Polycystic Kidney Disease and the Vasopressin Pathway

Ann Nutr Metab. 2017;70 Suppl 1:43-50. doi: 10.1159/000463063. Epub 2017 Jun 15.

Abstract

Vasopressin, also known as arginine vasopressin or antidiuretic hormone, plays a pivotal role in maintaining body homeostasis. Increased vasopressin concentrations, measured by its surrogate copeptin, have been associated with disease severity as well as disease progression in polycystic kidney disease (PKD), and in experimental studies vasopressin has been shown to directly regulate cyst growth. Blocking vasopressin effects on the kidney via the vasopressin V2-receptor and lower circulating vasopressin concentration are potential treatment opportunities that have been the subject of study in PKD in recent years. Treatment with vasopressin V2-receptor antagonist tolvaptan has been shown to inhibit disease progression in experimental studies, as well as in a large randomized controlled trial involving 1,445 patients with autosomal dominant PKD, lowering total kidney volume growth from 5.5 to 2.8%, and the slope of the reciprocal of the serum creatinine level from -3.81 to -2.61 mg per mL-1/year. Alternatively, lowering circulating vasopressin could delay disease progression. Vasopressin is secreted in response to an increased plasma osmolality, which in turn is caused by a low fluid or high osmolar intake. Other lifestyle factors, like smoking, increase vasopressin concentration. Here, we provide a comprehensive review of the physiology as well as pathophysiology of vasopressin in PKD, the promising effects of tolvaptan treatment, and potential synergistic or additive treatments in combination with tolvaptan. In this study, we also review current evidence regarding the effect of influencing disease progression in PKD by lifestyle changes, especially by fluid intake.

Keywords: Aquaporin-2; Autosomal dominant polycystic kidney disease; Cyclic AMP; Hydration; Polycystic kidney disease; Vasopressin; Vasopressin V2-receptor.

Publication types

  • Review

MeSH terms

  • Antidiuretic Hormone Receptor Antagonists / therapeutic use
  • Benzazepines / therapeutic use
  • Disease Progression
  • Humans
  • Polycystic Kidney, Autosomal Dominant / drug therapy
  • Polycystic Kidney, Autosomal Dominant / physiopathology*
  • Tolvaptan
  • Vasopressins / metabolism*

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Vasopressins
  • Tolvaptan