Pyelonephritis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]


Pyelonephritis is caused by the spread of the infection to the renal parenchyma. The infection, which is the most common cause of pyelonephritis, can either be classified as ascending or descending. Ascending infections stem from a urinary tract which can either be a result of urethritis or cystitis. Descending infections from the blood (hematogenous spread) are a less common cause of pyelonephritis than ascending infections. The Urine is normally sterile and the normal flow of urine washes away bacteria, if any, so that they do not accumulate in a significant amount to cause an infection. Any mechanism that disturbs this normal process like the presence of a catheter, a stone or a tumor can result in stasis and abnormal accumulation of bacteria. These bacteria can ascend through the urethra into the urinary bladder and from the bladder through the ureters to the kidneys and their parenchyma. This results in pyelonephritis and its manifestations.


Following important aspects about the pathophysiology of pyelonephritis need to be understood:[1][2][3][4]

General Pathogenesis

  • Pyelonephritis results mostly from an ascending infection, from the urethra (when colonised by organisms) to bladder and then through the ureters to the renal parenchyma or from a hematogenous spread.
  • Uncomplicated pyelonephritis occurs in otherwise healthy individuals and because of the normal defence mechanisms of the body it is easy to treat and requires a shorter duration of therapy.
  • Complicated pyelonephritis occurs in otherwise unhealthy individuals, pregnant or post menopausal women or other immunocompromised patients and thus requires aggressive, long term and broad spectrum treatment.
  • Acute pyelonephritis is an exudative inflammation of the renal pelvis and the kidney and can be purulent in nature.
  • The abscesses in the renal parenchyma depict suppurative necrosis. This may consist of pus which is a purulent exudate and may contain neutrophils, fibrin, cell debris and central germ colonies.
  • Neutrophil casts may be found as the damage occurs to the tubules by the neutrophils within it. Initially the glomeruli and vessels are normal.
  • A decreased expression of CXCR1 which is a receptor for interleukin 8 is considered to be a reason for pyelonephritis in individuals with positive family history.
  • The infection can spread to the peritoneum. The inflammation and infection can irritate the nerve endings resulting in the specific mild costovertebral tenderness that can progress to severe abdominal pain radiating to back.
  • Chronic infections may be secondary to kidney stones or a tumor constantly obstructing the normal urinary flow or secondary vesicouretral reflux.
  • Chronic or recurrent infections result when pathogens like E.coli invade the epithelium at any place in the urinary tract and avoid body defense mechanism. These reservoirs act as a continuous source of pathogen. Chronic infections can result in fibrosis and scarring of the kidneys.

Emphysematous Pyelonephritis

  • Emphysematous pyelonephritis is caused by bacteria following the same pathogenesis as described above. It is a necrotising infection of the renal substance with production of gas. The gas accumulates in the parenchyma of the kidney, the perinephric space and the collecting system. Majority of the patients with emphysematous pyelonephritis have diabetes mellitus.[5][6][7]
  • Emphysematous pyelonephritis can be divided into 2 subtypes:[8]
    • Type 1: It is the destruction of parenchyma without fluid collection or mottled or streaky gas presence (69% mortality).
    • Type 2: It is the destruction of parenchyma with the collection of fluid in renal or peritoneal area with gas in collecting system or loculated or bubble appearance of gas (18% mortality).

Xanthogranulomatous Pyelonephritis

  • Xanthogranulomatous pyelonephritis is a rare type of pyelonephritis. It is associated with nephrolithiasis. Many kidney stones are seen and stag horn calculi are very commonly associated with it. Xanthogranulomatous pyelonephritis is usually confused due to its appearance, with a malignancy and aggressive management requiring a surgical resection is done. The histopathology of the specimen confirms xanthogranulomatous pyelonephritis rather than a tumor. The initial presentation can be abdominal distention owing to the formation of a peritoneal abscess. Proteus mirabilis is the most common organism involved in case of a peritoneal abscess associated with xanthogranulomatous pyelonephritis.[9]


Though the genetics of pyelonephritis have not been studied extensively. It is understood that family history of urinary tract infections is a strong risk factor recurrent urinary infections and pyelonephritis in relatives. This risk is stronger in closer than distant relatives suggesting the role of a genetic component. A decreased expression of CXCR1 which is a receptor for interleukin 8 is considered to be a reason for pyelonephritis in individuals with positive family history.[4][10][11]

Associated Conditions

The following conditions are associated with the development of pyelonephritis:[12][13][14]

Gross Pathology

Gross pathology of pyelonephritis often reveals pathognomonic radiations of hemorrhage and suppuration through the renal pelvis to the renal cortex.[15]

Microscopic Pathology

The microscopic examination can have the following features:[15]

  • Acute pyelonephritis
  • Chronic pyelonephritis
    • Interstitial fibrosis
    • Renal casts
    • Mononuclear tubulointerstitial infiltarte
  • Xanthogranulomatous pyelonephritis

Acute pyelonephritis


Chronic pyelonephritis



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  2. Nielubowicz GR, Mobley HL (2010). "Host-pathogen interactions in urinary tract infection". Nat Rev Urol. 7 (8): 430–41. doi:10.1038/nrurol.2010.101. PMID 20647992.
  3. Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ (2007). "Detection of intracellular bacterial communities in human urinary tract infection". PLoS Med. 4 (12): e329. doi:10.1371/journal.pmed.0040329. PMC 2140087. PMID 18092884.
  4. 4.0 4.1 Lundstedt AC, Leijonhufvud I, Ragnarsdottir B, Karpman D, Andersson B, Svanborg C (2007). "Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection". J Infect Dis. 195 (8): 1227–34. doi:10.1086/512620. PMID 17357062.
  5. Hirose Y, Kaida H (2016). "Emphysematous Pyelonephritis". N Engl J Med. 375 (17): 1671. doi:10.1056/NEJMicm1501812. PMID 27783923.
  6. Ambaram PR, Kala UK, Petersen KL (2016). "Emphysematous Pyelonephritis in Children". Pediatr Infect Dis J. 35 (10): 1159–61. doi:10.1097/INF.0000000000001254. PMID 27622688.
  7. Misgar RA, Mubarik I, Wani AI, Bashir MI, Ramzan M, Laway BA (2016). "Emphysematous pyelonephritis: A 10-year experience with 26 cases". Indian J Endocrinol Metab. 20 (4): 475–80. doi:10.4103/2230-8210.183475. PMC 4911836. PMID 27366713.
  8. Wan YL, Lee TY, Bullard MJ, Tsai CC (1996). "Acute gas-producing bacterial renal infection: correlation between imaging findings and clinical outcome". Radiology. 198 (2): 433–8. doi:10.1148/radiology.198.2.8596845. PMID 8596845.
  9. Yeow Y, Chong YL (2016). "Xanthogranulomatous pyelonephritis presenting as Proteus preperitoneal abscess". J Surg Case Rep. 2016 (12). doi:10.1093/jscr/rjw211. PMC 5159021. PMID 27915241.
  10. Franco AV (2005). "Recurrent urinary tract infections". Best Pract Res Clin Obstet Gynaecol. 19 (6): 861–73. doi:10.1016/j.bpobgyn.2005.08.003. PMID 16298166.
  11. Scholes D, Hawn TR, Roberts PL, Li SS, Stapleton AE, Zhao LP; et al. (2010). "Family history and risk of recurrent cystitis and pyelonephritis in women". J Urol. 184 (2): 564–9. doi:10.1016/j.juro.2010.03.139. PMC 3665335. PMID 20639019.
  12. Hooton TM (2000). "Pathogenesis of urinary tract infections: an update". J Antimicrob Chemother. 46 Suppl A: 1–7. PMID 10969044.
  13. Platt R, Polk BF, Murdock B, Rosner B (1986). "Risk factors for nosocomial urinary tract infection". Am J Epidemiol. 124 (6): 977–85. PMID 3776980.
  14. Zhong YH, Fang Y, Zhou JZ, Tang Y, Gong SM, Ding XQ (2011). "Effectiveness and safety of patient initiated single-dose versus continuous low-dose antibiotic prophylaxis for recurrent urinary tract infections in postmenopausal women: a randomized controlled study". J Int Med Res. 39 (6): 2335–43. PMID 22289552.
  15. 15.0 15.1 Libre Pathology Accessed on Jan 24,2017
  16. Libre Pathology Accessed on Jan 24, 2017
  17. Libre Pathology Accessed on Jan 24, 2017

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