Inflammation Drives Renal Scarring in Experimental Pyelonephritis.

Inflammation Drives Renal Scarring in Experimental Pyelonephritis. Am J Physiol Renal Physiol. 2016 Oct 19;:ajprenal.00471.2016 Authors: Li B, Haridas B, Jackson AR, Cortado H, Mayne N, Kohnken R, Bolon B, McHugh KM, Schwaderer AL, Spencer JD, Ching CB, Hains DS, Justice SS, Partida-Sanchez S, Becknell B 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 post infection. The recruitment of neutrophils and inflammatory macrophages to infected kidneys is proportional to renal bacterial burden. Transcriptome analysis reveals molecular signatures associated with renal ischemia-reperfusion injury, immune cell chemotaxis, and leukocyte activation. This murine model recapitulates the cardinal histopathologic features observed in humans with acquired renal scarring following pyelonephritis. The integratio...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research