Progression of Chronic Kidney Disease: The Role of Blood Pressure Control, Proteinuria, and Angiotensin-Converting Enzyme Inhibition: A Patient-Level Meta-Analysis

  1. Tazeen H. Jafar, MD, MPH;
  2. Paul C. Stark, ScD;
  3. Christopher H. Schmid, PhD;
  4. Marcia Landa, MA;
  5. Giuseppe Maschio, MD;
  6. Paul E. de Jong, MD, PhD;
  7. Dick de Zeeuw, MD, PhD;
  8. Shahnaz Shahinfar, MD;
  9. Robert Toto, MD;
  10. Andrew S. Levey, MD; and
  11. for the AIPRD Study Group*
  1. From Tufts–New England Medical Center, Boston, Massachusetts; The Aga Khan University, Karachi, Pakistan; Ospedale Civile Maggiore, Verona, Italy; University of Groningen, Groningen, the Netherlands; Merck Research Laboratories, West Point, Pennsylvania; and University of Texas at Southwestern Medical Center, Dallas, Texas.

    Abstract

    Background: Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and urine protein excretion and slow the progression of chronic kidney disease.

    Purpose: To determine the levels of blood pressure and urine protein excretion associated with the lowest risk for progression of chronic kidney disease during antihypertensive therapy with and without ACE inhibitors.

    Data Sources: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens with or without ACE inhibitors for patients with predominantly nondiabetic kidney disease.

    Study Selection: MEDLINE database search for English-language studies published between 1977 and 1999.

    Data Extraction: Data on 1860 nondiabetic patients were pooled in a patient-level meta-analysis. Progression of kidney disease was defined as a doubling of baseline serum creatinine level or onset of kidney failure. Multivariable regression analysis was performed to assess the association of systolic and diastolic blood pressure and urine protein excretion with kidney disease progression at 22 610 patient visits.

    Data Synthesis: Mean duration of follow-up was 2.2 years. Kidney disease progression was documented in 311 patients. Systolic blood pressure of 110 to 129 mm Hg and urine protein excretion less than 2.0 g/d were associated with the lowest risk for kidney disease progression. Angiotensin-converting enzyme inhibitors remained beneficial after adjustment for blood pressure and urine protein excretion (relative risk, 0.67 [95% CI, 0.53 to 0.84]). The increased risk for kidney progression at higher systolic blood pressure levels was greater in patients with urine protein excretion greater than 1.0 g/d (P < 0.006).

    Conclusion: Although reverse causation cannot be excluded with certainty, a systolic blood pressure goal between 110 and 129 mm Hg may be beneficial in patients with urine protein excretion greater than 1.0 g/d. Systolic blood pressure less than 110 mm Hg may be associated with a higher risk for kidney disease progression.

    *For members of the AIPRD Study Group, see the Appendix.

    Article and Author Information

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

    • Potential Financial Conflicts of Interest:Employment: S. Shahinfar (Merck & Co.); Stock ownership or options (other than mutual funds): S. Shahinfar (Merck & Co.); Consultancies: R.D. Toto (Merck & Co.); Honoraria: R.D. Toto (Merck & Co.); Grants received: R.D. Toto (Merck & Co.), A.S. Levey (Merck & Co.).

    • Requests for Single Reprints: Andrew S. Levey, MD, Division of Nephrology, Tufts–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.

    • Drs. Stark and Schmid: Division of Clinical Care Research, Biostatistics Research Center, Tufts–New England Medical Center, Box 63, 750 Washington Street, Boston, MA 02111.

    • Dr. Landa: Division of Clinical Care Research, Tufts–New England Medical Center, 35 Kneeland Street #827, Boston, MA 02111.

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

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

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

    • Dr. Toto: Patient-Oriented Research in Nephrology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8856.

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

    • Author Contributions: Conception and design: C.H. Schmid, A.S. Levey.

    • Analysis and interpretation of the data: T.H. Jafar, P.C. Stark, C.H. Schmid, A.S. Levey.

    • Drafting of the article: T.H. Jafar, P.C. Stark, C.H. Schmid, G. Maschio, P.E. de Jong, D. de Zeeuw, S. Shahinfar, R. Toto, A.S. Levey.

    • Critical revision of the article for important intellectual content: T.H. Jafar, P.C. Stark, C.H. Schmid, G. Maschio, P.E. de Jong, D. de Zeeuw, S. Shahinfar, R. Toto, A.S. Levey.

    • Final approval of the article: P.C. Stark, C.H. Schmid, G. Maschio, P.E. de Jong, D. de Zeeuw, S. Shahinfar, R. Toto, A.S. Levey.

    • Provision of the study materials or patients: G. Maschio, P.E. de Jong, D. de Zeeuw, S. Shahinfar, R. Toto.

    • Statistical expertise: P.C. Stark, C.H. Schmid, A.S. Levey.

    • Obtaining of funding: T.H. Jafar, C.H. Schmid, A.S. Levey.

    • Administrative, technical, or logistic support: P.C. Stark, C.H. Schmid, A.S. Levey.

    • Collection and assembly of the data: T.H. Jafar, P.C. Stark, C.H. Schmid, M. Landa, G. Maschio, P.E. de Jong, D. de Zeeuw, S. Shahinfar, R. Toto.

    Summary for Patients

    • Summaries for Patients:Blood Pressure and Urine Protein Levels with the Least Risk for Worsening Kidney Disease Ann Intern Med August 19, 2003 139:I-36
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    1. Ann Intern Med August 19, 2003 vol. 139 no. 4 244-252
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