Association of serum uromodulin with diabetic kidney disease: a systematic review and meta-analysis.

Background: Several studies have investigated the association between the changes of serum uromodulin and diabetic kidney disease (DKD). However, the results are still controversial. Therefore, this meta-analysis was conducted to provide a comprehensive evaluation of the association between serum uromodulin levels and DKD.

Methods: PubMed, Cochrane library, Web of Science, and Scopus were systemically searched following the PRISMA protocol to identify the studies that reported the relationship between serum uromodulin level and DKD. To investigate the association between uromodulin and DKD, a standardized mean difference (SMD) with a 95% confidence interval (CI) was used. When significant heterogeneity was detected (I > 50%), sensitivity and subgroup analyses were performed to determine the source of heterogeneity. The quality assessment was determined using the Newcastle-Ottawa scale (NOS), and the publications bias were determined by the funnel plot and Egger's test.

Results: In total, 6 studies with 1774 patients were included in the final analysis. The random effect model was used. The pooled results showed that the serum uromodulin levels were significantly decreased in patients with DKD (SMD: -0.31; 95% CI: -0.48 to -0.13) (I = 45%). Upon applying the sensitivity analysis, it showed (SMD: -0.38; 95% CI: -0.49 to -0.27) (I = 3%). Subgroup analysis showed that uromodulin level was significantly decreased in DKD regardless of the region of study, in America (SMD: -0.34; 95% CI: -0.51 to -0.17; p < 0.0001), Europe (SMD: -0.54; 95% CI: -1.06 to -0.02; p = 0.04), and Asia (SMD: -0.63; 95% CI: -1.15 to -0.11; p = 0.02), with stronger predictive value in America and Asia than in Europe. Additionally, uromodulin levels were significantly decreased in both type 1 (SMD: -0.34; 95% CI: -0.51 to -0.17; p < 0.0001) and type 2 diabetes (SMD: -0.58; 95% CI: -0.95 to -0.22; p = 0.002).

Conclusion: This meta-analysis showed a significant association between low levels of serum uromodulin and DKD. So, it could have a predictive role for DKD. However, its performance varied across subgroup analyses restricted by race and clinical settings. Moreover, further studies are required with a focus on the cut-off value for predicting diagnostic accuracy.