When polyuria follows methotrexate: drug-induced nephrogenic diabetes insipidus

An 83-year-old male was recently diagnosed with primary central nervous system lymphoma involving bilateral frontal lobes and corpus callosum. He received rituximab and methotrexate for his first treatment cycle. In view of advanced age, the methotrexate dose was reduced from the usual 3.5 g/m2 to 1 g/m2. He tolerated this well, with plasma methotrexate levels falling below 0.1 μmol/L by 48 hours. His comorbidities included hyperlipidaemia and bronchiectasis. Seventeen days later, he underwent his second treatment cycle comprising rituximab, procarbazine, and an increased methotrexate dose of 1.5 g/m2. To mitigate methotrexate nephrotoxicity, urinary alkalinisation was achieved with bicarbonate-containing intravenous fluids and supplemental 8.4% sodium bicarbonate boluses to maintain a urinary pH > 7. Intravenous furosemide 20 mg was administered on the day of methotrexate administration and repeated the following day to promote diuresis and methotrexate clearance. Folinic acid prophylaxis was initiated within 24 hours of methotrexate administration and continued for 11 days until plasma methotrexate levels fell below 0.1 μmol/L. Methotrexate levels were monitored daily, peaking at 12.73 μmol/L at 24 hours and declining to 4.86 μmol/L at 48 hours.