Prospective randomized study of the tolerability and efficacy of combination therapy for hypertensive chronic kidney disease: results of the PROTECT-CKD study

Background: We conducted a randomized, open-label trial to determine which of the antihypertensive drugs was most beneficial for CKD patients with hypertension in spite of treatment with an angiotensin receptor blocker (ARB). Methods: Patients 20–75 years of age who had CKD according to the definition in the K/DOQI Guidelines and hypertension (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg) with the usual dose of an ARB were randomly assigned to receive losartan 50 mg plus 5 mg of the calcium channel blocker amlodipine (CCB group, n = 37), 5 mg of the angiotensin-converting enzyme inhibitor enalapril (ACEI group, n = 36), or 12.5 mg of the thiazide diuretic hydrochlorothiazide (HCTZ group, n = 36). The primary endpoints were changes in blood pressure (BP), ratio of urinary excretion of protein to creatinine (UPCR), tolerability, and eGFR during the 12-month treatment period compared with control period. Results: There were no significant differences in BP and tolerability between the three groups. The percentage changes in UPCR at 12 months after start of the combination therapy were significantly different in the HCTZ group (−26.3 ± 11.1 %, mean ± SE) and CCB group (+46.7 ± 33.6 %, p < 0.05), while eGFR was significantly lower in the HCTZ group than in the ACEI group or CCB group at 4 months but not at 12 months. Conclusion: Addition of diuretics, CCB, or ACEI to ARB was equally effective for the control of hypertension in CKD, while, in terms of urinary excretion of protein, diuretics may be better than CCB.