Immune Check Point Inhibitor–Associated Endothelialitis

Bobart, Shane A.; Owoyemi, Itunu; Grande, Joseph P.; Leung, Nelson; Herrmann, Sandra M.

doi:10.1016/j.ekir.2020.05.027

Cited by 7 publications

(7 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On a mechanistic level, AIN in patients receiving ICIs is associated with tubular upregulation of PD-L1, suggesting that PD-L1 positivity reflects susceptibility to develop irAE ( 3 ). In addition to AIN, glomerular disease and renal vasculitis have also been described in the context of ICI-related kidney injury ( 5 , 6 ). These observations implicate distinct roles of PD-L1 among different renal compartments dependent on its presence.…”

Section: Discussionmentioning

confidence: 99%

“…AIN in patients receiving ICIs is associated with tubular positivity for PD-L1, suggesting that PD-L1 positivity reflects susceptibility to develop renal complications with these agents ( 3 , 4 ). Additionally to AIN, there is increasing recognition that glomerular disease and renal vasculitis are associated with ICI-related kidney injury with reports describing both, nephrotic and nephritic clinical presentations ( 5 , 6 ). These observations reveal distinct roles of PD-L1 among different renal compartments dependending on its presence or absence.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Variable Expression of Programmed Cell Death Protein 1-Ligand 1 in Kidneys Independent of Immune Checkpoint Inhibition

et al. 2021

View full text Add to dashboard Cite

ContextDue to recent advantages in cancer therapy, immune checkpoint inhibitors (ICIs) are new classes of drugs targeting programmed cell death protein 1 (PD-1) or its ligand programmed cell death protein 1-ligand 1 (PD-L1) used in many cancer therapies. Acute interstitial nephritis (AIN) is a potential and deleterious immune-related adverse events (irAE) in the kidney observed in patients receiving ICIs and the most common biopsy-proven diagnosis in patients who develop acute kidney injury (AKI). Based on previous reports, AIN in patients receiving ICIs is associated with tubular positivity for PD-L1, implicating that PD-L1 positivity reflects susceptibility to develop renal complications with these agents. It remains unclear if PD-L1 positivity is acquired specifically during ICI therapy or expressed independently in the kidney.MethodsPD-L1 was analyzed in experimental mouse models of ischemia-reperfusion injury (IRI), folic acid-induced nephropathy (FAN), unilateral ureteral obstruction (UUO), and nephrotoxic serum nephritis (NTN) by immunostaining, SDS-PAGE, and subsequent immunoblotting. In addition, we included a total number of 87 human kidney samples (six renal biopsies with AIN related to ICI therapy, 13 nephrectomy control kidneys, and 68 ICI-naïve renal biopsies with various underlying kidney diseases to describe PD-L1 expression.ResultsWe here report distinct PD-L1 expression in renal compartments in multiple murine models of kidney injury and human cases with various underlying kidney diseases, including ICI-related AIN and renal pathologies independent of ICI therapy. PD-L1 is frequently expressed in various renal pathologies independent of ICI therapy and could potentially be a pre-requisit for susceptibility to develop AKI and deleterious immune-related AIN. In addition, we provide evidence that tubular PD-L1 positivity in the kidney is associated with detection of urinary PD-L1+ tubular epithelial cells.ConclusionOur study implicates that PD-L1 is frequently expressed in various renal pathologies independent of ICI therapy and could potentially be a pre-requisit for susceptibility to develop AKI and deleterious immune-related AIN. Because non-invasive detection of PD-L1+ cells in corresponding urine samples correlates with intrarenal PD-L1 positivity, it is attractive to speculate that further non-invasive detection of PD-L1+ cells may identify patients at risk for ICI-related AIN.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Variable Expression of Programmed Cell Death Protein 1-Ligand 1 in Kidneys Independent of Immune Checkpoint Inhibition

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Recently a case of endotheliialitis in a patient with prostate and bladder carcinoma with metastatic squamous cell carcinoma who was on cemiplimab was reported. 15 There is no other reports on renal side effects of cemiplimab. Our report shows that cemiplimab can affect the kidney in different ways like other immune checkpoint inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Renal tubular acidosis and acute kidney injury secondary to cemiplimab

Rashidi

Herlitz

Tariq

2021

Journal of Onco-Nephrology

View full text Add to dashboard Cite

Immune therapies have transformed the landscape of oncology. Immune checkpoint inhibitors are group of medications, which activate T-Cells to fight against cancer cells. Acute tubulointrestitial nephritis is the most common form of kidney immune-related adverse event. With more use of ICPIs, renal immune related side effects are being recognized more. Here we present a case of renal tubular acidosis with acute kidney injury in a patient with squamous cell carcinoma of the skull who was on Cemiplimab.

show abstract

“…In a case study by Gallan et al three cases of kidney vasculitis and one case of pauci-immune crescentic glomerulonephritis were observed (23). A more recent case study revealed a case of renal endothelialitis during ICPIs therapy (24).…”

Section: The Mechanisms Of Renal Toxicity Due To Icpi Treatmentmentioning

confidence: 97%

“…ICPI-induced AKI demonstrates relatively similar clinical and laboratory characteristics to AKI caused by other substances such as sub-nephrotic range proteinuria, bland urinalysis or sterile pyuria. However, active urine sediment can be seen if there is glomerular or vascular involvement (16,(23)(24)(25).…”

Section: The Mechanisms Of Renal Toxicity Due To Icpi Treatmentmentioning

confidence: 99%

Immune-related adverse kidney events by immune checkpoint inhibitors; a narrative review on current studies

et al. 2021

View full text Add to dashboard Cite

Chemotherapy-associated renal injury is considered one of the major concerns among nephrological and oncological practice. The use of novel anti-neoplastic therapies that target carcinomas has helped in the detection of this form of renal injury. Immune checkpoint inhibitors (ICPIs) are a group of monoclonal antibodies targeting inhibitory receptors that exist on tumor cells and T cells. ICPIs are able to suppress tumors that might have escaped from the immune surveillance. Meanwhile, although ICPIs have shown promising efficacy in cancer treatment, their immune-related side effects limit their widespread use in cancer therapy schedules. One of the major side effects limiting ICPIs’ usage is nephrotoxicity. Glomerular disease, acute interstitial nephritis (AIN), and acute tubular necrosis (ATN) are considered different infusion-related adverse events. Infiltration of eosinophils, T lymphocytes, and plasma cells, as well as interstitial inflammation and edema, leading to acute tubulointerstitial nephritis (ATIN). It is conceivable that the rupture of self-tolerance by ICPIs induces an autoimmune reaction against some specific self-antigens in the organs including kidneys. The exact nature of the antigen is unclear; however, it is possible that it is found in the renal tubular cells, as indicated by a greater frequency of ATIN in kidney biopsies. The current review paper discusses the relationship between ICPIs therapy and kidney disorders or more specifically, their possible role in renal damage along with renal toxicity profile in the setting of ICPIs treatment.

show abstract

Immune Check Point Inhibitor–Associated Endothelialitis

Cited by 7 publications

References 9 publications

Variable Expression of Programmed Cell Death Protein 1-Ligand 1 in Kidneys Independent of Immune Checkpoint Inhibition

Variable Expression of Programmed Cell Death Protein 1-Ligand 1 in Kidneys Independent of Immune Checkpoint Inhibition

Renal tubular acidosis and acute kidney injury secondary to cemiplimab

Immune-related adverse kidney events by immune checkpoint inhibitors; a narrative review on current studies

Contact Info

Product

Resources

About