The Role of Uromodulin in Chronic Kidney Disease – A Systematic Review and Meta-Analysis

Abstract

Background: Numerous studies have investigated the function of the biomarker uromodulin (UMD), which has shown promise in the diagnosis and severity assessment of chronic kidney disease (CKD). However, the results continue to be contradictory and inconclusive. Consequently, our goal was to investigate the connection between UMD and CKD patients, with a focus on their diagnostic utility and association with the severity of CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) classification. Methods: We systematically searched PubMed, EMBASE, and Scopus using a predefined string to identify relevant studies. Included studies diagnosed CKD based on GFR according to Kidney Disease Outcomes Quality Initiative KDOQI guidelines or by calculating eGFR using the MDRD formula, meeting predefined criteria. Quality assessment was conducted using the Newcastle Ottawa Scale (NOS). The main outcome was the mean difference (MD) in serum UMD levels across CKD stages. Results: A total of 5 articles involving 1,094 subjects fulfilled our inclusion criteria and were included in our systematic review and meta-analysis. Significant differences in UMD levels were observed across multiple comparisons. When comparing CKD patients to controls, UMD levels showed a substantial MD of –115.719 (95% CI –163.297, -68.141). Similarly, UMD levels exhibited significant MDs when comparing controls vs. CKD 1 71.185 (95% CI 39.572, 102.798), controls vs. CKD 2 81.531 (95% CI 40.570, 122.491), controls vs. CKD 3 130.886 (95% CI 99.095, 162.677), controls vs. CKD 4 180.317 (95% CI 141.373, 219.262), controls vs. CKD 5 198.033 (95% CI 155.573, 240.494) and CKD 1-2-3 vs. CKD 4-5 89.540 (95% CI 47.561, 131.518). Conclusions: In conclusion, our systematic review and meta-analysis highlights pronounced differences in UMD levels across multiple comparisons in CKD. When comparing CKD patients with controls, a significant decrease in UMD levels is evident, indicative of potential implications in renal pathology. Moreover, the observed variations in UMD levels between different CKD stages underscore its potential utility as a biomarker for disease severity and progression. These findings contribute to our understanding of UMD dynamics in CKD and suggest avenues for further research into its diagnostic and prognostic significance in clinical practice.