title: Physiological basis for an animal model of the renal Fanconi syndrome: use of succinylacetone in the rat.
abstract: 1. The biochemical basis for the human renal Fanconi syndrome, including glucosuria, phosphaturia and aminoaciduria, remains enigmatic. This is due, in part, to the lack of an appropriate animal model. Since there is an association between the human genetic disease hereditary tyrosinaemia, for which urinary excretion of the compound succinylacetone constitutes a biochemical marker, and a renal Fanconi syndrome, we have examined the relationship between succinylacetone and renal tubular function in the rat. 2. Intraperitoneal injection of succinylacetone for 3 consecutive days into adult male Sprague-Dawley rats resulted in succinylacetone plasma concentration of 3 mmol/l. This concentration was associated with glucosuria, aminoaciduria, polyuria, reduced renal phosphate reabsorption and normal creatinine clearance. In addition, urinary porphobilinogen and total porphyrin excretions were markedly reduced. In animals permitted to recover for 7 days after succinylacetone administration, these renal functional changes remitted partially or completely. Ultrastructural examination of the kidneys after the 3 days of treatment showed no fine structural changes. 3. We conclude that the physiological alterations produced in normal rat renal tubules by succinylacetone provide the basis for the study of the biochemical changes underlying the human renal Fanconi syndrome.
authors.affiliation: Department of Medicine, Medical College of Virginia, Richmond.
authors.forename: P A
authors.initials: PA
authors.lastname: Wyss
authors.forename: S B
authors.initials: SB
authors.lastname: Boynton
authors.forename: J
authors.initials: J
authors.lastname: Chu
authors.forename: R F
authors.initials: RF
authors.lastname: Spencer
authors.forename: K S
authors.initials: KS
authors.lastname: Roth
mesh_terms: D000596:Amino Acids / Q000652:urine; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D006537:Heptanoates; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D010710:Phosphates / Q000378:metabolism; D011162:Porphobilinogen / Q000378:metabolism; D011166:Porphyrins / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000596:Amino Acids; D006537:Heptanoates; D010710:Phosphates; D011166:Porphyrins; C020804:succinylacetone; D011162:Porphobilinogen; D003404:Creatinine; D005947:Glucose