Elevated leucine-rich alpha-2 glycoprotein levels and mortality risk in end-stage renal disease: evidence for gender differences

Abstract Background Leucine-rich α-2 glycoprotein (LRG) is an inflammation-related serum protein implicated in cardiovascular pathology. Its prognostic role in patients with end-stage renal disease (ESRD) remains unclear. We investigated the association between serum LRG levels and all-cause mortality in maintenance hemodialysis patients, with a focus on sex-specific effects. Methods In this prospective cohort study, 313 stable hemodialysis patients (206 males, 107 females) were enrolled and followed for 5 years. Baseline serum LRG concentrations were quantified by ELISA. Receiver operating characteristic (ROC) analysis identified an optimal mortality risk cut-off (45.5 µg/mL). Survival analyses used Kaplan–Meier curves and multivariable Cox regression models adjusted for demographic, clinical, and laboratory covariates. Analyses were stratified by sex. Results During follow-up, 103 deaths occurred (78 males, 25 females). Higher LRG levels were significantly associated with increased mortality risk in males (log-rank p < 0.001), but not females (p = 0.17). In adjusted Cox models, male patients with LRG > 45.5 µg/mL had an approximately twofold higher mortality risk (hazard ratio [HR = 2.07; 95% confidence interval [CI] = 1.32–3.23) compared to those below the cut-off. The association remained robust after further adjustment for C-reactive protein, albumin, dialysis vintage, and comorbidities. No significant association was observed in females (HR = 1.24; 95% CI = 0.65–2.34). ROC analysis yielded an AUC of 0.604 for LRG in predicting mortality. Conclusions Elevated serum LRG independently predicts all-cause mortality in male, but not female, hemodialysis patients. These findings highlight the potential of LRG as a sex-specific biomarker for risk stratification in ESRD and underscore the need for mechanistic studies on sex differences in LRG-related pathways.