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Lin, J. ; Nano, J. ; Petrera, A. ; Hauck, S.M. ; Zeller, T.* ; Koenig, W.* ; Müller, C.L. ; Peters, A. ; Thorand, B.

Proteomic profiling of longitudinal changes in kidney function among middle-aged and older men and women: The KORA S4/F4/FF4 study.

BMC Med. 21:245 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Background: Due to the asymptomatic nature of the early stages, chronic kidney disease (CKD) is usually diagnosed at late stages and lacks targeted therapy, highlighting the need for new biomarkers to better understand its pathophysiology and to be used for early diagnosis and therapeutic targets. Given the close relationship between CKD and cardiovascular disease (CVD), we investigated the associations of 233 CVD- and inflammation-related plasma proteins with kidney function decline and aimed to assess whether the observed associations are causal. Methods: We included 1140 participants, aged 55–74 years at baseline, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort study, with a median follow-up time of 13.4 years and 2 follow-up visits. We measured 233 plasma proteins using a proximity extension assay at baseline. In the discovery analysis, linear regression models were used to estimate the associations of 233 proteins with the annual rate of change in creatinine-based estimated glomerular filtration rate (eGFRcr). We further investigated the association of eGFRcr-associated proteins with the annual rate of change in cystatin C-based eGFR (eGFRcys) and eGFRcr-based incident CKD. Two-sample Mendelian randomization was used to infer causality. Results: In the fully adjusted model, 66 out of 233 proteins were inversely associated with the annual rate of change in eGFRcr, indicating that higher baseline protein levels were associated with faster eGFRcr decline. Among these 66 proteins, 21 proteins were associated with both the annual rate of change in eGFRcys and incident CKD. Mendelian randomization analyses on these 21 proteins suggest a potential causal association of higher tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) level with eGFR decline. Conclusions: We reported 21 proteins associated with kidney function decline and incident CKD and provided preliminary evidence suggesting a potential causal association between TNFRSF11A and kidney function decline. Further Mendelian randomization studies are needed to establish a conclusive causal association.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Chronic Kidney Disease ; Cohort Study ; Glomerular Filtration Rate ; Mendelian Randomization ; Proteomics; Brain Natriuretic Peptide; Impaired Renal-function; Central Venous-pressure; Function Decline; Mendelian Randomization; Risk; Variants; Bias
ISSN (print) / ISBN 1741-7015
e-ISSN 1741-7015
Journal BMC Medicine
Quellenangaben Volume: 21, Issue: 1, Pages: , Article Number: 245 Supplement: ,
Publisher BioMed Central
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Computational Biology (ICB)
Grants China Scholarship Council (CSC)