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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 58; no. 1; pp. 2 - 7
• Main Authors: Miao, Yan, Ottenbros, Stefan A., Laverman, Goos D., Brenner, Barry M., Cooper, Mark E., Parving, Hans-Henrik, Grobbee, Diederick E., Shahinfar, Shahnaz, de Zeeuw, Dick, Lambers Heerspink, Hiddo J.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.07.2011; Lippincott Williams & Wilkins
• Subjects: Angiotensin II Type 1 Receptor Blockers - administration & dosage; Antihypertensive agents; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; 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; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Risk Factors; Time Factors; Treatment Outcome; Uric Acid - blood; Endocrinopathy; Type 2 diabetes; Imidazole derivatives; Tetrazole derivatives; Prognosis; Peptide hormone; Non peptide compound; Cardiovascular disease; angiotensin receptor blocker; Octapeptide; Losartan; type 2 diabetes mellitus; serum uric acid; Angiotensin II; Kidney disease; Hypertension; Urinary system disease; Metabolic diseases; Uric acid; Nephropathy; Treatment; Biphenyl derivatives; Antihypertensive agent; Sartan derivatives; Angiotensin antagonist; diabetic nephropathy
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.111.171488

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% CI10% 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 losartanʼs renoprotective effect from 22% (95% CI6% to 35%) to 17% (95% CI1% to 31%), suggesting that approximately one fifth of losartanʼs 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 losartanʼs renoprotective effect. These findings support the view that SUA may be a modifiable risk factor for renal disease.