Inflammation drives renal scarring in experimental pyelonephritis

Birong Li, Babitha Haridas, Ashley R. Jackson, Hanna Cortado, Nicholas Mayne, Rebecca Kohnken, Brad Bolon, Kirk M. McHugh, Andrew L. Schwaderer, John David Spencer, Christina B. Ching, David Hains, Sheryl S. Justice, Santiago Partida-Sanchez, Brian Becknell

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment, and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The extent of fibrosis correlates most significantly with inflammation at 7 and 28 days postinfection. The recruitment of neutrophils and inflammatory macrophages to infected kidneys is proportional to renal bacterial burden. Transcriptome analysis reveals molecular signatures associated with renal ischemiareperfusion injury, immune cell chemotaxis, and leukocyte activation. This murine model recapitulates the cardinal histopathological features observed in humans with acquired renal scarring following pyelonephritis. The integration of histopathology, quantification of cellular immune influx, and unbiased transcriptional profiling begins to define potential mechanisms of tissue injury during pyelonephritis in the context of an intact immune response. The clear relationship between inflammatory cell recruitment and fibrosis supports the hypothesis that acquired renal scarring arises as a consequence of excessive host inflammation and suggests that immunomodulatory therapies should be investigated to reduce renal scarring in patients with pyelonephritis.

Original languageEnglish (US)
Pages (from-to)F43-F53
JournalAmerican Journal of Physiology - Renal Physiology
Volume312
Issue number1
DOIs
StatePublished - Jan 1 2017

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Pyelonephritis
Cicatrix
Inflammation
Kidney
Fibrosis
Wounds and Injuries
Leukocyte Chemotaxis
Uropathogenic Escherichia coli
Interstitial Nephritis
Vesico-Ureteral Reflux
Immunomodulation
Neutrophil Infiltration
Inbred C3H Mouse
Gene Expression Profiling
Chronic Renal Insufficiency
Proteinuria
Urinary Tract Infections
Fever
Macrophages
Hypertension

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Li, B., Haridas, B., Jackson, A. R., Cortado, H., Mayne, N., Kohnken, R., ... Becknell, B. (2017). Inflammation drives renal scarring in experimental pyelonephritis. American Journal of Physiology - Renal Physiology, 312(1), F43-F53. https://doi.org/10.1152/ajprenal.00471.2016

Inflammation drives renal scarring in experimental pyelonephritis. / Li, Birong; Haridas, Babitha; Jackson, Ashley R.; Cortado, Hanna; Mayne, Nicholas; Kohnken, Rebecca; Bolon, Brad; McHugh, Kirk M.; Schwaderer, Andrew L.; Spencer, John David; Ching, Christina B.; Hains, David; Justice, Sheryl S.; Partida-Sanchez, Santiago; Becknell, Brian.

In: American Journal of Physiology - Renal Physiology, Vol. 312, No. 1, 01.01.2017, p. F43-F53.

Research output: Contribution to journalArticle

Li, B, Haridas, B, Jackson, AR, Cortado, H, Mayne, N, Kohnken, R, Bolon, B, McHugh, KM, Schwaderer, AL, Spencer, JD, Ching, CB, Hains, D, Justice, SS, Partida-Sanchez, S & Becknell, B 2017, 'Inflammation drives renal scarring in experimental pyelonephritis', American Journal of Physiology - Renal Physiology, vol. 312, no. 1, pp. F43-F53. https://doi.org/10.1152/ajprenal.00471.2016
Li, Birong ; Haridas, Babitha ; Jackson, Ashley R. ; Cortado, Hanna ; Mayne, Nicholas ; Kohnken, Rebecca ; Bolon, Brad ; McHugh, Kirk M. ; Schwaderer, Andrew L. ; Spencer, John David ; Ching, Christina B. ; Hains, David ; Justice, Sheryl S. ; Partida-Sanchez, Santiago ; Becknell, Brian. / Inflammation drives renal scarring in experimental pyelonephritis. In: American Journal of Physiology - Renal Physiology. 2017 ; Vol. 312, No. 1. pp. F43-F53.
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