Histological diagnosis of immune checkpoint inhibitor induced acute renal injury in patients with metastatic melanoma: a retrospective case series report

Abstract

Background Immune checkpoint inhibitors (ICI) have become the standard of care in many oncological conditions but are associated with a spectrum of renal immune-related adverse events (IrAEs). We aimed to describe the spectrum, histology, management and outcomes of renal IrAE in patients with metastatic melanoma undergoing ICI therapy. Methods We conducted a retrospective review of 23 patients with a diagnosis of metastatic melanoma treated with ICI between January 2017 and April 2019 who developed a renal IrAE. Baseline demographic data, biochemical and histopathological results, management and outcomes were analyzed. Results The majority of patients who developed renal irAE were male and received combination immunotherapy. The median time of onset from initiation of ICI therapy to renal IrAE was 4 months. 52% of the treated renal IrAE had histopathologically confirmed renal IrAE. The most common histological pattern of injury was acute tubulo-interstitial nephritis (92%). One patient developed anti-GBM disease with non-dialysis dependent stage 5 CKD. In tubulointerstitial injury, there was no association between peak creatinine, renal recovery and histologically reported inflammation or fibrosis. Patients with renal IrAE demonstrated persisting renal dysfunction at 3, 6 and 12 months with a mean baseline, 3 and 12 month creatinine of 90.0 μmol/L, 127.0 μmol/L and 107.5 μmol/L respectively. Conclusion Renal IrAE is most commonly attributable to steroid responsive acute tubulointerstitial nephritis. The outcome of rarer pathologies such as anti-GBM disease may be adversely affected by a delayed diagnosis. There is persisting renal dysfunction following an episode of renal IrAE that may have impact on future renal and overall survival outcomes.

Acute kidney injury in patients treated with immune checkpoint inhibitors

“…Direct renal toxicity from ICPis, referred to here as ICPi-associated acute kidney injury (ICPi-AKI), occurs with an estimated incidence of 3%-5%. [2][3][4][5][6][7][8][9] ICPi-AKI can have serious consequences for patients including dose delay or permanent discontinuation of ICPi therapy, irreversible loss of kidney function (which can impact eligibility to receive other anticancer treatments), and prolonged courses of immunosuppression. Additionally, when a patient undergoing treatment with ICPis develops AKI, there is often uncertainty regarding its etiology, since AKI occurs Open access commonly in patients with cancer and can be due to a variety of causes.…”

Potential therapies for immune-related adverse events associated with immune checkpoint inhibition: from monoclonal antibodies to kinase inhibition

“…Such histological changes indicate that TNF-α, IL-1, IL-6, IL-12/IL-23, and JAK–STAT signaling may be involved in their development. Autoantibody-mediated toxicities include renal, 23 rheumatological, 24 cutaneous (eg, bullous pemphigoid), 25 and central nervous system irAEs, 26 and theoretically implicate JAK–STAT and BTK signaling in their pathogenesis. Recognition of these specific histological findings further supports investigation of tailored approaches to management of irAEs.…”

Kidney injury associated with antitumor therapy: focus on the adverse events of modern immuno-oncological drugs

“…Однако наиболее частым вариантом поражения почек на фоне терапии ингибиторами ИКТ является острый интерстициальный/ тубулоинтерстициальный нефрит (ОТИН). В первых опубликованных работах диагноз ОТИН морфологически подтвержден у 87,5-92,3% пациентов с ОПП [24,21,43,48,74]. В 2019 г. M. Perazella и соавт.…”