The longitudinal associations of selected Tubular Biomarkers Predict the Risk of Nephropathy Progression in Diabetic Patients: systematic review and meta-analysis
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Aims: This study systematically reviewed and conducted a meta-analysis to assess the predictive value of tubular biomarkers for diabetic nephropathy (DN) progression among diabetic patients. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to May 2024. Longitudinal cohort studies measuring biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and liver fatty acid-binding protein (L-FABP) were included. The outcomes assessed included the incidence and progression of DN, characterized by an eGFR decrease, albuminuria, and progression to end-stage renal disease (ESRD) or mortality. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated via random effects models, with subgroup and meta-regression analyses. Results: Thirty-one studies involving 29,818 patients met the inclusion criteria. Elevated levels of serum KIM1 (RR=1.68, 95% CI: 1.42–1.98) and urinary biomarkers, including KIM-1 (RR=1.42, 95% CI: 1.11–1.81), NGAL (RR=1.30, 95% CI: 1.06–1.60), NAG (RR=1.22, 95% CI: 1.13–1.32), and LFABP (RR=1.83, 95% CI: 1.03–3.25), were significantly associated with DN progression. In terms of heterogeneity and effect size, urinary KIM1 and LFABP are more effective and reliable relative risk factors for DN progression. Subgroup analysis showed that serum and urinary KIM1 and urinary LFABP were particularly effective in predicting early progression of DN. In contrast, urinary NGAL and NAG were more associated with advanced stages of DN, including progression to ESRD and mortality. Conclusions: These results highlight the potential of selected tubular biomarkers for predicting diabetic nephropathy progression. Their application may enable earlier diagnosis and targeted management, improving patient outcomes in DN patients. PROSPERO ID: CRD42025636435
