Biomarkers of cardiovascular stress and incident chronic kidney disease

BACKGROUND: Growth differentiation factor-15 (GDF- 15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) are emerging predictors of adverse clinical outcomes. We examined whether circulating concentrations are related to the development of kidney disease in the community. METHODS: Plasma GDF-15, sST2, and hsTnI concentrations were measured in 2614 Framingham Offspring cohort participants (mean age 57 years, 54% women) at the sixth examination cycle (1995-1998). Associations of biomarkers with incident chronic kidney disease [CKD, eGFR < 60 mL min^-1 .(1.73 m²) ^-1, n=276], microalbuminuria (urinary albumin to creatinine ratio ≤25 mg/g in women and 17 mg/g in men, n =191), and rapid decline in renal function [decline in eGFR ≥ 3 mL min^-1 .(1.73 m²) ^-1 per year, n = 237], were evaluated using multivariable logistic regression; P < 0.006 was considered statistically significant in primary analyses. RESULTS: Participants were followed over a mean of 9.5 years. Higher plasma GDF-15 was associated with incident CKD [multivariable-adjusted odds ratio (OR) 1.9 per 1-U increase in log-GDF-15, 95% CI 1.6 -2.3, P < 0.0001] and rapid decline in renal function (OR, 1.6; 95% CI, 1.3-1.8; P ≤ 0.0001). GDF-15, sST2, and hsTnI had suggestive associations with incident microalbuminuria but did not meet the prespecified P-value threshold after multivariable adjustment. Adding plasma GDF-15 to clinical covariates improved risk prediction of incident CKD: The c-statistic increased from 0.826 to 0.845 (P = 0.0007), and categorical net reclassification was 6.3% (95% CI, 2.7-9.9%). CONCLUSIONS: Higher circulating GDF-15 is associated with incident renal outcomes and improves risk prediction of incident CKD. These findings may provide insights into the mechanisms of renal injury.