Amino acid therapy in the treatment of experimental acute renal failure in the rat

Amino acid therapy in the treatment of experimental acute renal failure in the rat. Rats injected with mercuric chloride, 1 mg/kg body wt i.v., or 50% glycerol, 10 mg/kg body wt i.m., were treated with various amino acid regimens to determine whether renal failure could be prevented or its course altered by such therapy. In the first protocol, amino acids were infused in massive amounts beginning 30 hours after mercuric chloride injection. The second protocol used amino acids at approximately one-third that rate beginning immediately after mercuric chloride or glycerol injection and lasting until the animals' sacrifice 48 hours later. The dose was further reduced in a third study of glycerol-induced acute renal failure. The last experiments used only essential amino acids given at a dose reasonably consistent with that used in clinical studies and continued for 5 days to assess whether such treatment would accelerate the rate of recovery of renal function. Rats given the largest doses of amino acids had inordinately high BUN concentrations, and their mortality rate greatly exceeded that of animals infused with equivalent volumes of 19% or 5% dextrose solution (36% vs. 2%). The mean creatinine concentration of myohemoglobinuric rats given amino acids, 3.2 g/24 hours, continuously for 48 hours rose significantly less than did that of glucose-infused controls. Of the 21 rats in this group, 10 died before the end of the study, however, and it seems likely (though unproven) that the lower mean serum creatinine value obtained reflects the exclusion of the large percentage of animals dying in renal failure whereas only the least affected were included in the 48-hour mean scoring. None of the remaining four protocols provided any significant protection of renal function, accelerated the rate of recovery from renal failure, or improved the survival rate of rats given amino acids after an acute renal failure challenge, however. It is thus unclear whether the lower serum creatinine concentration found in but one of the five protocols truly represents partial protection of renal function or instead reflects the death of the most severely azotemic animals and the consequent inclusion of only those rats with the least severe renal function impairment. Inefficacite du traitement par les acides amines de l'insuffisance renale aigue experimentale du rat. Des rats ont recu des injections i.v. de 1 mg/kg de chlorure de mercury ou intra-musculaires de 10 mg/kg de glycerol 50% et ont ete traites par divers regimes d'acides amines afin de savoir si l'insuffisance renale peut etre empechee ou modifiee dans son evolution au moyen d'une telle therapeutique. Dans le premier protocole les acides amines ont ete perfuses en quantite importante a partir de la 30e heure apres l'ingestion de chlorure de mercury. Dans le second protocole les acides amines ont ete utilises a un debit reduit au tiers, en commencant immediatement apres l'administration de chlorure de mercury ou de glycerol. La dose d'acides amines a encore ete reduite dans une troisieme etude de l'insuffisance renale aigue myohemoglobinurique. Pour ces dernieres experiences seuls des acides amines essentiels a des doses semblables a celles utilisees en clinique humaine ont ete employes, pendant 5 jours, de facon a etablir si un tel traitement peut accelerer l'amelioration de la fonction renale. Les rats qui ont recu les doses les plus elevees d'acides amines avaient des concentrations d'uree sanguine plus elevees qu'a l'ordinaire et leur mortalite a ete superieure (36% et 2%, respectivement) a celle des animaux qui ont recu des volumes equivalents de solution de dextrose a 19 ou 5%. La concentration moyenne de creatinine des rats myohemoglobinuriques qui ont recu 3,2 g/24 heure d'acides amines de facon continue pendant 48 heures a augmente significativement moins que celle des controles recevant du glucose. Douze parmi les 21 rats de ce groupe sont morts avant la fin de l'etude et il semble probable (quoique non demontre) que la creatininemie moyenne faible reflete l'exclusion de cette moyenne des animaux morts d'insuffisance renale et l'inclusion des seuls animaux les moins atteints. Aucun des quatre autres protocoles n'a permis de montrer une protection significative de la fonction renale, une acceleration significative de la recuperation, ou une amelioration de la survie des rats qui ont recu des acides amines apres la creation d'une insuffisance renale aigue.