Immune Check Point Inhibitor–Associated Glomerulonephritis

Ashour, Tarek; Nakhoul, Georges; Patil, Pradnya D.; Funchain, Pauline; Herlitz, Leal

doi:10.1016/j.ekir.2018.10.017

Cited by 22 publications

(16 citation statements)

References 10 publications

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“…Yet, the possibility of complement-mediated MPGN (i.e., C3 glomerulonephritis) must be considered given that IgM may also result from nonspecific trapping, especially when the staining is weak. A recent report by Ashour et al showed similar C3-dominant subepithelial and mesangial deposits with sequential exposure to pembrolizumab and nivolumab, though in their case it was IgG predominant deposition [16]. Our case hints more to the potential of complement-mediated disease.…”

Section: Discussionsupporting

confidence: 59%

Membranoproliferative Glomerulonephritis Associated with Nivolumab Therapy

Cruz-Whitley

Giehl

Jen

et al. 2020

Case Reports in Nephrology

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Nivolumab is an immune checkpoint inhibitor that targets programmed death-1 on T cells and is designed to amplify an immunologic reaction against cancer cells. However, upregulation of the immune system with checkpoint inhibition is nonspecific, and it can be associated with certain renal side effects, the best documented of which is acute tubulointerstitial nephritis. We present a unique case of a patient with acute kidney injury associated with nephrotic syndrome shortly after starting nivolumab therapy for metastatic anal carcinoma. Subsequent renal biopsy revealed membranoproliferative glomerulonephritis (MPGN). We believe this represents the first reported direct case of nivolumab-associated MPGN. As immunotherapy becomes more widely used in cancer treatment, particular attention must be paid to possible consequences of immune checkpoint inhibitors.

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Section: Discussionsupporting

confidence: 59%

Membranoproliferative Glomerulonephritis Associated with Nivolumab Therapy

Cruz-Whitley

Giehl

Jen

et al. 2020

Case Reports in Nephrology

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“…Histopathological information associated to renal IrAE, remains insufficiently studied, with most information on renal IrAE derived from post hoc analysis of large randomized controlled oncology trials or from case series reports [17][18][19][20][21][22]24] . This is at least partly due to the reluctance of performing a kidney biopsy, due to perceived risk and little clinical benefit.…”

Section: Discussionmentioning

confidence: 99%

“…Immunotherapy related acute kidney injury (AKI) or renal IrAE was reported in early clinical trials with an overall AKI incidence rate of 2.1% from PD-1 ICI therapy alone and 5% with combination therapy [15][16][17]. Case reports suggest that the most common renal IrAE is acute interstitial nephritis (AIN), with or without granulomas, but focal segmental glomerulosclerosis (FSGS), thrombotic microangiopathy (TMA), immune-complex glomerulonephritis, drug induced lupus, anti-glomerular basement membrane (anti-GBM) glomerulonephritis, and minimal change disease (MCD) have also been reported [17][18][19][20][21][22]. The clinical presentation, management and outcomes of renal IrAE is highly variable, without consensus for the role of renal biopsy.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…24,29 Other nonspecific immune complexes deposited were C3, IgG, kappa, lambda, and C1q. 30 In all of these cases, steroid-based and immunosuppressive therapy was used for treatment. • • C3 glomerulopathy was observed in a patient with smoldering multiple myeloma treated with pembrolizumab for 8 weeks.…”

Section: Glomerulopathymentioning

confidence: 99%

Cancer immunotherapy and its renal effects

Mamlouk

Abudayyeh

2019

Journal of Onco-Nephrology

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With the advent of the era of immunotherapy, there has been marked increased survival in several cancers such as advanced melanoma, renal cell carcinoma, non-small cell lung cancer, urothelial carcinoma, and head and neck cancers. Harnessing the immune system against tumor by releasing the breaks off the regulators of the immune system, such as cytotoxic T-lymphocyte–associated antigen 4, programmed cell death protein 1, and its ligand, has resulted in also unregulated organ-specific toxicity. In this review, we will discuss the renal toxicities associated with a checkpoint inhibitor from the typical acute tubulointerstitial nephritis to glomerulonephritis and their proposed mechanisms. In addition, we discuss the available data associated with transplant rejection and the use of checkpoint inhibitor.

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Immune Check Point Inhibitor–Associated Glomerulonephritis

Cited by 22 publications

References 10 publications

Membranoproliferative Glomerulonephritis Associated with Nivolumab Therapy

Membranoproliferative Glomerulonephritis Associated with Nivolumab Therapy

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

Cancer immunotherapy and its renal effects

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