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

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.

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Acknowledgments

We wish to thank Prof. Jean-Pierre Guignard for allowing us the unique opportunity to work with him, as well as the freedom to work independently for the present project. We wish to thank the Swiss National Science Foundation (SNSF) for supporting the Pediatric Nephrology Unit of the Lausanne University Medical Center (CHUV) throughout the years. Dr A. Prévot and this study were supported by SNSF grant no. 3200-064041.00.

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Correspondence to Anne Prévot.

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Prévot, A., Julita, M., Tung, D.K. et al. Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit. Pediatr Nephrol 24, 973–981 (2009). https://doi.org/10.1007/s00467-008-1098-1

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Keywords

  • Hypoxemia
  • Insulin-like growth factor-1
  • Kidney
  • Newborn rabbit
  • Survival