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J Am Soc Nephrol. 2020 Jan 2. pii: ASN.2019070676. doi: 10.1681/ASN.2019070676. [Epub ahead of print]

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.

Author information

1
Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts; frankcortazar24@gmail.com.
2
New York Nephrology Vasculitis and Glomerular Center, Albany, New York.
3
Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
4
Renal Service, Memorial Sloan Kettering Cancer Center and Weil Cornell Medical College, New York, New York.
5
Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Dana Farber Cancer Institute, Boston, Massachusetts.
7
Division of Nephrology, Mayo Clinic, Rochester, Minnesota.
8
Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut.
9
Division of Nephrology, University of Toronto, University Health Network, Ontario, Canada.
10
Division of Nephrology and.
11
Division of Hematology-Oncology, Columbia University Medical Center, New York, New York.
12
Division of Nephrology, Washington University in St. Louis, St. Louis, Missouri.
13
Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia.
14
Division of Nephrology, Duke University Medical Center, Durham, North Carolina.
15
Divisions of Nephrology and Hematology-Oncology, The University of Alabama at Birmingham, Birmingham, Alabama.
16
Division of Nephrology, University of Washington, Seattle, Washington.
17
Division of Nephrology, Hypertension and Electrolytes, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
18
Division of Hematology and Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California.
19
Division of Hematology and Oncology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California.
20
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
21
Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida.
22
Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, Tennessee; and.
23
Division of Oncology, Massachusetts General Hospital, Boston, Massachusetts.
24
Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts.

Abstract

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.

KEYWORDS:

acute kidney injury; immune checkpoint inhibitors; tubulointerstitial nephritis

PMID:
31896554
DOI:
10.1681/ASN.2019070676

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