Clinicopathological Features of Acute Kidney Injury Associated With Immune Checkpoint Inhibitors

Kidney Int. 2016 Sep;90(3):638-47. doi: 10.1016/j.kint.2016.04.008. Epub 2016 Jun 7.

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.

Keywords: acute kidney injury; ipilimumab; nivolumab; pembrolizumab.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / pathology*
  • Acute Kidney Injury / therapy
  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Creatinine / blood
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunologic Factors / antagonists & inhibitors*
  • Immunotherapy / adverse effects*
  • Immunotherapy / methods
  • Kidney / blood supply
  • Kidney / pathology
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Nephritis, Interstitial / blood
  • Nephritis, Interstitial / chemically induced
  • Nephritis, Interstitial / pathology*
  • Nephritis, Interstitial / therapy
  • Renal Dialysis
  • Thrombotic Microangiopathies / blood
  • Thrombotic Microangiopathies / chemically induced
  • Thrombotic Microangiopathies / pathology*
  • Thrombotic Microangiopathies / therapy

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Glucocorticoids
  • Immunologic Factors
  • Creatinine

Supplementary concepts

  • Acute Tubulointerstitial Nephritis