Enhanced recovery from acute renal failure by the postischemic infusin of adenine nucleotides and magnesium chloride in rats
Siegel, N.J.; Glazier, W.B.; Chaudry, I.H.; Gaudio, K.M.; Lytton, B.; Baue, A.E.; Kashgarian, M.
Kidney International 17(3): 338-349
ISSN/ISBN: 0085-2538 PMID: 7401453 Accession: 005363548
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. Adenine nucleotides (AMP, ADP, or ATP) combined with MgCl2 were infused after an ischemic renal injury. Twenty-four hours later, rats that received no infusion or one of the components of the mixture alone had reduced CIn [clearance of inulin] (355 .+-. 40 .mu.l/min per 100 g of body wt vs. 977 .+-. 40 control value), decreased RBF (3550 .+-. 205 .mu.l/min per 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). Rats given dopamine or phenoxybenzamine maintained low CIn (365 .+-. 50) despite inproved RBF (4678 .+-. 222). Rats infused with either AMP, ADP, or ATP combined with MgCl2 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 MgCl2, ultrastructural studies demonstrated focal cellular necrosis and marked generalized tubular cell and mitochondrial swelling, whereas rats infused with ATP and MgCl2 had fewer ultrastructural changes with better preservation of cellular morphology. Rats treated with ATP and MgCl2 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 MgCl2 administered. The cellular content of exogenously administered ATP was 2.5 times greater in previously ischemic kidneys than in nonischemic kidneys. Adenine nucleotides combined with MgCl2 when infused after the initiation of acute renal failure significantly improve both CIn and tubular function and these agents may effectively enhance recovery following an ischemic renal insult.