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Joy M. Weinberg, MD; Lawrence J. Appel, MD, MPH; George Bakris, MD; Jennifer J. Gassman, PhD; Tom Greene, PhD; Cynthia A. Kendrick, BS; Xuelei Wang, MS; James Lash, MD; Julia A. Lewis, MD; Velvie Pogue, MD; Denyse Thornley-Brown, MD; Robert A. Phillips, MD, PhD; for the African American Study of Hypertension and Kidney Disease Collaborative Research Group

Arch Intern Med. 2009;169(17):1587-1594.

Background  The incidence and factors associated with hyperkalemia in patients with chronic kidney disease (CKD) treated with angiotensin converting enzyme inhibitors (ACEIs) and other antihypertensive drugs was investigated using the African American Study of Kidney Disease and Hypertension (AASK) database.

Methods  A total of 1094 nondiabetic adults with hypertensive CKD (glomerular filtration rate [GFR], 20-65 mL/min/1.73 m²) were followed for 3.0 to 6.4 years in the AASK trial. Participants were randomly assigned to ACEI, β-blocker (BB), or dihydropyridine calcium channel blocker (CCB). The outcome variables for this analysis were a serum potassium level higher than 5.5 mEq/L (to convert to millimoles per liter, multiply by 1.0), or a clinical center initiated hyperkalemia stop point.

Results  A total of 6497 potassium measurements were obtained, and 80 events in 51 subjects were identified (76 events driven by a central laboratory result and 4 driven by a clinical center–initiated hyperkalemia stop point). Compared with a GFR higher than 50 mL/min/1.73 m², after multivariable adjustment, the hazard ratio (HR) for hyperkalemia in patients with a GFR between 31 and 40 mL/min/1.73 m² and a GFR lower than 30 mL/min/1.73 m² was 3.61 (95% confidence interval [CI], 1.42-9.18 [P = .007]) and 6.81 (95% CI, 2.67-17.35 [P < .001]), respectively; there was no increased risk of hyperkalemia if GFR was 41 to 50 mL/min/1.73 m². Use of ACEIs was associated with more episodes of hyperkalemia compared with CCB use (HR, 7.00; 95% CI, 2.29-21.39 [P < .001]) and BB group (HR, 2.85; 95% CI, 1.50-5.42 [P = .001]). Diuretic use was associated with a 59% decreased risk of hyperkalemia.

Conclusions  In nondiabetic patients with hypertensive CKD treated with ACEIs, the risk of hyperkalemia is small, particularly if baseline and follow-up GFR is higher than 40 mL/min/1.73 m². Including a diuretic in the regimen may markedly reduce risk of hyperkalemia.

Author Affiliations: Nephrology Division, Lenox Hill Hospital, New York, New York (Dr Weinberg); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland (Dr Appel); Hypertensive Diseases Unit, Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois (Dr Bakris); Department of Biostatistics and Epidemiology, The Cleveland Clinic Foundation, Cleveland, Ohio (Drs Gassman and Greene and Mss Kendrick and Wang); Section of Nephrology, University of Illinois, Chicago (Dr Lash); Division of Nephrology, Vanderbilt University, Nashville, Tennessee (Dr Lewis); Division of Nephrology, Harlem Hospital, New York (Dr Pogue); Division of Nephrology, University of Alabama at Birmingham, Birmingham (Dr Thornley-Brown); and Heart and Vascular Center of Excellence, UMass Medical School and UMass Memorial Medical Center, Worcester, Massachusetts (Dr Phillips).

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