Association between interleukin 6, C-reactive protein, and kidney transplantation outcomes: A systematic review and meta-analysis

Abstract

Background: Kidney transplant recipients experience heightened systemic inflammation, and biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), and high-sensitivity CRP (hsCRP) have been proposed as prognostic indicators. Objective: This meta-analysis evaluates the associations between IL-6, CRP, and hsCRP levels and all-cause mortality, cardiovascular events, and graft dysfunction in kidney transplant recipients. Methods: A comprehensive search of PubMed, Web of Science, Scopus, Ovid MEDLINE, and the Cochrane Library until October 11, 2024, identified eligible studies reporting associations between IL-6, CRP, or hsCRP and clinical outcomes in adult kidney transplant recipients. Results: The systematic review included 40 studies, with 18 meeting criteria for meta-analysis. Elevated IL-6 was associated with a higher risk of graft dysfunction (HR 1.53, 95 % CI 1.28-1.83; I2 = 0 %) and all-cause mortality (HR 1.66, 95 % CI 1.05-2.61; I2 = 97.2 %), but not cardiovascular events. CRP was associated with all-cause mortality (HR 2.07, 95 % CI 1.59-2.70; I2 = 0 %) and cardiovascular events (HR 6.89, 95 % CI 2.52-18.85; I2 = 0 %), but not cardiovascular mortality or graft dysfunction. Elevated hsCRP was associated with all-cause mortality (HR 1.29, 95 % CI 1.15-1.44; I2 = 61 %), but not with cardiovascular events or graft dysfunction. Conclusions: Among kidney transplant recipients, elevated levels of IL-6, CRP, and hsCRP were significantly associated with increased all-cause mortality, though the association of IL-6 with all-cause mortality showed substantial heterogeneity and should be interpreted with caution. IL-6 also emerged as a predictor of graft dysfunction, while CRP demonstrated a strong association with cardiovascular events. These findings highlight the potential role of inflammatory biomarkers, particularly IL-6 and CRP, in post-transplant risk stratification; however, further studies are needed to establish causality and clarify their clinical utility.