RESUMEN
Urinary metabolite profiling, using randomly voided samples, has become accepted practice for such compounds as organic acids. To date, however, published methods for examining urinary porphyrin excretion have been based upon examination of 24-h urine collections. The inherent difficulties of obtaining an accurate collection, coupled with the intrinsic liabilities of porphyrins suggest that a method based upon random void analysis would be of great use. Thus, we have examined the porphyrin pattern of randomly excreted urine samples from normal adults of both genders, comparing our results with those obtained from analysis of 24-h collections. We have also evaluated the use of different alkalinizing agents. Finally, we have investigated the possibility that an underlying diurnal pattern of porphyrin excretion might influence the results obtained from random urine voids. The results indicate that NaOH retards spontaneous conversion of porphyrins within the first 24 h, thus optimizing recovery of uroporphyrin. Data from random voids mirror those obtained from 24-h collections and diurnal variations were not found to influence these results. Normal values are provided for random samples obtained from males and females. Thus, we conclude that random urine profiling is a rapid and accurate means of initial evaluation.
Asunto(s)
Porfirinas/orina , Adulto , Carbonatos/química , Cromatografía Líquida de Alta Presión , Ritmo Circadiano , Creatinina/orina , Femenino , Humanos , Masculino , Valores de Referencia , Hidróxido de Sodio/química , Factores de Tiempo , Urinálisis/métodosRESUMEN
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.
Asunto(s)
Modelos Animales de Enfermedad , Síndrome de Fanconi/fisiopatología , Heptanoatos , Riñón/fisiopatología , Aminoácidos/orina , Animales , Creatinina/metabolismo , Síndrome de Fanconi/inducido químicamente , Síndrome de Fanconi/metabolismo , Síndrome de Fanconi/patología , Glucosa/metabolismo , Riñón/metabolismo , Riñón/ultraestructura , Masculino , Fosfatos/metabolismo , Porfobilinógeno/metabolismo , Porfirinas/orina , Ratas , Ratas EndogámicasRESUMEN
Succinylacetone (SA), a metabolic end-product found in urine from individuals with hereditary tyrosinemia and associated renal Fanconi syndrome and a known inhibitor of hepatic 5-aminolevulinic acid dehydratase (ALAD), has been used to study heme metabolism in isolated rat renal tubules. Heme biosynthetic porphyrin precursors are increased selectively in the presence of 4 mmol/1 SA. Total porphyrin content of the tubules are increased approximately 2-fold, while both ferrochelatase and heme oxygenase activities remain unaffected by SA. Nonetheless, total heme content is reduced, as was incorporation of radioactive label from amino[14C]levulinic acid. Cytochrome P-450 content remained unaffected. Impairment of iron uptake and/or transport within the cell or enhancement of heme catabolism via a non-heme oxygenase-dependent pathway could explain the observations.