Biomarkers of Cardiovascular Stress and Incident Chronic Kidney Disease

Study Questions:

What is the association of growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hs-TnI), with incident renal outcomes including chronic kidney disease (CKD), microalbuminuria, and progressive decline in renal function?

Methods:

Plasma GDF-15, sST2, and hs-TnI concentrations were measured in 2,614 Framingham Offspring cohort participants (mean age 57 years, 54% women) at the sixth examination cycle (1995–1998). Associations of biomarkers with incident CKD (estimated glomerular filtration rate [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% confidence interval [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 hs-TnI 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:

The authors concluded that higher circulating GDF-15 is associated with incident renal outcomes and improved risk prediction of incident CKD.

Perspective:

This study reports that GDF-15 is associated with incident CKD and rapid decline in renal function in participants from the Framingham Heart Study. The addition of GDF-15 to clinical covariates also resulted in improvement in the prediction of incident CKD, including the c-statistic and risk reclassification metrics. The data suggest that GDF-15 may be useful in predicting the development of CKD years before the clinical onset of disease, and aid in targeting preventive efforts in the future.

Keywords: Risk, Biological Markers, Troponin I, Growth Differentiation Factor 15, Glomerular Filtration Rate, Renal Insufficiency, Chronic


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