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 = 1110, mean age 70.3 years, 48.7% male) and ESTHER (replication, n = 1672, 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 of 71 inflammatory biomarkers were inversely associated with eGFR 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 independent of cardiorenal risk factors in the meta-analysis of the KORA (n = 142, mean follow-up 6.5 years) and ESTHER (n = 103, mean follow-up 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.
|Number of pages
|Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
|Published - 1 Oct 2022
Bibliographical noteFunding Information:
The study was funded by grants from the German Center for Diabetes Research (to C.Herder and B.T.). The KORA study was initiated and financed by the Helmholtz Zentrum München-German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences, Ludwig-Maximilians-Universität, as part of LMUinnovativ. This work was further supported by the Ministry of Culture and Science of the State of North Rhine-Westphalia and theGerman FederalMinistry ofHealth. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research. The funders of the study had no role in study design; data collection, analysis or interpretation or writing of the report.
© 2021 The Author(s).