Evaluation of the Effectiveness of Xanthine Oxidoreductase Inhibitors on Haemodialysis Patients using a Marginal Structural Model

A lower serum uric acid (UA) level has been associated with a higher mortality rate in haemodialysis patients. We investigated the long-term confounding factors of UA and mortality, and fitted a marginal structural model (MSM) based on the causal effect of xanthine oxidoreductase inhibitors (XORi). In total, 2429 patients on regular dialysis from April 2013 to March 2016 were included, and divided into quintiles by serum UA with Kaplan Meier (KM) curves and log rank analysis. Baseline characteristics were evaluated for relationships with all-cause mortality and cardiovascular disease (CVD) using the Cox hazard model. The MSM was used to control for time-dependent confounders of the XORi treatment effect. KM curves indicated that patients in the highest UA quintile had better outcomes than those in the lowest UA quintile. UA was not correlated with all-cause mortality or CVD events in the Cox model; however, the hazard ratio (HR) for mortality was 0.96 for the baseline administration of XORi. The MSM analysis for the effect of XORi treatment on all-cause mortality revealed a HR of 0.24 (95% confidence interval: 0.15-0.38) in all cohorts. These results suggest that XORi improved all-cause mortality in end-stage renal disease, irrespective of the serum UA level.