Renal Toxicity of Systemic Therapy for Renal Cell Carcinoma

Semin Nephrol. 2020 Jan;40(1):49-58. doi: 10.1016/j.semnephrol.2019.12.006.

Abstract

The incidence of kidney cancer has been increasing steadily and, until recently, there was a substantial lack of effective therapies for a cancer that is now among the 10 most common cancers in men and women. During the past 10 years, novel therapies have been developed including antiangiogenic drugs targeting vascular endothelial growth factor and its receptors, immune checkpoint inhibitors, and mammalian target of rapamycin inhibitors that have resulted in a significant improvement in clinical outcomes in a traditionally difficult-to-treat cancer. These new drugs, however, also have important side effects and toxicities that often have an impact on the treatment of these patients. The use of anti-angiogenic drugs often results in the development of hypertension and, less frequently, varying degrees of proteinuria including nephrotic range proteinuria. A variety of agents are used for the treatment of hypertension and proteinuria including blockers of the renin angiotensin system and calcium channel blockers, but there are no randomized clinical trials comparing different therapeutic agents in these patients. Immune checkpoint inhibitors have become one of the cornerstones of therapy in kidney cancer, but their use is linked to a variety of side effects that affect almost every organ and resemble autoimmune diseases. In the kidney, these drugs can induce acute interstitial nephritis in close to 5% of patients with varying degrees of severity that in some cases require discontinuation of treatment and systemic treatment with corticosteroids. Although mammalian target of rapamycin inhibitors now also are part of the therapeutic armamentarium available for these patients, all clinical trials have been performed in patients with normal renal function and therefore their effects in patients with abnormal renal function are not known.

Keywords: Renal cell carcinoma; acute kidney injury; anti-angiogenic therapy; hypertension; immune checkpoint inhibitors; proteinuria.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects*
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Glucocorticoids / therapeutic use
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / drug therapy
  • Immune Checkpoint Inhibitors / adverse effects*
  • Kidney Neoplasms / drug therapy*
  • Nephritis, Interstitial / chemically induced*
  • Nephritis, Interstitial / drug therapy
  • Protein Kinase Inhibitors / adverse effects*
  • Proteinuria / chemically induced*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Glucocorticoids
  • Immune Checkpoint Inhibitors
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases