Original Report: Patient-Oriented, Translational Research

Predictors of Hyperkalemia Risk following Hypertension Control with Aldosterone Blockade
Nitin Khosla^a, Rigas Kalaitzidis^b, George L. Bakris<sup>b

a</sup>Department of Medicine, Section of Nephrology and Hypertension, University of California at San Diego, San Diego, Calif., and
^bDepartment of Medicine, Hypertensive Diseases Unit, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago Medical Center, Chicago, Ill., USA

Address of Corresponding Author

Am J Nephrol 2009;30:418-424 (DOI: 10.1159/000237742)

  Key Words

• Aldosterone
• Kidney
• Hypertension
• Potassium
• Diabetes
• African-Americans

  Abstract

Background: Aldosterone antagonists have proven efficacy for management of resistant hypertension and proteinuria reduction; however, they are not widely used due to risk of hyperkalemia. This study assesses the risk factors for hyperkalemia in patients with chronic kidney disease (CKD) and resistant hypertension whose blood pressure (BP) is reduced to a guideline goal. Methods: This is a two-center study conducted in university-based hypertension clinics directed by clinical hypertension specialists. Forty-six patients with resistant hypertension and stages 2 or 3 CKD (mean estimated glomerular filtration rate (eGFR) 56.5 ± 16.2 ml/min/1.73 m²) were evaluated for safety and efficacy of aldosterone blockade added to preexisting BP-lowering regimens. All patients were on three mechanistically complementary antihypertensive agents including a diuretic and a renin-angiotensin system blocker. Patients were evaluated after a median of 45 treatment days. The primary endpoint was change in systolic BP. Secondary endpoints included change in serum potassium, creatinine, eGFR, diastolic BP and tolerability. Results: The mean age of the patients studied was 64.9 ± 10.7 years, all were obese and 86% had type 2 diabetes, with 82% being African-American. Addition of aldosterone antagonism yielded a further mean reduction in systolic BP of 14.7 ± 5.1 mm Hg (p = 0.001). Females with BMI >30 and those with a baseline systolic BP >160 mm Hg were more likely to have a greater BP reduction to aldosterone antagonism. In total, 39% of the patients had a >30% decrease in eGFR when the BP goal was achieved. The mean increase in serum potassium was 0.4 mEq/l above baseline (p = 0.001), with 17.3% manifesting hyperkalemia, i.e. serum potassium >5.5 mEq/l. Predictors of hyperkalemia included a baseline eGFR of 45 ml/min/1.73 m² in whom serum potassium was >4.5 mEq/l on appropriately dosed diuretics. Contributing risks in this subgroup included a systolic BP reduction of >15 mm Hg associated with an eGFR fall of >30%. Conclusion: Aldosterone antagonism is effective and safe for achieving a BP goal among people with diabetic nephropathy when added to a triple antihypertensive regimen that includes a blocker of the renin-angiotensin system and an appropriately selected and dosed diuretic. Caution is advised when using aldosterone blockade for BP control in people with advanced stage 3 nephropathy with a serum potassium of >4.5 mEq/l for safety reasons.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

George L. Bakris, MD
Hypertensive Diseases Unit, University of Chicago Pritzker School of Medicine
5841 S. Maryland Ave MC 1027, Chicago, IL 60637 (USA)
Tel. +1 773 702 7936, Fax +1 773 834 0486
E-Mail gbakris@gmail.com

  Article Information

Received: June 15, 2009
Accepted: July 22, 2009
Published online: September 9, 2009
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 2, Number of References : 28