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Antiproteinuric and blood pressure-lowering effects of a fixed-dose combination of losartan and hydrochlorothiazide in hypertensive patients with stage 3 chronic kidney disease.

Author(s): Abe M, Okada K, Maruyama T, Matsumoto K

Affiliation(s): Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. mabe@med.nihon-u.ac.jp

Publication date & source: 2009-09, Pharmacotherapy., 29(9):1061-72.

Publication type: Randomized Controlled Trial

STUDY OBJECTIVE: To compare the renoprotective and blood pressure-lowering effects of combination losartan-low-dose hydrochlorothiazide with losartan alone in hypertensive patients with stage 3 chronic kidney disease (CKD). DESIGN: Prospective, open-label, randomized, controlled study. SETTING: Outpatient clinic at a university-affiliated hospital in Japan. PATIENTS: Sixty adults (mean age 67 yrs) with stage 3 CKD who had been receiving losartan 50 mg/day and had not achieved their target blood pressure of 130/80 mm Hg. INTERVENTION: Patients were randomly assigned to receive combination losartan 50 mg-hydrochlorothiazide 12.5 mg/day in addition to losartan 50 mg/day (combination therapy group, 30 patients) or to receive losartan 100 mg/day (control group, 30 patients) over a 24-week period. MEASUREMENTS AND MAIN RESULTS: Efficacy was determined by monitoring clinical and laboratory parameters. Mean baseline systolic and diastolic blood pressures were 158/90 mm Hg in both groups; at 24 weeks of treatment, these blood pressures significantly decreased to 133/79 mm Hg in the combination therapy group compared with both baseline and the values in the control group (145/83 mm Hg). Although serum creatinine concentration increased and the estimated glomerular filtration rate decreased significantly in both groups, the urinary protein:creatinine ratio was significantly lower in the combination therapy group. With stratification of patients on the basis of whether they had diabetes mellitus, we found that the reduction in the urinary protein:creatinine ratio was more evident in the combination therapy group. No significant increase in the occurrence of adverse metabolic effects was noted in either group. CONCLUSION: In these hypertensive patients with stage 3 CKD, combination therapy with the maximum recommended daily dose of losartan of 100 mg and a low dose of hydrochlorothiazide of 12.5 mg ameliorated proteinuria and reduced blood pressure more effectively than treatment with losartan 100 mg alone, irrespective of whether the patients had diabetes.

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