Treatment of Hyperuricemia and Incident CKD in Patients with Normal Kidney Function

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Background: Hyperuricemia is associated with incident chronic kidney disease (CKD) independent of established metabolic risk factors. Treatment of hyperuricemia with uric-acid lowering therapy (ULT) was not beneficial in clinical trials of patients with CKD, but the effects of ULT on incident CKD in patients with no pre-existing CKD is unclear. Methods: We identified a national cohort of US Veterans with normal kidney function (eGFR ≥60 ml/min/1.73m2 and no proteinuria) and serum uric acid measurement. We examined the association of incident new ULT use (vs. no ULT), with the incidence of CKD (defined as 2 measurements of eGFR <60 ml/min/1.73m2 or UACR >30 mg/gm at least 90 days apart), using time dependent Cox models adjusted for baseline demographic characteristics, comorbid conditions, and time dependent eGFR and serum uric acid concentration. Results: We identified 1,152,040 patients with a serum uric acid measurement, of whom 111,508 (10%) patients received de novo ULT during 2006-2019. The overall mean (SD) age was 59 ±13 years, 94% were male, 76% were white, and the mean (SD) eGFR was 84 (17) ml/min/1.73m2 at the cohort entry. There were 308,311 cases of incident CKD (event rate, 40.4/1000 PY; 95%CI, 40.3-41.6) over a median follow-up of 6.1 years. ULT was associated with higher risk of incident CKD in both crude models (hazard ratio, 2.57; 95%CI, 2.55-2.60) and after multivariable adjustments (HR, 1.45; 95%CI, 1.44-1.47) [table]. Conclusions: Although hyperuricemia is independently associated with risk of CKD, treatment of hyperuricemia with ULT was not associated with lower risk of incident CKD in patients with baseline normal kidney function and no proteinuria in a large national cohort. Funding: Veterans Affairs Support

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