Renal effects of immune checkpoint inhibitors

Nephrol Dial Transplant. 2017 Jun 1;32(6):936-942. doi: 10.1093/ndt/gfw382.

Abstract

Recent advances in immune checkpoint inhibitor (ICPI) development have led to major improvements in oncology patient outcomes. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are two essential immune checkpoint receptors. Ipilimumab and tremelimumab (anti-CTLA-4-blocking antibodies) and pembrolizumab and nivolumab (antibodies targeting PD-1 receptors) have already been approved by US Food and Drug Administration in several malignancies. Two different forms of ICPI-induced renal damage have been identified, including acute (granulomatous) tubulointerstitial nephritis and immune complex glomerulonephritis. The observed acute renal damage can be reversed upon ICPI drug discontinuation and renal function can recover back to normal following the introduction of systemic corticosteroid treatment. Any delay in treating this complication could result in definitive and irreversible renal injury.

Keywords: checkpoint blockade; immunotherapy; ipilimumab; nivolumab; pembrolizumab.

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / drug therapy
  • Adrenal Cortex Hormones / therapeutic use
  • Animals
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / therapeutic use
  • CTLA-4 Antigen / antagonists & inhibitors
  • Humans
  • Immune System / drug effects
  • Kidney / drug effects*
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors

Substances

  • Adrenal Cortex Hormones
  • Antineoplastic Agents, Immunological
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Programmed Cell Death 1 Receptor