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Angiotensin-Converting Enzyme Inhibitors and Progression of Nondiabetic Renal Disease: A Meta-Analysis of Patient-Level Data

Tazeen H. Jafar, MD, MPH; Christopher H. Schmid, PhD; Marcia Landa, MA; Ioannis Giatras, MD; Robert Toto, MD; Giuseppe Remuzzi, MD; Giuseppe Maschio, MD; Barry M. Brenner, MD; Annelise Kamper, MD; Pietro Zucchelli, MD; Gavin Becker, MD; Andres Himmelmann, MD; Kym Bannister, MD; Paul Landais, MD; Shahnaz Shahinfar, MD; Paul E. de Jong, MD, PhD; Dick de Zeeuw, MD; Joseph Lau, MD; Andrew S. Levey, MD, the ACE Inhibition in Progressive Renal Disease Study Group*
[+] Article and Author Information

From New England Medical Center, Tufts University School of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts; University of Texas at Southwestern, Dallas, Texas; Institute di Recherche, Farmacologiche “Mario Negri,” Bergamo, Ospedale Civile Maggiore, Verona, and Ospedale M. Malphigi, Bologna, Italy; Herlev Hospital, University of Copenhagen, Copenhagen, Denmark; The Royal Melbourne Hospital, Melbourne, and Royal Adelaide Hospital, Adelaide, Australia; Sahlgrenska University Hospital, Göteborg, Sweden; Hôpital Necker, Paris, France; Merck Research Laboratories, West Point, Pennsylvania; and University of Groningen, Groningen, the Netherlands.


Presented in abstract form at the 31st Annual Meeting of the American Society of Nephrology, 25 October 1998, Philadelphia, Pennsylvania; the 15th Congress of the International Society of Nephrology, 5 May 1999, Buenos Aires, Argentina; and the 32nd Annual Meeting of the American Society of Nephrology, 5 and 7 November 1999, Miami, Florida.

Grant Support: By grant RO1 DK53869A from the National Institute of Diabetes and Digestive and Kidney Diseases (Dr. Levey); grants RO1 HS08532 (Drs. Schmid and Lau) and RO1 HS 10064 (Dr. Schmid) from the Agency for Healthcare Research and Quality; grant 1097-5 from the Dialysis Clinic, Inc., Paul Teschan Research Fund (Dr. Jafar); New England Medical Center-St. Elizabeth's Hospital Medical Center Clinical Research Fellowship Program, Boston, Massachusetts (Dr. Jafar); and an unrestricted grant from Merck Research Laboratories, West Point, Pennsylvania (Dr. Levey).

Requests for Single Reprints: Andrew S. Levey, MD, Division of Nephrology, New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111.

Current Author Addresses: Dr. Jafar: Department of Medicine, The Aga Khan University, Stadium Road, PO Box 3500, Karachi, Pakistan.

Dr. Schmid: Division of Clinical Care Research, Biostatistics Research Center, New England Medical Center, Box 63, 750 Washington Street, Boston, MA 02111.

Ms. Landa: Division of Clinical Care Research, New England Medical Center, Box 63, 750 Washington Street, Boston, MA 02111.

Dr. Giatras: 50 G. Papandreou Street, Nea Erythrea, 14671 Athens, Greece.

Dr. Toto: Dallas Nephrology Associates, 6010 Forest Park Road, Suite 100, Dallas, TX 75235.

Dr. Remuzzi: Institute di Recherche, Farmacologiche “Mario Negri,” Via Gavezzeni 11, 24125 Bergamo, Italy.

Dr. Maschio: Division Nefrologia, Ospedale Civile Maggiore, 37126 Verona, Italy.

Dr. Brenner: Renal Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02111.

Dr. Kamper: Department of Nephrology, Herlev Hospital, University of Copenhagen, DK 2730 Herlev, Denmark.

Dr. Zucchelli: Department of Nephrology, Ospedale M. Malphigi, Via P. Palagi 9, Bologna, Italy.

Dr. Becker: Department of Nephrology, The Royal Melbourne Hospital, Grattan Street, Melbourne, Victoria 3050, Australia.

Dr. Himmelmann: Department of Clinical Pharmacology, Sahlgrenska University Hospital, S41345 Göteborg, Sweden.

Dr. Bannister: Renal Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Dr. Landais: Service d'Informatique et de Statistiques Médicales, Hôpital Necker, 161 rue de Sèvres, 75743 Paris Cedex 15, France.

Dr. Shahinfar: Merck Research Laboratories, 10 Sentry Parkway, Walton and Stenton Avenue, BL-1, Blue Bell, PA 19422.

Drs. de Jong and de Zeeuw: University of Groningen, Oostersingel 59, 9713 EZ Groningen, the Netherlands.

Dr. Lau: Division of Clinical Care Research, New England Medical Center, Box 827, 750 Washington Street, Boston, MA 02111.

Dr. Levey: Division of Nephrology, New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111.

Author Contributions: Conception and design: C.H. Schmid, I. Giatras, R. Toto, G. Remuzzi, G. Maschio, B.M. Brenner, A. Kamper, P. Zucchelli, G. Becker, A. Himmelmann, K. Bannister, P. Landais, S. Shahinfar, P.E. de Jong, D. de Zeeuw, J. Lau, A.S. Levey.

Analysis and interpretation of the data: T.H. Jafar, C.H. Schmid, M. Landa, J. Lau, A.S. Levey.

Drafting of the article: T.H. Jafar, C.H. Schmid, A.S. Levey.

Critical revision of the article for important intellectual content: T.H. Jafar, C.H. Schmid, M. Landa, R. Toto, P.E. de Jong, A.S. Levey.

Final approval of the article: T.H. Jafar, C.H. Schmid, M. Landa, I. Giatras, R. Toto, G. Remuzzi, G. Maschio, B.M. Brenner, A. Kamper, P. Zucchelli, G. Becker, A. Himmelmann, K. Bannister, P. Landais, S. Shahinfar, P.E. de Jong, D. de Zeeuw, J. Lau, A.S. Levey.

Provision of study materials or patients: R. Toto, G. Remuzzi, G. Maschio, B.M. Brenner, A. Kamper, P. Zucchelli, G. Becker, A. Himmelmann, K. Bannister, P. Landais, S. Shahinfar, P.E. de Jong, D. de Zeeuw, A.S. Levey.

Statistical expertise: C.H. Schmid, J. Lau.

Obtaining of funding: T.H. Jafar, C.H. Schmid, S. Shahinfar, J. Lau, A.S. Levey.

Administrative, technical, or logistic support: C.H. Schmid, M. Landa, A.S. Levey.

Collection and assembly of data: T.H. Jafar, M. Landa, I. Giatras, A.S. Levey.


Ann Intern Med. 2001;135(2):73-87. doi:10.7326/0003-4819-135-2-200107170-00007
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Chronic renal disease is a major public health problem in the United States. According to the 1999 Annual Data Report of the U.S. Renal Data System, more than 357 000 people have end-stage renal disease (ESRD), and the annual cost of treatment with dialysis and renal transplantation exceeds $15.6 billion (1). Patients undergoing dialysis have reduced quality of life, a high morbidity rate, and an annual mortality rate of 20% to 25% (1). Identification of therapies to prevent ESRD is an important public health goal.

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Figure 1.
Blood pressure (A), urinary protein excretion (B), survival without end-stage renal disease (ESRD) (C), or the combined outcome of doubling of baseline serum creatinine concentration or ESRD (D) during follow-up among patients taking angiotensin-converting enzyme inhibitors (ACEI) (dotted line) and controls (solid line).

Follow-up measurements were reported more often during the first 2 years and less often thereafter. Mean blood pressure and mean urinary protein excretion during follow-up were defined as the mean of all available follow-up values for each patient. Change during follow-up was defined as the baseline value minus the mean follow-up value for each patient. The number of patients with follow-up data available for analysis of survival without ESRD is shown below the x-axis of panel C. Slightly fewer patients had follow-up measurements of blood pressure and urinary protein excretion than for ascertainment of ESRD.

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Figure 2.
Risk for end-stage renal disease (ESRD) (A), combined outcome of doubling of serum creatinine or ESRD (B), or relative risk for these outcomes (CandD) in patients taking angiotensin-converting enzyme inhibitors (squares) and controls (circles), according to baseline urinary protein excretion.upper rowlower rowP

The values above the graphs in panels A and B are the fraction of patients with events in the control group ( ) and angiotensin-converting enzyme inhibitor group ( ). Relative risks were calculated from multivariable models controlling for significant baseline patient and study characteristics. The solid horizontal line at a relative risk of 1.0 in panels C and D indicates no difference between the ACE inhibitor and control groups; the solid and dotted curved lines represent point estimates and 95% CIs for the relative risks. values for tests for interaction between baseline urinary protein excretion and treatment were 0.03 and 0.001, respectively.

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Summary for Patients

Using a Type of Blood Pressure Medicine, Angiotensin-Converting Enzyme Inhibitors, To Prevent Worsening of Kidney Disease Unrelated to Diabetes

The summary below is from the full report titled “Angiotensin-Converting Enzyme Inhibitors and Progression of Nondiabetic Renal Disease. A Meta-Analysis of Patient-Level Data.” It is in the 17 July 2001 issue of Annals of Internal Medicine (volume 135, pages 73-87). The authors are TH Jafar, CH Schmid, M Landa, I Giatras, R Toto, G Remuzzi, G Maschio, BM Brenner, A Kamper, P Zucchelli, G Becker, A Himmelmann, K Bannister, P Landais, S Shahinfar, PE de Jong, D de Zeeuw, J Lau, and AS Levey, for the ACE Inhibition in Progressive Renal Disease Study Group.

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