Effect of a reduction in uric acid on renal outcomes during losartan treatment: a post hoc analysis of the reduction of endpoints in non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan Trial

Hypertension. 2011 Jul;58(1):2-7. doi: 10.1161/HYPERTENSIONAHA.111.171488. Epub 2011 May 31.

Abstract

Emerging data show that increased serum uric acid (SUA) concentration is an independent risk factor for end-stage renal disease. Treatment with the antihypertensive drug losartan lowers SUA. Whether reductions in SUA during losartan therapy are associated with renoprotection is unclear. We therefore tested this hypothesis. In a post hoc analysis of 1342 patients with type 2 diabetes mellitus and nephropathy participating in the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan Trial, we determined the relationship between month 6 change in SUA and renal endpoints, defined as a doubling of serum creatinine or end-stage renal disease. Baseline SUA was 6.7 mg/dL in placebo and losartan-treated subjects. During the first 6 months, losartan lowered SUA by -0.16 mg/dL (95% CI: -0.30 to -0.01; P=0.031) as compared with placebo. The risk of renal events was decreased by 6% (95% CI: 10% to 3%) per 0.5-mg/dL decrement in SUA during the first 6 months. This effect was independent of other risk markers, including estimate glomerular filtration rate and albuminuria. Adjustment of the overall treatment effects for SUA attenuated losartan's renoprotective effect from 22% (95% CI: 6% to 35%) to 17% (95% CI: 1% to 31%), suggesting that approximately one fifth of losartan's renoprotective effect could be attributed to its effect on SUA. Losartan lowers SUA levels compared with placebo treatment in patients with type 2 diabetes mellitus and nephropathy. The degree of reduction in SUA is subsequently associated with the degree in long-term renal risk reduction and explains part of losartan's renoprotective effect. These findings support the view that SUA may be a modifiable risk factor for renal disease.

Trial registration: ClinicalTrials.gov NCT00308347.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / administration & dosage*
  • Creatinine / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Hypertension / blood
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Losartan / administration & dosage*
  • Male
  • Middle Aged
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Uric Acid / blood*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Uric Acid
  • Creatinine
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT00308347