Acute pyelonephritis results from bacterial invasion of the renal parenchyma. Escherichia coli reigns as the most causative organism, but Proteus species, Pseudomonas species, Staphylococcus aureus, and Enterococcus faecalis may also cause this infection. Typically, the infection spreads from the bladder to the ureters then to the kidneys, as in vesicoureteral reflux due to congenital weakness at the junction of the ureter and bladder. Bacteria refluxed to the intrarenal tissue may create colonies of infection within 24 to 48 hours. Infection may also result from instrumentation (catheterization, cystoscopy, or urologic surgery), from hematogenic infection (septicemia or endocarditis), or from lymphatic infection. Pyelonephritis may also result from an inability to empty the bladder (such as in patients with neurogenic bladder), urinary stasis, or urinary obstruction due to tumors, strictures, or benign prostatic hyperplasia. Sexual activity increases the risk of bacterial contamination, particularly the use of diaphragms and other spermicidals, which can result in secondary infection. Pregnant women and people with diabetes or other renal diseases also seem to be more susceptible.

Each episode of pyelonephritis can cause significant kidney damage. Acute pyelonephritis can eventually result in chronic pyelonephritis, kidney failure, abscess formation, signs of shock, sepsis, or multiorgan system failure.