Background Angiotensin-convertingenzyme inhibitors providerenal protection in patients with mild-to-moderate renal insufficiency(serum creatinine level, 3.0 mg per deciliter or less). We assessedthe efficacy and safety of benazepril in patients without diabeteswho had advanced renal insufficiency.
Methods We enrolled 422 patients in a randomized, double-blindstudy. After an eight-week run-in period, 104 patients withserum creatinine levels of 1.5 to 3.0 mg per deciliter (group1) received 20 mg of benazepril per day, whereas 224 patientswith serum creatinine levels of 3.1 to 5.0 mg per deciliter(group 2) were randomly assigned to receive 20 mg of benazeprilper day (112 patients) or placebo (112 patients) and then followedfor a mean of 3.4 years. All patients received conventionalantihypertensive therapy. The primary outcome was the compositeof a doubling of the serum creatinine level, end-stage renaldisease, or death. Secondary end points included changes inthe level of proteinuria and the rate of progression of renaldisease.
Results Of 102 patients in group 1, 22 (22 percent) reachedthe primary end point, as compared with 44 of 108 patients givenbenazepril in group 2 (41 percent) and 65 of 107 patients givenplacebo in group 2 (60 percent). As compared with placebo, benazeprilwas associated with a 43 percent reduction in the risk of theprimary end point in group 2 (P=0.005). This benefit did notappear to be attributable to blood-pressure control. Benazepriltherapy was associated with a 52 percent reduction in the levelof proteinuria and a reduction of 23 percent in the rate ofdecline in renal function. The overall incidence of major adverseevents in the benazepril and placebo subgroups of group 2 wassimilar.
Conclusions Benazepril conferred substantial renal benefitsin patients without diabetes who had advanced renal insufficiency.(ClinicalTrials.gov number, NCT00270426
[ClinicalTrials.gov]
.)
Source Information
From the Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Address reprint requests to Dr. Hou at the Renal Division, Nanfang Hospital, 1838 N. Guangzhou Ave., Guangzhou 510515, China, or at ffhou{at}public.guangzhou.gd.cn.
Fang, W., Oreopoulos, D. G., Bargman, J. M.
(2008). Use of ACE inhibitors or angiotensin receptor blockers and survival in patients on peritoneal dialysis. Nephrol Dial Transplant
0: gfn321v1-gfn321
[Abstract][Full Text]
Appel, L. J., Wright, J. T. Jr, Greene, T., Kusek, J. W., Lewis, J. B., Wang, X., Lipkowitz, M. S., Norris, K. C., Bakris, G. L., Rahman, M., Contreras, G., Rostand, S. G., Kopple, J. D., Gabbai, F. B., Schulman, G. I., Gassman, J. J., Charleston, J., Agodoa, L. Y., for the African American Study of Kidney Disease a,
(2008). Long-term Effects of Renin-Angiotensin System-Blocking Therapy and a Low Blood Pressure Goal on Progression of Hypertensive Chronic Kidney Disease in African Americans. Arch Intern Med
168: 832-839
[Abstract][Full Text]
Garg, A. X., Greene, T., Levin, N. W.
(2008). A well-conducted randomized trial that establishes no benefit of therapy is an important medical advance. Nephrol Dial Transplant
23: 52-55
[Full Text]
van Domburg, R. T., Hoeks, S. E., Welten, G. M.J.M., Chonchol, M., Elhendy, A., Poldermans, D.
(2008). Renal Insufficiency and Mortality in Patients with Known or Suspected Coronary Artery Disease. J. Am. Soc. Nephrol.
19: 158-163
[Abstract][Full Text]
Goldfarb, S.
(2008). Update in Nephrology. ANN INTERN MED
148: 49-54
[Full Text]
Jennings, D. L, Taber, D. J
(2008). Use of Renin-Angiotensin-Aldosterone System Inhibitors Within the First Eight to Twelve Weeks After Renal Transplantation. The Annals of Pharmacotherapy
42: 116-120
[Abstract][Full Text]
Harrington, D. W., Munekata, M. T.
(2007). Update in General Internal Medicine. ANN INTERN MED
147: 104-116
[Full Text]
Hou, F. F., Xie, D., Zhang, X., Chen, P. Y., Zhang, W. R., Liang, M., Guo, Z. J., Jiang, J. P.
(2007). Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: A Randomized Controlled Study of Benazepril and Losartan in Chronic Renal Insufficiency. J. Am. Soc. Nephrol.
18: 1889-1898
[Abstract][Full Text]
Mizobuchi, M., Morrissey, J., Finch, J. L., Martin, D. R., Liapis, H., Akizawa, T., Slatopolsky, E.
(2007). Combination Therapy with an Angiotensin-Converting Enzyme Inhibitor and a Vitamin D Analog Suppresses the Progression of Renal Insufficiency in Uremic Rats. J. Am. Soc. Nephrol.
18: 1796-1806
[Abstract][Full Text]
Zitta, S., Holzer, H., Reibnegger, G., Estelberger, W.
(2007). Recalibration of population-based GFR formulae by pharmacokinetic methods. Nephrol Dial Transplant
22: 665-665
[Full Text]
Vernaglione, L.
(2007). Impact of enalapril on renal function in patients with severe chronic kidney disease. Nephrol Dial Transplant
22: 665-666
[Full Text]
Kamper, A.-L.
(2007). The importance of a correct evaluation of progression in studies on chronic kidney disease. Nephrol Dial Transplant
22: 3-5
[Full Text]
Edwards, N.C., Steeds, R.P., Ferro, C.J., Townend, J.N.
(2006). The treatment of coronary artery disease in patients with chronic kidney disease. QJM
99: 723-736
[Abstract][Full Text]
Jose, P., Skali, H., Anavekar, N., Tomson, C., Krumholz, H. M., Rouleau, J. L., Moye, L., Pfeffer, M. A., Solomon, S. D., for the SAVE Investigators,
(2006). Increase in Creatinine and Cardiovascular Risk in Patients with Systolic Dysfunction after Myocardial Infarction. J. Am. Soc. Nephrol.
17: 2886-2891
[Abstract][Full Text]
Mann, J. F. E., McClellan, W. M., Kunz, R., Ritz, E.
(2006). Progression of renal disease--can we forget about inhibition of the renin-angiotensin system?. Nephrol Dial Transplant
21: 2348-2351
[Full Text]
Griffin, K. A., Bidani, A. K.
(2006). Progression of Renal Disease: Renoprotective Specificity of Renin-Angiotensin System Blockade. CJASN
1: 1054-1065
[Abstract][Full Text]
Strauss, M. H., Hall, A. S.
(2006). Angiotensin Receptor Blockers May Increase Risk of Myocardial Infarction: Unraveling the ARB-MI Paradox. Circulation
114: 838-854
[Full Text]
(2006). Additional articles abstracted in ACP Journal Club. Evid. Based Med.
11: 126-126
[Full Text]
Solomon, S. D., Rice, M. M., A. Jablonski, K., Jose, P., Domanski, M., Sabatine, M., Gersh, B. J., Rouleau, J., Pfeffer, M. A., Braunwald, E., for the Prevention of Events with ACE inhibition (,
(2006). Renal Function and Effectiveness of Angiotensin-Converting Enzyme Inhibitor Therapy in Patients With Chronic Stable Coronary Disease in the Prevention of Events with ACE inhibition (PEACE) Trial. Circulation
114: 26-31
[Abstract][Full Text]
Bloom, J. M., Jaber, B. L., Madias, N. E., Hou, F. F., Zhang, X.
(2006). Benazepril for advanced chronic renal insufficiency.. NEJM
354: 1530-1531
[Full Text]
Malik, I.
(2006). JournalScan. Heart
92: 430-432
[Full Text]
Mahmoudi, A., Blumenthal, D., Hsiao, W.
(2006). The evolving Chinese health care system.. NEJM
354: 876-876
[Full Text]