TY - JOUR
T1 - Biomarkers of cardiovascular stress and incident chronic kidney disease
AU - Ho, Jennifer E.
AU - Hwang, Shih Jen
AU - Wollert, Kai C.
AU - Larson, Martin G.
AU - Cheng, Susan
AU - Kempf, Tibor
AU - Vasan, Ramachandran S.
AU - Januzzi, James L.
AU - Wang, Thomas J.
AU - Fox, Caroline S.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
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U2 - 10.1373/clinchem.2013.205716
DO - 10.1373/clinchem.2013.205716
M3 - Article
C2 - 23873716
AN - SCOPUS:84887043096
SN - 0009-9147
VL - 59
SP - 1613
EP - 1620
JO - Clinical Chemistry
JF - Clinical Chemistry
IS - 11
ER -