Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors Journal Article


Authors: Cortazar, F. B.; Marrone, K. A.; Troxell, M. L.; Ralto, K. M.; Hoenig, M. P.; Brahmer, J. R.; Le, D. T.; Lipson, E. J.; Glezerman, I. G.; Wolchok, J.; Cornell, L. D.; Feldman, P.; Stokes, M. B.; Zapata, S. A.; Hodi, F. S.; Ott, P. A.; Yamashita, M.; Leaf, D. E.
Article Title: Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors
Abstract: 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. © 2016 International Society of Nephrology
Keywords: ipilimumab; acute kidney injury; nivolumab; pembrolizumab
Journal Title: Kidney International
Volume: 90
Issue: 3
ISSN: 0085-2538
Publisher: Elsevier Inc.  
Date Published: 2016-09-01
Start Page: 638
End Page: 647
Language: English
DOI: 10.1016/j.kint.2016.04.008
PROVIDER: scopus
PMCID: PMC4983464
PUBMED: 27282937
DOI/URL:
Notes: Article -- Export Date: 6 December 2016 -- Source: Scopus
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  1. Jedd D Wolchok
    701 Wolchok