Androgen-Influenced Polarization of Activin A-Producing Macrophages Accompanies Post-pyelonephritic Renal Scarring

Ascending bacterial pyelonephritis, a form of urinary tract infection (UTI) that can result in hospitalization, sepsis, and other complications, occurs in ~250,000 US patients annually; uropathogenic Escherichia coli (UPEC) cause a large majority of these infections. Although UTIs are primarily a disease of women, acute pyelonephritis in males is associated with increased mortality and morbidity, including renal scarring, and end-stage renal disease. Preclinical models of UTI have only recently allowed investigation of sex and sex-hormone effects on pathogenesis. We previously demonstrated that renal scarring after experimental UPEC pyelonephritis is augmented by androgen exposure; testosterone exposure increases both the severity of pyelonephritis and the degree of renal scarring in both male and female mice. Activin A is an important driver of scarring in non-infectious renal injury, as well as a mediator of macrophage polarization. In this work, we investigated how androgen exposure influences immune cell recruitment to the UPEC-infected kidney and how cell-specific activin A production affects post-pyelonephritic scar formation. Compared with vehicle-treated females, androgenized mice exhibited reduced bacterial clearance from the kidney, despite robust myeloid cell recruitment that continued to increase as infection progressed. Infected kidneys from androgenized mice harbored more alternatively activated (M2) macrophages than vehicle-treated mice, reflecting an earlier s...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Conclusion Bacteria traditionally considered to be more pathogenic outside of pregnancy do not progress to pyelonephritis at higher rates than E. coli in pregnancy, and are associated with similar pyelonephritis-related morbidity. Larger studies are needed to confirm these findings. Key Points [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: American Journal of Perinatology - Category: Perinatology & Neonatology Authors: Tags: SMFM Fellowship Series Article Source Type: research
Conclusion: fimH and aer were found in> 50% of isolates suggesting the importance of both genes in UPEC. The majority of isolates had fimH as adhesion factor for colonization. Determining antibiotic resistance patterns in specific geographical areas is necessary for appropriate treatment of urinary tract infection. The high rate of resistance to cephalosporins is most likely due to incorrect drug administration. PMID: 32685119 [PubMed]
Source: Iranian Journal of Microbiology - Category: Microbiology Tags: Iran J Microbiol Source Type: research
Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis.What is Known:•Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to disti...
Source: European Journal of Pediatrics - Category: Pediatrics Source Type: research
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Source: Surgical Practice - Category: Surgery Authors: Tags: CASE REPORT Source Type: research
Circulating androgens prime the kidney for fibrosis upon infectious injury (Escherichia coli pyelonephritis) by enhancing local TGF β1 production and myofibroblast activation. AbstractRenal scarring after pyelonephritis is linked to long ‐term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenicEscherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti ‐androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL RESEARCH Source Type: research
This article aimed to describe the literature regarding spectrum of activity, dosing and administration, including pharmacokinetic and pharmacodynamics properties, safety profile, and efficacy end points. METHODS: The terms meropenem, vaborbactam, RPX7009, and meropenem-vaborbactam were used to search for literature via PubMed,, and published abstracts from 2013 to July 2019. Abstracts from IDWeek 2019 were also searched via these terms. Results were limited to availability in English. FINDINGS: Meropenem-vaborbactam covers a spectrum of gram-negative bacterial pathogens, including K pneumoniae...
Source: Clinical Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Ther Source Type: research
Discussion Neuropenia is defined as a neutrophil count
Source: - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Authors: Bientinesi R, Murri R, Sacco E Abstract Introduction: Urinary tract infections (UTIs) are among the most common causes of sepsis presenting to hospitals. Treating complicated UTIs is extremely important due to their potential mortality. Levofloxacin is a fluoroquinolone antibacterial that has become one of the cornerstones of antibiotic therapy of complicated UTIs and pyelonephritis since its introduction in the 1990s because of its exceptional pharmacokinetic (PK) and pharmacodynamic (PD) profile. However, the emergence of widespread fluoroquinolone resistance over the past decade has prompted investigato...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
Conclusion: Due to the good therapeutic effects and advantages of PGPs, it could be considered as an alternative medicine to treat APN. PMID: 31911807 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
GBS colonization of the lower urinary tract in pregnancy is associated with severe infections such as chorioamnionitis, endometritis, and pyelonephritis. We sought to explore pregnancy morbidity secondary to lower urinary tract colonization or infection with GBS as compared to E. coli, a more common urinary pathogen.
Source: American Journal of Obstetrics and Gynecology - Category: OBGYN Authors: Tags: Poster Session II Source Type: research
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