Abstract: FR-PO737
Sirolimus Toxicity Manifested with Fanconi Syndrome in a Kidney Transplant Patient
Session Information
- Post-Transplantation and Case Reports
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Middleman, Christopher F., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Joshi, Megha Raj, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Introduction
Sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, decreases antigen and cytokine stimulated T-lymphocyte activation and proliferation, and inhibits antibody production. It has been shown to prolong kidney allograft survival, and reverse acute rejection. In transplant patients with recurrent basal and squamous cell carcinomas, sirolimus is frequently used to prevent or reduce recurrence of these malignancies. This case highlights a rare but important to recognize side effect of the drug and how it can be managed.
Case Description
A 75-year-old female, with end stage kidney disease due to hypertension, received a living related kidney transplant in 2017. Over the next 5 years her course was complicated by recurrent non-melanomatous skin cancers requiring multiple Mohs surgeries. Immunosuppressive therapy was changed from tacrolimus to sirolimus to reduce skin cancer recurrence while preventing rejection. The sirolimus trough goal was 4-6 ng/mL. Her baseline serum creatinine (sCr) was 0.8-0.9 mg/dL without proteinuria.
Within two months of transitioning to sirolimus, she developed lower extremity edema, loss of appetite and generalized fatigue. She was found to have proteinuric acute kidney injury with 1.6 gm protein/gm Cr, sCr 1.1mg/dL, hypokalemia (2.8 mmol/L) and hypophosphatemia (2.3 mg/dL). Sirolimus trough level was 12.9 ng/mL. Further urine testing revealed elevated fractional excretions of potassium, phosphorus, and uric acid. The sirolimus dose was reduced, with subsequent normalization of serum creatinine, electrolytes, and complete resolution of proteinuria. The patient’s symptoms also resolved.
Discussion
Long-term use of sirolimus may be associated with proteinuria and sCr increases in kidney transplant patients, however this is the first case to our knowledge where a supratherapeutic level of sirolimus induced a generalized proximal tubular dysfunction (i.e., Fanconi’s syndrome), which completely resolved with dose reduction to therapeutic range. As sirolimus is increasingly used in the setting of non-melanomatous skin cancers after kidney transplant, improving awareness and early diagnosis and treatment of associated Fanconi syndrome is critical for allograft survival.
Disclaimer: The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Defense, or the United States government.