Bendamustine-induced nephrogenic diabetes insipidus

Abstract

A 59-year-old man presented with polyuria and polydipsia immediately following his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia. He initially compensated by increasing his oral fluid intake at home, but later developed septic shock and was admitted with orders to be kept nil per os (NPO). This prompted an episode of acute hypernatremia during which he exhibited continued polyuria with inappropriately dilute urine. Desmopressin challenge yielded no response in the urine osmolality, indicating a nephrogenic source of his diabetes insipidus (DI). He had no known exposure to other causative agents and had demonstrated a robust response to chemotherapy. The patient became eunatremic once oral intake was resumed and his infection was treated. Two months after presentation, he remained symptomatic. A trial with hydrochlorothiazide resulted in a significant increase in urine osmolality and subsequent decrease in urine output. To our knowledge, this is the first case of nephrogenic diabetes insipidus after rituximab and bendamustine exposure. We propose that bendamustine, similar to the alkylating agent ifosfamide, is toxic to the glomerulus and proximal tubule cells and is the most likely cause of the patient's nephrogenic DI. .

Bendamustine-induced nephrogenic diabetes insipidus – A case report

“…8 The second case is a 59-year-old male who developed NDI within days of completing his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia. 9 Our patient's presentation is similar to these case reports found in the literature. All three cases had an onset of DI symptoms within a few days of taking bendamustine, although the case by Derman et al (2017) only developed DI after the sixth cycle.…”

“…Although rare cases of bendamustine-related diabetes insidipus have been described, this report is the first involving BeEAM conditioning preceding autologous HSCT. 8,9 Despite the rarity of this entity, prompt treatment is essential. In our patient's case, it occurred a few days after he received bendamustine, and presented itself as partial nephrogenic diabetes insipidus with polyuria and urinary osmolality below 300 mOsm/kg.…”

“…Furthermore, the timing between the administration of bendamustine and the onset of dilute polyuria consisted of a few days, similar to other cases in the literature. 8,9 This suggests bendamustine was the cause of NDI and not cyclophosphamide. The drug was already discontinued at the time of DI diagnosis and there was no rechallenge.…”

“…Few cases of drug-induced NDI have been published with bendamustine. 8,9 To date, no study in the literature states a clear association between NDI and bendamustine. This adverse event needs prompt recognition for optimal management.…”

Anticancer Medications and Sodium Dysmetabolism

“…45,51 CYC and bendamustine have also been associated with NDI. 91,92 Hypernatraemia can occur if patients receiving these drugs have restricted fluid intake or develop dehydration from other causes, and has been reported with bendamustine. 92 Hypernatraemia has not been…”