Effects of Irbesartan on Uric Acid Metabolism in Patients with Treated Essential Hypertension

Background: Irbesartan has been reported to inhibit renal uric acid reabsorption and thereby decrease serum uric acid (Sur) levels. However, its effect on uric acid metabolism in hypertensive patients has not been reported. Methods and Results: We conducted a retrospective observational study that included 40 hypertensive patients to clarify the effects of irbesartan (mean dose 87.5 mg) on blood pressure (BP) and uric acid metabolism [Sur, urinary uric acid (Uur), serum creatinine (Scr), urinary creatinine (Ucr), uric acid clearance (Cur), creatinine clearance (Ccr), urinary uric acid to urinary creatinine ratio (Uur/Ucr), and uric acid clearance to creatinine clearance ratio (Cur/Ccr)] at baseline and after 3 months of treatment. We allocated patients into two groups, patients with Uur/Ucr <0.5 (low Uur/Ucr group) or those with Uur/Ucr 0.5 (normal/ high Uur/Ucr group), into other two groups, patients with Cur/Ccr <5.5% (low Cur/Ccr group) or those with Cur/Ccr 5.5% (normal/ high Cur/Ccr group). The hypoexcretion group contained low Uur/Ucr group and low Cur/Ccr group, and the normal/ hyperexcretion group contained normal/high Uur/Ucr group and normal/ high Cur/Ccr group. Further, we allocated patients into another two groups, patients with Sur 7 mg/dl (hyperuricemic group) or those with Sur <7 mg/dl (normouricemic group). Irbesartan significantly decreased systolic BP without affecting heart rate, and decreased Sur without altering Uur/Ucr or Cur/Ccr. In the hypoexcretion group, irbesartan decreased Sur while increasing Uur/Ucr and Cur/Ccr. In contrast, in the normal/hyperexcretion and hyperuricemic groups, irbesartan decreased Sur without changing Uur/Ucr or Cur/ Ccr. In a normouricemic group, patients showed no changes in Sur after treatment with irbesartan. Conclusions: Irbesartan improved the secretion of uric acid, and reduced Sur in the hypoexcretion group, but did not influence uric acid excretion in the normal/hyperexcretion group. In hyperuricemic patients, irbesartan did not affect uric acid excretion but may have influenced uric acid production.

[1]  I. Hisatome,et al.  Depletion of Uric Acid Due to SLC22A12 (URAT1) Loss-of-Function Mutation Causes Endothelial Dysfunction in Hypouricemia. , 2015, Circulation journal : official journal of the Japanese Circulation Society.

[2]  Y. Moriwaki,et al.  Effects of azelnidipine on uric acid metabolism in patients with essential hypertension , 2014, Clinical and experimental hypertension.

[3]  I. Hisatome,et al.  Effects of irbesartan on serum uric acid levels in patients with hypertension and diabetes , 2014, Clinical pharmacology : advances and applications.

[4]  Xiang-dong Chen,et al.  [The efficacy and safety of high-dose irbesartan in treatment of clinical proteinuria in patients with chronic kidney disease]. , 2011, Zhonghua nei ke za zhi.

[5]  Hisashi Yamanaka,et al.  Japanese Guideline for the Management of Hyperuricemia and Gout: Second Edition , 2011, Nucleosides, nucleotides & nucleic acids.

[6]  G. Derosa,et al.  Endothelial function, blood pressure control, and risk modification: impact of irbesartan alone or in combination , 2010, Integrated blood pressure control.

[7]  I. Hisatome,et al.  Plasma Urate Level Is Directly Regulated by a Voltage-driven Urate Efflux Transporter URATv1 (SLC2A9) in Humans* , 2008, Journal of Biological Chemistry.

[8]  I. Hisatome,et al.  Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients. , 2008, American journal of hypertension.

[9]  T. Tsuchihashi,et al.  Prevalence and Lifestyle Characteristics of Hypertensive Patients with Metabolic Syndrome Followed at an Outpatient Clinic in Fukuoka, Japan , 2007, Hypertension Research.

[10]  A. Palmer,et al.  Cost-effectiveness of irbesartan in diabetic nephropathy: a systematic review of published studies. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[11]  K. Tuttle,et al.  Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? , 2003, Hypertension.

[12]  Hirotaka Matsuo,et al.  Molecular identification of a renal urate–anion exchanger that regulates blood urate levels , 2002, Nature.

[13]  K. Iseki,et al.  Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. , 2001, Hypertension research : official journal of the Japanese Society of Hypertension.

[14]  K. Okada,et al.  Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: The Osaka Health Survey , 2001, Journal of hypertension.

[15]  I. Hisatome,et al.  The release of the substrate for xanthine oxidase in hypertensive patients was suppressed by angiotensin converting enzyme inhibitors and α1-blockers , 2001, Journal of hypertension.

[16]  H. Ward.  Uric acid as an independent risk factor in the treatment of hypertension , 1998, The Lancet.

[17]  R. Bigazzi,et al.  Effect of insulin on renal sodium and uric acid handling in essential hypertension. , 1996, American journal of hypertension.

[18]  F. Messerli,et al.  Serum uric acid in essential hypertension: an indicator of renal vascular involvement. , 1980, Annals of internal medicine.

[19]  J. Laragh,et al.  Hyperuricemia in primary and renal hypertension. , 1966, The New England journal of medicine.

[20]  P. Jutabha,et al.  Concentration-dependent inhibitory effect of irbesartan on renal uric acid transporters. , 2010, Journal of pharmacological sciences.

[21]  B. Wang,et al.  Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population , 2006, Journal of Human Hypertension.

[22]  I. Hisatome,et al.  Renal hypouricemia with both drug-insensitive secretion and defective reabsorption of urate: a novel type of renal hypouricemia. , 1993, Nephron.

[23]  I. Hisatome,et al.  Cause of persistent hypouricemia in outpatients. , 1989, Nephron.