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

Yan Miao, Stefan A. Ottenbros, Goos D. Laverman, Barry M. Brenner, Mark E. Cooper, Hans Henrik Parving, Diederick E. Grobbee, Shahnaz Shahinfar, Dick De Zeeuw, Hiddo Lambers Heerspink

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124 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2-7
Number of pages6
JournalHypertension
Volume58
Issue number1
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

Keywords

  • angiotensin receptor blocker
  • diabetic nephropathy
  • losartan
  • serum uric acid
  • type 2 diabetes mellitus

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