Biomarkers of cardiovascular stress and incident chronic kidney disease.

Ho JE, Hwang SJ, Wollert KC, Larson MG, Cheng S, Kempf T, Vasan RS, Januzzi JL, Wang TJ, Fox CS
Clin Chem. 2013 59 (11): 1613-20

PMID: 23873716 · PMCID: PMC3972213 · DOI:10.1373/clinchem.2013.205716

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 m(2)) (-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 m(2)) (-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.

MeSH Terms (15)

Albuminuria Biomarkers Cardiovascular Diseases Female Growth Differentiation Factor 15 Humans Incidence Interleukin-1 Receptor-Like 1 Protein Kidney Function Tests Longitudinal Studies Male Middle Aged Receptors, Cell Surface Renal Insufficiency, Chronic Troponin I

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