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Jennifer E Ho, Shih-Jen Hwang, Kai C Wollert, Martin G Larson, Susan Cheng, Tibor Kempf, Ramachandran S Vasan, James L Januzzi, Thomas J Wang, Caroline S Fox, Biomarkers of Cardiovascular Stress and Incident Chronic Kidney Disease, Clinical Chemistry, Volume 59, Issue 11, 1 November 2013, Pages 1613–1620, https://doi.org/10.1373/clinchem.2013.205716
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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.
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.
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%).
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.
