Predictors of the Development of Hyperkalemia in Patients Using Angiotensin-Converting Enzyme Inhibitors

Abstract

Background/Aims: Angiotensin-converting enzyme inhibitors (ACEI) are the antihypertensives of choice in patients with chronic renal failure (CRF). ACEI by decreasing the synthesis of aldosterone, the main regulator of serum potassium, predispose to the development of hyperkalemia. Although hyperkalemia with administration of ACEI is uncommon in patients with a normal renal function, a preexisting abnormality in potassium hemostasis, as seen in patients with chronic renal failure, may increase the risk of hyperkalemia. Method: To determine the predictors of development of hyperkalemia (K >5.1 mEq/l) in patients on ACEI, we retrospectively reviewed medical records of 119 patients followed in our renal clinic. Results: The mean age of the patients was 56 ± (SD) 13 (range 20–84) years. Sixty-three percent were males, and 37% were females. Sixty-seven percent had a history of diabetes. Eighty five percent of the patients had CRF [creatinine clearance (CrCl) <80 ml/min]. The baseline serum Cr was 2.3 ± 1.2 (range 0.6–6.9) mg/dl, and the CrCl was 50 ± 27.5 ml/min. Of the 119 patients 46 (38.6%) developed hyperkalemia (mean K 5.68 ± 0.3, range 5.2–6.7 mEq/l). Ninety-six percent of the patients who developed hyperkalemia had CRF, and 84% were diabetics. Pearson product-moment correlation revealed a significant positive correlation of hyperkalemia with Cr and a negative correlation of hyperkalemia with CrCl and HCO₃ (Cr: r = 0.42, p < 0.0001; CrCl: r = –0.34, p < 0.0001; HCO₃: r = –0.41, p < 0.0001). Multivariate logistic regression analysis revealed diabetes and serum creatinine to be the main predictors of hyperkalemia. In 31 patients hyperkalemia resolved either with a low-potassium (2 g/day) diet or with diet and a decrease in the dose of ACEI. In 15 patients ACEI had to be discontinued due to persistent hyperkalemia. Conclusions: We conclude that hyperkalemia is common in patients with CRF on ACEI. The majority of the patients who develop hyperkalemia on ACEI have CRF and diabetes. A large number of patients with CRF require discontinuation of ACEI due to hyperkalemia and are deprived of their renoprotective effects.

Spontaneous reporting of adverse drug reactions at a department of Internal Medicine

“…A side effect of such therapy is the development of hyperkalemia. Hyperkalemia has been attributed to the use of ACE inhibitors in 10% to 38% of hospitalized patients with this complication [30][31][32][33]. Hyperkalemia develops in approximately 10% of outpatients within a year after these drugs are prescribed [34].…”

Long-Term Plasma Levels and Dose Modulation of Alacepril in Patients with Chronic Renal Failure

“…Severe side effects were not observed in the current study. Since alacepril suppresses the renin-angiotensin-aldosterone system, some subjects may develop metabolic acidosis and subsequent hyperkalemia and require careful follow-up (11). Only a few subjects developed hyperkalemia in our study.…”

“…Most of the ACE inhibitors are excreted into urine, and their doses have to be titrated depending upon the renal function. ACE inhibitors suppress the synthesis of angiotensin II and aldosterone, which can sometimes induce hyperkalemia in patients with reduced renal function (11). Therefore, it is generally recommended that the doses be reduced under certain circum-stances, especially in patients with a serum creatinine level of more than 2.5 mg/dL, to avoid excess doses and the resultant hyperkalemia (12).…”

Importance of etiologic factors and electrocardiographic findings for diagnosis of emergency hyperkalemic patients

“…[11] Patients who have renal dysfunction and who use medications that renal angiotensin aldosterone bloker have a high risk of developing hyperkalemia. In the study by Reardon and Macpherson, ACE inhibitors was found to be an independent risk factor for hyperkalemia in patients with a creatinine value of >1.5 mg/dl.…”