Abstract: FR-PO204
Sequential Development of Immune Checkpoint Inhibitor-Induced Acute Tubulointerstitial Nephritis (ICI-ATIN) following Stevens-Johnson Syndrome (SJS)-Like Reaction in Patient on Pembrolizumab and Meropenem: A Common Drug Trigger?
Session Information
- Onconephrology: Immunotherapy Nephrotoxicity and Assessment of GFR
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Andres, Julia G., Singapore General Hospital, Singapore, Singapore
- Lee, Joycelyn Jie Xin, National Cancer Center Singapore, Singapore, Singapore
- Tan, Hui Zhuan, Singapore General Hospital, Singapore, Singapore
Introduction
Multisystem immune-related adverse events can occur with immunotherapy but their predictors and implications remain unknown. We report a case of immune checkpoint-related acute tubulo-interstitial nephritis (ICI-ATIN) occurring successively after progressive immunotherapy-related mucocutaneous eruption (PIRME), an ICI-related Steven Johnson syndrome (SJS)-like reaction, in the context of meropenem exposure.
Case Description
A 71-year-old Chinese Male receiving pembrolizumab therapy for Stage IV bronchial squamous cell carcinoma, was referred for evaluation of KDIGO Stage 3, non-oliguric AKI [baseline sCr 76 µmol/L, peak sCr 353 µmol/L], occurring one week after the development of biopsy-proven PIRME. Notably, patient received meropenem in the last two weeks for treatment of lung abscess. There was no exposure to PPIs or NSAIDs. First and last dose of ICI were given 9 weeks and 3 weeks prior to AKI, respectively.
Evaluation showed mild pyuria (urinary WBC 10/µL) and sub-nephrotic range proteinuria (uPCR 0.90 g/g). Serum C-reactive protein was elevated at 90.5 mg/L. Autoimmune markers and virologies were negative. Prednisolone at 60mg OD (1mg/kg) was started empirically. Kidney biopsy performed subsequently confirmed ATIN. Rebound of AKI observed after 4 weeks, and mycophenolic acid 360mg BD was added. Partial renal remission was observed after 3 months (sCr 107µmol/L).
Discussion
Our case supports the hypothesis that multisystem irAEs may represent a combination of irAEs that share common pathobiology such as HLA genotypes, autoantibody formation or external triggers such as co-medications (PPIs, NSAIDs and antibiotics). Co-medications have been increasingly implicated in the development of ICI-ATIN, which is postulated to be a result of drug-mediated, kidney-specific immune responses occurring unchecked in the setting of lowered immune tolerance during ICI use. A similar phenomenon has been proposed in the development of PIRME. It is probable that meropenem triggered both cutaneous and renal irAEs in our patient. Patients with PIRME should receive close monitoring of renal function during and after the event. ICI-ATIN occurring together with PIRME may warrant extended or additional immunosuppression, although more research is required to confirm our findings.