Benazepril for Advanced Chronic Renal Insufficiency
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In the article by Hou et al. and the accompanying editorial by Hebert (Jan. 12 issue)1,2 regarding the safety of therapy with angiotensin-converting–enzyme (ACE) inhibitors for patients with advanced chronic renal insufficiency, it is important to note that patients with diabetes were excluded from the study. Moreover, the population of the United States has a much higher incidence of diabetes mellitus as a cause of advanced chronic renal insufficiency than does the population of China.3 Since the hyperkalemic manifestation of type 4 renal tubular acidosis commonly associated with diabetes mellitus may predispose patients to considerable hyperkalemia when an ACE inhibitor is added, caution is needed before the widespread application of ACE inhibitors in the United States.
Jeffrey M. Bloom, M.D.
Central Coast Primary Care
San Luis Obispo, CA 93401
jmb4u2c@charter.net
References
Hou FF, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 2006;354:131-140.
Hebert LA. Optimizing ACE-inhibitor therapy for chronic kidney disease. N Engl J Med 2006;354:189-191.
Young EW. An improved understanding of the causes of end-stage renal disease. Semin Nephrol 1997;17:170-175.
To the Editor: Hou et al. demonstrated that benazepril has renal protective effects and is safe in Chinese patients with advanced chronic kidney disease. Their results (as shown in Figure 3A of the article) indicate that after eight months of treatment, blood pressure was lower than 130/80 mm Hg, the established target for chronic kidney disease.1 This attained blood pressure is remarkably lower than that achieved in two other trials,2,3 in which the stage of kidney disease was less advanced, probably in association with less resistant hypertension. We can only speculate about whether this patient population was more diligent in adhering to dietary sodium restriction and to antihypertensive-drug therapy and whether genetic differences might have contributed to the difference in blood-pressure response. Indeed, the D allele of the insertion–deletion polymorphism of the ACE gene is associated with elevated ACE activity, and its frequency varies between white and Asian populations.4 It is plausible that benazepril was more effective in light of these speculative differences. Data on adherence to sodium restriction and the drug regimen throughout the trial and the performance of stratified analyses according to insertion–deletion genotypes of ACE might offer insight.
Bertrand L. Jaber, M.D.
Nicolaos E. Madias, M.D.
Caritas St. Elizabeth's Medical Center
Boston, MA 02135
bertrand.jaber@caritaschristi.org
References
K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004;43:Suppl 1:S1-S290.
Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996;334:939-945.
The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997;349:1857-1863.
Kunz R, Bork JP, Fritsche L, Ringel J, Sharma AM. Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: a methodologic appraisal and systematic review. J Am Soc Nephrol 1998;9:1653-1663.
The authors reply: Our article indicates that the ACE inhibitor benazepril has renal protective effects and appears safe in patients without diabetes who have stage 4 chronic kidney disease. Although the trial was conducted among Chinese patients, similar renal benefits from ACE inhibitors have also been reported in non-Asian patients with advanced nondiabetic chronic kidney disease.1,2
Our results indicate that therapy with ACE inhibitors was superior to therapy with conventional antihypertensive agents when the currently recommended target blood pressure (130/80 mm Hg) was achieved. This is particularly notable when one considers that, in many published trials, attained blood pressures were consistently higher than the target. It is plausible that the renal protective effect of ACE inhibitors is at least partially independent of a reduction in blood pressure. We agree with the supposition of Drs. Jaber and Madias that the optimal blood-pressure control in our patients might be associated with good adherence to dietary salt restriction and to the drug regimen. Indeed, we observed that more than 80 percent of participants appeared to adhere to therapy, on the basis of clinical evaluation throughout the follow-up period. Studies examining the association between differences in the ACE gene polymorphism and the efficacy of ACE inhibitors have had contradictory results.3 However, in a controlled trial performed among Japanese patients with nondiabetic chronic kidney disease whose blood pressure was maintained at an average of 126/72 mm Hg with ACE inhibitors, no significant correlation was observed between the ACE gene polymorphism and the efficacy of the intervention or renal outcome.4
We agree with Dr. Bloom's comments. Given the lack of controlled studies of either the efficacy or the safety of ACE inhibitors (or angiotensin-receptor blockers) in patients with diabetes who have advanced chronic kidney disease, the issue of whether ACE inhibitors (or angiotensin-receptor blockers) can be used safely in this patient population remains to be clarified.
Fan Fan Hou, M.D., Ph.D.
Xun Zhang, M.D.
Nanfang Hospital
Guangzhou 510515, China
ffhou@public.guangzhou.gd.cn
References
Ihle BU, Whitworth JA, Shahinfar S, Cnaan A, Kincaid-Smith PS, Becker GJ. Angiotensin-converting enzyme inhibition in nondiabetic progressive renal insufficiency: a controlled double-blind trial. Am J Kidney Dis 1996;27:489-495.
Ruggenenti P, Perna A, Remuzzi G, Gruppo Italiano di Studi Epidemiologici in Nefrologia. ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. J Am Soc Nephrol 2001;12:2832-2837.
Praga M. Slowing the progression of renal failure. Kidney Int Suppl 2002;80:18-22.
Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2003;361:117-124.
Jeffrey M. Bloom, M.D.
Central Coast Primary Care
San Luis Obispo, CA 93401
jmb4u2c@charter.net
References
Hou FF, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 2006;354:131-140.
Hebert LA. Optimizing ACE-inhibitor therapy for chronic kidney disease. N Engl J Med 2006;354:189-191.
Young EW. An improved understanding of the causes of end-stage renal disease. Semin Nephrol 1997;17:170-175.
To the Editor: Hou et al. demonstrated that benazepril has renal protective effects and is safe in Chinese patients with advanced chronic kidney disease. Their results (as shown in Figure 3A of the article) indicate that after eight months of treatment, blood pressure was lower than 130/80 mm Hg, the established target for chronic kidney disease.1 This attained blood pressure is remarkably lower than that achieved in two other trials,2,3 in which the stage of kidney disease was less advanced, probably in association with less resistant hypertension. We can only speculate about whether this patient population was more diligent in adhering to dietary sodium restriction and to antihypertensive-drug therapy and whether genetic differences might have contributed to the difference in blood-pressure response. Indeed, the D allele of the insertion–deletion polymorphism of the ACE gene is associated with elevated ACE activity, and its frequency varies between white and Asian populations.4 It is plausible that benazepril was more effective in light of these speculative differences. Data on adherence to sodium restriction and the drug regimen throughout the trial and the performance of stratified analyses according to insertion–deletion genotypes of ACE might offer insight.
Bertrand L. Jaber, M.D.
Nicolaos E. Madias, M.D.
Caritas St. Elizabeth's Medical Center
Boston, MA 02135
bertrand.jaber@caritaschristi.org
References
K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004;43:Suppl 1:S1-S290.
Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996;334:939-945.
The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997;349:1857-1863.
Kunz R, Bork JP, Fritsche L, Ringel J, Sharma AM. Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: a methodologic appraisal and systematic review. J Am Soc Nephrol 1998;9:1653-1663.
The authors reply: Our article indicates that the ACE inhibitor benazepril has renal protective effects and appears safe in patients without diabetes who have stage 4 chronic kidney disease. Although the trial was conducted among Chinese patients, similar renal benefits from ACE inhibitors have also been reported in non-Asian patients with advanced nondiabetic chronic kidney disease.1,2
Our results indicate that therapy with ACE inhibitors was superior to therapy with conventional antihypertensive agents when the currently recommended target blood pressure (130/80 mm Hg) was achieved. This is particularly notable when one considers that, in many published trials, attained blood pressures were consistently higher than the target. It is plausible that the renal protective effect of ACE inhibitors is at least partially independent of a reduction in blood pressure. We agree with the supposition of Drs. Jaber and Madias that the optimal blood-pressure control in our patients might be associated with good adherence to dietary salt restriction and to the drug regimen. Indeed, we observed that more than 80 percent of participants appeared to adhere to therapy, on the basis of clinical evaluation throughout the follow-up period. Studies examining the association between differences in the ACE gene polymorphism and the efficacy of ACE inhibitors have had contradictory results.3 However, in a controlled trial performed among Japanese patients with nondiabetic chronic kidney disease whose blood pressure was maintained at an average of 126/72 mm Hg with ACE inhibitors, no significant correlation was observed between the ACE gene polymorphism and the efficacy of the intervention or renal outcome.4
We agree with Dr. Bloom's comments. Given the lack of controlled studies of either the efficacy or the safety of ACE inhibitors (or angiotensin-receptor blockers) in patients with diabetes who have advanced chronic kidney disease, the issue of whether ACE inhibitors (or angiotensin-receptor blockers) can be used safely in this patient population remains to be clarified.
Fan Fan Hou, M.D., Ph.D.
Xun Zhang, M.D.
Nanfang Hospital
Guangzhou 510515, China
ffhou@public.guangzhou.gd.cn
References
Ihle BU, Whitworth JA, Shahinfar S, Cnaan A, Kincaid-Smith PS, Becker GJ. Angiotensin-converting enzyme inhibition in nondiabetic progressive renal insufficiency: a controlled double-blind trial. Am J Kidney Dis 1996;27:489-495.
Ruggenenti P, Perna A, Remuzzi G, Gruppo Italiano di Studi Epidemiologici in Nefrologia. ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. J Am Soc Nephrol 2001;12:2832-2837.
Praga M. Slowing the progression of renal failure. Kidney Int Suppl 2002;80:18-22.
Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2003;361:117-124.