Circulating beta2 and alpha1 microglobulins predict progression of nephropathy in diabetic patients: a meta-analysis of prospective cohort studies

Abstract

AIMS: To study the association of circulating beta2 (B2M) and alpha1 microglobulins (A1M) with diabetic nephropathy (DN) progression, a meta-analysis was performed on the prospective cohort studies. METHODS: Up to October 2021, a comprehensive search of the PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library databases was performed. The primary outcome (progression of DN) was defined as a decrease in eGFR or the occurrence of end stage renal disease or DN-related mortality. Eligible studies were included in a pooled analysis that used either fixed-effect or random-effect models to compensate for variation in measurement standards between studies. The funnel plot and Egger's test were used to assess publication bias. RESULTS: The meta-analysis included 4398 people from 9 prospective trials (8 cohorts) for B2M and 3110 people from 4 prospective trials (3 cohorts) for A1M. Diabetic individuals with higher B2M levels had an increased risk for DN (relative risk RR: 1.81, 95% confidence interval CI: 1.56-2.09). Likewise, higher A1M was associated with augmented probability of DN (RR: 1.96, 95% CI: 1.46-2.62). The funnel plot and Egger's tests indicated no publication bias for A1M. Additionally, to compensate for putative publication bias for B2M, using trim and fill analysis, four studies were filled for this marker and the results remained significant (RR: 1.62, 95% CI: 1.37-1.92). CONCLUSIONS: The elevated serum levels of B2M and A1M could be considered as potential predictors of DN progression in diabetic patients. PROTOCOL REGISTRATION: PROSPERO CRD42021278300.