Prognostic value of multiple biomarkers for kidney function decline in type 2 diabetes with relatively preserved...

Diabetic kidney disease (DKD) is a dominant driver of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Current risk assessment tools, however, lack adequate sensitivity for early disease detection. This study evaluated the prognostic value of multiple biomarkers for kidney function decline in patients with type 2 diabetes and relatively preserved kidney function.

This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from inception to December 31, 2025. Articles were independently screened by two reviewers against pre-specified criteria. Prospective cohort studies reporting associations between baseline biomarkers and kidney function decline were included. Methodological quality was assessed using the Quality In Prognosis Studies (QUIPS) tool. Quantitative pooling was performed only when studies were homogeneous in effect measure and outcome definition. When these criteria were not met, results were presented descriptively.

Nine prospective cohort studies comprising 4,569 participants were included. Circulating TNFR1, TNFR2, and KIM-1 showed potential positive associations with kidney function decline. One study reported an inverse association for circulating Klotho. No significant associations were found for circulating FGF-23. Findings for urinary NGAL and urinary KIM-1 were inconsistent across studies. Due to heterogeneity in effect measures, exposure scales, and outcome definitions, several biomarkers could not be quantitatively pooled. For pooled analyses, each analysis included only two studies; therefore, effect estimates, heterogeneity, and prediction intervals may be unstable, and the results should be considered exploratory.

Current evidence suggests potential associations of circulating TNFR1, TNFR2, and KIM-1 with kidney function decline in type 2 diabetes with relatively preserved kidney function. Given the limited number of studies, these findings are exploratory and require validation in larger prospective studies with standardized assays and outcome definitions.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261401816.