Calcineurin Inhibitor Sparing Immunosuppression in a 12-year-old Heart Transplant Recipient with a Single Kidney

Abstract

Introduction Renal dysfunction requires renal transplant or dialysis in up to 10% of transplant patients at 15 years. Those with chronic renal disease or single kidney are at high risk, but there has been limited study of calcineurin inhibitor (CNI)-sparing heart transplantation (HT) in pediatrics. Case Report A 12 year old female with history of Wilms tumor status post left nephrectomy developed anthracycline-induced dilated cardiomyopathy. She had decompensated heart failure bridged to transplant with milrinone. Given prior recurrent acute kidney injury (AKI) in the setting of a single kidney, she was at increased risk of receiving dialysis post-operatively, but a combined heart-kidney transplant was not felt indicated. She was induced with thymoglobulin and initially managed with concomitant mycophenolate mofetil and methylprednisolone. At approximately 3 weeks post-transplant, sirolimus was added. Within 2 week postoperatively, she developed hypertension, acute tubular necrosis, and oliguric AKI. Prior to starting Sirolimus, she also developed pleural and pericardial effusions requiring a chest tube, pericardiocentesis, and pericardial window. Despite these complications there was no evidence of transplant rejection or graft reperfusion injury on biopsy, but filling pressures were upwards of 25 mmHg bilaterally. Aggressive hypertensive management and judicious diuretic use improved her filling pressures and overall clinical status. She was discharged home 60 days after HT. At her 3 month post-op catheterization she had normal filling pressures and no signs of rejection (ISHLT grade A0, AMR grade 0) on low dose prednisone, mycophenolate, and sirolimus. Her AKI has resolved and she remains dialysis free. Summary AKI after HT is due to a constellation of renal hypoperfusion, low cardiac output, and drug-induced nephrotoxicity requiring dialysis in some patients. Prior studies showed improved renal function in those converted from CNIs to mTOR inhibitors. In our case, the morbidity associated with AKI was deemed too severe to pursue standard use of CNIs. While some pediatric patients have undergone immunosuppression with reduced CNI dosing, few have completed HT without CNI. Her case illustrates the utility of mTOR inhibitors for its nephrotoxic sparing profile while maintaining adequate immunosuppression protection and graft function.