FUNDAMENTAL AND APPLIED TOXICOLOGY 4, 909-921 (1984) Pathophysiology of Drug-Induced

Toxicol. 4, 909-921. Papillary necrosis, a common cause of renal failure, is a life-threatening pathophysiologic event which may have a multiplicity of mechanisms. The primary functional lesions are salt wastage, impairment of urinary concentrating ability, polyuria, and imbalances of potassium, calcium and phosphate homeostasis; urinary acidification is completely normal. Papillary necrosis is associated with a profound decrease in juxtamedullary nephron glomerular filtration rate, in addition to damage to the papillary collecting duct. 2-Bromoethylamine hydrobromide (BEA) has proved to be a useful tool in elucidating the generation of this important clinical syndrome, o I9M Society of Toucoioiy. Papillary necrosis is a clinical syndrome de-fined as an ischemic infarction of the inner medulla and papilla of the kidney. The lesion clinically is seen in association with obstruc-tive uropathy, sickle cell disease, and diabetes mellitus (Eknoyan et al., 1982). In neonates, papillary necrosis has been reported in asso-ciation with the respiratory distress syndrome (Lelong-Tissier et al., 1979). It represents the hallmark of analgesic abuse. In general, the disease usually begins as a febrile illness associated with dysuria, flank pain, and renal colic. In very severe cases in which virtually all the papillae are infarcted, there may be shock and anuria. Examination of the urine may reveal pieces of renal tissue, red cells, white cells, and bacteria. There is rapid, and essentially total, loss of renal function. The mortality rate from complete papillary necrosis approaches 100%, and de-spite vigorous hemodialysis the patients usu-ally die from infection. If the disease enters a chronic phase, or if only some of the papillae are infarcted, the lesions will ofte