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Updated: Dec 6, 2025
Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis
Published on: July 18, 2017
Metabolic acidosis exacerbates pyelonephritis in mice prone to vesicoureteral reflux
Jeffrey M Purkerson1,2, Janine L Corley1,2, George J Schwartz1,2
1Pediatric Nephrology, University of Rochester Medical Center, Rochester, NY, USA.
Insights
Metabolic acidosis (MA) worsens acute pyelonephritis in children by hindering the body's ability to clear urinary tract infections. This impairment increases inflammation and kidney injury risk during bacterial infections.
Area of Science:
- Pediatric Infectious Diseases
- Renal Pathophysiology
- Immunology
Background:
- Acute pyelonephritis is a common pediatric bacterial infection, often linked to vesicoureteral reflux (VUR).
- Metabolic acidosis (MA) is frequently observed in children with pyelonephritis, but its specific impact on disease progression remains unclear.
Purpose of the Study:
- To investigate the effect of metabolic acidosis on the progression of acute pyelonephritis in a mouse model prone to VUR.
Main Methods:
- MA was induced in C3H mice using ammonium chloride supplementation.
- Mice were infected with uropathogenic Escherichia coli (UPEC).
- Immune cell roles were assessed via antibody-mediated depletion; inflammatory markers and bacterial burden were quantified.
Main Results:
- MA impaired UPEC clearance in immune-competent mice but not in Tlr-4-deficient mice.
- Depletion of myeloid cells exacerbated UPEC burden, highlighting neutrophil and macrophage importance.
- MA increased pro-inflammatory cytokine and chemokine mRNA expression in kidneys and elevated neutrophil infiltration.
Conclusions:
- Metabolic acidosis intensifies pyelonephritis by impeding bacterial clearance and potentiating renal inflammation.
- MA increases kidney injury risk in pediatric pyelonephritis through enhanced inflammation and reduced infection clearance.
Abstract:
Acute pyelonephritis is a common, serious bacterial infection in children. The prevalence of acute pyelonephritis is due at least in part to vesicoureteral reflux (VUR). Although an association between abnormalities in electrolyte and acid-base balance and pyelonephritis is common in young children, the impact of metabolic acidosis (MA) on progression of acute pyelonephritis is not fully understood. In this study, the effect of MA on pyelonephritis was studied in C3H mouse strains prone to VUR. MA induced by ammonium chloride supplementation in food specifically impaired clearance of urinary tract infection with uropathogenic Escherichia. coli (UPEC-UTI) in innate immune competent C3H strains (HeOuJ, HeN), whereas kidney UPEC burden in Tlr-4-deficient HeJ mice was unaffected. Antibody-mediated depletion of myeloid cells (monocytes, neutrophil) markedly increased UPEC burden in the bladder and kidney confirming the pivotal role of neutrophils and tissue-resident macrophages in clearance of UPEC-UTI. MA concurrent with UPEC-UTI markedly increased expression of cytokine (TNFα, IL-1β, IL-6) and chemokine (CXCL 1, 2, and 5) mRNA in isolated kidney CD cells and kidney neutrophil infiltrates were increased four- to fivefold compared to normal, UPEC-infected mice. Thus, MA intensified pyelonephritis and increased the risk of kidney injury by impairing clearance of UPEC-UTI and potentiating renal inflammation characterized by an elevated kidney neutrophil infiltrate.
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01:27Acute Pyelonephritis I: Introduction
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
01:25Urinary Tract Infection II: Pathophysiology