Maleic acid-induced reabsorptive dysfunction in the proximal and distal nephron.
Micropuncture and clearance studies were performed to assess reabsorptive function in the proximal and distal nephron of rats with experimental Fanconi's syndrome induced by maleic acid. Anesthetized rats were studied by free-flow micropuncture of the late proximal tubule 90-120 min after continuous intravenous administration of maleic acid, 100 mg X kg-1 X h-1. Compared with control rats, the reabsorption of sodium and phosphate was significantly reduced (P less than 0.001 and less than 0.02, respectively). Tubular fluid-to-ultrafiltrate (TF/UF) chloride concentration ratio was 1.00 +/- 0.02 compared with 1.16 +/- 0.03 (P less than 0.01) in controls, suggesting a nearly total inhibition of proximal bicarbonate reabsorption. Whole kidney fractional excretions of sodium and chloride were increased significantly (P less than 0.02) but could not be explained by enhanced delivery of these solutes out of the late proximal tubule. To assess whether distal nephron reabsorption of sodium and chloride were inhibited by maleic acid, clearance studies were performed during water diuresis in awake rats. During maleic acid administration, 200 mg X kg-1 X h-1, urine flow rate (P less than 0.02) and the fractional excretions of sodium and chloride (P less than 0.001) increased significantly, but fractional free water clearance decreased from 7.16 +/- 0.42 to 4.03 +/- 0.68% (P less than 0.001). In acetazolamide-treated control rats but not in maleic acid-treated rats with similar bicarbonaturia, the magnitude of fractional free water clearance closely approximated the simultaneously measured fractional distal delivery of chloride. These studies suggest that maleic acid inhibits reabsorption at a distal nephron site or sites as well as in the proximal tubule.
D000042:Absorption; D000818:Animals; D004231:Diuresis; D005919:Glomerular Filtration Rate; D007684:Kidney Tubules / Q000187:drug effects / Q000503:physiopathology*; D007686:Kidney Tubules, Distal / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D008297:Male; D008298:Maleates / Q000633:toxicity*; D009399:Nephrons / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D014556:Urine
D008298:Maleates; C030272:maleic acid