Increased Nectin-4 levels in chronic ketamine abusers and the relationship with lower urinary tract symptoms

Environ Toxicol Pharmacol. 2021 Oct:87:103714. doi: 10.1016/j.etap.2021.103714. Epub 2021 Jul 22.

Abstract

Persistent ketamine use causes susceptibility to addiction and bladder toxicity. We examined the association of lower urinary tract symptoms and levels of Nectin-4, a member of the cell adhesion molecules that is essential for maintaining the urothelium barrier in chronic ketamine abusers. We measured the plasma levels of Nectin-4 in 88 patients with ketamine dependence and 69 controls. Patients with ketamine dependence were assessed for ketamine use variables, psychological symptoms, and lower urinary tract symptoms. We found Nectin-4 levels were increased in ketamine-dependent patients compared to the controls (p < 0.0001). Patients with urinary tract symptoms exhibited lower Nectin-4 levels than those without (p = 0.021). Our results suggest an up-regulation of Nectin-4 following chronic and heavy ketamine use. Patients with ketamine dependence with a compromised upregulation of Nectin-4 are likely to have more severe urinary tract symptoms. The mechanisms underlying the involvement of Nectin-4 in ketamine addiction and bladder toxicity warrant future investigation.

Keywords: Addiction; Bladder toxicity; Ketamine abuse; Lower urinary tract symptoms; Nectin-4.

MeSH terms

  • Adult
  • Cell Adhesion Molecules / blood*
  • Excitatory Amino Acid Antagonists / toxicity*
  • Female
  • Humans
  • Ketamine / toxicity*
  • Lower Urinary Tract Symptoms / blood*
  • Lower Urinary Tract Symptoms / etiology
  • Male
  • Substance-Related Disorders / blood*
  • Substance-Related Disorders / complications
  • Young Adult

Substances

  • Cell Adhesion Molecules
  • Excitatory Amino Acid Antagonists
  • NECTIN4 protein, human
  • Ketamine