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 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.

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 Safety of Influenza Vaccine in Patients With Cancer Receiving Pembrolizumab

2020 ◽  
Vol 16 (7) ◽  
pp. e573-e580 ◽  
Author(s):  
Jarrett J. Failing ◽  
Thanh P. Ho ◽  
Siddhartha Yadav ◽  
Neil Majithia ◽  
Irbaz Bin Riaz ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Immune Checkpoint ◽  
Medical Records ◽  
Patient Population ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Patients With Cancer ◽  
Cumulative Incidence Curve ◽  
Checkpoint Inhibitor Therapy ◽  
Multivariable Analyses

PURPOSE: There is a concern that influenza vaccination could increase the incidence of immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors. The aim of our study was to determine the safety of influenza vaccination in this patient population. PATIENTS AND METHODS: We retrospectively identified patients who received at least 1 dose of pembrolizumab during any influenza season from September 2014 to August 2017 and reviewed medical records for irAEs. The primary endpoint was the incidence of irAEs. We used multivariable logistic regression and cumulative incidence curve with competing risks for comparison. RESULTS: Among 162 patients with cancer included in this study, 70 patients (43.2%) received at least 1 influenza vaccination. The vaccinated group was significantly older ( P = .002) and received more cycles of pembrolizumab ( P = .006). The incidence of any grade irAEs in the vaccinated group trended toward being lower (25.7% v 40.2%; P = .07) compared with the nonvaccinated group. Influenza vaccination was independently associated with fewer irAEs, with an odds ratio of 0.4 (95% CI, 0.2 to 0.9; P = .03) in multivariable analyses. The vaccinated group was less likely to have irAEs compared with the nonvaccinated group (24.7% v 34.4% at 12 months; P = .05), with death as a competing risk. The median irAE-free duration in the vaccinated group was longer than the nonvaccinated group (not reached v 28 months; P = .037). CONCLUSION: Influenza vaccination in patients with cancer receiving immune checkpoint inhibitor therapy was not associated with increased irAEs. This supports the safety of influenza vaccination in this patient population.

scholarly journals Immune Checkpoint Inhibitor Nephrotoxicity: Update 2020

Kidney360 ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 130-140 ◽  
Author(s):  
Shruti Gupta ◽  
Frank B. Cortazar ◽  
Leonardo V. Riella ◽  
David E. Leaf
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Solid Organ Transplantation ◽  
Treatment Strategies ◽  
Solid Organ ◽  
Diagnostic Uncertainty ◽  
Patients With Cancer ◽  
Underlying Malignancy

Immune checkpoint inhibitors (ICPIs) have transformed the landscape of oncology, but are associated with a variety of autoimmune adverse events, including AKI. ICPI-associated AKI (ICPI-AKI) is emerging as an increasingly frequent cause of AKI in patients with cancer, and poses unique diagnostic and management challenges to clinicians who care for these patients. In this review, we describe the incidence and risk factors for ICPI-AKI, including proton pump inhibitor use, CKD, and combination immunotherapy. We discuss the limitations of the various definitions used for ICPI-AKI in prior studies, and propose a novel classification system (definite, probable, and possible ICPI-AKI) that recognizes the diagnostic uncertainty inherent in many cases. We discuss the key clinicopathologic features and treatment strategies for ICPI-AKI, including the role of kidney biopsy versus empirical treatment with steroids. We also explore the under-studied area of ICPI use in the setting of solid organ transplantation, where nephrologists and oncologists must balance the risk of rejection versus treating the underlying malignancy. Finally, we summarize existing data on the role of ICPI rechallenge after an episode of ICPI-AKI.

scholarly journals Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors

2016 ◽  
Vol 90 (3) ◽  
pp. 638-647 ◽  
Author(s):  
Frank B. Cortazar ◽  
Kristen A. Marrone ◽  
Megan L. Troxell ◽  
Kenneth M. Ralto ◽  
Melanie P. Hoenig ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Clinicopathological Features

MO404ACUTE KIDNEY INJURY DUE TO IMMUNE CHECKPOINT INHIBITORS (CPIS) NEPHROTOXICITY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Fausta Catapano ◽  
Elisa Persici ◽  
Giulia Ubaldi ◽  
Francesca Romani ◽  
Elena Mancini
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Renal Outcome ◽  
Long Term Follow Up

Abstract Background and Aims The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding; however the immune-related toxicities associated with CPIs can limit its efficacy. Case Report. A 52 year-old female diagnosed with left ocular melanoma and treated for 14 months with nivolumab developed non-oliguric, stage 3 (KDIGO), Acute Kidney Injury (AKI) and mixed proteinuria (0.6 g/day), then was transferred in our Unit. As known causes of AKI were excluded, kidney biopsy was performed. By Optical Microscopy, there were 33 normal glomeruli; arteries and arterioles were normal. The main damage was interstitial and characterized by tubulitis, tubular necrosis, non-isometric citoplasmatic vacuolization and diffuse, acute and chronic, CD4+, inflammatory infiltrate (Figure 1, 2). By Immunofluorescence, 27 glomeruli were negative for all eight tested antibodies (IgA, IgM, IgG, F, C3, C1q, kappa and lambda light chains). On the basis of these histological findings, Nivolumab-induced Acute Tubulo-Interstitial Nephritis was diagnosed. Nivolumab was discontinuated. Patient was treated by steroids and she achieved almost complete renal function recovery (Figure 3). Conclusions. CPIs can induce a long-term Acute Kidney Injury. Histological features are characterized by Acute Tubulo-Interstitial Nephritis. Steroids can improve renal outcome. In patients treated with CPIs a multidisciplinary management between oncologists and nephrologists is desirable for monitoring renal function at basal, after drug administration and in the long-term follow-up.

scholarly journals A new expression of immune checkpoint inhibitors’ renal toxicity: when distal tubular acidosis precedes creatinine elevation

2019 ◽  
Vol 13 (1) ◽  
pp. 42-45
Author(s):  
Xavier Charmetant ◽  
Cécile Teuma ◽  
Jennifer Lake ◽  
Frédérique Dijoud ◽  
Vincent Frochot ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Renal Toxicity ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Tubular Dysfunction ◽  
Distal Tubular Acidosis

Abstract The main manifestation of acute interstitial nephritis (AIN) due to immune checkpoint inhibitors is acute kidney injury. We report here a biopsy-proven AIN revealed by tubular acidosis. This case highlights that immune checkpoint inhibitor prescribers must be aware of electrolytic disorders since tubular dysfunction can precede serum creatinine increase and reveal renal toxicity.

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