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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The effect of N-phenylanthranilic acid-induced renal papillary necrosis on urinary acidification and renal electrolyte handling.

The oral administration of a suspension of N-phenylanthranilic acid (N-PAA), over the range of 0.5 to 2 mmol/kg for 14 consecutive days, caused a dose-related renal papillary necrosis (RPN), which involved no more than 30% of the medullary apex. This area of necrosis was no greater following daily doses of 3 and 5 mmol/kg of N-PAA for 14 days, but cortical degenerative changes were induced. The area of the necrotic lesion was greater in the left kidneys of individual rats than in the right kidneys. The apex-limited histopathological changes associated with the administration of low doses of N-PAA were not reflected by altered electrolyte or water homeostasis and only high doses of N-PAA caused significant changes. Urinary volume was significantly increased (in animals treated with 5 mmol/kg), whereas urinary osmolality (greater than 2 mmol/kg N-PAA), and Na+ (5 mmol/kg), K+ (5 mmol/kg), and Cl- (5 mmol/kg) excretion was decreased compared to controls. Blood urea nitrogen was increased at doses greater than 3 mmol/kg in association with cortical degenerative changes. When untreated rats were dosed orally with NH4Cl (400 mg/kg) there was a lag period between 0 and 2 hr (when no changes in H+ excretion occurred), but the urinary pH was depressed in the 2- to 4-hr collection period. Only those rats treated with the highest dose of N-PAA (5 mmol/kg) showed a significantly impaired urinary acidification after NH4Cl loading. There was, however, a statistically significant dose-related decrease in the excretion of Cl- following NH4Cl dosing, provided urine was sampled between 0 and 2 hr. These data highlight the failure of the commonly used renal function tests (such as urinary volume, osmolality, and electrolyte excretion) to reflect apex-limited RPN, unless cortical degenerative changes were also present. The dose-related depression of Cl- excretion in the 0- to 2-hr period following oral NH4Cl loading, suggests that appropriately timed sampling of this urinary anion could offer an improved criterion for the diagnosis of RPN.[1]


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