Safety of Eplerenone for Kidney-Transplant Recipients with Impaired Renal Function and Receiving Cyclosporine A

<div><p>Background</p><p>Animal studies have highlighted the role of vascular mineralocorticoid receptor during Cyclosporine A-induced nephrotoxicity. Mineralocorticoid receptor antagonists could improve kidney survival but are not commonly used during renal impairment and in association with several immunosuppressive drugs due to a supposed higher risk of adverse events. We tested the tolerance of eplerenone according to its expected adverse events: hyperkalemia, metabolic acidosis, hypotension, acute kidney failure, or any other adverse event.</p><p>Methods</p><p>We conducted a single-center, prospective, open-label study in 31 kidney-transplant recipients with impaired renal function (30 and 50 mL/min/1.73m²) and receiving cyclosporine A. All patients received eplerenone 25 mg/d for 8 weeks. Serum potassium, renal function and expected adverse events were closely monitored.</p><p>Results</p><p>Eight patients experienced mild hyperkalemia (>5 mmol/L), one moderate hyperkalemia (>5.5 mmol/L) and had to receive potassium-exchange resin. No severe hyperkalemia (>6 mmol/L) occurred. One acute kidney failure was observed, secondary to diarrhea. Basal serum potassium and bicarbonate were independently associated with a higher risk of developing mild hyperkalemia (>5 mmol/L) under treatment (OR 6.5, <i>p</i> = 0.003 and 0.7, <i>p</i> = 0.007, respectively). A cut-off value of 4.35 mmol/L for basal serum potassium was the best factor to predict the risk of developing mild hyperkalemia (>5 mmol/L).</p><p>Conclusions</p><p>Until eGFR falls to 30 mL/min/1.73m², eplerenone could be safely given to kidney-transplant recipients receiving cyclosporine A, if kalemia is closely monitored. When renal function is impaired and if basal kalemia is >4.35 mmol/L, then clinicians should properly balance risk and benefit of eplerenone use and offer dietary advice. An adequately powered prospective randomized study is now needed to test its efficiency (and safety) in this population.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01834768" target="_blank">NCT01834768</a></p></div

Risk factors for developing mild hyperkalemia under treatment.

<p>Receiver-operating characteristic (ROC) curves for <b>(A)</b> serum potassium and <b>(B)</b> serum bicarbonate at baseline.</p

Risk factors for developing mild hyperkalemia under treatment.

<p>Receiver-operating characteristic (ROC) curves for <b>(A)</b> serum potassium and <b>(B)</b> serum bicarbonate at baseline.</p

Design of the EpleCsAT: Safety trial.

<p>Sequential inclusion was performed: 14 patients during step 1; then 17 new patients during step 2.</p

Eplerenone induced mild hyperkalemia.

<p><b>(A)</b> Kalemia increased from day 2 (D2) and became stable during the treatment period. <b>(B)</b> Systolic blood pressure (SBP), <b>(C)</b> body weight, and <b>(D)</b> serum bicarbonate did not change during the treatment period. Data are represented as their median and range (whiskers). * <i>p</i> <0.05 <i>vs</i>. D0.</p

Candidate parameters for predicting the risk of mild hyperkalemia.

<p>Candidate parameters for predicting the risk of mild hyperkalemia.</p

Flowchart of study participants.

<p>Flowchart of study participants.</p

Clinical and demographic characteristics of the 45 patients.

<p>Clinical and demographic characteristics of the 45 patients.</p

Modified Medical Research Council (mMRC) dyspnea scale.

<p>Modified Medical Research Council (mMRC) dyspnea scale.</p

Comparison of clinical parameters, 6-minute walk test, arterial blood gases, pulmonary function tests and laboratory parameters before and after bariatric surgery.

<p>Comparison of clinical parameters, 6-minute walk test, arterial blood gases, pulmonary function tests and laboratory parameters before and after bariatric surgery.</p