Urate-lowering therapy and kidney outcomes in patients with chronic kidney disease and hyperuricemia

Hyperuricemia is considered a modifiable risk factor for the development and progression of chronic kidney disease (CKD). There remains controversy over the effects of urate-lowering therapy (ULT) on kidney outcomes in patients with CKD and hyperuricemia. We conducted a cohort study using a sequential target trial emulation framework to evaluate the composite kidney outcomes in patients with CKD and hyperuricemia initiating ULT versus supportive care alone (control). A total of 269,831 eligible person trials (56,936 unique persons) with CKD and hyperuricemia who had received supportive care were included from the China Renal Data System database. The primary outcome was a composite kidney outcome defined as a greater than 40% decline in the estimated GFR or end-stage kidney disease (ESKD). The 3-year cumulative incidence rates of the composite kidney outcomes were 19.69% and 23.22% in the ULT group and the control group, respectively, with a risk difference of -3.53% (95% CI, -5.25% to -1.94%). The estimated 3-year risk differences for ESKD, all-cause mortality, and cardiovascular mortality were -1.88% (-3.28% to -0.45%), -2.25% (-3.02% to -1.51%), and -0.69% (-1.33% to -0.05%), respectively, all of which favor the ULT group. The estimates from the subgroup and sensitivity analyses were consistent with those from the primary analysis. Thus, ULT is associated with a significantly lower risk of kidney disease progression and mortality in patients with stage 3 or higher CKD and hyperuricemia. Large randomized clinical trials with refined designs are needed to assess the effect of ULT in these patients.