Abstract: [PUB597] N-Acetyl Cysteine in Management of Methotrexate Induced Kidney Damage

Rikin Kartikbhai Shah, MD, Osvaldo Regueira, MD, Curtis W. Turner, MD, Tetyana L. Vasylyeva, MD, PhD. Department of Pediatrics, Texas Tech University Health Science Center, Amarillo, TX.

Background: High Dose Methotrexate (HD MTX) /Leucovorin Rescue (LCV) alternating with Doxorubicin/Cisplatinum is the current therapy for Osteosarcoma in the Pediatric Population. NAC has been demonstrated to decrease MTX induced oxidative renal damage in preclinical models (Cetinkaya, 2007). We describe the use of NAC to reverse MTX induced nephrotoxicity in an adolescent treated with MTX/LCV for osteosarcoma. Methods: 18-year old women initiated chemotherapy for osteogenic sarcoma of the left proximal humerus with alternating cycles of Doxorubicin/Cisplatinum (Doxo/CDDP) and High Dose Methotrexate (HD MTX) /Leucovorin Rescue (LCV). Pretreatment serum creatinine level was 0.57 mg/dl and received prehydration with IV fluids at 3000 cc/m2. The patient was admitted for a sixth overall systemic chemotherapy encounter (Doxo/CDDP - cycles 1 and 3) and specifically the fourth admission for intravenous HD MTX which was administered at a dose of 12 grams/m2 over 4 hours. She received post hydration intravenous fluids and LCV 15mg/ m2 IV /PO every 6 hours beginning at hour 0. Serum MTX levels at 24, 48 and 72 hours after MTX infusion demonstrated toxic range. Serial serum creatinine levels increased from baseline 0.57 mg/dl to 0.87 and 1.43 mg/dl at 24 and 48 hours respectively.
Sixty hours after the MTX infusion, we began NAC 600 mg orally every 8 hours. Subsequent creatinine levels decreased to 1.01 and 0.80 mg/dl on day 4 and day 5 respectively. For subsequent admissions for HD MTX/LCV therapy, we coadministered prophylactic NAC and creatinine level remained between 0.65 to 0.95 mg/dl. MTX levels have remained in therapeutic levels. Results: Conclusions: NAC may have ameliorated the MTX induced nephrotoxicity in our patient. NAC may act as an antioxidant and reverse free-radical mediated cell damage and mitochondrial injury in the renal cells.
Further prospective clinical trials for oncology patients receiving nephrotoxic drugs may be warranted. Additional preclinical studies may clarify the mechanisms of action.

Course: Annual Meeting: Abstract Sessions
Session: Publication Only Abstracts

Individual author disclosures are available in the Kidney Week 2012 Disclosure Digest which is available to each meeting participant or upon request in November.

 

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