scholarly journals Ipilimumab-induced renal granulomatous arteritis: a case report

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Mathilde Lemoine ◽  
Baptiste Dilly ◽  
Alexandre Curie ◽  
Vivien Hébert ◽  
Charlotte Laurent ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Kidney Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Oral Prednisone ◽  
Kidney Injury ◽  
New Drugs ◽  
Case Presentation ◽  
Cell Death Protein

Abstract Background Immune Checkpoint Inhibitors (ICPIs) are promising new drugs in treatment of advanced tumours targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD1) or its ligand (PDL-1). Ipilimumab is a monoclonal antibody targeting the CTLA-4 receptor used in treatment of metastatic melanoma. By increasing activity of the immune system, ICPIs lead to immune-related adverse events, such as dermatitis, colitis or hepatitis. ICPIs-related kidney adverse events are rare and acute tubulointerstitial nephritis with or without granuloma have mainly been reported. Case presentation We report a case of acute kidney injury in a patient with melanoma treated by ipilimumab. Kidney biopsy revealed acute interlobular and juxtaglomerular granulomatous arteritis, which has not yet been reported in patients treated by ICPIs. Kidney function partially recovered after ipilimumab discontinuation and oral prednisone. Unfortunately, the patient died a few months later from progression of his melanoma. Conclusion This case highlights a new mechanism of acute kidney injury related to ICPIs and supports the interest of kidney biopsy in case of ICPIs related acute renal failure.

scholarly journals Acute kidney injury from immune checkpoint inhibitor use

2019 ◽  
Vol 12 (10) ◽  
pp. e231211 ◽  
Author(s):  
Lexis Gordon ◽  
Pouneh Dokouhaki ◽  
Kimberly Hagel ◽  
Bhanu Prasad
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Programmed Death ◽  
Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

scholarly journals Rheumatic immune-related adverse events from checkpoint inhibitor therapy: a case series

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Antonella Laria ◽  
Alfredomaria Lurati ◽  
Laura Castelnovo ◽  
Antonio Tamburello ◽  
Paola Maria Faggioli ◽  
...  
Keyword(s):  
Adverse Events ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Hematologic Malignancies ◽  
Checkpoint Inhibitor Therapy ◽  
Cancer Immunotherapies ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and its ligand PD-L1 are established cancer immunotherapies for solid tumor and hematologic malignancies. These therapies are involved in immune-related adverse events (irAE), both general and rheumatic ones. In general, immune-related adverse events (irAE) management includes drug-holding, tapering doses of corticosteroids, and specific immunosuppression for clinically severe cases, such as infliximab or mycophenolate.

Tubulitis in a patient treated with nivolumab: Case report and literature review

2018 ◽  
Vol 2 (2-3) ◽  
pp. 107-112
Author(s):  
Viral Vakil ◽  
Mark Birkenbach ◽  
Katti Woerner ◽  
Lihong Bu
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint Inhibitors ◽  
Kidney Biopsy ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Metastatic Urothelial Carcinoma ◽  
Programmed Death 1

Kidney injury associated with use of immune checkpoint inhibitors that target the programmed death-1 molecule commonly manifests as acute tubulointerstitial nephritis on kidney biopsy. We present a case of a 66-year-old man who developed acute kidney injury at 6 months after initiation of treatment with anti-programmed death-1 antibody, nivolumab, for treatment of metastatic urothelial carcinoma. A renal biopsy showed focal moderate-to-severe lymphocytic tubulitis with minimal interstitial inflammation. Programmed death ligand-1 immunopositivity was detected only in tubules exhibiting lymphocytic tubulitis. The patient’s renal function improved to baseline with conservative management consisting of discontinuation of nivolumab followed by prednisone treatment.

scholarly journals P0306ACUTE KIDNEY INJURY AFTER CHECKPOINT INHIBITOR TREATMENT: FACING THE FUTURE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Clara Garcã­a Carro ◽  
Mónica Bolufer ◽  
Diana Oleas ◽  
María A Azancot ◽  
Irene Agraz ◽  
...  
Keyword(s):  
Kidney Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Acute Interstitial Nephritis ◽  
University Hospital ◽  
Induction Treatment ◽  
Renal Lesion ◽  
Solid Organ

Abstract Background and Aims Checkpoint inhibitors (CPI) are used to treat solid organ metastatic malignancies. They act on by triggering a vigorous immune response against tumoral cells, preventing their proliferation. CPIs reinvigorate antitumor immune responses by interrupting co-inhibitory signaling pathways and promote immune-mediated elimination of tumor cells.This is not a selective response, deriving in immune related adverse events (irAEs). The kidney can potentially be damaged with an incidence of 13-29%. The most frequent type of toxicity is acute interstitial nephritis (AIN). Method We evaluated all the patients with solid organ metastatic malignancies treated with immunotherapy that developed acute renal injury (AKI) and underwent to kidney biopsy from March 2018 to November 2019 at Vall d’Hebron University Hospital. Results 11 patients with solid organ metastatic malignancies treated with immunotherapy developed AKI and underwent to kidney biopsy during the study period. The most frequent malignancy was lung cancer - in 6 patients-, followed by 3 patients with melanoma. 8 patients (72%) had already received previous oncological therapy, and for the remaining 3 patients (27%), CPI was the first line therapy. 8 patients (72%) were treated with anti-PD1 (programmed cell death protein 1), 4 patients (36 %) received anti PDL-1 (programmed death-ligand 1) 1 of these patients in combination with an anti CTLA-4 (cytotoxic T-lymphocyte antigen 4) and another patient received both anti PD1 and anti PDL-1. The time between the start of CPI and the onset of the AKI ranged between 2-11 months. The most frequent urine findings were subnephrotic range proteinuria with a mean protein/creatinine (mg/g creatinine) 503.6 ± 190.5 and leukocyturia in 9 of 11 patients. Mean creatinine (mg/dl) at diagnosis was 3.4 ± 1.3. 10 out of the 11 patients were diagnosed of AIN after performing a kidney biopsy. The remaining patient presented chronic changes (IFTA and glomerulosclerosis) in the biopsy, performed after receiving steroids for a month. 3 patients who presented AIN received pulses of methylprednisolone 250-500mg as induction treatment and 7 patients received prednisone 1mg/kg/day. Mean prednisone accumulated dose (mg) during the first month of treatment was 1387.5 ± 540. 9 patients experienced complete recovery of kidney function and two patients progressed to CKD. Conclusion We reported 11 patients who presented AKI associated to CPI treatment and underwent to kidney biopsy in the last 20 months at our center. 10 out of 11 presented biopsy confirmed CPI related AIN. In our experience, CPI related AIN is the most frequent renal lesion associated to the novel immunotherapy treatments. This entity seems to have good renal prognosis as long as steroid treatment is early started.

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

2021 ◽  
Vol 93 (6) ◽  
pp. 649-660
Author(s):  
Elena S. Kamyshova ◽  
Irina N. Bobkova ◽  
Marina I. Sekacheva
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Inhibitory Effect ◽  
Immune System Activation ◽  
Programmed Death ◽  
Programmed Death Protein 1 ◽  
System Activation ◽  
New Generation

Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death protein 1 (PD-1) or its ligand (PD-L1), are a new generation of immuno-oncological drugs that to date have demonstrated efficacy in a number of malignancies. The mechanism of ICT inhibitors action consist in the potentiation of the immune response by eliminating the tumor cells inhibitory effect on the T-lymphocytes activation. However, excessive immune system activation can cause the development of a special class of immune-related adverse events (irAEs) involved a wide variety of organs and systems, including the kidneys. Despite the fact that immuno-mediated kidney injury caused by ICI therapy develops quite rarely, it can be serious and determine the patient's prognosis, which necessitates early diagnosis and timely start of treatment. In this regard, awareness of the manifestations of ICI-associated renal irAEs is particularly relevant not only for oncologists and for nephrologists, but for doctors of other specialties. In this review, we elucidated the main variants of immuno-mediated kidney injury caused by ICI therapy, discussed possible predictors and mechanisms of their development, and considers the general principles of diagnosis and management of patients according to the severity of irAEs.

scholarly journals Letrozole-Induced Acute Interstitial Nephritis

2020 ◽  
pp. 1-3
Author(s):  
Prianka Puri ◽  
M Fadia ◽  
Prianka Puri ◽  
Simon Jiang ◽  
Wajih Z
Keyword(s):  
Acute Kidney Injury ◽  
Aromatase Inhibitor ◽  
Interstitial Nephritis ◽  
Renal Damage ◽  
Oral Prednisone ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Class Effect ◽  
Case Presentation ◽  
Chemotherapy Agents

Background: Acute interstitial nephritis is often associated with drug therapy. It can be a common cause of acute kidney injury, traditional chemotherapy agents have been associated with various forms of renal damage, but this is not commonly seen with anti-hormone therapy. Here we report a case of aromatase inhibitor associated acute interstitial nephritis with the use of letrozole. Case Presentation: We present the case of an 84-year-old female commended on letrozole for the management of estrogen sensitive breast cancer. The patient developed oliguric acute kidney injury 3-weeks after initiation, with a creatinine rise to 1069µmol/L, from a previously normal baseline. She had no response to hydration and underwent a renal biopsy which demonstrated acute interstitial nephritis. She was commended on 4 weeks of oral prednisone starting at 20mg with a tapering dose. Renal function returned to baseline on discharge and her aromatase inhibitor was ceased. Conclusions: This is the first reported case of letrozole induced acute interstitial nephritis. It appears the disease was steroid responsive however it is unclear if this is a class effect of aromatase inhibitors or letrozole alone.

scholarly journals T follicular helper cells: linking cancer immunotherapy and immune-related adverse events

2021 ◽  
Vol 9 (6) ◽  
pp. e002588
Author(s):  
Dirk Baumjohann ◽  
Peter Brossart
Keyword(s):  
Adverse Events ◽  
Cancer Immunotherapy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Underlying Mechanism ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Programmed Death ◽  
Cancer Types ◽  
Cell Death Protein

Cancer immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of numerous cancer types. As the underlying mechanism of these treatments lies in the interference with inhibitory signals that usually impair potent antitumor immunity, for example, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein 1 (PD-1):programmed death-ligand 1/2 (PD-L1/2) pathway, it is not surprising that this could also promote exaggerated adaptive immune responses to unrelated antigen specificities. One of the side effects of ICI-based cancer immunotherapy that is increasingly observed in the clinic is immune-related adverse events (irAEs), including various types of autoimmunity. However, the precise etiology is incompletely understood. T follicular helper (Tfh) cells provide essential help to B cells for potent antibody responses and their tumor tissue presence is often correlated with a better outcome in several solid tumor entities. Importantly, these CD4+ T cells express very high amounts of PD-1 and other co-stimulatory and inhibitory receptors. Here, we address the hypothesis that targeting CTLA-4 or PD-1 and its ligand PD-L1 critically impacts the function of Tfh cells in patients that receive these ICIs, thereby providing a link between ICI treatment and the development of secondary autoimmunity.

scholarly journals Acute kidney injury in patients treated with immune checkpoint inhibitors

2021 ◽  
Vol 9 (10) ◽  
pp. e003467
Author(s):  
Shruti Gupta ◽  
Samuel A P Short ◽  
Meghan E Sise ◽  
Jason M Prosek ◽  
Sethu M Madhavan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Kidney Biopsy ◽  
Checkpoint Inhibitors ◽  
Cox Model ◽  
Kidney Injury ◽  
Renal Recovery ◽  
Patients With Cancer ◽  
Lower Baseline

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

scholarly journals Toxicidade Cutânea dos Inibidores de Checkpoint Imunológico: Uma Revisão Narrativa

2020 ◽  
Vol 33 (5) ◽  
pp. 335
Author(s):  
Nuno Gomes ◽  
Vincent Sibaud ◽  
Filomena Azevedo ◽  
Sofia Magina
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Cutaneous Toxicity ◽  
Cell Death Protein

Introduction: Immune checkpoint inhibitors revolutionized anti-neoplastic treatment. Recently, the European Medicines Agency and the United States Food and Drug Administration approved inhibitors of various immune checkpoints, namely the cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and its ligand. Despite the added benefits in the treatment of several neoplasms, immune checkpoint blockade may also be associated with multiple immune-related adverse events.Material and Methods: A literature review in PubMed database on the cutaneous toxicity of immune checkpoint inhibitors was performed until April 30, 2019.Results and Discussion: A total of 380 articles were initially screened, of which 75 are the basis of this bibliographic review. The immune checkpoint inhibitors monoclonal antibodies produce their beneficial effects by activating the patient’s immune system. This activation also results in adverse events that can affect any organ, whereas cutaneous toxicity is the most frequent and precocious. The adverse events of the programmed cell death protein 1 and its ligand and of the cytotoxic T-lymphocyte-associated protein 4 are similar (class effect), despite the apparent higher skin toxicity of inhibitors of the cytotoxic T-lymphocyte-associated protein 4 (or its use in combination with inhibitors of programmed cell death protein 1 and its ligand). The most common cutaneous toxicities are maculopapular exanthema and pruritus, but other more specific adverse effects (e.g. lichenoid or psoriasiform reaction, vitiligo, sarcoidosis, among others) or located in the oral mucosa and/or adnexa are underreported.Conclusion: Given the high rate of cutaneous toxicity associated with new immune checkpoint inhibitors and their impact on quality of life, their early recognition and appropriate approach are crucial in the treatment of cancer patients. Observation by a dermatologist should be provided in patients with certain toxicities.

scholarly journals Management of Immune Checkpoint Inhibitor-Related Rheumatological Toxicities

2020 ◽  
Vol 20 (01) ◽  
pp. 25-34
Author(s):  
Pak Yui Fong ◽  
Shing Chuen Chow ◽  
Bernard Ming Hong Kwong ◽  
Charlene Cheuk Lam Lau ◽  
Christy Yik Ching Lau ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Eosinophilic Fasciitis ◽  
Low Grade ◽  
Programmed Death ◽  
Rheumatological Diseases ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) have forged a new direction for the treatment of cancer. However, ICIs – programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors – are also known to cause immune-related adverse events (irAEs). Rheumatological adverse events are uncommon and often low grade, but flares of underlying rheumatological diseases may be triggered. Guidelines are available for the effective management of the rheumatological adverse events that more frequently arise from the use of ICIs, such as inflammatory arthritis, inflammatory myopathies, Sjogren syndrome, scleroderma, and polymyalgia rheumatica and eosinophilic fasciitis.

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