Candesartan Cilexetil on Regular Hemodialysis: Inability to Reduce Excessive Thirst, but Good Tolerance and Efficacy in Hypertensive Patients

It has been postulated that hypertension and interdialytic weight gain in hemodialysis patients are related to the activation of the renin-angiotensin system. Angiotensin II type 1 (ATI) receptor antagonists are new anti-hypertensive agents and are currently the most specific means of blocking the renin-angiotensin enzymatic cascade. Recent studies show that candesartan cilexetil regulates thirst and hypertension in rodents, via cerebral AT1 receptor blockade. We therefore conducted a prospective open study of candesartan cilexetil in 21 hypertensive patients on long-term hemodialysis during 6 weeks, focusing on thirst regulation. We also performed a prospective follow-up study of tolerance of candesartan and its anti-hypertensive efficacy after this 6-week study, while the patients remained on this therapy. Weight gain between hemodialysis sessions did not differ between the periods before and during candesartan cilexetil therapy. Median absolute interdialytic weight gain was 2.35 kg (range: 0.55-5) before therapy, compared to 2.25 kg (range: 0.35-4.65) during therapy (p > 0.05, Wilcoxon test). The median interdialytic weight gain/dry weight index was 3.7% (range: 1.15-7) before therapy and 3.6% (range: 0.7-6.6) during candesartan therapy (p > 0.05, Wilcoxon test). The median dose of candesartan cilexetil was 12 mg/day (range: 4-24). The median total duration of therapy with candesartan (including the 6 weeks of the thirst study) was 12 months (range: 2-25). During candesartan cilexetil therapy, the number of concomitant anti-hypertensive drugs per patient fell significantly (median number of anti-hypertensive drugs before candesartan =2 (range: 1-6); during candesartan =1 (range: 1-5) (p < 0.02, Wilcoxon test). No anaphylactoid reactions occurred. A total of 161 episodes of hypotension (5%) occurred during 3074 hemodialysis sessions (including the 6 weeks of the thirst study) We conclude that, like angiotensin converting enzyme inhibitors and the other angiotensin receptor antagonists, candesartan cilexetil is unable to reduce interdialytic weight gain in hemodialysis patients. This study also shows that the irreversible angiotensin II receptor antagonist candesartan cilexetil is a safe and effective therapeutic option for hypertensive hemodialysis patients.