The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy, страница 12

cellular depletion of ATP, an essential requisite for the metabolic functions of cells. The postischemic infusion of ATP together with magnesium chloride (MgCl₂) replenishes tissue ATP stores and improves glomerular and tubular function [132]. This beneficial effect of ATP is not dependent on its renal vasodilatory action. Administration of ATP-MgCl₂ is probably a better long-term protective strategy than giving renal vasodilators [133]. The future use of ATP-MgCl₂ in human newborns will, however, be limited, because anoxic, immature, tubular cells maintain cellular ATP levels that are twofold higher than in mature tubules [134].

A significant rise in the intracellular calcium content has been shown to play a key role in the pafhophysiolog-ical mechanism of several types of ARF [135, 136]. This observation prompted the use of calcium channel block-ers in ARF. Calcium antagonists can reverse renal afferent arteriolar vasoconstriction, thus improving GFR. The

systemic infusion of verapamil to anesthetized rabbits prevented, or partly reversed, the hypoxemia-induced renal vasoconstnction and its accompanying fall in GFR [137] Intrarenal administration of the inorganic calcium channel blocker manganese resulted in a selective protection from renal hypoxemic changes [137] In hypo-xemic human neonates, the use of calcium antagonists such as verapamil and nifedipme is still under investigation [138] Unfortunately the presently available calcium antagonists produce severe systemic effects that overshadow their beneficial renal actions

The beneficial effects of thyroxine treatment on renal cellular injury are probably also mediated by restoration of the cellular ATP pool [139] Stabilization of cell membranes and activation of Na⁺-K⁺-ATP-ase achieve this. When thyroxine was given to rats immediately after the induction of renal ischemia, the recovery from lsch-emic ARF was accelerated [140] This protection was sustained and accompanied not only by renal functional improvement but also by enhanced repair of damaged tubular epithelium. Eight children with ARF have been successfully treated with thyroxine (5-6 pg/kg per day) [141]. Thyroxine (50 ug) was recently also effective in neonatal, hypoxemic ARF [142].

A variety of growth factors are implicated in renal parenchymal damage The exogenous administration of several of these cytokines offers theoretical possibilities to prevent, reverse, or ameliorate ARF [112, 143] Future treatment with disintegnns to counteract the mtratu-bular obstruction with cell debris may also be beneficial.

References

1  Bnon LP, Satlin LM, Edelmann CM Jr (1994) Renal disease In Avery GB, Fletcher MA, MacDonald MG (eds) Neonatolo- gy  pathophysiology and management ot the newborn  Lipp- mcott. Philadelphia, pp 792-886

2  Stapleton FB, Jones DP, Green RS (1987) Acute renal failure in neonates incidence, etiology and outcome Pediatr Nephrol 1 314-320

3  Hentschel R, Lodige B, Bulla M (1996) Renal insufficiency in the neonatal period Chn Nephrol 46 54-58

4  Chevalier RL, Campbell F, Brenbndge AG (1984) Prognostic factors in neonatal acute renal failure Pediatrics 74 265-272

5  Guillery EN, Nuyt AM, Robillard JE (1998) Functional devel opment ot the kidney in utero In Pohn RA, Fox WW (eds) Fetal and neonatal physiology, 2nd edn   Saunders, Philadel phia, pp 1560-1572

6  Yared A, Ichikawa I (1998) Postnatal development of glomer- ular filtration In Pohn RA, Fox WW (eds) Fetal and neonatal physiology, 2nd edn Saunders, Philadelphia, , pp 1588-1592

7  Guignard J-P, Gouyon J-B, John EG (1991) Vasoactive factors in the immature kidney Pediatr Nephrol 5 443-446

8  Tutro-McReddie A, Gomez RA (1993) Ontogeny ot the renm- angiotensin system Semin Nephrol 13 519-530

9  Drukker A, Goldsmith DI,