Prévot Anne, Julita Monique, Tung David K, Mosig Dolores
Nephrology Unit, Department of Pediatrics, Lausanne University Medical Center (CHUV), Lausanne, Switzerland.
Pediatr Nephrol. 2009 May;24(5):973-81. doi: 10.1007/s00467-008-1098-1. Epub 2009 Jan 24.
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.
急性等碳酸血症性低氧血症可通过增加肾血管阻力(RVR)导致功能性肾功能不全,进而引起肾灌注不足和肾小球滤过率(GFR)降低。胰岛素样生长因子1(IGF-1)在胎儿和新生儿中的活性较低,在缺氧时会进一步降低。对人类和成年动物给予IGF-1可诱导肾小球前和肾小球后血管舒张,从而增加GFR和肾血流量(RBF)。在低氧血症诱导的肾功能不全的新生兔中评估了IGF-1对肾功能的潜在保护作用。对17只麻醉并机械通气的新生兔评估了肾功能和血流动力学参数。低氧血症稳定后,静脉推注生理盐水(时间对照)或IGF-1(1mg/kg),并在六个30分钟时间段内测定肾功能。等碳酸血症性低氧血症显著增加了RVR(+16%),导致GFR(-14%)、RBF(-19%)和尿量(-12%)降低,滤过分数(FF)增加。生理盐水导致受低氧血症影响的参数恶化。相反,尽管平均血压略有但显著下降,但IGF-1阻止了RVR的进一步增加,随后GFR、RBF和尿量得到改善。FF表明肾小球后血管相对舒张。尽管低氧血症诱导的急性肾衰竭未被完全预防,但IGF-1引起了出球小动脉舒张,从而防止了肾功能的进一步下降。