Biomarkers of cardiovascular stress and incident chronic kidney disease.

Abstract

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.

• Authors: 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
• Journal: Clinical chemistry (Clin Chem) Vol. 59 Issue 11 Pg. 1613-20 (Nov 2013) ISSN: 1530-8561 [Electronic] England
• PMID: 23873716 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Growth Differentiation Factor 15
• IL1RL1 protein, human
• Interleukin-1 Receptor-Like 1 Protein
• Receptors, Cell Surface
• Troponin I

Topics

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