Blood Pressure Control, Proteinuria, and the Progression of Renal Disease

The Modification of Diet in Renal Disease Study

  1. John C. Peterson, MD;
  2. Sharon Adler, MD;
  3. John M. Burkart, MD;
  4. Tom Greene, PhD;
  5. Lee A. Hebert, MD;
  6. Lawrence G. Hunsicker, MD;
  7. Andrew J. King, MD;
  8. Saulo Klahr, MD;
  9. Shaul G. Massry, MD;
  10. Julian L. Seifter, MD; and
  11. Modification of Diet in Renal Disease (MDRD)Study Group*
  1. From the Modification of Diet in Renal Disease Study Group, Cleveland, Ohio. Grant Support: By the National Institute of Diabetes, Digestive and Kidney Diseases and the Health Care Financing Administration. Requests for Reprints: MDRD Study Data Coordinating Center, Department of Biostatistics and Epidemiology, P88, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. Current Author Addresses: Dr. Peterson: University of Florida, Division of Nephrology, P.O. Box 100224, Gainesville, FL 32610-0224.

    Abstract

    Objective: To examine the relations among proteinuria, prescribed and achieved blood pressure, and decline in glomerular filtration rate in the Modification of Diet in Renal Disease Study.

    Design: 2 randomized trials in patients with chronic renal diseases of diverse cause.

    Setting: 15 outpatient nephrology practices at university hospitals.

    Patients: 840 patients, of whom 585 were in study A (glomerular filtration rate, 25 to 55 mL/min·1.73 m2) and 255 were in study B (glomerular filtration rate, 13 to 24 mL/min·1.73 m2). Diabetic patients who required insulin were excluded.

    Interventions: Patients were randomly assigned to a usual blood pressure goal (target mean arterial pressure, less than equals 107 mm Hg for patients less than equals 60 years of age and less than equals 113 mm Hg for patients more than equals 61 years of age) or a low blood pressure goal (target mean arterial pressure, less than equals 92 mm Hg for patients less than equals 60 years of age and less than equals 98 mm Hg for patients more than equals 61 years of age).

    Main Outcome Measures: Rate of decline in glomerular filtration rate and change in proteinuria during follow-up.

    Results: The low blood pressure goal had a greater beneficial effect in persons with higher baseline proteinuria in both study A (P = 0.02) and study B (P = 0.01). Glomerular filtration rate declined faster in patients with higher achieved blood pressure during follow-up in both study A (r = −0.20; P < 0.001) and study B (r = −0.34; P < 0.001), and these correlations were stronger in persons with higher baseline proteinuria (P < 0.001 in study A; P < 0.01 in study B). In study A, the association between decline in glomerular filtration rate and achieved follow-up blood pressure was nonlinear (P = 0.011) and was stronger at higher mean arterial pressure. In both studies, the low blood pressure goal significantly reduced proteinuria during the first 4 months after randomization. This, in turn, correlated with a slower subsequent decline in glomerular filtration rate.

    Conclusions: Our study supports the concept that proteinuria is an independent risk factor for the progression of renal disease. For patients with proteinuria of more than 1 g/d, we suggest a target blood pressure of less than 92 mm Hg (125/75 mm Hg). For patients with proteinuria of 0.25 to 1.0 g/d, a target mean arterial pressure of less than 98 mm Hg (about 130/80 mm Hg) may be advisable. The extent to which lowering blood pressure reduces proteinuria may be a measure of the effectiveness of this therapy in slowing the progression of renal disease.

    *For a list of MDRD participants, see reference 10.

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    1. Ann Intern Med November 15, 1995 vol. 123 no. 10 754-762
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