Abstract: FR-PO203
Delayed Immune Checkpoint Inhibitor-Induced Acute Tubulointerstitial Nephritis (ICI-ATIN) Relapse with Proton-Pump Inhibitor Re-exposure Despite ICI Discontinuation: A Case Report
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
While immune-related adverse events (irAEs) usually occur during active use of immune checkpoint inhibitors (ICI), their sporadic development after ICI discontinuation has been rarely described. We report a case of delayed ICI-acute tubulo-interstitial nephritis (ICI-ATIN) relapse occurring in context of proton pump inhibitor (PPI) re-exposure despite ICI cessation.
Case Description
An 84-year-old Chinese female with colorectal cancer was referred for KDIGO Stage 2, non-oliguric acute kidney injury (AKI) [baseline sCr 84µmol/L, peak sCr 162µmol/L] 4 months after initiation of pembrolizumab. Urinalysis showed hematuria (28 RBC/µL), pyuria (85 WBC/µL) and minimal proteinuria (uPCR 0.35g/g). Only ANA was borderline detected (titre 1:160), while the remaining autoimmune markers were negative. PPI use, but not NSAIDs or antibiotics, was noted. As ICI-ATIN was highly suspected, she received a 10-week tapering course of empiric prednisolone (0.7mg/kg starting dose) with clinical improvement (recovery sCr 112µmol/L). She remained off immunotherapy over the next 5 months, but was inadvertently restarted on PPI for dyspepsia. AKI was observed 4 weeks later (peak sCr of 190µmol/L). ATIN was confirmed on kidney biopsy. Prednisolone at 1mg/kg was recommenced, with improvement of sCr to 124µmol/L after 7 weeks. Vonaprazan was started for dyspepsia. PPI was permanently stopped and recorded as an adverse drug reaction.
Discussion
Our case highlights important observations concerning the use of PPI in ICI-treated patients. The temporal correlation of PPI re-exposure and ATIN relapse supports the postulation that PPI potentiates the development of ICI-ATIN. While PPI avoidance is recommended in ICI rechallenge, it is unknown if and when PPI can be safely resumed after ICI is permanently withdrawn. Long-lasting effects of ICIs surpassing their pharmacokinetic half-lives have been described, with resultant implications for their related immune-related toxicities. We advise continued caution with PPI use in all patients with a history of ICI-ATIN, even when ICI is stopped. Awareness of this association amongst healthcare providers (HCPs) is necessary as PPI use is common. Systematic documentation of irAEs with disease-specific codes, as well as implementation of EHR alerts to identify and inform HCPs of potential irAE triggers are additionally required.