Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.
Immune checkpoint inhibitors (CPIs), monoclonal antibodies that target inhibitory receptors expressed on T cells, represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies. We describe the clinical and histologic features of 13 patients with CPI-induced acute kidney injury (AKI) who underwent kidney biopsy. Median time from initiation of a CPI to AKI was 91 (range, 21 to 245) days. Pyuria was present in 8 patients, and the median urine protein to creatinine ratio was 0.48 (range, 0.12 to 0.98) g/g. An extrarenal immune-related adverse event occurred prior to the onset of AKI in 7 patients. Median peak serum creatinine was 4.5 (interquartile range, 3.6-7.3) mg/dl with 4 patients requiring hemodialysis. The prevalent pathologic lesion was acute tubulointerstitial nephritis in 12 patients, with 3 having granulomatous features, and 1 thrombotic microangiopathy. Among the 12 patients with acute tubulointerstitial nephritis, 10 received treatment with glucocorticoids, resulting in complete or partial improvement in renal function in 2 and 7 patients, respectively. However, the 2 patients with acute tubulointerstitial nephritis not given glucocorticoids had no improvement in renal function. Thus, CPI-induced AKI is a new entity that presents with clinical and histologic features similar to other causes of drug-induced acute tubulointerstitial nephritis, though with a longer latency period. Glucocorticoids appear to be a potentially effective treatment strategy. Hence, AKI due to CPIs may be caused by a unique mechanism of action linked to reprogramming of the immune system, leading to loss of tolerance.
Renal Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
Frank B
FB
Cortazar
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Kristen A
KA
Marrone
Department of Pathology, Oregon Health and Science University, Portland, Oregon, USA.
Megan L
ML
Troxell
Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Kenneth M
KM
Ralto
Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Melanie P
MP
Hoenig
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Julie R
JR
Brahmer
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Dung T
DT
Le
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Evan J
EJ
Lipson
Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ilya G
IG
Glezerman
Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Jedd
J
Wolchok
Department of Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Lynn D
LD
Cornell
Advanced Kidney Care of Hudson Valley, Poughkeepsie, New York, USA.
Paul
P
Feldman
Department of Pathology, Columbia University Medical Center, New York, New York, USA.
Michael B
MB
Stokes
Division of Nephrology, Kaiser Permanente, Portland, Oregon, USA.
Sarah A
SA
Zapata
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
F Stephen
FS
Hodi
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Patrick A
PA
Ott
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Michifumi
M
Yamashita
Divison of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address: DELEAF@partners.org.
David E
DE
Leaf
D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000037:antagonists & inhibitors*; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D009395:Nephritis, Interstitial / Q000097:blood / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy; D006435:Renal Dialysis; D057049:Thrombotic Microangiopathies / Q000097:blood / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D005938:Glucocorticoids; D007155:Immunologic Factors; D003404:Creatinine
acute kidney injury; ipilimumab; nivolumab; pembrolizumab