Acute kidney injury in patients treated with immune checkpoint inhibitors.
Shruti Gupta,Samuel A.P. Short,Meghan E. Sise,Jason Prosek,Sethu M. Madhavan,María José Soler,Marlies Ostermann,Sandra M. Herrmann,Ala Abudayyeh,Shuchi Anand,Ilya G. Glezerman,Shveta S. Motwani,Naoka Murakami,Rimda Wanchoo,David I. Ortiz-Melo,Arash Rashidi,Ben Sprangers,Ben Sprangers,Vikram Aggarwal,A. Bilal Malik,Sebastian Loew,Christopher A. Carlos,Wei-Ting Chang,Wei-Ting Chang,Pazit Beckerman,Zain Mithani,Chintan V. Shah,Amanda DeMauro Renaghan,Sophie De Seigneux,Luca Campedel,Abhijat Kitchlu,Daniel Sanghoon Shin,Sunil Rangarajan,Priya Deshpande,Gaia M. Coppock,Mark Eijgelsheim,Harish Seethapathy,Meghan Lee,Ian A. Strohbehn,Dwight H. Owen,Marium Husain,Clara García-Carro,Sheila Bermejo,Nuttha Lumlertgul,Nuttha Lumlertgul,Nina Seylanova,Nina Seylanova,Lucy Flanders,Busra Isik,Omar Mamlouk,Jamie S. Lin,Pablo Garcia,Aydin Kaghazchi,Yuriy Khanin,Sheru K Kansal,Els Wauters,Sunandana Chandra,Kai M. Schmidt-Ott,Kai M. Schmidt-Ott,Raymond K. Hsu,Maria C Tio,Suraj Sarvode Mothi,Harkarandeep Singh,Deborah Schrag,Kenar D. Jhaveri,Kerry L. Reynolds,Frank B. Cortazar,David E. Leaf +67 more
TLDR
In this paper, a multivariable logistic regression model was used to identify predictors of ICPi-AKI and its recovery, and the effect of rechallenge versus no re-challenge on survival was estimated.Abstract:
Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We 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. Results ICPi-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. Conclusions Patients 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.read more
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Drug-Induced Acute Kidney Injury
TL;DR: In this paper , the authors focus on three specific types of tubulointerstitial injury, namely, intratubular obstruction, direct tubular injury, and localized inflammation, leading to acute interstitial nephritis.
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Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy
Megan Leila Baker,Yu Yamamoto,Mark A. Perazella,Nazli Dizman,Anushree C. Shirali,Navid Hafez,Jason S. Weinstein,Michael Simonov,Jeffrey M. Testani,Harriet M. Kluger,Lloyd G. Cantley,Chirag R. Parikh,F. F. Wilson,Dennis G. Moledina +13 more
TL;DR: In patients treated with ICI, mortality was higher in those with AKI unrelated to ICI but lower in those where the underlying etiology was AIN, and future studies could evaluate the association of biopsy-proven or biomarker-proven AIN with mortality in those receiving ICI therapy.
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Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy
TL;DR: In this article , the authors highlight the several associated electrolyte disorders seen with immunotherapy, such as hypercalcemia and hyperphosphatemia associated with immune checkpoint inhibitors and chimeric antigen receptor T cell therapy.
Journal ArticleDOI
Diagnosis and management of immune checkpoint inhibitor-associated acute kidney injury
TL;DR: The evaluation of patients with suspected ICI-AKI requires careful diagnostic work-up and kidney biopsy for patients with moderate-to-severe ICI -AKI to ensure accurate diagnosis and inform appropriate treatment.
Journal ArticleDOI
Soluble and cell-based markers of immune checkpoint inhibitor-associated nephritis
Meghan E. Sise,Qiyu Wang,Harish Seethapathy,D. Moreno,D. Harden,Rex Neal Smith,Ivy A. Rosales,Robert B. Colvin,Sarah Chute,Lynn D. Cornell,Sandra M. Herrmann,Riley Fadden,Ryan J. Sullivan,Nancy Yang,Sara Barmettler,Sophia Wells,Shruti Gupta,Alexandra-Chloé Villani,Kerry L. Reynolds,Jocelyn R. Farmer +19 more
TL;DR: Elevated sIL-2R level and flow cytometric markers of both B and T cell dysregulation may aid the diagnosis of ICI-nephritis.
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