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

Journal of the American Society of Nephrology : JASN - Tập 31 Số 2 - Trang 435-446 - 2020
Frank B. Cortazar1,2, Zoé A. Kibbelaar3, Ilya Glezerman4, Ala Abudayyeh5, Omar Mamlouk5, Shveta S. Motwani6,3, Naoka Murakami3, Sandra M. Herrmann7, Sandhya Manohar7, Anushree C. Shirali8, Abhijat Kitchlu9, Shayan Shirazian10, Amer Assal11, Anitha Vijayan12, Amanda D Renaghan13, David I. Ortiz-Melo14, Sunil Rangarajan15, A. Bilal Malik16, Jonathan J. Hogan17, Alex Dinh17, Daniel Sanghoon Shin18,19, Kristen A. Marrone20, Zain Mithani21, Douglas B. Johnson22, Afrooz Hosseini3, Deekchha Uprety3, Shreyak Sharma3, Shruti Gupta3, Kerry L. Reynolds23, Meghan E. Sise1, David E. Leaf3
1Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts
2New York Nephrology Vasculitis and Glomerular Center, Albany, New York;
3Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts
4Renal Service, Memorial Sloan Kettering Cancer Center and Weil Cornell Medical College, New York, New York;
5Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, Texas
6Dana Farber Cancer Institute, Boston, Massachusetts
7Division of Nephrology, Mayo Clinic, Rochester, Minnesota
8Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut
9Division of Nephrology, University of Toronto, University Health Network, Ontario, Canada;
10Division of Nephrology and
11Division of Hematology-Oncology, Columbia University Medical Center, New York, New York;
12Division of Nephrology, Washington University in St. Louis, St. Louis, Missouri;
13Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia
14Division of Nephrology, Duke University Medical Center, Durham, North Carolina
15Divisions of Nephrology and Hematology-Oncology, The University of Alabama at Birmingham, Birmingham, Alabama;
16Division of Nephrology, University of Washington, Seattle, Washington
17Division of Nephrology, Hypertension and Electrolytes, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
18Division of Hematology and Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California;
19Division of Hematology and Oncology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California
20Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
21Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida;
22Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, Tennessee; and
23Division of Oncology, Massachusetts General Hospital, Boston, Massachusetts

Tóm tắt

Significance Statement Kidney toxicity from use of immune checkpoint inhibitors is being recognized as an increasingly frequent complication of treatment. However, existing data on immune checkpoint inhibitor–associated AKI have been limited to small, mostly single-center studies. In this multicenter study of 138 patients with immune checkpoint inhibitor–associated AKI and 276 controls, the authors characterize the clinical features of this complication and identify risk factors associated with its development, clinicopathologic features, and determinants of kidney recovery after an episode. Failure to achieve kidney recovery was associated with worse overall survival, and a minority (23%) of patients who were retreated with immune checkpoint inhibitors had a recurrence of AKI. The study provides insights into immune checkpoint inhibitor–associated AKI, although further study is needed to inform the care of affected patients. 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.

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Journal of the American Society of Nephrology : JASN

Tập 31 Số 2

435-446

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