Impaired aldosterone response to potassium and hyperkalemia in patients receiving a renin-angiotensin-aldosterone system inhibitor

Abstract

Background/Aims: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are associated with the development of hyperkalemia. We evaluated the relationship between the serum aldosterone-to-potassium ratio (APR) and the risk of developing hyperkalemia in patients with chronic kidney disease (CKD) receiving ACEIs or ARBs. Methods: One hundred eighty-six patients with stage 3–4 CKD receiving an ACEI or ARB for at least 3 months were evaluated. Serum aldosterone and potassium concentrations were measured simultaneously, and serum APR was calculated (ng/mL per mmol/L). Patients were divided into two groups for comparison according to the median value above or below 2.42. The primary outcome was the difference between the two groups in the development of hyperkalemia (defined as a serum potassium level > 5.5 mmol/L). Incidence rates and risk factors of hyperkalemia were assessed. Results: During the follow-up period, 144 hyperkalemic events in 81 patients (43.5%) were identified, yielding an incidence rate of 24.6 events/100 person-years. The incidence rate was significantly higher in patients with a low serum APR than in patients with a high APR (35.8 events/100 patient-years vs. 12.9 events/100 patient-years, p < 0.001). In addition, diabetes mellitus, history of hyperkalemia, CKD progression during the follow-up period, and low serum APR were predictors of the development of hyperkalemia. Conclusions: Low serum APR was associated with the occurrence of hyperkalemia in patients with CKD receiving ACEIs or ARBs, suggesting that the identification of patients administered these drugs who are at high risk for hyperkalemia may be achieved using this index.