44% for African Americans after adjusting for sociodemographic, lifestyle and clinical factors [3, 6]. CKD prognosis largely depends on traditional markers such as estimated glomerular filtration rate (eGFR) and albuminuria, these biomarkers only offer modest risk prediction in people with preserved levels of renal function [7] and are subject to intra-individual variability over time when hydration and medication use are involved. Studies in cardiovascular disease (CVD) and metabolic syndrome, have benefited from the use of circulating biomarkers in risk prediction [11,12,13]. While multi-marker approach to predict CKD has been reported in whites [10], the predictive value of models incorporating multiple biomarkers in CKD prediction among African Americans is not well studied
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