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The aim of the study is to compare the effects of hydrochlorothiazide and indapamide on the kidney in patients with hypertension inadequately controlled with losartan. A total of 140 patients who met the criteria and inadequately controlled with losartan 50 mg per day for 2 weeks were randomized in two groups and administered either hydrochlorothiazide 12.5 mg per day (n = 70) or indapamide (sustained release) 1.5 mg per day (n = 70) in combination with losartan 50 mg per day. Office blood pressure (BP) were collected at baseline and upon each follow-up visit. Creatinine, urine albumin-creatinine ratio (ACR), urine neutrophil gelatinaseassociated lipocalin (NGAL) and renal resistive index (RRI) were also collected at baseline and at the 24-week follow-up. None of the baseline characteristics was statistically significantly different between the two groups. After excluding those patients with office BP uncontrolled, 46 patients in the hydrochlorothiazide group (45.7% males, 58.8 ± 10.8 years) and 44 patients in the indapamide group (38.4% males, 61.5 ± 10.9 years) were analysed. There were insignificant changes in creatinine and significant decreases in ACR, NGAL and RRI compared to baseline levels in the two groups. The decrease in ACR (3.8 (0, 28.7) vs 4.2 (0.4, 64.8) mg g-1, P = 0.485) was not significantly different between the two groups, while the decrease in NGAL (16.07 ± 7.07 vs 28.77 ± 7.64 ng ml-1, P < 0.001) and RRI (0.04 ± 0.02 vs 0.07 ± 0.04, P < 0.001) was more significant in the indapamide group than in the hydrochlorothiazide group. In conclusion, indapamide is superior to hydrochlorothiazide to improve renal tubular injury and renal haemodynamics in combination with losartan in hypertensive patients with controlled BP.