Calcium Channel Blocker versus Angiotensin II Receptor Blocker in Autosomal Dominant Polycystic Kidney Disease

Abstract

Background: Although hypertension is commonly found in patients with autosomal dominant polycystic kidney disease (ADPKD), there is no consensus about which antihypertensive agents are most appropriate. The effects of calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB) on blood pressure and renoprotection were compared in hypertensive patients with ADPKD. Methods: We randomly assigned 49 participants to CCB amlodipine-based (2.5–10 mg/day) or ARB candesartan-based (2–8 mg/day) regimens. Twenty-five patients (13 males and 12 females) received amlodipine, and 24 patients (13 males and 11 females) received candesartan. This was followed up for 36 months. Results: Baseline characteristics were similar, and blood pressure was well controlled in both groups throughout the study period. Six out of 25 (24.0%) amlodipine and 1 out of 24 (4.2%) candesartan patients were terminated from the protocol due to a twofold increase in serum creatinine and/or decrease in creatinine clearance (Ccr) to half of the baseline. The renal event-free survival rate was significant (p < 0.05, Breslow-Gehan-Wilcoxon test). Serum creatinine was higher in the amlodipine group than in the candesartan group at 24 and 36 months (p < 0.05). The decrease in Ccr at 36 months was larger in the amlodipine group than in the candesartan group (ΔCcr: –20.9 ± 13.1 vs. –4.8 ± 13.8 ml/min, p < 0.01). Urinary protein excretion was significantly lower in the candesartan group than in the amlodipine group at 36 months. Urinary albumin excretion was significantly lower in the candesartan group than in the amlodipine group at 12, 24 and 36 months. Conclusions: The renoprotective effect of candesartan is considered more favorable than amlodipine in the treatment of ADPKD. This is independent of the antihypertensive effect per se.

The HALT Polycystic Kidney Disease Trials

“…With increasing cyst size, activation of the RAAS occurs, BP increases, and a vicious cycle ensues with enhanced cyst growth, hypertension, and more cyst growth, ultimately leading to ESRD. There are multiple randomized controlled trials in kidney disease addressing the impact of inhibition of RAAS on disease progression using ACEi that include ADPKD subjects (4,(15)(16)(17)(18)(19)(20)(21)(22). To date, no benefit of inhibition of the RAAS has shown benefit on progression to ESRD or rate of GFR decline (7).…”

A comparison of the effects of ramipril and losartan on blood pressure control and left ventricle hypertrophy in patients with autosomal dominant polycystic kidney disease

“…Considering the fact that the researchers claim that hypertension in polycystic kidney disease is renin dependent, the drugs that block the RAS may be more effective on the control of BP in these patients. 3,4,[10][11][12] In our study, we gave ramipril as an initial treatment to 13 of 32 hypertensive polycystic kidney disease patients and losartan to 19 patients. Four patients in the ramipril group and seven in the losartan group needed combination therapy.…”

“…The patients were followed up for 5 years, and their Cr Cl decrease was about 3.6 mL/min per year. In the study by Nutahara et al 4 in Japan, the efficacy of amlodipine and candesartan on 49 hypertensive polycystic kidney patients was compared. The Cr Cl decrease in the amlodipine group was about 5.5 mL/min per year and 1.6 mL/min in the candesartan group.…”

“…Although the exact mechanism of hypertension in ADPKD is not clarified yet, the most emphasized mechanism is activation of the reninangiotensin system (RAS) because of cyst expansion and pressure on the nearby tissues as a result of ischemia. 4 In this study, we aimed to find out whether ramipril or losartan, which blocks the RAS in different stages, would provide effective blood pressure (BP) control in this patient group and to compare their effects on LVH.…”

A Young Patient with a Family History of Hypertension

“…A number of small clinical trials have compared RAAS blockers (ACE inhibitors in most studies) with other drug classes on a variety of end points related in ADPKD, such as changes in renal function, albumin excretion, and left ventricular mass. In some studies, RAAS blockers performed better than calcium channel blockers or diuretics in slowing disease progression (37)(38)(39) or reducing proteinuria (37-39), but in others, RAAS blockers were equivalent to b-blockers for these same measures (40,41) or the progression of left ventricular hypertrophy (41). In no trial to date were RAAS blockers inferior to other agents; therefore, RAAS blockers should be used as preferred agents for not only the possible benefit in ADPKD but also, their well established value in prevention of cardiovascular disease in high-risk groups.…”