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

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 × 2 factorial trial. A total of 1094 African Americans with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m ²) 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 β-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 m ² lower baseline GFR, an associated mean ± SE 0.38 ± 0.08-mL/ min per 1.73 m ² 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 m ² 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.