Plasma Biomarkers as Risk Factors for Incident CKD
Mark J. Sarnak, Ronit Katz, Joachim H. Ix, Paul L. Kimmel, Joseph V. Bonventre, Jeffrey R. Schelling, Mary Cushman, Ramachandran S. Vasan, Sushrut S. Waikar, Jason H. Greenberg, Chirag R. Parikh, Steven G. Coca, Venkata Sabbisetti, Manasi P. Jogalekar, Casey M. Rebholz, Zihe Zheng, Orlando M. Gutiérrez, Michael G. Shlipak
Abstract
IntroductionEarlier identification of individuals at high risk of chronic kidney disease (CKD) may facilitate improved risk factor mitigation.MethodsWe evaluated the association of novel plasma biomarkers with incident CKD using a case-cohort design in participants without diabetes and with baseline estimated glomerular filtration rate (eGFR) ≥ 60 ml/min per 1.73 m2 in the Multi-Ethnic Study of Atherosclerosis (MESA) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohorts. Incident CKD was defined as development of eGFR < 60 ml/min per 1.73 m2 and ≥40% decline in eGFR from baseline. We measured plasma markers of inflammation/fibrosis—soluble tumor necrosis factor receptors (TNFRs) 1 and 2 (TNFR-1 and TNFR-2), monocyte chemotactic protein-1 (MCP-1), chitinase 3-like protein 1 (YKL-40), and soluble urokinase-type plasminogen activator receptor (suPAR)—and tubular injury (kidney injury molecule 1 [KIM-1]). Cox regression models weighted for the case-cohort design were used to estimate hazard ratios (HRs) of incident CKD after adjustment for CKD risk factors, eGFR, and albuminuria.ResultsIn MESA (median follow-up of 9.2 years), there were 497 individuals in the random subcohort and 163 incident CKD cases. In REGARDS (median follow-up of 9.4 years), there were 497 individuals in the random subcohort and 497 incident CKD cases. Each 2-fold higher plasma KIM-1 (adjusted HR 1.38 [95% CI 1.05–1.81]), suPAR (1.96 [1.10–3.49]), TNFR-1 (1.65 [1.04–2.62]), TNFR-2 (2.02 [1.21–3.38]), and YKL-40 (1.38 [1.09–1.75]) concentrations were associated with incident CKD in MESA. In REGARDS, TNFR-1 (1.99 [1.43–2.76]) and TNFR-2 (1.76 [1.22–2.54]) were associated with incident CKD.ConclusionPlasma concentrations of soluble TNFR-1 and TNFR-2 are consistently associated with incident CKD in nondiabetic community-living individuals in MESA and REGARDS.