Renoprotect and blood pressure lowering effect of low-dose hydrochlorothiazide added to intensive renin-angiotensin inhibition in hypertensive patients with chronic kidney disease

Abstract

Combination therapy with angiotensin II Type I receptor blocker 50 mg of losartan and a fixed combination of losartan (50 mg)/hydrochlorothiazide (12.5 mg) was administered to hypertensive patients with Stage 3 - 4 chronic kidney disease to investigate its renoprotective effect. Subjects already being administered the angiotensin I-converting enzyme inhibitor enalapril and losartan 100 mg daily were enrolled in this open-labeled trial (n = 40). Administration of 100 mg losartan twice daily was replaced with losartan (50 mg)/hydrochlorothiazide (12.5 mg) once daily after the morning meal and losartan at 50 mg once daily after the evening meal for the 24-week study period. The mixture of losartan/hydrochlorothiazide significantly reduced systolic and diastolic blood pressures by 14.7 and 7.4 mmHg, respectively, compared with the baseline values. No significant changes were observed in the serum creatinine levels and estimated glomerular filtration rate. The urinary protein/creatinine ratio was, however, significantly decreased. Similarly, the regression line of 1/serum creatinine level was significantly increased after administration of losartan/hydrochlorothiazide. None of the patients exhibited a significant increase in the occurrence of adverse effects. Our results demonstrated that a low dose of hydrochlorothiazide had a renoprotective effect due to its blood pressure-lowering effect. We accordingly propose that a low dose of hydrochlorothiazide should be administered to those patients in whom the blood pressure is not well controlled by intensive renin-angiotensin system inhibition therapy using the maximum recommended doses of angiotensin II Type I receptor blockers and angiotensin I-converting enzyme inhibitors.