Medline ® Abstracts for References 84,85

of 'Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults'

84
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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.
AU
Lea J, Greene T, Hebert L, Lipkowitz M, Massry S, Middleton J, Rostand SG, Miller E, Smith W, Bakris GL
SO
Arch Intern Med. 2005;165(8):947.
 
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 1.73m(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.
AD
Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
PMID
85
TI
Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern?
AU
Bakris GL, Weir MR
SO
Arch Intern Med. 2000;160(5):685.
 
BACKGROUND: Reducing the actions of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACEIs) slows nephropathy progression in patients with or without diabetes. Post hoc analyses of many ACEI-based clinical trials demonstrate the greatest slowing of renal disease progression in patients with the greatest degree of renal insufficiency at study initiation. However, many physicians fail to use ACEIs or angiotensin receptor blockers in patients with renal insufficiency for fear that either serum creatinine or potassium levels will rise.
OBJECTIVE: To determine if limited initial reduction in either glomerular filtration rate (GFR) or elevation in serum creatinine levels, associated with ACEI or angiotensin receptor blocker use, results in long-term protection against decline in renal function in patients with renal insufficiency.
METHODS: We reviewed 12 randomized clinical trials that evaluated renal disease progression among patients with preexisting renal insufficiency. Six of these studies were multicenter, double-blinded,and placebo controlled, with the remainder being smaller randomized studies with a minimum 2-year follow-up on renal function. These investigations evaluated patients with and without diabetes or systolic heart failure. Average duration of follow-up for all studies was 3 years. Trials were examined in the context of changes in either serum creatinine levels or GFR in the group randomized to an ACEI (N = 1,102). Sixty-four percent of these individuals (705/1,102) had renal function data at both less than 6 months and at the end of the study.
RESULTS: Most trials demonstrated that patients with preexisting renal insufficiency manifested an acute fall in GFR, a rise in serum creatinine, or both. Those randomized to an ACEI with a serum creatinine level of 124 pmol/L or greater (>or =1.4 mg/dL) demonstrated a 55% to 75% risk reduction in renal disease progression compared with those with normal renal function randomized to an ACEI. An inverse correlation was observed between the amount of renal function loss at baseline and the subsequent rate of annual decline in renal function following randomization to an antihypertensive regimen that contained an ACEI.
CONCLUSIONS: A strong association exists between acute increases in serum creatinine of up to 30% that stabilize within the first 2 months of ACEI therapy and long-term preservation of renal function. This relationship holds for persons with creatinine values of greater than 124 pmol/L (>1.4 mg/dL). Thus, withdrawal of an ACEI in such patients should occur only when the rise in creatinine exceeds 30% above baseline within the first 2 months of ACEI initiation, or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater.
AD
Rush University Hypertension/Clinical Research Center, Department of Preventive Medicine, Rush Presbyterian-St Luke's Medical Center, Chicago, Ill 60612, USA. gbakris@rush.edu
PMID