Acute kidney injury in patients treated with immune checkpoint inhibitors.
CTLA-4 antigen
immunotherapy
programmed cell death 1 receptor
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
accepted:
31
08
2021
entrez:
9
10
2021
pubmed:
10
10
2021
medline:
13
1
2022
Statut:
ppublish
Résumé
Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34625513
pii: jitc-2021-003467
doi: 10.1136/jitc-2021-003467
pmc: PMC8496384
pii:
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK120868
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144566
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK117014
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK119466
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK123411
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079337
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA133250
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK118120
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125786
Pays : United States
Investigateurs
Luca Campedel
(L)
Joe-Elie Salem
(JE)
Corinne Isnard Bagnis
(CI)
Shruti Gupta
(S)
David E Leaf
(DE)
Harkarandeep Singh
(H)
Shveta S Motwani
(SS)
Naoka Murakami
(N)
Maria C Tio
(MC)
Osama E Rahma
(OE)
Suraj S Mothi
(SS)
Umut Selamet
(U)
Deborah Schrag
(D)
Sebastian Loew
(S)
Kai M Schmidt-Ott
(KM)
Weiting Chang
(W)
Kenar D Jhaveri
(KD)
Rimda Wanchoo
(R)
Yuriy Khanin
(Y)
Jamie S Hirsch
(JS)
Vipulbhai Sakhiya
(V)
Daniel Stalbow
(D)
Sylvia Wu
(S)
David I Ortiz-Melo
(DI)
Marlies Ostermann
(M)
Nuttha Lumlertgul
(N)
Nina Seylanova
(N)
Lucy Flanders
(L)
Armando Cennamo
(A)
Sophie Papa
(S)
Anne Rigg
(A)
Nisha Shaunak
(N)
Zoe A Kibbelaar
(ZA)
Karolina Benesova
(K)
Priya Deshpande
(P)
Meghan E Sise
(ME)
Kerry L Reynolds
(KL)
Harish S Seethapathy
(HS)
Meghan Lee
(M)
Ian A Strohbhen
(IA)
Sandra M Herrmann
(SM)
Busra Isik
(B)
Ilya G Glezerman
(IG)
Frank B Cortazar
(FB)
Vikram Aggarwal
(V)
Sunandana Chandra
(S)
Jason M Prosek
(JM)
Sethu M Madhavan
(SM)
Dwight H Owen
(DH)
Marium Husain
(M)
Pazit Beckerman
(P)
Sharon Mini
(S)
Shuchi Anand
(S)
Pablo Garcia
(P)
Aydin Kaghazchi
(A)
Sunil Rangarajan
(S)
Daniel Sanghoon Shin
(DS)
Grace Cherry
(G)
Christopher A Carlos
(CA)
Raymond K Hsu
(RK)
Andrey Kisel
(A)
Arash Rashidi
(A)
Sheru K Kansal
(SK)
Nicole Albert
(N)
Katherine Carter
(K)
Vicki Donley
(V)
Tricia Young
(T)
Heather Cigoi
(H)
Sophie De Seigneux
(S)
Thibaud Koessler
(T)
Els Wauters Ben Sprangers
(EW)
Chintan V Shah
(CV)
Mark Eijgelsheim
(M)
Zain Mithani
(Z)
Javier A Pagan
(JA)
Gaia Coppock
(G)
Jonathan J Hogan
(JJ)
Ala Abudayyeh
(A)
Omar Mamlouk
(O)
Jamie S Lin
(JS)
Valda Page
(V)
Abhijat Kitchlu
(A)
Samuel Ap Short
(SA)
Amanda D Renaghan
(AD)
Elizabeth M Gaughan
(EM)
A Bilal Malik
(A)
Maria Jose Soler
(MJ)
Clara García-Carro
(C)
Sheila Bermejo
(S)
Enriqueta Felip
(E)
Eva Muñoz-Couselo
(E)
Maria Josep Carreras
(MJ)
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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