Novel biomarkers of inflammation, kidney function and chronic kidney disease in the general population.

BACKGROUND Inflammatory processes have been implicated in the development of chronic kidney disease (CKD). We investigated the association of a large panel of inflammatory biomarkers reflecting aspects of immunity with kidney function and CKD incidence. METHODS We used data from two independent population-based studies, KORA F4 (discovery, n = 1,110, mean age 70.3 years, 48.7% male) and ESTHER (replication, n = 1,672, mean age 61.9 years, 43.6% male). Serum levels of biomarkers were measured using proximity extension assay technology. The association of biomarkers with estimated glomerular filtration rate (eGFR) at baseline and with incident CKD was investigated using linear and logistic regression models adjusted for cardiorenal risk factors. Independent results from prospective analyses of both studies were pooled. The significance level was corrected for multiple testing by false-discovery rate (PFDR < 0.05.). RESULTS In the KORA F4 discovery study, 52 out of 71 inflammatory biomarkers were inversely associated with eGFR estimated based on serum creatinine. Top biomarkers included CD40, TNFRSF9 and IL10RB. Forty-two of these 52 biomarkers were replicated in the ESTHER study. Nine of the 42 biomarkers were associated with incident CKD independently of cardiorenal risk factors in the meta-analysis of the KORA (n = 142, mean follow-up of 6.5 years) and ESTHER (n = 103, mean follow-up of 8 years) studies. Pathway analysis revealed the involvement of inflammatory and immunomodulatory processes reflecting cross-communication of innate and adaptive immune cells. CONCLUSIONS Novel and known biomarkers of inflammation were reproducibly associated with kidney function. Future studies should investigate their clinical utility and underlying molecular mechanisms in independent cohorts.