Goodpasture’s disease in a patient with advanced lung cancer treated with nivolumab: An autopsy case report

Takahashi, Naoki; Tsuji, Kazuya; Tamiya, Hiroyuki; Shinohara, Tsutomu; Takeuchi, Eiji

doi:10.1016/j.lungcan.2018.05.015

Cited by 28 publications

(19 citation statements)

References 10 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…The clinically important finding is that DAH is a possible irAE due to durvalumab. There have been only 3 case reports of DAH induced by PD-1 inhibitors (Table 1) [8][9][10]. Except for an autopsy case of DAH due to nivolumab-induced Goodpasture's disease, the etiology of the other 2 DAH cases is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…There are three pathological patterns that can induce DAH: pulmonary capillaritis, diffuse alveolar damage, and bland pulmonary hemorrhage [6]. Except for the autopsy case of Goodpasture's disease, neither an autopsy nor a lung biopsy was performed in the other 2 DAH cases [8][9][10]. Thus, the pathological mechanism underlying DAH as an irAE has remained unknown.…”

Section: Discussionmentioning

confidence: 99%

Durvalumab-Induced Diffuse Alveolar Hemorrhage: An Autopsy Case Report

et al. 2020

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Durvalumab, a programmed cell death ligand 1 inhibitor, induces various immune-related adverse events (irAEs), including lung injury. However, diffuse alveolar hemorrhage (DAH) is a rare type of lung injury due to immune checkpoint inhibitors. A 76-year-old man with c-stage IIIA squamous cell carcinoma of the lung received maintenance durvalumab therapy after chemoradiotherapy. He developed dyspnea and malaise after 11 cycles of durvalumab. Chest computed tomography showed rapidly spreading bilateral ground-glass opacity in the lungs. We diagnosed DAH by hemosiderin-laden macrophages in bloody bronchoalveolar lavage fluid. Despite mechanical ventilation, steroids, and cyclophosphamide, he died of respiratory failure. The autopsy revealed that fresh and old bleeding areas coexisted, and neither pulmonary vasculitis nor diffuse alveolar damage was detected microscopically. Furthermore, CD3+ and CD8+ lymphocytes were observed in the lung interstitium, whereas CD20+ and CD4+ lymphocytes were scarcely detected. We report the first case of durvalumab-induced DAH. We should be alert to irAEs with DAH as a potential differential diagnosis of lung injury during durvalumab treatment.

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“…84,85 There also have been case reports of focal segmental glomerulosclerosis, Goodpasture disease, and IgA nephropathy associated specifically with the use of nivolumab. [51][52][53][86][87][88] Lupus-like nephritis also has been reported with anti−CTLA-4 blockade. 89…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 91%

Renal Toxicity of Systemic Therapy for Renal Cell Carcinoma

Jaimes

2020

Seminars in Nephrology

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Goodpasture’s disease in a patient with advanced lung cancer treated with nivolumab: An autopsy case report

Cited by 28 publications

References 10 publications

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

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

Durvalumab-Induced Diffuse Alveolar Hemorrhage: An Autopsy Case Report

Renal Toxicity of Systemic Therapy for Renal Cell Carcinoma

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