Fetuin-A (Alpha 2 HS Glycoprotein) as a predictor of urolithiasis: A systematic review and meta-analysis

Background: The global incidence of urolithiasis has doubled over the past four decades, potentially exacerbated by climate change. Fetuin-A (alpha-2-Heremans-Schmid glycoprotein) is a novel biomarker known for inhibiting calcification and is linked to chronic kidney disease and metabolic syndrome. This study aims to evaluate the association between fetuin-A levels and urolithiasis. Methods: A systematic search of MEDLINE, ScienceDirect, ProQuest, EBSCO, Google Scholar, and Cochrane Library was conducted for case-control studies comparing fetuin-A levels in urolithiasis patients versus controls. Study quality was assessed using the JBI Critical Appraisal tool. Meta-analysis was performed with RevMan and JASP. Results: Seven case-control studies comprising 395 urolithiasis patients and 282 controls (total n = 677) were included. Urinary fetuin-A levels were significantly lower in urolithiasis patients (SMD = -2.24, 95% CI: -4.24 to -0.23, p = 0.029, I² = 98%). Six studies also reported a trend of reduced serum fetuin-A levels. Conclusions: Fetuin-A may serve as a potential predictive biomarker for urolithiasis, particularly in recurrent cases. Significant urinary differences and serum trends warrant further research to clarify its diagnostic and prognostic value. Level of evidence: Not applicable