Abstract

Abstract Background and Aims Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have demonstrated efficacy in improving outcomes in patients with chronic kidney disease (CKD). However, these medications have also been associated with the development of hyperkalemia. The aim of this study was to evaluate the relation of serum aldosterone to potassium ratio to the risk of the development of hyperkalemia in CKD patients receiving ACEIs or ARBs. Method Between January 2017 and December 2021, 186 patients with CKD 3-4 (estimated glomerular filtration rate, eGFR, of 15-59 ml/min/1.73 m2) who were receiving an ACEI or an ARB for at least 3 months and had serum aldosterone and potassium measured simultaneously were analyzed. Serum aldosterone to potassium (Aldo/K) ratio was calculated (ng/ml per mmol/l) and patients were divided into two groups according to the median value of serum Aldo/K ratio above or below 2.42. Follow-up serum potassium concentrations were measured every 2 to 3 months. The primary outcome was the occurrence of hyperkalemia (defined as serum potassium level > 5.5 mEq/l). Incidence rates for hyperkalemic events were computed as the ratio of the total number of hyperkalemic events to the total patient-time at risk. In addition, the times from the index date to the first occurrence of hyperkalemia for were computed. Cox proportional hazards models were used to identify patients at the risk of the occurrence of hyperkalemia. Results During a median follow-up period of 3.1 years, 2505 times of serum potassium were measured (mean ± standard deviation number of annual potassium measurements per patient, 4.5 ± 1.7 measurements/year per patient). A total of 144 hyperkalemic events in 81 patients (43.5%) were identified, yielding an incidence rate of 24.6 per 100 person-years (95% confidence intervals [CIs] 20.4–28.8). The incidence of hyperkalemic events was significantly higher in patients with low serum Aldo/K ratio than in those with high serum Aldo/K ratio (35.8 events/100 patient-years, 95% CI 28.9‒42.7 events/100 patient-years vs. 12.9 events/100 patient-years, 95% CI 8.8‒17.0 events/100 patient-years, p < 0.001). In multivariate Cox proportional hazards analysis, diabetes mellitus (Hazard ratio [HR], 1.842; 95% CI, 1.046-3.243; P=0.034), prior history of hyperkalemia (HR, 2.288; 95% CI, 1.372-3.815; P=0.002), low baseline eGFR (HR, 0.973; 95% CI, 0.948-0.998; P=0.037) and a low serum Aldo/K ratio (HR, 3.654; 95% CI, 2.066-6.463; P < 0.001) were predictors of subsequent development of hyperkalemia. Conclusion This study revealed that low serum Aldo/K ratio ( < 2.42) was strongly associated with the occurrence of hyperkalemia in CKD patients receiving ACEIs or ARBs, suggesting that the identification of patients at a risk for subsequent hyperkalemia could be made by measuring serum aldosterone and potassium levels simultaneously on these drugs.

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