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 x 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 beta-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.
Lea
Janice
J
Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Greene
Tom
T
Hebert
Lee
L
Lipkowitz
Michael
M
Massry
Shaul
S
Middleton
John
J
Rostand
Stephen G
SG
Miller
Edgar
E
Smith
Winifred
W
Bakris
George L
GL
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D001741:Black or African American; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004095:Dihydropyridines / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000208:ethnology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000208:ethnology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000150:complications / Q000208:ethnology / Q000652:urine*; D017257:Ramipril / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D008790:Metoprolol; D017257:Ramipril