Age-related physiological and molecular biomarkers associated with kidney function: a systematic review and meta-analysis

BACKGROUND: The prevalence of chronic kidney disease (CKD) is rising rapidly due to population ageing, with significant consequences for morbidity and mortality. The use of effective, predictive biomarkers would enable early introduction of targeted, proactive management of kidney disease. AIM: The aim of this review is to summarize all available studies investigating the association of neurocardiovascular, inflammatory and epigenetic biomarkers with kidney function and their ability to predict CKD incidence or progression. DESIGN: Systematic review and meta-analysis. METHODS: Systematic searches were conducted in Scopus, Embase, MEDLINE and CINAHL covering available literature until 29 November 2023. Studies assessing the relationship between named biomarkers and kidney outcomes in adults were included. Title, abstract and full text screening involved two independent reviewers using Covidence software. Data extraction and quality assessment, using the Newcastle-Ottawa scale (NOS), were completed by two reviewers. Systematic narrative analysis was performed for all biomarkers, and meta-analysis was conducted for studies reporting odds or hazard ratios. RESULTS: Sixty-eight observational studies were included. Several biomarkers showed significant association with kidney function but significant independent associations with CKD incidence and progression were limited. Results from the meta-analysis: heart rate variability and CKD progression: pooled hazard ratio 1.75 (1.25-2.45), arterial stiffness and kidney function and CKD incidence: pooled odds ratios 1.08 (1.03-1.13) and 1.14 (1.01-1.29). CONCLUSIONS: Further longitudinal research focussing on the outcomes of CKD incidence and progression is required. The use of physiological and molecular biomarkers has the potential to improve the management and prognostication of CKD.