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

We would like to thank Dr. Deray for his constructive comments on our article entitled “Amlodipine is comparable to ACEI for long-term renoprotection in hypertensive patients with renal dysfunction: a one-year, prospective, randomized study.”1 We would like to respond to his comments. We know that NIH halted the amlodipine arm of the AASK study for the reason that decline of GFR in patients treated with amlodipine whose proteinuria was >1 g/day was a little greater than that with ramipril. However, patient population of our study1 was completely different from that in the AASK study. Pathogenesis of renal dysfunction of Japanese patients in our study was predominantly chronic glomerulonephritis, whereas pathogenesis in the AASK study was hypertensive nephrosclerosis of African American people. Moreover, the proportion of hypertensives that go on to any degree of renal dysfunction is far greater in African American than in whites or Japanese patients; only 7% of Japanese patients with hypertensive nephrosclerosis develop to this complication. Therefore, different findings in AASK study from ours are due to the special population. In AASK study, it was not planned to analyze the renal effect in terms of the level of baseline proteinuria. And yet, only 17% of 217 patients of amlodipine arm had proteinuria >1 g/day whose renal function deteriorated faster than those assigned to the ACEI. In other words, majority (83%) of patients was reno-protected with amlodipine who had proteinuria <1 g/day. The NIH decision of stopping amlodipine treatment was made based on post-hoc analysis, and it was applied to the very small portion of amlodipine group. Therefore, we do not think that it is appropriate to criticize our study by extrapolating the results of the AASK study. It is well known that renal response to Ca antagonists in any settings depends on the magnitude of basal renal vascular tone.2 In our article, we may have overemphasized the vasodilatory effect on the efferent arterioles of amlodipine to explain the observed comparable effects on serum creatinine and proteinuria of amlodipine to that of ACEI. Conversely, we recognize that amlodipine can dilate predominantly the afferent arterioles, and there is unique mechanism of the drug for renal blood flow (RBF) since Licata et al3 demonstrated that amlodipine increased RBF but did not increase GFR or filtration fraction. Finally, as Dr. Deray pointed out, since the dropout rate of this study is relatively high, a strong final analysis may be difficult to make.