Risk of hyperkalemia in patients with moderate chronic kidney disease initiating angiotensin converting enzyme inhibitors or angiotensin receptor blockers: a randomized study

Abstract

BackgroundAngiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are renoprotective but both may increase serum potassium concentrations in patients with chronic kidney disease (CKD). The proportion of affected patients, the optimum follow-up period and whether there are differences between drugs in the development of this complication remain to be ascertained.MethodsIn a randomized, double-blind, phase IV, controlled, crossover study we recruited 30 patients with stage 3 CKD under restrictive eligibility criteria and strict dietary control. With the exception of withdrawals, each patient was treated with olmesartan and enalapril separately for 3 months each, with a 1-week wash-out period between treatments. Patients were clinically assessed on 10 occasions via measurements of serum and urine samples. We used the Cochran–Mantel–Haenszel statistics for comparison of categorical data between groups. Comparisons were also made using independent two-sample t-tests and Welch’s t-test. Analysis of variance (ANOVA) was performed when necessary. We used either a Mann–Whitney or Kruskal-Wallis test if the distribution was not normal or the variance not homogeneous.ResultsEnalapril and olmesartan increased serum potassium levels similarly (0.3 mmol/L and 0.24 mmol/L respectively). The percentage of patients presenting hyperkalemia higher than 5 mmol/L did not differ between treatments: 37% for olmesartan and 40% for enalapril. The mean e-GFR ranged 46.3 to 48.59 ml/mint/1.73 m2 in those treated with olmesartan and 46.8 to 48.3 ml/mint/1.73 m2 in those with enalapril and remained unchanged at the end of the study. The decreases in microalbuminuria were also similar (23% in olmesartan and 29% in enalapril patients) in the 4 weeks time point. The percentage of patients presenting hyperkalemia, even after a two month period, did not differ between treatments. There were no appreciable changes in sodium and potassium urinary excretion.ConclusionsDisturbances in potassium balance upon treatment with either olmesartan or enalapril are frequent and without differences between groups. The follow-up of these patients should include control of potassium levels, at least after the first week and the first and second month after initiating treatment.Trial registrationThe trial EudraCT “2008-002191-98”.

Hyperkalemia After Initiating Renin–Angiotensin System Blockade: The Stockholm Creatinine Measurements (SCREAM) Project

“…Our observed rates of hyperkalemia generally coincide with those reported in the general population without risk factors (≈2%) . However, the increased risk with lower eGFR is also consistent with previous reports, where rates may be as high as 40% . This variation in hyperkalemia risk supports recommendations that tailor monitoring strategies to the individual patient, such as that put forth by KDOQI in 2004 .…”

Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system

“…Specifically, and alike a previous report [12], we found that the hyperkalemia risk associated to ACEi or MRA were similar, and higher than that of the risk associated to ARB or potassium-sparing diuretics. Our estimates are therefore in line with some [35,36], but not all [23] trials suggesting that ACEi have stronger effect in raising potassium than ARBs. Recent RCTs suggest that the use of potassium binder medications may allow the use of RAASi in patients prone to hyperkalemia [37][38][39][40], but the long-term benefit of such strategies on clinical outcomes is yet to be demonstrated.…”

Tolerability of Antihypertensive Medications in Older Adults

“…Means to help predict a predisposition include estimating the GFR, baseline serum potassium check, and obtaining information on the intake of dietary potassium, supplements, and drugs that raise potassium [87]. Serum potassium needs to be measured after the first week and first and second months following the initiation of therapy; should hyperkalemia develop, prompt recognition of cardiac dysrhythmias is necessary to manage and optimize outcomes [87,88]. Hyperkalemia may be totally asymptomatic.…”