Immune Checkpoint Inhibitor-Induced Nephrogenic Diabetes Insipidus

Introduction: In the evolving world of cancer immunotherapy, immune-related adverse events (irAEs) are becoming increasingly recognized, with an impact on a wide range of organ systems. Case Description: A 70-year-old man with non-small cell lung cancer completed neoadjuvant chemoimmunotherapy, lung lobe resection, and subsequently received adjuvant immunotherapy with pembrolizumab. He experienced rapid onset of polyuria and polydipsia, and on presentation to his outpatient oncologist, was found to have AKI. He was referred to the ED for further evaluation. Initial physical exam was notable for a well-appearing male, nontender abdomen, and no lower extremity edema. Initial labs were notable for sodium 142, creatinine 1.7 (baseline 1.0), glucose 107, serum osmolality 302, urine osmolality 199, no glucosuria, and no proteinuria. While inpatient, he produced > 4.3 L of urine in 24 hours, confirming true polyuria. A water deprivation test was performed, and after 12 hours of water deprivation, the patient was only able to concentrate his urine to a maximum urine osmolality of 312 mOsm/kg. At 14 hours into the water deprivation, 2 mcg of DDAVP was administered. One hour later, urine osmolality had only increased to 341 mOsm/kg. Serum sodium reached a peak of 144 during the test. Random copeptin level drawn the day prior was elevated at 36 pmol/L (normal <13). Soluble IL-2 receptor level was mildly elevated. He was discharged with outpatient nephrology follow up. He underwent a kidney biopsy which demonstrated acute tubulointerstitial nephritis with focal tubulitis. He was treated with steroids, and repeat kidney biopsy demonstrated resolution of the interstitial nephritis. Discussion: Though not total AVP resistance given the urine osmolality of 341mOsm/kg during water deprivation, this case demonstrates partial AVP resistance. The patient had an inability to maximally concentrate the urine and respond to DDAVP. The copeptin was markedly elevated prior to water deprivation. This patient had biopsy-confirmed immune checkpoint inhibitor (ICI)-induced nephritis. We suggest that the AKI led to the defect in concentrating ability. Central diabetes insipidus (DI) is a known irAE, but to date there have been no reported cases of ICI-induced nephrogenic DI (AVP resistance). This case demonstrates that the spectrum of renal irAEs extends to the tubular response to AVP.