Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.
acute kidney injury
immune checkpoint inhibitors
tubulointerstitial nephritis
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
09
07
2019
accepted:
21
11
2019
pubmed:
4
1
2020
medline:
5
9
2020
entrez:
4
1
2020
Statut:
ppublish
Résumé
Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.
Sections du résumé
BACKGROUND
Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse.
METHODS
We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI.
RESULTS
Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI.
CONCLUSIONS
This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.
Identifiants
pubmed: 31896554
pii: ASN.2019070676
doi: 10.1681/ASN.2019070676
pmc: PMC7003302
doi:
Substances chimiques
B7-H1 Antigen
0
Programmed Cell Death 1 Receptor
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
Pagination
435-446Subventions
Organisme : NIDDK NIH HHS
ID : T32 DK007219
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK120868
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK118120
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA090625
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144566
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK117014
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK106448
Pays : United States
Informations de copyright
Copyright © 2020 by the American Society of Nephrology.
Références
Clin J Am Soc Nephrol. 2010 Sep;5(9):1690-5
pubmed: 20688882
Clin J Am Soc Nephrol. 2013 Feb;8(2):194-202
pubmed: 23124779
J Clin Oncol. 2015 Oct 1;33(28):3193-8
pubmed: 26282644
Am J Kidney Dis. 2016 Aug;68(2):287-291
pubmed: 27113507
Clin J Am Soc Nephrol. 2018 Dec 7;13(12):1851-1858
pubmed: 30397027
Nephrol Dial Transplant. 2004 Nov;19(11):2778-83
pubmed: 15340098
Cancer Discov. 2018 Sep;8(9):1069-1086
pubmed: 30115704
J Clin Oncol. 2017 Dec 1;35(34):3807-3814
pubmed: 28841387
JAMA Netw Open. 2019 May 3;2(5):e192535
pubmed: 31050774
Am J Kidney Dis. 2014 Oct;64(4):558-66
pubmed: 24927897
N Engl J Med. 2015 Jul 2;373(1):23-34
pubmed: 26027431
N Engl J Med. 2018 May 31;378(22):2078-2092
pubmed: 29658856
Kidney Int. 2016 Sep;90(3):638-47
pubmed: 27282937
J Am Soc Nephrol. 2018 Aug;29(8):2039-2052
pubmed: 29959196
Ann Oncol. 2017 Jul 1;28(suppl_4):iv119-iv142
pubmed: 28881921
Clin Kidney J. 2019 Feb;12(1):81-88
pubmed: 30746132
BMC Nephrol. 2018 Feb 27;19(1):48
pubmed: 29486725
Kidney Int. 2014 Oct;86(4):837-44
pubmed: 24646856
J Clin Oncol. 2018 Jun 10;36(17):1714-1768
pubmed: 29442540
J Natl Cancer Inst. 2018 Nov 13;:
pubmed: 30423160
Kidney Int. 2008 Apr;73(8):940-6
pubmed: 18185501
Clin J Am Soc Nephrol. 2019 Jul 5;14(7):1077-1079
pubmed: 31048326
Clin J Am Soc Nephrol. 2015 Nov 6;10(11):1900-10
pubmed: 26342047
Clin Nephrol. 2007 Aug;68(2):65-72
pubmed: 17722704
N Engl J Med. 2017 Oct 5;377(14):1345-1356
pubmed: 28889792
N Engl J Med. 2018 Jan 11;378(2):158-168
pubmed: 29320654
Clin J Am Soc Nephrol. 2008 May;3(3):844-61
pubmed: 18337550
J Immunother Cancer. 2019 Jan 6;7(1):2
pubmed: 30612580