Amlodipine and long-term renoprotection in hypertensive patients with renal dysfunction

I have read with great interest Kumagai's study on the effect of amlodipine in 28 patients with renal dysfunction.1 The authors have prospectively compared the effects of amlodipine and ACEI (Enalapril) on renal function in hypertensive patients with renal impairment. They conclude that after 1 year “the effect of amlodipine on renal function is likely to be the same as that of ACEI.” I would like to make several comments on this study. Less than 40% of initially included patients were analyzed at 1 year. Such a high rate of drop out preclude from a strong final analysis. The American study of kidney disease and hypertension (AASK) pilot study2 is proposed as supporting Kumagai's results. Indeed after 6 months of treatment glomerular filtration rate (GFR) had increased by 5.7 mL/min/1.73 m2 with amlodipine, whereas it had decreased by 1.1 mL/min/1.73 m2 with enalapril. Unfortunately, recent results3 have obliged the safety committee of this study to stop amlodipine. Among individuals with roughly 1 or more grams per day of proteinuria, renal function deteriorated more slowly in those assigned to the ACEI ramipril and the beta blocker, metoprolol, than in those assigned to the calcium channel blocker amlodipine. The authors indicate that they would have shown earlier that amlodipine has an ability to dilate the efferent arterioles.4 In the cited article,4 it was clearly showed and stated by the authors that “at concentrations of 10−6 to 10−9 M, nifedipine, nicardipine and amlodipine dilated the afferent but not the efferent arteriole preconstricted with angiotensin II.” Those results may explain why GFR has increased in the first 6 months of treatment with amlodipine in the AASK study, and amlodipine was not shown to be renoprotective in this study. Only certain Ca blockers can dilate the efferent arteriole, ie, manidipine,4 efonidipine4 and felodipine.5 Those drugs may have renoprotective effects that will not be observed with amlodipine.