Etiology and pathophysiology of pyelonephritis. Escherichia coli is the most frequent cause of pyelonephritis. Its possible virulence factors include the ability to adhere and colonize the urinary tract, an important initiating factor in all urinary tract infections (UTIs). The importance of P fimbriae in this adhesion is stressed and the evidence for its importance in pyelonephritis is presented in epidemiologic studies of patients, as well as in animal studies. It appears that both host receptor density and the nonsecretor state is responsible for susceptibility to urinary tract infection. Vesicoureteral reflux can be responsible for ascending upper tract infection, but infection with P-fimbriated E coli may lead to ascending pyelonephritis without reflux because of the paralytic effect of lipid A on ureteral peristaltic activity. Renal ischemia leads to renal damage following infection by reperfusion damage due to the release of superoxide. Experimentally, this ischemic damage can be prevented by allopurinol, a xanthine oxidase inhibitor. The acute inflammatory response can produce renal damage because of the respiratory burst of phagocytosis, which while killing phagocytosed bacteria also damages renal tubules. An amelioration of the inflammatory response by treatment with superoxide dismutase or corticosteroids has been shown to modulate renal damage. Vaccination with P fimbriae has been shown experimentally to prevent the initiation of the disease. However, since vaccines are not clinically available, the clinical and animal studies on therapy of acute disease are stressed. Acute pyelonephritis during the first 3 years of life more often produced the renal damage that could lead to end-stage renal disease. 