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

被引：278

作者：

Cortazar, Frank B. ^{[1
,2
]}

Kibbelaar, Zoe A. ^{[3
]}

Glezerman, Ilya G. ^{[4
,5
]}

Abudayyeh, Ala ^{[6
]}

Mamlouk, Omar ^{[6
]}

Motwani, Shveta S. ^{[3
,7
]}

Murakami, Naoka ^{[3
]}

Herrmann, Sandra M. ^{[8
]}

Manohar, Sandhya ^{[8
]}

Shirali, Anushree C. ^{[9
]}

Kitchlu, Abhijat ^{[10
]}

Shirazian, Shayan ^{[11
]}

Assal, Amer ^{[12
]}

Vijayan, Anitha ^{[13
]}

Renaghan, Amanda DeMauro ^{[14
]}

Ortiz-Melo, David, I ^{[15
]}

Rangarajan, Sunil ^{[16
,17
]}

Malik, A. Bilal ^{[18
]}

Hogan, Jonathan J. ^{[19
]}

Dinh, Alex R. ^{[19
]}

Shin, Daniel Sanghoon ^{[20
,21
]}

Marrone, Kristen A. ^{[22
]}

Mithani, Zain ^{[23
]}

Johnson, Douglas B. ^{[24
]}

Hosseini, Afrooz ^{[3
]}

Uprety, Deekchha ^{[3
]}

Sharma, Shreyak ^{[3
]}

Gupta, Shruti ^{[3
]}

Reynolds, Kerry L. ^{[25
]}

Sise, Meghan E. ^{[1
]}

Leaf, David E. ^{[3
]}

机构：

[1] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA

[2] New York Nephrol Vasculitis & Glomerular Ctr, 62 Hackett Blvd, New York, NY 12209 USA

[3] Brigham & Womens Hosp, Div Renal Med, 75 Francis St, Boston, MA 02115 USA

[4] Mem Sloan Kettering Canc Ctr, Renal Serv, 1275 York Ave, New York, NY 10021 USA

[5] Weill Cornell Med Coll, New York, NY USA

[6] Univ Texas MD Anderson Canc Ctr, Sect Nephrol, Houston, TX 77030 USA

[7] Dana Farber Canc Inst, Boston, MA 02115 USA

[8] Mayo Clin, Div Nephrol, Rochester, MN USA

[9] Yale Univ, Sch Med, Sect Nephrol, New Haven, CT USA

[10] Univ Toronto, Univ Hlth Network, Div Nephrol, Toronto, ON, Canada

[11] Columbia Univ, Med Ctr, Div Nephrol, New York, NY USA

[12] Columbia Univ, Med Ctr, Div Hematol Oncol, New York, NY USA

[13] Washington Univ, Div Nephrol, St Louis, MO 63110 USA

[14] Univ Virginia, Sch Med, Div Nephrol, Charlottesville, VA 22908 USA

[15] Duke Univ, Med Ctr, Div Nephrol, Durham, NC USA

[16] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL USA

[17] Univ Alabama Birmingham, Div Hematol Oncol, Birmingham, AL USA

[18] Univ Washington, Div Nephrol, Seattle, WA 98195 USA

[19] Univ Penn, Div Nephrol Hypertens & Electrolytes, Perelman Sch Med, Philadelphia, PA 19104 USA

[20] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[21] Vet Affairs Greater Los Angeles Healthcare Syst, Div Hematol & Oncol, Los Angeles, CA USA

[22] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[23] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Miami, FL 33136 USA

[24] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA

[25] Massachusetts Gen Hosp, Div Oncol, Boston, MA 02114 USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2020年 / 31卷 / 02期

关键词：

ACUTE INTERSTITIAL NEPHRITIS; COMBINED NIVOLUMAB; ADVERSE EVENTS; KIDNEY INJURY; IPILIMUMAB; SURVIVAL; RISK;

D O I：

10.1681/ASN.2019070676

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 rechal lenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. Conclusions This multicenter study identifies insights into the riskfactors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.

引用

页码：435 / 446

页数：12

共 29 条

[11] Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].

Haanen, J. B. A. G. ;

Carbonnel, F. ;

Robert, C. ;

Kerr, K. M. ;

Peters, S. ;

Larkin, J. ;

Jordan, K. .

ANNALS OF ONCOLOGY, 2017, 28 :119-142

[12] Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs [J].

Haslam, Alyson ;

Prasad, Vinay .

JAMA NETWORK OPEN, 2019, 2 (05)

Horvat, Troy Z. ;

Adel, Nelly G. ;

Thu-Oanh Dung ;

Momtaz, Parisa ;

Postow, Michael A. ;

Callahan, Margaret K. ;

Carvajal, Richard D. ;

Dickson, Mark A. ;

D'Angelo, Sandra P. ;

Woo, Kaitlin M. ;

Panageas, Katherine S. ;

Wolchok, Jedd D. ;

Chapman, Paul B. .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (28) :3193-+

[14] Renal toxicities associated with pembrolizumab [J].

Izzedine, Hassan ;

Mathian, Alexis ;

Champiat, Stephane ;

Picard, Cecile ;

Mateus, Christine ;

Routier, Emilie ;

Varga, Andrea ;

Malka, David ;

Leary, Alexandra ;

Michels, Judith ;

Michot, Jean-Marie ;

Marabelle, Aurelien ;

Lambotte, Olivier ;

Amoura, Zahir ;

Soria, Jean-Charles ;

Kaaki, Sihem ;

Quellard, Nathalie ;

Goujon, Jean-Michel ;

Brocheriou, Isabelle .

CLINICAL KIDNEY JOURNAL, 2019, 12 (01) :81-88

[15] Acute Kidney Injury in Patients Receiving Systemic Treatment for Cancer: A Population-Based Cohort Study [J].

Kitchlu, Abhijat ;

McArthur, Eric ;

Amir, Eitan ;

Booth, Christopher M. ;

Sutradhar, Rinku ;

Majeed, Habeeb ;

Nash, Danielle M. ;

Silver, Samuel A. ;

Garg, Amit X. ;

Chan, Christopher T. ;

Kim, S. Joseph ;

Wald, Ron .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2019, 111 (07) :727-736

[16] Immune checkpoint inhibitor (nivolumab)-associated kidney injury and the importance of recognizing concomitant medications known to cause acute tubulointerstitial nephritis: a case report [J].

Koda, Ryo ;

Watanabe, Hirofumi ;

Tsuchida, Masafumi ;

Iino, Noriaki ;

Suzuki, Kazuo ;

Hasegawa, Go ;

Imai, Naofumi ;

Narita, Ichiei .

BMC NEPHROLOGY, 2018, 19

[17]

Larkin J, 2015, NEW ENGL J MED, V373, P1270, DOI [10.1056/NEJMoa1504030, 10.1056/NEJMc1509660]

[18] Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience [J].

Mamlouk, Omar ;

Selamet, Umut ;

Machado, Shana ;

Abdelrahim, Maen ;

Glass, William F. ;

Tchakarov, Amanda ;

Gaber, Lillian ;

Lahoti, Amit ;

Workeneh, Biruh ;

Chen, Sheldon ;

Lin, Jamie ;

Abdel-Wahab, Noha ;

Tayar, Jean ;

Lu, Huifang ;

Suarez-Almazor, Maria ;

Tannir, Nizar ;

Yee, Cassian ;

Diab, Adi ;

Abudayyeh, Ala .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2019, 7

[19] Biopsy-Proven Acute Interstitial Nephritis, 1993-2011: A Case Series [J].

Muriithi, Angela K. ;

Leung, Nelson ;

Valeri, Anthony M. ;

Cornell, Lynn D. ;

Sethi, Sanjeev ;

Fidler, Mary E. ;

Nasr, Samih H. .

AMERICAN JOURNAL OF KIDNEY DISEASES, 2014, 64 (04) :558-566

[20] Association between AKI, Recovery of Renal Function, and Long-Term Outcomes after Hospital Discharge [J].

Pannu, Neesh ;

James, Matthew ;

Hemmelgarn, Brenda ;

Klarenbach, Scott .

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 8 (02) :194-202

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