Abstract: SA-PO0219
A Question of Dose: Evaluating Renal Risk with High-Dose Pembrolizumab in Postnephrectomy Renal Cell Carcinoma
Session Information
- Onconephrology: MGRS, HSCT, Electrolytes, RCC, and More
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Worwa, Stefanie, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Pickthorn, Sean, Minneapolis VA Medical Center, Minneapolis, Minnesota, United States
- Reule, Scott, Minneapolis VA Medical Center, Minneapolis, Minnesota, United States
Introduction
Immune checkpoint inhibitors have significantly improved cancer treatment but can cause adverse events such as immune checkpoint inhibitor-associated acute interstitial nephritis (ICI-AIN). Pembrolizumab is dosed in fixed regimens (200 mg every 3 weeks or 400 mg every 6 weeks), with the higher dose approved based on similar pharmacokinetic profiles. The comparative safety of the different doses in post-nephrectomy renal cell carcinoma (RCC) is unknown. We present two RCC post-nephrectomy patients with presumed ICI-AIN after initiating higher-dose pembrolizumab, suggesting an increased risk of ICI-AIN with higher dosing in patients with reduced renal mass.
Case Description
Two 77-year-old men, each with a prior nephrectomy for high-risk RCC, received adjuvant therapy with pembrolizumab (400 mg every 6 weeks). Patient 1, with a history of hypertension, developed a rash and AKI (creatinine 5.4 mg/dL) 4 weeks after initiating treatment. Patient 2, with a history of hypertension, type 2 diabetes, and mechanical aortic valve, experienced diarrhea, rash, and AKI (creatinine 7.2 mg/dL) after 6 weeks. Both patients had proteinuria and sterile pyuria, and both pre- and post-renal causes were excluded. Biopsy was not pursued in either case due to increased risk factors, and they were placed on high-dose steroids over 4 weeks with creatinine improvement to presumed baseline after nephrectomy.
Discussion
Our post-nephrectomy RCC patients who developed rash and AKI after starting pembrolizumab, with similar presentation and response to steroids, strongly suggest ICI-AIN despite the lack of biopsy. The mechanisms of ICI-AIN may involve loss of self-tolerance, reactivation of drug-specific T cells, or kidney-specific autoantibodies. It is plausible that the higher fixed dose regimen of pembrolizumab may increase the risk of ICI-AIN in nephrectomy patients. Comparative safety data in solitary kidney RCC patients is lacking, underscoring the need for research comparing the safety of different dosing regimens in this population.
Learning points:
-Higher dose pembrolizumab regimens may carry an increased risk of ICI-AIN in post-nephrectomy patients, despite pharmacokinetic equivalence in other populations.
-ICI-AIN can be diagnosed presumptively, particularly when there are other immune-mediated adverse effects, allowing for timely corticosteroid treatment.