Abstract: SA-PO1282
When the Cure Triggers the Crisis: Rapid-Onset, Life-Threatening Diabetic Ketoacidosis (DKA) as a Consequence of Immune Checkpoint Inhibition with Nivolumab
Session Information
- Onconephrology: Epidemiological Trends, Risk Stratification, and Clinical Outcomes
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Hashmi, Razi Haider, Baystate Health, Springfield, Massachusetts, United States
- Landry, Daniel L., Baystate Health, Springfield, Massachusetts, United States
- Braden, Gregory Lee, Baystate Health, Springfield, Massachusetts, United States
Group or Team Name
- Baystate Docs
Introduction
Anti-PD-1 immunotherapy (nivolumab) is increasingly used for urothelial carcinoma but carries a rare risk of immune-mediated endocrinopathies, including type 1 diabetes mellitus (T1DM). Although DKA has been reported with other checkpoint inhibitors, no prior case of life-threatening DKA specifically attributed to nivolumab with seronegative autoantibody status has been described.
Case Description
A 72-year-old woman with urothelial carcinoma on adjuvant nivolumab presented with a 4-day prodrome of polyuria, polydipsia, and confusion three weeks after her third infusion. She had no prior diabetes and a baseline HbA1c of 5.0%. On admission: glucose 946 mg/dL, venous pH 6.95, anion gap 39 mmol/L, beta-hydroxybutyrate 14.7 mmol/L, and HbA1c rose acutely to 7.4%. C-peptide was undetectable (0.1 ng/mL). GAD-65 (glutamic acid decarboxylase 65), IAA (insulin autoantibody), IA-2 (islet-antigen-2) and ZnT8 (zinc transporter 8) autoantibodies were all negative. Concurrent AKI, hyponatremia, and an elevated osmolar gap (32) prompted nephrology consultation to exclude toxic alcohol ingestion, which was ruled out. She was treated with insulin infusion, IV fluids, and empiric fomepizole, with prompt resolution. Nivolumab was subsequently withheld.
Discussion
This case is, to our knowledge, the first reported instance of life-threatening DKA specifically attributed to nivolumab. The seronegative autoantibody profile makes it even more unique in contrast to published reports where GAD-65 antibody is predominantly seropositive. Rather than indicating a lesser degree of immune activation, the seronegative profile in this patient — combined with an undetectable C-peptide and fulminant clinical course — points to a T-cell–driven mechanism of beta-cell destruction. This is consistent with experimental data demonstrating that PD-1 pathway blockade accelerates diabetes through expansion of autoreactive T-cells and their markers without a required antibody response. Clinically, this has a direct implication: Nivoloumab-induced DKA can be life-threatening. The absence of autoantibodies has not been reported before with Nivolumab and does not exclude ICI-induced T1DM, and the pace of deterioration in this case — from a normal A1c to fulminant DKA within months —reinforces the need for close monitoring of immune-mediated adverse events (irAEs).