Effect of uric acid-lowering therapy on renal function in patients with chronic kidney disease: a systematic review and meta-analysis

Background Whether uric acid (UA)-lowering therapy (ULT) is effective in reducing the progression of renal dysfunction in patients with chronic kidney disease (CKD) remains controversial. Since several advances have been made in therapies for hyperuricemia, including novel xanthine oxidoreductase (XOR) inhibitors, we conducted a systematic review to clarify the effectiveness of ULT in preserving renal function among CKD patients. Methods In this systematic review, the MEDLINE database was searched up to June 2019. We included complete randomized controlled trials comparing renal events between adult non-dialyzed CKD patients, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2), with and without ULTs. Changes in eGFR were expressed as the mean difference (MD). The incidence of dichotomous outcomes was expressed as a risk ratio. This review was performed using the predefined protocol published in PROSPERO (CRD 42019140346). Results Eleven studies with 4277 CKD patients were included. Drugs used in the intervention groups of all studies were XOR inhibitors (allopurinol, febuxostat or topiroxostat). Although patients with ULT tended to show superior preservation of eGFR as compared to those without ULT, no significant differences were identified (MD, 2.52; 95% confidence interval, - 0.15 to 5.18). In subgroup analysis, the use of allopurinol was associated with superior preservation of eGFR, whereas the newer XOR inhibitors, febuxostat and topiroxostat, showed no significant effects on eGFR changes. Neither incidence of end-stage kidney disease nor treatment-emergent adverse events differed significantly between groups. Conclusions The present systematic review and meta-analysis suggested that CKD patients with ULT tend to show superior eGFR preservation as compared to patients without ULT, but further studies are needed to verify the renoprotective effects of ULT.