#4220 NOT JUST AIN? OTHER IMMUNE-CHECKPOINT INHIBITOR LESIONS: A SINGLE INSTITUTION'S EXPERIENCE OVER 12 YEARS
Authors: Mignano Salvatore , Chowdhury Raad , Alexander Mariam , Buglioni Alessia , Herrmann Sandra 
Published: June 2023

Abstract

Background and Aims
Immune-checkpoint inhibitors (ICI) are antineoplastic therapies that unleash the immune-system and have revolutionized cancer outcomes. Though they are a drug class with great potential, their effects are not always limited to the malignant cells and can cause a spectrum of immune-related adverse events (irAEs). Roughly 5% of patients will experience acute kidney injury (AKI) with acute interstitial nephritis (AIN) being the predominant pathologic lesion. Glomerular and vascular lesions are thought to be rare and, as a result, not well-defined. We aim to document glomerular and vascular pathology in this context at our institution.

Method
We performed a retrospective review of internal native renal biopsies from 2010-2022 that had known ICI treatment. Standard processing of renal biopsies included light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM). We reviewed the biopsies and pathology reports, as well as clinical data from patient electronic medical records.

Results
Our search yielded 32 kidney biopsies; of those, most had AIN (27/32), 8 cases had glomerular pathology, and 1 case had arterial endotheliitis. Of the cases with glomerular pathology, 4 had subacute glomerular thrombotic microangiopathy (TMA). Among the cases with TMA, 2 were also treated with vascular endothelial growth factor inhibitor (VEGFi),1 with gemcitabine, and 1 with BRAF-inhibitor therapy. Further, only one of these patients had complement testing, which did not reveal definitive deficiency. One patient had proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), IgG-κ. One patient had IgA nephropathy (IgAN) and another had membranous nephropathy (MN). Most patients were biopsied for rising serum creatinine (SCr) (median: 1.6 mg/dL; range: 0.55-5.5); 1 had nephrotic-range proteinuria (median urine protein/creatinine ratio (UPCR): 0.3; range: 0.12-5.64). One, with thin basement membrane disease, had significant hematuria (&gt;100 RBC/hpf). Five patients had irAEs in other organs. 7/9 patients died or entered hospice care (median: 14 months post-biopsy; range: 2-48 months) due to malignancy progression. Of the deceased patients, 2 were dialysis-dependent. Of the living patients, 1 has dialysis-independent chronic kidney disease (CKD).

Conclusion
Overall, glomerular and vascular pathology due to ICI-use appears rare though difficult to isolate since other drugs and neoplasia can cause similar lesions. In our cohort, TMA was the most common glomerular lesion, though direct causation due to ICI is difficult to prove. In all patients with TMA, we identified concurrent use of other known causative drugs. IgAN and MN have been reported in association with neoplasia. PGNMID has been reported in a variety of malignant and nonmalignant conditions, and ICI-use could be a triggering factor. In conclusion, the patterns of glomerular injury seen in our cohort may be secondary to other concurrent risk factors other than ICI use. Arterial endotheliitis appears to be a rare but significant secondary effect to ICI-use.