Enhanced recovery from acute renal failure by the postischemic infusion of adenine nucleotides and magnesium chloride in rats

Abstract

Although a number of manipulations prior to or during the initiation phase of an acute renal injury will modify the degree of functional impairment, agents administered after the acute insult usually have been ineffective. In the present study, adenine nucleotides (AMP, ADP, or ATP) combined with magnesium chloride were infused after an ischemic renal injury. Twenty-four hours later: (1) rats that received no infusion or one of the components of the mixture alone had reduced CIn (355 +/- 40 microliter/min/100 g of body wt vs. 977 +/- 40 control value), decreased RBF (3550 +/- 205 microliter/min/100 g of body wt vs. 5095 +/- 171 control value), elevated FENa (0.65 +/- 0.10% vs. 0.17 +/- 0.04 control value), and diminished UOsm (862 +/- 110 mOsm/kg vs. 1425 +/- 132 control value); (2) rats given dopamine or phenoxybenzamine maintained low CIn (365 +/- 50) despite improved RBF (4678 +/- 222); (3) rats infused with either AMP, ADP, or ATP combined with magnesium chloride had markedly improved CIn (594 +/- 44, P < 0.01), increased RBF (4269 +/- 223, P < 0.01); normalized FENa (0.18 +/- 0.07%, P < 0.01), and improved UOsm (1201 +/- 106 mOsm/kg, P < 0.05). In animals given no infusion or only magnesium chloride, ultrastructural studies demonstrated focal cellular necrosis and marked generalized tubular cell and mitochondrial swelling, whereas rats infused with ATP and magnesium chloride had fewer ultrastructural changes with better preservation of cellular morphology. Rats treated with ATP and magnesium chloride had improved CIn despite ischemic periods of 30, 45, and 60- min; and the degree of improvement was directly related to the quantity of ATP and magnesium chloride administered. The cellular content of exogenously administered ATP was 2.5 times greater in previously ischemic kidneys than in nonischemic kidneys. The data indicate that adenine nucleotides combined with magnesium chloride when infused after the initiation of acute renal failure significantly improve both CIn and tubular function and suggest that these agents effectively enhance recovery following an ischemc renal insult.

Mechanisms whereby exogenous adenine nucleotides improve rabbit renal proximal function during and after anoxia.

“…Various investigators have demonstrated that infusion of adenine nucleotides protect the kidney from the pathological effects of ischemia (11,12). However, the mechanism(s) whereby this protection occurs has been difficult to ascertain in the intact kidney.…”

Purinergic signalling in the kidney in health and disease

“…Hepatocyte growth factor has been shown to enhance recovery from renal tubular ischaemia and to promote adhesion of the ATP-depleted renal collecting duct cell line, mIMCD-3, in a MAPK-dependent manner [228]. Restoration after ischaemia by perfusion of ATP-MgCl 2 was described early [104,335]. A 3 receptor knock-out mice are protected against ischaemic renal failure [208].…”

Acute renal failure: definitions, diagnosis, pathogenesis, and therapy

“…On this background, the administration of exogenous ATP has been shown to afford protection in experimental ischemic ATP. While ATP salvage has been shown to be protective against experimental tubular necrosis (84), recent experimental evidence has suggested that GTP salvage may be preferred in preventing apoptosis associated with acute renal injury (85). The effect of the administration of synthetic RGD peptides to attenuate tubular obstruction has yet to be examined in clinical ARF.…”