The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy, страница 4

33].

VMNP can be caused by a basic disease of the newborn interfering with renal perfusion or can be secondary to activation of some of the vasoregulatory systems. For example, hypotension increases the activity of the RAAS and the sympathetic nervous system, hypoxemia stimulates ET, ANP, and PG release, whereas septicemia raises ET and NO activity. The interactions between these regulatory forces are rather complex. To complicate matters, several of the vasoconstrictor and/or vasodilatory factors differ in their effects on the systemic and (intra) renal circulation. A factor having a beneficial effect on the systemic circulation may even have harmful renal consequences. An example is the activation of All in hy-potensive states. All stimulation results in increased MAP but may also decrease renal perfusion. The therapeutic use of the PG synthesis inhibitor indomethacin represents another example. By closing a PDA, indo-

Hypoxemia

The second most-frequent condition leading to neonatal VMNP is perinatal hypoxemia or asphyxia, generally in the course of a severe respiratory distress syndrome (RDS) [2, 35]. Hypoxemia by itself reduces RBF and GFR. In a recent study, 61% of severely asphyxiated newborns developed ARF [36]. Hypotension, hypovolemia, activation of the RAAS and the intrarenal adenosine system, as well as stimulation of catecholamines and increased vasopressin release, are some of the factors observed in human neonates or neonatal animal models with RDS-induced hypoxia [37-40]. All of these factors can result in disturbances of glomerular hemodynamics (Fig. 1). Hypercapnic acidosis, another consequence of a variety of respiratory disorders, including neonatal RDS, can cause renal vasoconstriction, thus contributing to the overall renal dysfunction seen in severe asphyxia [41].

Septicemia

Septicemia is also an important cause of neonatal ARF. This form of vasomotor ARF is generally part of multi-organ failure with renal hypoperfusion - secondary to systemic hypotension - and activation of several vasoac-tive mediators [42]. These vasoactive mediators, such as the RAAS, ET, the renal KK-kinin system, and throm-boxane (TXA₂), are probably more important than the hypoperfusion, and are potential future targets for specific therapeutic interventions [43].