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

Bertocchio JP, Barbe C, Lavaud S, Toupance O, Nazeyrollas P, Jaisser F, Rieu P - PLoS ONE (2016)

Bottom Line: Basal serum potassium and bicarbonate were independently associated with a higher risk of developing mild hyperkalemia (>5 mmol/L) under treatment (OR 6.5, p = 0.003 and 0.7, p = 0.007, respectively).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.

View Article: PubMed Central - PubMed

Affiliation: Nephrology, Dialysis and Transplantation Unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.

ABSTRACT

Background: 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.

Methods: We conducted a single-center, prospective, open-label study in 31 kidney-transplant recipients with impaired renal function (30 and 50 mL/min/1.73 m2) 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.

Results: 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, p = 0.003 and 0.7, p = 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).

Conclusions: Until eGFR falls to 30 mL/min/1.73 m2, 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.

Trial registration: ClinicalTrials.gov NCT01834768.

No MeSH data available.


Related in: MedlinePlus

Eplerenone induced mild hyperkalemia.(A) Kalemia increased from day 2 (D2) and became stable during the treatment period. (B) Systolic blood pressure (SBP), (C) body weight, and (D) serum bicarbonate did not change during the treatment period. Data are represented as their median and range (whiskers). * p <0.05 vs. D0.
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pone.0153635.g002: Eplerenone induced mild hyperkalemia.(A) Kalemia increased from day 2 (D2) and became stable during the treatment period. (B) Systolic blood pressure (SBP), (C) body weight, and (D) serum bicarbonate did not change during the treatment period. Data are represented as their median and range (whiskers). * p <0.05 vs. D0.

Mentions: A total of 31 patients were included (Table 1) and all completed the study period (8 weeks), except one (last follow-up on D35 due to an unplanned move). Serum potassium increased slightly from baseline (4.2±0.4 mmol/L): on d2, serum potassium became increased and then remained in a steady state (Fig 2A). Nine patients experienced at least one episode of mild hyperkalemia (>5 mmol/L) but there was only one episode of moderate hyperkalemia (>5.5 mmol/L). This patient received a specific intervention (potassium-exchange resin) on D35. Half the incidences of mild hyperkalemia (>5 mmol/L) occurred within 7 days after beginning eplerenone treatment.


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

Bertocchio JP, Barbe C, Lavaud S, Toupance O, Nazeyrollas P, Jaisser F, Rieu P - PLoS ONE (2016)

Eplerenone induced mild hyperkalemia.(A) Kalemia increased from day 2 (D2) and became stable during the treatment period. (B) Systolic blood pressure (SBP), (C) body weight, and (D) serum bicarbonate did not change during the treatment period. Data are represented as their median and range (whiskers). * p <0.05 vs. D0.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835088&req=5

pone.0153635.g002: Eplerenone induced mild hyperkalemia.(A) Kalemia increased from day 2 (D2) and became stable during the treatment period. (B) Systolic blood pressure (SBP), (C) body weight, and (D) serum bicarbonate did not change during the treatment period. Data are represented as their median and range (whiskers). * p <0.05 vs. D0.
Mentions: A total of 31 patients were included (Table 1) and all completed the study period (8 weeks), except one (last follow-up on D35 due to an unplanned move). Serum potassium increased slightly from baseline (4.2±0.4 mmol/L): on d2, serum potassium became increased and then remained in a steady state (Fig 2A). Nine patients experienced at least one episode of mild hyperkalemia (>5 mmol/L) but there was only one episode of moderate hyperkalemia (>5.5 mmol/L). This patient received a specific intervention (potassium-exchange resin) on D35. Half the incidences of mild hyperkalemia (>5 mmol/L) occurred within 7 days after beginning eplerenone treatment.

Bottom Line: Basal serum potassium and bicarbonate were independently associated with a higher risk of developing mild hyperkalemia (>5 mmol/L) under treatment (OR 6.5, p = 0.003 and 0.7, p = 0.007, respectively).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.

View Article: PubMed Central - PubMed

Affiliation: Nephrology, Dialysis and Transplantation Unit, Reims University Hospital, Avenue Cognacq Jay, 51092 Reims CEDEX, France.

ABSTRACT

Background: 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.

Methods: We conducted a single-center, prospective, open-label study in 31 kidney-transplant recipients with impaired renal function (30 and 50 mL/min/1.73 m2) 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.

Results: 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, p = 0.003 and 0.7, p = 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).

Conclusions: Until eGFR falls to 30 mL/min/1.73 m2, 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.

Trial registration: ClinicalTrials.gov NCT01834768.

No MeSH data available.


Related in: MedlinePlus