Abstract: PUB222
An Interesting Case of Proximal Renal Tubular Acidosis and Fanconi Syndrome due to Ifosfamide Nephrotoxicity
Session Information
Category: Trainee Case Report
- 1500 Onco-Nephrology
Authors
- Sundararajan, Anusha, Yale University School of Medicine, New Haven, Connecticut, United States
- Turner, Jeffrey M., Yale University School of Medicine, New Haven, Connecticut, United States
Introduction
Ifosfamide is an alkalyting agent that is used in treatment of lymphoma, sarcoma and germ cell tumors. Ifosfamide causes kidney injury as an important adverse effect- Proximal tubular injury, Fanconi syndrome and Nephrogenic diabetes insipidus.
Case Description
50 year old male with past medical history of hypertension, kidney stones and peripheral T cell lymphoma since 1.5 years who was on multiple chemotherapy in past who was admitted for ICE chemotherapy.
Patient reported fatigue and chills, sore throat and non-productive cough. Patient did not have any vomiting or diarrhea or fever or rash or leg swelling or shortness of breath. Had dizziness for 2 days. No lower urinary tract symptoms. No NSAID use. No IV contrast exposure. No hypotension.
Patient got chemotherapy with ifosfamide, carboplatin, etoposide (carboplatin and etoposide -day 1 to day 3) with ifosfamide 5 g/m2 on day 2 along with mesna for 24 hrs.
Patient's baseline creatinine was 0.9 to 1.2. Patient's creatinine went up to 1.48 ( 4 days after ifosfamide dose) and then progressively went up to 1.8 -> 2.4 ( in 10-12 days after dose). Patient developed a non-anion gap hyperchloremic metabolic acidosis around that time. There was associated hypokalemia and hypophosphatemia. Urine pH was 8 and patient had 2+ proteinuria and 3+ glycosuria and protein creatinine ratio was 4.69 and on repeat, it was 10 g/mg creat. Urine sediment exam showed granular casts. He had proximal RTA and Fanconi syndrome due to ifosfamide nephrotoxicity. He was managed with supportive treatment with repletion of potassium and phosphate and bicarbonate drip.
This was notable given lower cumulative dose (11.25g) resulting in nephrotoxicity. Case reports mention nephrotoxicity mostly in children with 60-120 g cumulative dose.
Discussion
Ifosfamide induced AKI is reversible but can be permanent. Biopsy shows tubular injury/necrosis with swollen mitochondria. Ifosfamide enters proximal tubule cells via OCT 2. Chloracetaldehyde is the toxic metabolite produced by ifosfamide that causes kidney injury. Usually, CKD, previous cisplatin exposure and cumulative dose >90 -120 g/m2 are risk factors for AKI. Management is mainly supportive such as repletion of deficient electrolytes and renal replacement therapy if indicated. Possible long term complications include permanent proximal tubulopathy, renal phosphaturia, CKD and ESRD.