SUN-060 LATE PRESENTATION OF NEPHROTOXICITY DUE TO OXALIPLATIN

Abstract

Oxaliplatin is a third-generation platinum derivative and considered less nephrotoxic than Cisplatin. It is frequently used as part of chemotherapy to treat various gastrointestinal tumors. Although hypokalemia, ATN and acute nephrotoxicity in the form of renal tubular acidosis due to Oxaliplatin has been reported; long term nephrotoxic effects of Oxaliplatin are not known. We report a novel case of 57- year old male who presented with muscle aches and electrolyte disturbances, several months after receiving oxaliplatin based chemotherapy. Patient had a premorbid history of diabetes mellitus, hypertension and he was diagnosed to have intrahepatic cholangiocarcinoma with neuroendocrine differentiation in September 2018. His creatinine was normal 74 umol/L at baseline. He received five cycles of chemotherapy with FOLFIRINOX (Folinic acid, Flourouracil, Irinotecan and Oxaliplatin). After five cycles he developed Oxaliplatin related ileus and nephropathy causing ATN and required few sessions of hemodialysis. Subsequently his kidney function improved partially with a new elevated baseline creatinine which was stable at 133 umol/L in February 2019. He presented on 28th September 2019 with severe muscle aches to emergency department (ED). His investigations done in ED revealed severe hypokalemia K 1.9 mmol/L, worsening of renal function, baseline creatinine had risen from 133 umol/L to 205 umol/L, he had severe metabolic acidosis with tCO 2 10, with normal anion gap 15 (range 7-16) and hyperchloremia 111 mmol/L, pH was 7.15. His serum phosphorus was low (0.63 mmol/L). Magnesium was normal. Urinary TTKG was calculated and was suggestive of urinary potassium loss. His Urinary Anion Gap was negative. He had glycosuria 4 + even though his blood sugars were well controlled. His urine pH was 5.5. Patient was treated with very high doses of potassium tricitrate and phosphorus supplements. He was discharged home after normalization of electrolytes and acid base status. Proximal renal tubular acidosis (type 2, pRTA) / Fanconi’s syndrome is characterized by bicarbonate wasting and low serum bicarbonate, proximal tubular dysfunction also leads to poor absorption of other substances, like glucose and phosphate. Further investigations were carried out to rule out other causes of Fanconi’s syndrome / Type 2 renal tubular acidosis in this patient. ANA, dsDNA, SPEP, IFE and serum Free light chain assay were all unremarkable. His Lactate was normal. A diagnosis of Fanconi’s syndrome and renal tubular acidosis type 2 (Proximal) due to remote exposure with Oxaliplatin was made. Fanconi’s syndrome due to platinum based drugs like Cisplatin and Oxaliplatin has been reported in Literature. Persistence of subtle partial renal tubular defects is well noted even after many months to years of exposure of Cisplatin but not with Oxaliplatin. We believe this is the first report of Type 2 pRTA and Fanconi’s syndrome presenting several months after exposure to Oxaliplatin. Physicians should be aware of unexpected late nephrotoxicity with Oxaliplatin use.