title: Effect of urate-lowering therapies on renal disease progression in patients with hyperuricemia.
abstract: OBJECTIVE
  To evaluate the association between hyperuricemia and renal disease progression in a real-world, large observational database study.
  
  
  METHODS
  We conducted a population-based retrospective cohort study identifying 111,992 patients with hyperuricemia (> 7 mg/dl) from a large medical group. The final cohort were ≥ 18 years old, urate-lowering therapy (ULT)-naïve, and had the following laboratory results available: at least 1 glomerular filtration rate (GFR) level before the index date and at least 1 serum uric acid (sUA) level and GFR in the followup 36-month period. The cohort was categorized into 3 groups: never treated (NoTx), ULT time receiving therapy of < 80% (< 80%), and ULT time receiving therapy of ≥ 80% (≥ 80%). Outcomes were defined as a ≥ 30% reduction in GFR from baseline, dialysis, or GFR of ≤ 15 ml/min. A subanalysis of patients with sUA < 6 mg/dl at study conclusion was performed. Cox proportional hazards regression model determined factors associated with renal function decline.
  
  
  RESULTS
  A total of 16,186 patients met inclusion criteria. There were 11,192 NoTx patients, 3902 with < 80% time receiving ULT, and 1092 with ≥ 80% time receiving ULT. Factors associated with renal disease progression were age, sex, hypertension, diabetes, congestive heart failure, hospitalizations, rheumatoid arthritis, and higher sUA at baseline. Time receiving therapy was not associated with renal outcomes. Patients who achieved sUA < 6 mg/dl had a 37% reduction in outcome events (p < 0.0001; HR 0.63, 95% CI: 0.5-0.78).
  
  
  CONCLUSIONS
  Hyperuricemia is an independent risk factor for renal function decline. Patients treated with ULT who achieved sUA < 6 mg/dl on ULT showed a 37% reduction in outcome events.
authors.affiliation: From the Southern California Permanente Medical Group, and Kaiser Permanente, Pharmacy Analytical Services, Downey, California, USA.
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Levy
authors.forename: Nazia
authors.initials: N
authors.lastname: Rashid
authors.forename: Fang
authors.initials: F
authors.lastname: Niu
authors.forename: T Craig
authors.initials: TC
authors.lastname: Cheetham
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003078:Colchicine / Q000627:therapeutic use*; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006074:Gout Suppressants / Q000627:therapeutic use; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*
chemical_list: D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006074:Gout Suppressants; D014527:Uric Acid; D003078:Colchicine
keywords: CHRONIC KIDNEY DISEASE; HYPERURICEMIA; URATE-LOWERING THERAPY; URIC ACID