Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit

Pediatr Nephrol. 2009 May;24(5):973-81. doi: 10.1007/s00467-008-1098-1. Epub 2009 Jan 24.

Abstract

Acute normocapnic hypoxemia can cause functional renal insufficiency by increasing renal vascular resistance (RVR), leading to renal hypoperfusion and decreased glomerular filtration rate (GFR). Insulin-like growth factor 1 (IGF-1) activity is low in fetuses and newborns and further decreases during hypoxia. IGF-1 administration to humans and adult animals induces pre- and postglomerular vasodilation, thereby increasing GFR and renal blood flow (RBF). A potential protective effect of IGF-1 on renal function was evaluated in newborn rabbits with hypoxemia-induced renal insufficiency. Renal function and hemodynamic parameters were assessed in 17 anesthetized and mechanically ventilated newborn rabbits. After hypoxemia stabilization, saline solution (time control) or IGF-1 (1 mg/kg) was given as an intravenous (i.v.) bolus, and renal function was determined for six 30-min periods. Normocapnic hypoxemia significantly increased RVR (+16%), leading to decreased GFR (-14%), RBF (-19%) and diuresis (-12%), with an increased filtration fraction (FF). Saline solution resulted in a worsening of parameters affected by hypoxemia. Contrarily, although mean blood pressure decreased slightly but significantly, IGF-1 prevented a further increase in RVR, with subsequent improvement of GFR, RBF and diuresis. FF indicated relative postglomerular vasodilation. Although hypoxemia-induced acute renal failure was not completely prevented, IGF-1 elicited efferent vasodilation, thereby precluding a further decline in renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Hemodynamics / drug effects
  • Hypoxia / complications*
  • Hypoxia / drug therapy
  • Injections, Intravenous
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / pharmacology*
  • Kidney Diseases / etiology
  • Kidney Diseases / mortality
  • Kidney Diseases / prevention & control*
  • Kidney Function Tests
  • Longevity / drug effects
  • Rabbits
  • Renal Circulation / drug effects
  • Survival Rate
  • Urinalysis
  • Vasodilation / drug effects

Substances

  • Insulin-Like Growth Factor I