Role of urinary concentrating ability in the generation of toxic papillary necrosis.

We studied the pathogenesis of chemically induced papillary necrosis in six groups of rats. Papillary necrosis was produced by a single injection of 2-bromoethylamine hydrobromide (BEA), 50 mg, i.v.; the animals were followed for 7 to 10 days after the administration of the compound. Following BEA, heterozygous Brattleboro rats developed all the functional and morphologic lesions of papillary necrosis that we previously described in Sprague-Dawley rats. They were unable to maintain sodium balance when dietary sodium was withdrawn. Homozygous Brattleboro rats, on the other hand, developed none of the manifestations of papillary necrosis (that is, animals with central diabetes insipidus were protected completely from the nephrotoxic effects of BEA). They adapted normally to a zero sodium diet. Chronic administration of vasopressin to homozygous Brattleboro rats fully restored the toxic effects of BEA. Lowering urinary concentrating ability by inducing a water diuresis in Sprague-Dawley rats completely protected against BEA-induced papillary necrosis. Decreasing papillary solute concentration by furosemide or increasing urine flow after abrupt withdrawal of vasopressin to homozygous Brattleboro rats did not protect against BEA-induced papillary necrosis. We conclude that the combination, but not either alone, of increased urine flow and decreased papillary solute concentration protects against the development of BEA-induced papillary necrosis.