Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors

Frank B. Cortazar, Kristen A. Marrone, Megan Troxell, Kenneth M. Ralto, Melanie P. Hoenig, Julie R. Brahmer, Dung T. Le, Evan J. Lipson, Ilya G. Glezerman, Jedd Wolchok, Lynn D. Cornell, Paul Feldman, Michael B. Stokes, Sarah A. Zapata, F. Stephen Hodi, Patrick A. Ott, Michifumi Yamashita, David E. Leaf

Research output: Contribution to journalArticle

102 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)638-647
Number of pages10
JournalKidney International
Volume90
Issue number3
DOIs
StatePublished - Sep 1 2016

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Acute Kidney Injury
Glucocorticoids
Kidney
Creatinine
Pyuria
Thrombotic Microangiopathies
Hematologic Neoplasms
Immunotherapy
Renal Dialysis
Immune System
Monoclonal Antibodies
Urine
T-Lymphocytes
Biopsy
Acute Tubulointerstitial Nephritis
Therapeutics
Serum
Pharmaceutical Preparations
Proteins

Keywords

  • acute kidney injury
  • ipilimumab
  • nivolumab
  • pembrolizumab

ASJC Scopus subject areas

  • Medicine(all)
  • Nephrology

Cite this

Cortazar, F. B., Marrone, K. A., Troxell, M., Ralto, K. M., Hoenig, M. P., Brahmer, J. R., ... Leaf, D. E. (2016). Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney International, 90(3), 638-647. https://doi.org/10.1016/j.kint.2016.04.008

Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. / Cortazar, Frank B.; Marrone, Kristen A.; Troxell, Megan; Ralto, Kenneth M.; Hoenig, Melanie P.; Brahmer, Julie R.; Le, Dung T.; Lipson, Evan J.; Glezerman, Ilya G.; Wolchok, Jedd; Cornell, Lynn D.; Feldman, Paul; Stokes, Michael B.; Zapata, Sarah A.; Hodi, F. Stephen; Ott, Patrick A.; Yamashita, Michifumi; Leaf, David E.

In: Kidney International, Vol. 90, No. 3, 01.09.2016, p. 638-647.

Research output: Contribution to journalArticle

Cortazar, FB, Marrone, KA, Troxell, M, Ralto, KM, Hoenig, MP, Brahmer, JR, Le, DT, Lipson, EJ, Glezerman, IG, Wolchok, J, Cornell, LD, Feldman, P, Stokes, MB, Zapata, SA, Hodi, FS, Ott, PA, Yamashita, M & Leaf, DE 2016, 'Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors', Kidney International, vol. 90, no. 3, pp. 638-647. https://doi.org/10.1016/j.kint.2016.04.008
Cortazar, Frank B. ; Marrone, Kristen A. ; Troxell, Megan ; Ralto, Kenneth M. ; Hoenig, Melanie P. ; Brahmer, Julie R. ; Le, Dung T. ; Lipson, Evan J. ; Glezerman, Ilya G. ; Wolchok, Jedd ; Cornell, Lynn D. ; Feldman, Paul ; Stokes, Michael B. ; Zapata, Sarah A. ; Hodi, F. Stephen ; Ott, Patrick A. ; Yamashita, Michifumi ; Leaf, David E. / Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. In: Kidney International. 2016 ; Vol. 90, No. 3. pp. 638-647.
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