Effectiveness of Drug Treatments for Lowering Uric Acid on Renal Function in Patients with Chronic Kidney Disease and Hyperuricemia: A Network Meta-Analysis of Randomized Controlled Trials

Backgrounds: Hyperuricemia is very common in CKD (chronic kidney disease) patients, the role of hyperuricemia in occurrence, development and progression of kidney disease is in considerable controversies, and whether urate lowering therapy (ULT) is warranted in CKD patients has not reached a consensus up till now. To summarize and compare the clinical outcomes and adverse events (AEs) associated with three common ULT drugs (febuxostat, allopurinol, benzbromarone), we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs). Methods: The databases of PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials were comprehensively searched up to June 1, 2020. The network meta-analysis was performed using the “gemtc 0.8-7” and its dependent packages in R software, mean differences (MD) with 95% credibility intervals (CrIs) were calculated for continuous variables, odds ratio (OR) with 95% CrIs of binary variables were logarithmic converted into Mean differences (MD) with 95% credibility intervals (CrIs). The primary outcome was change of renal fuction and uric acid; creatinine, proteinuria, blood pressure, adverse events were assessed as the secondary outcomes. Findings: 13 RCTs involving 1248 patients were included in the final network analysis. We found that febuxostat, allopurinol, and benzbromarone were statistically superior to placebo in lowering urate, and febuxostat was associated with better improvement of uric acid compared with allopurinol (MD: -1.531; 95%CrI: -2.624- -0.434); it was also demonstrated that febuxostat could control both systolic and diastolic blood pressure better while no differences were shown when compared allopurinol and benzbromarone to placebo. Furthermore, less gastrointestinal symptoms occurred in febuxostat group comparing to allopurinol (MD: -16.19, 95%CrI: -53.06 - -0.3853) and benzbromarone (MD: -31.56, 95%CrI: -74.69 - -6.034). No renoprotective functions were found in the three agents. These results are stable in the subgroup analysis by CKD stages and follow-up time (6 months). Interpretation: Febuxostat seems to an satisfying alternative to allopurinol and benzbromarone, it is safer, more effective to lower SUA, and control blood pressure better in hyperuricemic patients with CKD; there is insufficient evidence to support the renoprotect efficiencies of the three ULT agents in these patients; large, doubling RCTs for studying the influencies and differences of ULT agents on renoprotective functions are needed. Funding: None to declare Declaration of Interest: None to declare