Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Abstract Rationale & Objective Identification of novel risk factors for chronic kidney disease (CKD) progression may inform mechanistic investigations and improve identification of high-risk subgroups. The current study aimed to characterize CKD progression across levels of numerous risk factors and to identify independent risk factors for CKD progression among those with and without diabetes. Study Design The Chronic Renal Insufficiency Cohort (CRIC) Study is a prospective cohort study of adults with CKD conducted at seven US clinical centers. Setting & Participants Participants (N=3379) had up to 12.3 years of follow-up; 47% had diabetes. Predictors Thirty risk factors for CKD progression across sociodemographic, behavioral, clinical and biochemical domains at baseline. Outcomes Study outcomes were estimated glomerular filtration rate (eGFR) slope and the composite of halving of eGFR or initiation of kidney replacement therapy (KRT). Analytical Approach Stepwise selection of independent risk factors was performed stratified by diabetes status using linear mixed effects and Cox proportional hazards models. Results Among those without and with diabetes, respectively, the mean (SD) eGFR slope was -1.4 (3.3) and -2.7 (4.7) mL/min/1.73m2/year. Among participants with diabetes, multivariable-adjusted hazard of the composite outcome was approximately twofold or greater with higher levels of the inflammatory chemokine CXCL12, the cardiac marker N-terminal pro-B-type natriuretic peptide (NTproBNP) and the kidney injury marker urine neutrophil gelatinase-associated lipocalin (NGAL). Among those without diabetes, low serum bicarbonate as well as higher high-sensitivity troponin T, NTproBNP and urine NGAL were all significantly associated with a 1.5-fold or greater rate of the composite outcome. Limitations The observational study design precludes causal inference. Conclusions Strong associations for cardiac markers, plasma CXCL12 and urine NGAL exceeded that of systolic blood pressure ≥140 mmHg, a well-established risk factor for CKD progression. This warrants further investigation into the potential mechanisms these markers indicate and opportunities to use them to improve risk stratification.