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The Relationship Between Magnitude of Proteinuria Reduction and Risk of End-stage Renal Disease
Results of the African American Study of Kidney Disease and Hypertension
Janice Lea, MD;
Tom Greene, PhD;
Lee Hebert, MD;
Michael Lipkowitz, MD;
Shaul Massry, MD;
John Middleton, MD;
Stephen G. Rostand, MD;
Edgar Miller, MD, PhD;
Winifred Smith, MPH;
George L. Bakris, MD; for the African American Study of Kidney Disease and Hypertension Study Group
Arch Intern Med. 2005;165:947-953.
Background The magnitude of proteinuria is associated with a graded increase in the risk of progression to end-stage renal disease and cardiovascular events. The objective of this study was to relate baseline and early changes in proteinuria and glomerular filtration rate (GFR) to long-term progression of hypertensive nondiabetic kidney disease.
Methods Post hoc analysis of a randomized 3 x 2 factorial trial. A total of 1094 African Americans with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m2) were followed up for a median of 3.8 years. Participants were randomized to a mean arterial pressure goal of 102 to 107 mm Hg (usual) or 92 mm Hg or less (lower) and to initial treatment with a  -blocker (metoprolol), an angiotensin-converting enzyme inhibitor (ramipril), or a dihydropyridine calcium channel blocker (amlodipine)
Results Baseline proteinuria and GFR predicted the rgate of GFR decline. For each 10–mL/min per 1.73 m2 lower baseline GFR, an associated mean ± SE 0.38 ± 0.08–mL/min per 1.73 m2 per year greater mean GFR decline occurred, and for each 2-fold higher proteinuria level, a mean ± SE 0.54 ± 0.05–mL/min per 1.73 m2 per year faster GFR decline was observed (P < .001 for both). In multivariate analysis, the effect of baseline proteinuria GFR decline persisted. Initial change in proteinuria from baseline to 6 months predicted subsequent progression, with this relationship extending to participants with baseline urinary protein levels less than 300 mg/d.
Conclusions The change in the level of proteinuria is a predictor of subsequent progression of hypertensive kidney disease at a given GFR. A prospective trial is needed to confirm this observation.
Author Affiliations: Department of Medicine, Emory University School of Medicine, Atlanta, Ga (Dr Lea); Department of Biostatistics, Cleveland Clinic Foundation, Cleveland, Ohio (Dr Greene); Department of Medicine, Ohio State University, Columbus (Dr Hebert); Department of Medicine, Mount Sinai Medical Center, New York, NY (Dr Lipkowitz); Department of Medicine, University of Southern California, Los Angeles (Dr Massry); Department of Medicine, Duke University, Durham, NC (Dr Middleton); Department of Medicine, University of Alabama at Birmingham (Dr Rostand); Department of Medicine, Johns Hopkins University Medical Center, Baltimore, Md (Dr Miller); Department of Medicine, Morehouse School of Medicine, Atlanta (Dr Smith); and Department of Preventive Medicine, Rush University Medical Center, Chicago, Ill (Dr Bakris).
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