Biomaterial Database

Metabolic acidosis exacerbates pyelonephritis in mice prone to vesicoureteral reflux. 2020

Jeffrey M Purkerson, and Janine L Corley, and George J Schwartz

Pediatric Nephrology, University of Rochester Medical Center, Rochester, NY, USA.

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.

UI	MeSH Term	Description	Entries
D008809	Mice, Inbred C3H	An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research.	Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D011704	Pyelonephritis	Inflammation of the KIDNEY involving the renal parenchyma (the NEPHRONS); KIDNEY PELVIS; and KIDNEY CALICES. It is characterized by ABDOMINAL PAIN; FEVER; NAUSEA; VOMITING; and occasionally DIARRHEA.	Necrotizing Pyelonephritis,Pyelonephritis, Acute Necrotizing,Pyelonephritides
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004927	Escherichia coli Infections	Infections with bacteria of the species ESCHERICHIA COLI.	E coli Infections,E. coli Infection,Infections, E coli,Infections, Escherichia coli,E coli Infection,E. coli Infections,Escherichia coli Infection,Infection, E coli,Infection, E. coli,Infection, Escherichia coli
D000138	Acidosis	A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up.	Metabolic Acidosis,Acidoses,Acidoses, Metabolic,Acidosis, Metabolic,Metabolic Acidoses
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014552	Urinary Tract Infections	Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA.	Infection, Urinary Tract,Infections, Urinary Tract,Tract Infection, Urinary,Tract Infections, Urinary,Urinary Tract Infection
D014718	Vesico-Ureteral Reflux	Retrograde flow of urine from the URINARY BLADDER into the URETER. This is often due to incompetence of the vesicoureteral valve.	Primary Vesicoureteral Reflux,Secondary Vesicoureteral Reflux,Vesicoureteral Reflux Grade1,Vesicoureteral Reflux1,Vesicoureteral Reflux,Vesicoureteral Reflux 1,Grade1, Vesicoureteral Reflux,Reflux, Primary Vesicoureteral,Reflux, Secondary Vesicoureteral,Reflux, Vesico-Ureteral,Reflux, Vesicoureteral,Reflux1, Vesicoureteral,Vesico Ureteral Reflux,Vesicoureteral Reflux, Primary,Vesicoureteral Reflux, Secondary,Vesicoureteral Reflux1s
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus