maleic-acid and Glycosuria

Maleic acid (MA), a known nephrotoxicant in experimental animals, and its chlorinated derivative dichloromaleic acid (DCMA) are present in urban drinking water supplies as by-products of the chlorination process. This study was designed to characterize the effects of simultaneous exposure of subtoxic doses of DCMA and MA on renal function in both sexes of the Sprague-Dawley rat. Urine was collected at 24-h intervals from rats housed individually in stainless steel metabolism cages. Subcutaneous administration of MA at a dose of 150 mg/kg had no effect on several parameters of renal function in either sex at 24 h and only modest effects at 48 h. Renal slice studies showed that treatment of both male and female rats with DCMA (300 mg/kg) reduced p-aminohippurate (PAH) accumulation at 24 h with no effect on the uptake of tetraethylammonium ion (TEA). The combination of MA + DCMA caused a depression of TEA accumulation by slices from the female. Also, changes in urinary glucose excretion and blood urea nitrogen, although additive in the male following coexposure, appeared synergistic or potentiated in the female. These results suggest an enhanced susceptibility of the female rate to the nephrotoxic action of combined exposure to MA and DCMA.

Topics: Animals; Biological Transport; Blood Urea Nitrogen; Dose-Response Relationship, Drug; Drug Interactions; Female; Glycosuria; Kidney; Liver; Male; Maleates; p-Aminohippuric Acid; Rats; Rats, Inbred Strains; Sex Factors; Sulfhydryl Compounds; Tetraethylammonium; Tetraethylammonium Compounds

In several models of acute renal failure leakage of glomerular filtrate out of the tubule is an important pathogenetic mechanism; however, bidirectional diffusion of solute to account for certain pathophysiologic features of acute renal failure has received meager attention. Using micropuncture and clearance methods, we assessed sequentially leakage of solutes and inulin across proximal straight tubules (PST) injured by two nephrotoxins. In d-serine-treated rats with extensive necrosis of PST, the basis for glucosuria and tubular leakage of inulin was studied. Glucose absorption by the proximal convoluted tubule and glucose delivery to the PST were normal, but glucose delivery to the distal tubule was increased nearly 8-fold, indicating diffusion of glucose from interstitial to tubular luminal fluid across the necrotic PST. Total kidney inulin clearance was greatly reduced, but single nephron glomerular filtration rate, based on proximal convoluted tubule samples, was normal, indicating tubular loss of inulin. Urinary recovery of [14C]inulin infused into tubular lumina revealed that proximal convoluted tubule and distal tubule were impermeable to inulin and that inulin diffused out of the necrotic PST. The progressive return over 6 days of tubular impermeability for inulin correlated with relining of PST with new cells. In maleic acid-treated rats the site and extent of tubular necrosis and the nature of urinary loss of solutes were studied. Microdissection revealed that maleic acid caused limited necrosis of PST which averaged 7.4% of total proximal tubular length. Increased urinary excretion of protein, phosphate, and glucose and increased tubular permeability to microinfused [14C]inulin occurred with the onset of PST necrosis, and return of these abnormalities to normal correlated with the degree of cellular repair of the PST. Together these data indicate that with severe cellular injury there is bidirectional, concentration-dependent diffusion of solutes between the interstitial and tubular fluids. Thus, experimental or human toxic nephropathies should not be classified as acquired Fanconi's syndrome unless specific tubular transport defects are present.

Topics: Acute Kidney Injury; Animals; Carbon Radioisotopes; Glomerular Filtration Rate; Glucose; Glycosuria; Inulin; Kidney Tubules; Male; Maleates; Phosphates; Proteins; Proteinuria; Rats; Rats, Inbred Strains; Serine

Topics: Animals; Creatinine; Glycosuria; Kanamycin; Kidney Diseases; Male; Maleates; Metals; Molecular Weight; Proteinuria; Rabbits; Renal Aminoacidurias

Topics: Amino Acids; Animals; Biological Transport; Fanconi Syndrome; Glycosuria; Humans; Imino Acids; Kidney; Kidney Tubules; Maleates; Metals; Phosphates; Renal Aminoacidurias

Topics: Glycosuria; Histocytochemistry; Kidney; Kidney Tubules; Maleates; Polyuria; Proteinuria; Rats; Renal Aminoacidurias; Research; Succinate Dehydrogenase; Sulfhydryl Compounds; Toxicology; Urine

Topics: Amino Acids; Body Fluids; Glycosuria; Humans; Maleates; Phosphates

Topics: Amino Acids; Glycosuria; Glycosuria, Renal; Humans; Hypophosphatemia, Familial; Kidney; Maleates; Phosphates; Urine