There are roughly 12–13 cases annually per 10,000 population in women receiving outpatient treatment and 3–4 cases requiring admission. In men, 2–3 cases per 10,000 are treated as outpatients and 1– cases/10,000 require admission. Young women are most often affected, probably reflecting sexual activity in that age group. Infants and the elderly are also at increased risk, reflecting anatomical changes and hormonal status. Xanthogranulomatous pyelonephritis is most common in middle-aged women. It can present somewhat differently in children, in whom it may be mistaken for Wilms' tumor.

Most cases of "community-acquired" pyelonephritis are due to bowel organisms that enter the urinary tract. Common organisms are "E. coli" (70–80%) and "Enterococcus faecalis". Hospital-acquired infections may be due to coliform bacteria and enterococci, as well as other organisms uncommon in the community (e.g., "Pseudomonas aeruginosa" and various species of "Klebsiella"). Most cases of pyelonephritis start off as lower urinary tract infections, mainly cystitis and prostatitis. "E. coli" can invade the superficial umbrella cells of the bladder to form intracellular bacterial communities (IBCs), which can mature into biofilms. These biofilm-producing "E. coli" are resistant to antibiotic therapy and immune system responses, and present a possible explanation for recurrent urinary tract infections, including pyelonephritis. Risk is increased in the following situations:

- Mechanical: any structural abnormalities in the urinary tract, vesicoureteral reflux (urine from the bladder flowing back into the ureter), kidney stones, urinary tract catheterization, ureteral stents or drainage procedures (e.g., nephrostomy), pregnancy, neurogenic bladder (e.g., due to spinal cord damage, spina bifida or multiple sclerosis) and prostate disease (e.g., benign prostatic hyperplasia) in men

- Constitutional: diabetes mellitus, immunocompromised states

- Behavioral: change in sexual partner within the last year, spermicide use

- Positive family history (close family members with frequent urinary tract infections)