Acute Pyelonephritis

Infectious Disease MONDO:0003529 Pathograph 15 Show in embeddings browser Bacterial urinary tract infection

Acute pyelonephritis is a bacterial upper urinary tract infection in which uropathogenic bacteria ascend from the bladder through the ureter, seed the renal pelvis and renal parenchyma, and provoke acute tubulointerstitial inflammation with fever, flank pain, and risk of bacteremia or sepsis.

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Classifications

Harrison's Part
KIDNEY URINARY TRACT INFECTIOUS DISEASES
⚙

Pathophysiology

3
Vesicoureteral Bacterial Ascent
Bacteria present in the bladder ascend the ureter and reach the renal pelvis or collecting-system epithelium.
ureter UBERON:0000056 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in ureter (UBERON:0000056). UBERON:0000056 is an anatomical location from the Uberon multi-species anatomy ontology. renal pelvis UBERON:0001224 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in renal pelvis (UBERON:0001224). UBERON:0001224 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Renal Parenchymal Bacterial Expansion Bacterial ascent into the upper tract seeds the renal pelvis, medulla, and cortical interstitium.
Renal Parenchymal Bacterial Expansion
Uropathogens proliferate within the renal collecting system and adjacent parenchyma.
kidney collecting duct epithelial cell CL:1000454 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves kidney collecting duct epithelial cell (CL:1000454). CL:1000454 is a cell type from the Cell Ontology.
kidney UBERON:0002113 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in kidney (UBERON:0002113). UBERON:0002113 is an anatomical location from the Uberon multi-species anatomy ontology. collecting duct of renal tubule UBERON:0001232 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in collecting duct of renal tubule (UBERON:0001232). UBERON:0001232 is an anatomical location from the Uberon multi-species anatomy ontology.
Animal models
Murine transurethral ascending UTI/pyelonephritis model (C3H/HeN) Mouse recapitulates FimH-dependent UPEC adhesion and renal colonisation are reproduced in the C3H/HeN ascending-infection model.
Downstream
Acute Tubulointerstitial Inflammation Local bacterial proliferation activates innate responses in the infected kidney.
Show evidence (2 references)
PMID:33513212 SUPPORT PRIMARY RESULT Model organism
"Bacterial mutants lacking the type 1 pilus adhesin (FimH) were unable to establish kidney infection in male C3H/HeN mice."
Supports FimH-dependent UPEC adhesion as a requirement for ascending kidney infection in a mouse pyelonephritis model.
PMID:33513212 SUPPORT PRIMARY RESULT In vitro / ex vivo
"The mannosylated extracellular domain of human DSG2 bound directly to the lectin domain of FimH in vitro"
Identifies desmoglein-2 as a human renal epithelial receptor for the UPEC FimH lectin in vitro.
Acute Tubulointerstitial Inflammation
Neutrophil-rich renal inflammation produces fever, flank pain, and systemic illness and can spill bacteria or cytokines into the bloodstream.
neutrophil CL:0000775 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neutrophil (CL:0000775). CL:0000775 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. defense response to bacterium GO:0042742 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased defense response to bacterium (GO:0042742). GO:0042742 is a biological process from the Gene Ontology. neutrophil activation GO:0042119 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased neutrophil activation (GO:0042119). GO:0042119 is a biological process from the Gene Ontology.
kidney UBERON:0002113 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in kidney (UBERON:0002113). UBERON:0002113 is an anatomical location from the Uberon multi-species anatomy ontology. kidney interstitium UBERON:0005215 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in kidney interstitium (UBERON:0005215). UBERON:0005215 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Fever Neutrophil-rich renal inflammation and the systemic cytokine response produce febrile illness.
Flank pain Parenchymal and pelvic inflammation of the kidney produces acute flank and costovertebral-angle pain.
Sepsis Bacteria and cytokines spilling from the inflamed kidney into the bloodstream can drive systemic sepsis.
Pyuria Neutrophils recruited into the infected kidney are shed into the urine as pyuria.
Show evidence (2 references)
PMID:11817650 SUPPORT REVIEW SYNTHESIS Other
"neutrophils are the critical effectors of the host defence and that neutrophil dysfunctions lead to acute pyelonephritis and renal scarring."
Supports the central role of neutrophil recruitment and function in containing upper-tract UPEC infection.
PMID:39321268 SUPPORT PRIMARY RESULT Model organism
"PADI4 inhibition in mice blocked NETosis and resulted in progression of cystitis into pyelonephritis"
Supports urinary neutrophil NETosis as a protective barrier that limits ascent from cystitis to kidney infection in a mouse UTI model.
⬡

Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Acute Pyelonephritis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

4
Genitourinary 1
Pyuria HP:0012085 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pyuria (HP:0012085). HP:0012085 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27313268 SUPPORT Human clinical
"Diagnosis was based on positive urine cultures obtained within 48 hours of enrollment showing 1–2 gram-negative uropathogens at ≥105 colony-forming units (CFU)/mL, and pyuria."
Pyuria is part of the enrolment case definition of complicated UTI/acute pyelonephritis in a Phase 3 trial, documenting it as a diagnostic feature.
Immune 1
Sepsis HP:0100806 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sepsis (HP:0100806). HP:0100806 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38020186 SUPPORT Human clinical
"which may lead to sepsis, acute kidney injury, kidney scarring, chronic kidney disease, and death"
Identifies sepsis as a recognised complication of acute pyelonephritis in a population-based cohort description.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27532362 SUPPORT Human clinical
"adults with flank pain, temperature >38.0°C, and a diagnosis of acute pyelonephritis, confirmed by culture."
Documents fever as part of the case definition for a prospective acute pyelonephritis culture-surveillance study.
Constitutional 1
Flank pain HP:0030157 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Flank pain (HP:0030157). HP:0030157 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27532362 SUPPORT Human clinical
"adults with flank pain, temperature >38.0°C, and a diagnosis of acute pyelonephritis, confirmed by culture."
Documents flank pain as part of the case definition for a prospective acute pyelonephritis culture-surveillance study.
🧬

Genetic Associations

3
IRF3 (An IRF3 promoter polymorphism with reduced promoter activity segregates with symptomatic kidney infection versus asymptomatic bacterial carriage, marking IRF3 as a host-susceptibility locus for ascending pyelonephritis.)
Gene: IRF3 hgnc:6118 gene page HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is IRF3 (hgnc:6118). hgnc:6118 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY variant_origin: GERMLINE
Show evidence (2 references)
PMID:20886096 SUPPORT Human clinical
"Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers."
IRF3 promoter genotypes differ between children with symptomatic kidney infection and asymptomatic carriers, supporting IRF3 as a susceptibility locus.
PMID:20886096 SUPPORT In vitro / ex vivo
"IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3(-/-) mice."
A promoter-activity assay shows the disease-associated genotype lowers IRF3 promoter activity, a plausible functional basis for susceptibility.
CXCL8 (The IL-8 (CXCL8) promoter variant rs4073 (-251A>T) is associated with pediatric parenchymal renal infection and with severity of acute lobar nephronia.)
Gene: CXCL8 hgnc:6025 gene page HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CXCL8 (hgnc:6025). hgnc:6025 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY variant_origin: GERMLINE
Show evidence (1 reference)
PMID:21042230 SUPPORT Human clinical
"only IL-8 (rs4073, -251A>T) showed significant differences in genotype and allele frequency between the control and APN or ALN cases"
Associates the CXCL8 rs4073 promoter variant with susceptibility to parenchymal renal infection in children.
CXCR1 (Low CXCR1 (IL-8 receptor) expression impairs neutrophil recruitment and is linked to recurrent pyelonephritis and renal scarring.)
Gene: CXCR1 hgnc:6026 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CXCR1 (hgnc:6026). hgnc:6026 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY variant_origin: GERMLINE
Show evidence (1 reference)
PMID:11817650 SUPPORT REVIEW SYNTHESIS Other
"the data linking low CXCR1 expression to recurrent pyelonephritis in man, as well as the information on the genetic basis for low CXCR1 expression in affected patients."
Review synthesis linking reduced CXCR1 expression, and its genetic basis, to susceptibility to recurrent pyelonephritis.
💊

Medical Actions

4
Culture-guided fluoroquinolone antimicrobial therapy
Action: Antibiotic TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Antibiotic Therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. NCIT:C15620
Agent: Ciprofloxacin NCIT:C375 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Ciprofloxacin (NCIT:C375). NCIT:C375 is a therapeutic agent from the NCI Thesaurus.
Platform: Small molecule
Community-acquired acute pyelonephritis is treated with an antibiotic active against the cultured uropathogen and tailored to susceptibility results and local resistance; ciprofloxacin is an oral fluoroquinolone option when the isolate is susceptible and patient factors permit it.
Mechanism Target:
INHIBITS Renal Parenchymal Bacterial Expansion — Susceptibility-guided antimicrobial therapy kills or suppresses the proliferating renal uropathogen population.
INHIBITS Acute Tubulointerstitial Inflammation — Bacterial eradication removes the trigger for ongoing neutrophilic tubulointerstitial inflammation.
Show evidence (1 reference)
PMID:22726802 SUPPORT PRIMARY RESULT Human clinical
"Short-term clinical cure occurred in 71 (97%) patients treated with ciprofloxacin for 7 days and 80 (96%) treated for 14 days"
Supports ciprofloxacin as an effective oral antibiotic in a randomized duration trial of women with community-acquired acute pyelonephritis.
Intravenous third-generation cephalosporin (ceftriaxone)
Action: Antibiotic TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Antibiotic Therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. NCIT:C15620
Agent: Ceftriaxone NCIT:C62020 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Ceftriaxone (NCIT:C62020). NCIT:C62020 is a therapeutic agent from the NCI Thesaurus.
Platform: Small molecule
Hospitalized or febrile acute pyelonephritis in hemodynamically stable patients is commonly treated empirically with an intravenous third-generation cephalosporin such as ceftriaxone.
Mechanism Target:
INHIBITS Renal Parenchymal Bacterial Expansion — Broad-spectrum beta-lactam therapy suppresses the proliferating renal uropathogen population.
Show evidence (1 reference)
PMID:42417339 SUPPORT Human clinical
"Empirical regimens included third-generation cephalosporins (ceftriaxone) in hemodynamically stable patients"
Supports ceftriaxone as a standard empirical regimen for purulent/severe pyelonephritis in stable patients.
Ceftazidime-avibactam
Action: Antibiotic TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Antibiotic Therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. NCIT:C15620
Agent: ceftazidime-avibactam NCIT:C127836 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses ceftazidime-avibactam, annotated with Ceftazidime/Avibactam Sodium (NCIT:C127836). NCIT:C127836 is a therapeutic agent from the NCI Thesaurus.
Platform: Small molecule
For complicated or resistant (including ESBL-producing) infection, ceftazidime-avibactam is a carbapenem-sparing option that was non-inferior to doripenem for complicated UTI including acute pyelonephritis in a Phase 3 program.
Mechanism Target:
INHIBITS Renal Parenchymal Bacterial Expansion — The ceftazidime-avibactam combination restores beta-lactam activity against resistant uropathogens and suppresses renal bacterial expansion.
Show evidence (1 reference)
PMID:27313268 SUPPORT Human clinical
"Ceftazidime-avibactam was highly effective for the empiric treatment of cUTI (including acute pyelonephritis), and may offer an alternative to carbapenems in this setting."
Phase 3 RCT evidence supporting ceftazidime-avibactam for complicated UTI including acute pyelonephritis.
Source control (decompression and drainage)
Action: urinary tract decompression and drainageNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is urinary tract decompression and drainage, annotated with Surgical Procedure (NCIT:C15329). NCIT:C15329 is a clinical intervention from the NCI Thesaurus. Ontology label: Surgical Procedure NCIT:C15329
Platform: Surgery
When obstruction or an abscess is present, antibiotics alone are insufficient: urgent decompression (nephrostomy or ureteral stent) and percutaneous drainage of large abscesses are required, with nephrectomy reserved for fulminant disease.
Mechanism Target:
INHIBITS Renal Parenchymal Bacterial Expansion — Relieving obstruction and draining pus removes the stasis and focus that sustain renal bacterial expansion.
Show evidence (1 reference)
PMID:42417339 SUPPORT Human clinical
"In cases of urinary tract obstruction, urgent decompression with nephrostomy or ureteral stenting was mandatory and led to improvement in >90% of cases."
Supports obstruction decompression as a required source-control intervention in severe pyelonephritis.
🌍

Environmental Factors

3
Diabetes mellitus
Diabetes, with high tissue glucose, is the dominant predisposing condition for severe necrotizing and emphysematous forms of acute pyelonephritis.
Show evidence (1 reference)
PMID:42221797 SUPPORT Human clinical
"Diabetes mellitus and urinary tract obstruction are the main predisposing factors implicated in the pathogenesis of EPN"
Names diabetes as a main predisposing factor for emphysematous pyelonephritis.
Mechanism Target:
PREDISPOSES Renal Parenchymal Bacterial Expansion — Hyperglycaemia and impaired perfusion favour uncontrolled parenchymal bacterial proliferation and gas-forming necrotizing infection.
Show evidence (1 reference)
PMID:42221797 SUPPORT Human clinical
"Overweight or obesity was present in 74%, and diabetes in 63%."
Diabetes is over-represented in critically-ill emphysematous pyelonephritis, supporting it as a predisposing condition for severe parenchymal disease.
Urinary tract obstruction
Obstruction or stones cause urinary stasis that predisposes to ascending infection and to severe, necrotizing pyelonephritis.
Show evidence (1 reference)
PMID:42221797 SUPPORT Human clinical
"Diabetes mellitus and urinary tract obstruction are the main predisposing factors implicated in the pathogenesis of EPN"
Names urinary tract obstruction as a main predisposing factor for emphysematous pyelonephritis.
Mechanism Target:
PREDISPOSES Renal Parenchymal Bacterial Expansion — Obstruction and stasis allow uropathogens to proliferate in the renal collecting system and parenchyma.
Show evidence (1 reference)
PMID:42221797 SUPPORT Human clinical
"Urinary tract obstruction was identified in 46%."
Obstruction is present in nearly half of severe emphysematous pyelonephritis cases, supporting it as a predisposing factor.
Pregnancy
Pregnancy-associated ureteral dilation and urinary stasis increase the risk of ascending infection and pyelonephritis.
Show evidence (1 reference)
PMID:41274602 SUPPORT Human clinical
"During pregnancy, there is increased risk of ascending urinary tract infection (UTI) resulting in pyelonephritis and associated preterm delivery and low birth weight."
Pregnancy raises the risk that a urinary tract infection ascends to cause pyelonephritis.
Mechanism Target:
PREDISPOSES Vesicoureteral Bacterial Ascent — Gestational ureteral dilation and stasis favour ascent of bladder uropathogens into the upper tract.
Show evidence (1 reference)
PMID:41274602 SUPPORT Human clinical
"During pregnancy, there is increased risk of ascending urinary tract infection (UTI) resulting in pyelonephritis and associated preterm delivery and low birth weight."
Pregnancy raises the risk that a urinary tract infection ascends to cause pyelonephritis.
🔬

Diagnosis

1
Urine culture and parenchymal imaging
Diagnosis rests on pyuria and a positive urine culture; DMSA scintigraphy is the reference standard for parenchymal involvement and scarring.
Markers: urine culture; dimercaptosuccinic acid (DMSA) renal scintigraphy
Show evidence (2 references)
PMID:27313268 SUPPORT Human clinical
"Diagnosis was based on positive urine cultures obtained within 48 hours of enrollment showing 1–2 gram-negative uropathogens at ≥105 colony-forming units (CFU)/mL, and pyuria."
Documents the quantitative urine-culture and pyuria case definition used for culture-confirmed acute pyelonephritis.
PMID:27748543 SUPPORT Human clinical
"renal scarring based on dimercaptosuccinic acid scintigraphy (DMSA) findings"
DMSA scintigraphy is used to define renal parenchymal lesions and scarring.
📈

Progression

4
Uncomplicated acute pyelonephritis
Acute parenchymal kidney infection; most cases resolve with prompt antibiotics.
Show evidence (1 reference)
PMID:38020186 SUPPORT Human clinical
"which may lead to sepsis, acute kidney injury, kidney scarring, chronic kidney disease, and death"
Frames acute pyelonephritis as the starting point of a progression that can reach sepsis, scarring, and CKD.
Emphysematous pyelonephritis
Gas-forming necrotizing infection, chiefly in diabetic or obstructed patients.
Show evidence (1 reference)
PMID:42221797 SUPPORT Human clinical
"Emphysematous pyelonephritis (EPN) is a rare, life-threatening necrotizing urinary tract infection marked by gas formation in the renal parenchyma and perirenal tissues."
Defines emphysematous pyelonephritis as a severe necrotizing stage of upper-tract infection.
Urosepsis and septic shock
Bacteremic spread with systemic sepsis; mortality is high once septic shock develops.
Show evidence (1 reference)
PMID:42417339 SUPPORT Human clinical
"in patients with septic shock, mortality reached 20-30%"
Documents the high mortality of the septic-shock stage of severe pyelonephritis.
Renal scarring and chronic kidney disease
Delayed or severe infection leaves permanent scars that can progress to hypertension and chronic kidney disease.
Show evidence (1 reference)
PMID:27748543 SUPPORT Human clinical
"Delay in treatment initiation of 72 hours or more was a risk factor for permanent renal scars after the first episode of febrile UTI."
Links delayed treatment to the permanent-scarring sequela of acute pyelonephritis.
📊

Prevalence

2
Denmark (women, hospital-diagnosed, 2018)
Annual incidence 154.0 per 100,000 person-years >1 in 1,000 per year
19-year Danish population-based cohort; women's rate rose from 6.8 to 15.4 per 10,000 person-years over 2000-2018.
Show evidence (1 reference)
PMID:38020186 SUPPORT Human clinical
"the incidence increased from 6.8 (95% CI: 6.8-6.8) to 15.4 (95% CI: 15.4-15.4) in women and from 2.7 (95% CI: 2.7-2.7) to 4.5 (95% CI: 4.5-4.5) in men."
Reports the 2018 hospital-diagnosed APN incidence in women (15.4 per 10,000 person-years = 154 per 100,000).
Denmark (men, hospital-diagnosed, 2018)
Annual incidence 45.0 per 100,000 person-years 1–9 per 10,000 per year
Same Danish cohort; men's rate rose from 2.7 to 4.5 per 10,000 person-years.
Show evidence (1 reference)
PMID:38020186 SUPPORT Human clinical
"the incidence increased from 6.8 (95% CI: 6.8-6.8) to 15.4 (95% CI: 15.4-15.4) in women and from 2.7 (95% CI: 2.7-2.7) to 4.5 (95% CI: 4.5-4.5) in men."
Reports the 2018 hospital-diagnosed APN incidence in men (4.5 per 10,000 person-years = 45 per 100,000).
🦠

Infectious Agent

1
Escherichia coli
Uropathogenic E. coli is the dominant bacterial cause of ascending acute pyelonephritis.
Escherichia coli NCBITaxon:562 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:27532362 SUPPORT PRIMARY RESULT Human clinical
"Cultures from 453 (86.9%) of 521 patients grew Escherichia coli."
Supports E. coli as the dominant organism in a prospective U.S. adult cohort with culture-confirmed acute pyelonephritis.
↔️

Transmission

1
Ascending bladder-to-kidney spread
Uropathogens ascend from the bladder through the ureter into the renal pelvis and renal parenchyma.
Show evidence (1 reference)
PMID:33513212 SUPPORT Model organism
"Here, we demonstrate in a recently developed mouse model that beyond bladder infection, type 1 pili also are critical for establishment of ascending pyelonephritis."
Supports the ascending bladder-to-kidney route as the mechanism by which uropathogens reach the renal parenchyma.
🐁

Animal Models

1
Murine transurethral ascending UTI/pyelonephritis model (C3H/HeN)
Transurethral UPEC inoculation of C3H/HeN mice reproduces ascending kidney infection and is the workhorse model for bacterial and host determinants of pyelonephritis.
Species
Mouse
Genotype
C3H/HeN wild-type, transurethral UPEC inoculation
Publication
PMID:33513212
Pathograph links
Renal Parenchymal Bacterial Expansion recapitulates fidelity: moderate observes: tissue FimH-dependent UPEC adhesion and renal colonisation are reproduced in the C3H/HeN ascending-infection model.
Limitations: Mice lack a direct IL-8/CXCL8 ortholog (functional homologs are used) and differ in urinary-tract anatomy, so the human chemokine-driven neutrophil axis and polymorphism spectrum are only partially captured.
Show evidence (1 reference)
PMID:33513212 SUPPORT Model organism
"Bacterial mutants lacking the type 1 pilus adhesin (FimH) were unable to establish kidney infection in male C3H/HeN mice."
The C3H/HeN model recapitulates FimH-dependent renal colonisation underlying parenchymal bacterial expansion.
{ }

Source YAML

click to show 
name: Acute Pyelonephritis
creation_date: "2026-09-30T09:47:36Z"
description: >-
  Acute pyelonephritis is a bacterial upper urinary tract infection in which
  uropathogenic bacteria ascend from the bladder through the ureter, seed the
  renal pelvis and renal parenchyma, and provoke acute tubulointerstitial
  inflammation with fever, flank pain, and risk of bacteremia or sepsis.
category: Infectious Disease
disease_term:
  preferred_term: acute pyelonephritis
  term:
    id: MONDO:0003529
    label: acute pyelonephritis
parents:
- Bacterial urinary tract infection
synonyms:
- Acute bacterial pyelonephritis
notes: >-
  Whether an ascending bladder infection is contained as asymptomatic
  bacteriuria or progresses to symptomatic parenchymal pyelonephritis is
  governed chiefly by the host innate-immune response (TLR4/IRF3 signalling and
  IL-8/CXCR1-driven neutrophil recruitment) rather than by a single Mendelian
  locus; the host-susceptibility genes are modelled under genetic as
  SUSCEPTIBILITY loci.
infectious_agent:
- name: Escherichia coli
  description: >-
    Uropathogenic E. coli is the dominant bacterial cause of ascending acute
    pyelonephritis.
  infectious_agent_term:
    preferred_term: Escherichia coli
    term:
      id: NCBITaxon:562
      label: Escherichia coli
  evidence:
  - reference: PMID:27532362
    reference_title: >-
      Fluoroquinolone-Resistant and Extended-Spectrum β-Lactamase-Producing
      Escherichia coli Infections in Patients with Pyelonephritis, United
      States(1).
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Cultures from 453 (86.9%) of 521 patients grew Escherichia coli.
    explanation: >-
      Supports E. coli as the dominant organism in a prospective U.S. adult
      cohort with culture-confirmed acute pyelonephritis.
classifications:
  harrisons_chapter:
  - classification_value: KIDNEY_URINARY_TRACT
  - classification_value: INFECTIOUS_DISEASES
transmission:
- name: Ascending bladder-to-kidney spread
  description: >-
    Uropathogens ascend from the bladder through the ureter into the renal
    pelvis and renal parenchyma.
  evidence:
  - reference: PMID:33513212
    reference_title: >-
      A host receptor enables type 1 pilus-mediated pathogenesis of Escherichia
      coli pyelonephritis.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Here, we demonstrate in a recently developed mouse model that beyond
      bladder infection, type 1 pili also are critical for establishment of
      ascending pyelonephritis.
    explanation: >-
      Supports the ascending bladder-to-kidney route as the mechanism by which
      uropathogens reach the renal parenchyma.
pathophysiology:
- name: Vesicoureteral Bacterial Ascent
  role: trigger
  biological_scale: TISSUE
  description: >-
    Bacteria present in the bladder ascend the ureter and reach the renal
    pelvis or collecting-system epithelium.
  locations:
  - preferred_term: ureter
    term:
      id: UBERON:0000056
      label: ureter
  - preferred_term: renal pelvis
    term:
      id: UBERON:0001224
      label: renal pelvis
  downstream:
  - target: Renal Parenchymal Bacterial Expansion
    causal_link_type: DIRECT
    description: >-
      Bacterial ascent into the upper tract seeds the renal pelvis, medulla, and
      cortical interstitium.
- name: Renal Parenchymal Bacterial Expansion
  biological_scale: TISSUE
  description: >-
    Uropathogens proliferate within the renal collecting system and adjacent
    parenchyma.
  cell_types:
  - preferred_term: kidney collecting duct epithelial cell
    term:
      id: CL:1000454
      label: kidney collecting duct epithelial cell
  locations:
  - preferred_term: kidney
    term:
      id: UBERON:0002113
      label: kidney
  - preferred_term: collecting duct of renal tubule
    term:
      id: UBERON:0001232
      label: collecting duct of renal tubule
  downstream:
  - target: Acute Tubulointerstitial Inflammation
    causal_link_type: DIRECT
    description: >-
      Local bacterial proliferation activates innate responses in the infected
      kidney.
  evidence:
  - reference: PMID:33513212
    reference_title: >-
      A host receptor enables type 1 pilus-mediated pathogenesis of Escherichia
      coli pyelonephritis.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: PRIMARY_RESULT
    snippet: >-
      Bacterial mutants lacking the type 1 pilus adhesin (FimH) were unable to
      establish kidney infection in male C3H/HeN mice.
    explanation: >-
      Supports FimH-dependent UPEC adhesion as a requirement for ascending
      kidney infection in a mouse pyelonephritis model.
  - reference: PMID:33513212
    reference_title: >-
      A host receptor enables type 1 pilus-mediated pathogenesis of Escherichia
      coli pyelonephritis.
    supports: SUPPORT
    evidence_source: IN_VITRO
    quote_role: PRIMARY_RESULT
    snippet: >-
      The mannosylated extracellular domain of human DSG2 bound directly to the
      lectin domain of FimH in vitro
    explanation: >-
      Identifies desmoglein-2 as a human renal epithelial receptor for the UPEC
      FimH lectin in vitro.
- name: Acute Tubulointerstitial Inflammation
  biological_scale: TISSUE
  description: >-
    Neutrophil-rich renal inflammation produces fever, flank pain, and systemic
    illness and can spill bacteria or cytokines into the bloodstream.
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  locations:
  - preferred_term: kidney
    term:
      id: UBERON:0002113
      label: kidney
  - preferred_term: kidney interstitium
    term:
      id: UBERON:0005215
      label: kidney interstitium
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: defense response to bacterium
    modifier: INCREASED
    term:
      id: GO:0042742
      label: defense response to bacterium
  - preferred_term: neutrophil activation
    modifier: INCREASED
    term:
      id: GO:0042119
      label: neutrophil activation
  downstream:
  - target: Fever
    causal_link_type: DIRECT
    description: >-
      Neutrophil-rich renal inflammation and the systemic cytokine response
      produce febrile illness.
  - target: Flank pain
    causal_link_type: DIRECT
    description: >-
      Parenchymal and pelvic inflammation of the kidney produces acute flank
      and costovertebral-angle pain.
  - target: Sepsis
    causal_link_type: DIRECT
    description: >-
      Bacteria and cytokines spilling from the inflamed kidney into the
      bloodstream can drive systemic sepsis.
  - target: Pyuria
    causal_link_type: DIRECT
    description: >-
      Neutrophils recruited into the infected kidney are shed into the urine as
      pyuria.
  evidence:
  - reference: PMID:11817650
    reference_title: "The 'innate' host response protects and damages the infected urinary tract."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      neutrophils are the critical effectors of the host defence and that
      neutrophil dysfunctions lead to acute pyelonephritis and renal scarring.
    explanation: >-
      Supports the central role of neutrophil recruitment and function in
      containing upper-tract UPEC infection.
  - reference: PMID:39321268
    reference_title: >-
      Neutrophil extracellular traps protect the kidney from ascending infection
      and are required for a positive leukocyte dipstick test.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: PRIMARY_RESULT
    snippet: >-
      PADI4 inhibition in mice blocked NETosis and resulted in progression of
      cystitis into pyelonephritis
    explanation: >-
      Supports urinary neutrophil NETosis as a protective barrier that limits
      ascent from cystitis to kidney infection in a mouse UTI model.
phenotypes:
- name: Fever
  description: >-
    Acute upper-tract infection produces systemic febrile illness.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:27532362
    reference_title: >-
      Fluoroquinolone-Resistant and Extended-Spectrum β-Lactamase-Producing
      Escherichia coli Infections in Patients with Pyelonephritis, United
      States(1).
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      adults with flank pain, temperature >38.0°C, and a diagnosis of acute
      pyelonephritis, confirmed by culture.
    explanation: >-
      Documents fever as part of the case definition for a prospective acute
      pyelonephritis culture-surveillance study.
- name: Flank pain
  description: >-
    Renal pelvic and parenchymal inflammation produces acute flank or
    costovertebral-region pain.
  phenotype_term:
    preferred_term: Flank pain
    term:
      id: HP:0030157
      label: Flank pain
  evidence:
  - reference: PMID:27532362
    reference_title: >-
      Fluoroquinolone-Resistant and Extended-Spectrum β-Lactamase-Producing
      Escherichia coli Infections in Patients with Pyelonephritis, United
      States(1).
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      adults with flank pain, temperature >38.0°C, and a diagnosis of acute
      pyelonephritis, confirmed by culture.
    explanation: >-
      Documents flank pain as part of the case definition for a prospective
      acute pyelonephritis culture-surveillance study.
- name: Pyuria
  description: >-
    Urinary neutrophils (pyuria) accompany acute pyelonephritis and underlie the
    positive leukocyte dipstick and urine microscopy.
  phenotype_term:
    preferred_term: Pyuria
    term:
      id: HP:0012085
      label: Pyuria
  evidence:
  - reference: PMID:27313268
    reference_title: >-
      Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated
      Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a
      Phase 3 Randomized Trial Program.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diagnosis was based on positive urine cultures obtained within 48 hours of
      enrollment showing 1–2 gram-negative uropathogens at ≥105 colony-forming
      units (CFU)/mL, and pyuria.
    explanation: >-
      Pyuria is part of the enrolment case definition of complicated UTI/acute
      pyelonephritis in a Phase 3 trial, documenting it as a diagnostic feature.
- name: Sepsis
  description: >-
    Bacteremic or cytokine-spilling acute pyelonephritis can progress to
    urosepsis.
  phenotype_term:
    preferred_term: Sepsis
    term:
      id: HP:0100806
      label: Sepsis
  evidence:
  - reference: PMID:38020186
    reference_title: >-
      Temporal changes in incidence of hospital-diagnosed acute pyelonephritis:
      A 19-year population-based Danish cohort study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      which may lead to sepsis, acute kidney injury, kidney scarring, chronic
      kidney disease, and death
    explanation: >-
      Identifies sepsis as a recognised complication of acute pyelonephritis in
      a population-based cohort description.
genetic:
- name: IRF3
  gene_term:
    preferred_term: IRF3
    term:
      id: hgnc:6118
      label: IRF3
  association: >-
    An IRF3 promoter polymorphism with reduced promoter activity segregates with
    symptomatic kidney infection versus asymptomatic bacterial carriage, marking
    IRF3 as a host-susceptibility locus for ascending pyelonephritis.
  relationship_type: SUSCEPTIBILITY
  variant_origin: GERMLINE
  evidence:
  - reference: PMID:20886096
    reference_title: >-
      Pathogen specific, IRF3-dependent signaling and innate resistance to human
      kidney infection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Relevance of this pathway for human disease was supported by polymorphic
      IRF3 promoter sequences, differing between children with severe,
      symptomatic kidney infection and children who were asymptomatic bacterial
      carriers.
    explanation: >-
      IRF3 promoter genotypes differ between children with symptomatic kidney
      infection and asymptomatic carriers, supporting IRF3 as a susceptibility
      locus.
  - reference: PMID:20886096
    reference_title: >-
      Pathogen specific, IRF3-dependent signaling and innate resistance to human
      kidney infection.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      IRF3 promoter activity was reduced by the disease-associated genotype,
      consistent with the pathology in Irf3(-/-) mice.
    explanation: >-
      A promoter-activity assay shows the disease-associated genotype lowers
      IRF3 promoter activity, a plausible functional basis for susceptibility.
- name: CXCL8
  gene_term:
    preferred_term: CXCL8
    term:
      id: hgnc:6025
      label: CXCL8
  association: >-
    The IL-8 (CXCL8) promoter variant rs4073 (-251A>T) is associated with
    pediatric parenchymal renal infection and with severity of acute lobar
    nephronia.
  relationship_type: SUSCEPTIBILITY
  variant_origin: GERMLINE
  evidence:
  - reference: PMID:21042230
    reference_title: >-
      Genetic polymorphisms and susceptibility to parenchymal renal infection
      among pediatric patients.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      only IL-8 (rs4073, -251A>T) showed significant differences in genotype and
      allele frequency between the control and APN or ALN cases
    explanation: >-
      Associates the CXCL8 rs4073 promoter variant with susceptibility to
      parenchymal renal infection in children.
- name: CXCR1
  gene_term:
    preferred_term: CXCR1
    term:
      id: hgnc:6026
      label: CXCR1
  association: >-
    Low CXCR1 (IL-8 receptor) expression impairs neutrophil recruitment and is
    linked to recurrent pyelonephritis and renal scarring.
  relationship_type: SUSCEPTIBILITY
  variant_origin: GERMLINE
  evidence:
  - reference: PMID:11817650
    reference_title: "The 'innate' host response protects and damages the infected urinary tract."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the data linking low CXCR1 expression to recurrent pyelonephritis in man,
      as well as the information on the genetic basis for low CXCR1 expression in
      affected patients.
    explanation: >-
      Review synthesis linking reduced CXCR1 expression, and its genetic basis,
      to susceptibility to recurrent pyelonephritis.
environmental:
- name: Diabetes mellitus
  description: >-
    Diabetes, with high tissue glucose, is the dominant predisposing condition
    for severe necrotizing and emphysematous forms of acute pyelonephritis.
  evidence:
  - reference: PMID:42221797
    reference_title: >-
      Clinical spectrum, outcome and impact of nephrectomy in critically-ill
      adult patients with emphysematous pyelonephritis: the PYELEMPHY
      observational retrospective multicenter Study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diabetes mellitus and urinary tract obstruction are the main predisposing
      factors implicated in the pathogenesis of EPN
    explanation: >-
      Names diabetes as a main predisposing factor for emphysematous
      pyelonephritis.
  influences_mechanisms:
  - target: Renal Parenchymal Bacterial Expansion
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Hyperglycaemia and impaired perfusion favour uncontrolled parenchymal
      bacterial proliferation and gas-forming necrotizing infection.
    evidence:
    - reference: PMID:42221797
      reference_title: >-
        Clinical spectrum, outcome and impact of nephrectomy in critically-ill
        adult patients with emphysematous pyelonephritis: the PYELEMPHY
        observational retrospective multicenter Study.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Overweight or obesity was present in 74%, and diabetes in 63%.
      explanation: >-
        Diabetes is over-represented in critically-ill emphysematous
        pyelonephritis, supporting it as a predisposing condition for severe
        parenchymal disease.
- name: Urinary tract obstruction
  description: >-
    Obstruction or stones cause urinary stasis that predisposes to ascending
    infection and to severe, necrotizing pyelonephritis.
  evidence:
  - reference: PMID:42221797
    reference_title: >-
      Clinical spectrum, outcome and impact of nephrectomy in critically-ill
      adult patients with emphysematous pyelonephritis: the PYELEMPHY
      observational retrospective multicenter Study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diabetes mellitus and urinary tract obstruction are the main predisposing
      factors implicated in the pathogenesis of EPN
    explanation: >-
      Names urinary tract obstruction as a main predisposing factor for
      emphysematous pyelonephritis.
  influences_mechanisms:
  - target: Renal Parenchymal Bacterial Expansion
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Obstruction and stasis allow uropathogens to proliferate in the renal
      collecting system and parenchyma.
    evidence:
    - reference: PMID:42221797
      reference_title: >-
        Clinical spectrum, outcome and impact of nephrectomy in critically-ill
        adult patients with emphysematous pyelonephritis: the PYELEMPHY
        observational retrospective multicenter Study.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Urinary tract obstruction was identified in 46%.
      explanation: >-
        Obstruction is present in nearly half of severe emphysematous
        pyelonephritis cases, supporting it as a predisposing factor.
- name: Pregnancy
  description: >-
    Pregnancy-associated ureteral dilation and urinary stasis increase the risk
    of ascending infection and pyelonephritis.
  evidence:
  - reference: PMID:41274602
    reference_title: >-
      Treatment of asymptomatic bacteriuria during pregnancy: A
      risk-factor-based approach.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      During pregnancy, there is increased risk of ascending urinary tract
      infection (UTI) resulting in pyelonephritis and associated preterm
      delivery and low birth weight.
    explanation: >-
      Pregnancy raises the risk that a urinary tract infection ascends to cause
      pyelonephritis.
  influences_mechanisms:
  - target: Vesicoureteral Bacterial Ascent
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Gestational ureteral dilation and stasis favour ascent of bladder
      uropathogens into the upper tract.
    evidence:
    - reference: PMID:41274602
      reference_title: >-
        Treatment of asymptomatic bacteriuria during pregnancy: A
        risk-factor-based approach.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        During pregnancy, there is increased risk of ascending urinary tract
        infection (UTI) resulting in pyelonephritis and associated preterm
        delivery and low birth weight.
      explanation: >-
        Pregnancy raises the risk that a urinary tract infection ascends to
        cause pyelonephritis.
prevalence:
- population: Denmark (women, hospital-diagnosed, 2018)
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 154.0
  rate_denominator: PERSON_YEARS
  notes: >-
    19-year Danish population-based cohort; women's rate rose from 6.8 to 15.4
    per 10,000 person-years over 2000-2018.
  evidence:
  - reference: PMID:38020186
    reference_title: >-
      Temporal changes in incidence of hospital-diagnosed acute pyelonephritis:
      A 19-year population-based Danish cohort study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the incidence increased from 6.8 (95% CI: 6.8-6.8) to 15.4 (95% CI:
      15.4-15.4) in women and from 2.7 (95% CI: 2.7-2.7) to 4.5 (95% CI:
      4.5-4.5) in men.
    explanation: >-
      Reports the 2018 hospital-diagnosed APN incidence in women (15.4 per
      10,000 person-years = 154 per 100,000).
- population: Denmark (men, hospital-diagnosed, 2018)
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 45.0
  rate_denominator: PERSON_YEARS
  notes: >-
    Same Danish cohort; men's rate rose from 2.7 to 4.5 per 10,000 person-years.
  evidence:
  - reference: PMID:38020186
    reference_title: >-
      Temporal changes in incidence of hospital-diagnosed acute pyelonephritis:
      A 19-year population-based Danish cohort study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the incidence increased from 6.8 (95% CI: 6.8-6.8) to 15.4 (95% CI:
      15.4-15.4) in women and from 2.7 (95% CI: 2.7-2.7) to 4.5 (95% CI:
      4.5-4.5) in men.
    explanation: >-
      Reports the 2018 hospital-diagnosed APN incidence in men (4.5 per 10,000
      person-years = 45 per 100,000).
diagnosis:
- name: Urine culture and parenchymal imaging
  description: >-
    Diagnosis rests on pyuria and a positive urine culture; DMSA scintigraphy is
    the reference standard for parenchymal involvement and scarring.
  markers: urine culture; dimercaptosuccinic acid (DMSA) renal scintigraphy
  evidence:
  - reference: PMID:27313268
    reference_title: >-
      Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated
      Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a
      Phase 3 Randomized Trial Program.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diagnosis was based on positive urine cultures obtained within 48 hours of
      enrollment showing 1–2 gram-negative uropathogens at ≥105 colony-forming
      units (CFU)/mL, and pyuria.
    explanation: >-
      Documents the quantitative urine-culture and pyuria case definition used
      for culture-confirmed acute pyelonephritis.
  - reference: PMID:27748543
    reference_title: >-
      Delayed treatment of the first febrile urinary tract infection in early
      childhood increased the risk of renal scarring.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      renal scarring based on dimercaptosuccinic acid scintigraphy (DMSA)
      findings
    explanation: >-
      DMSA scintigraphy is used to define renal parenchymal lesions and
      scarring.
progression:
- phase: Uncomplicated acute pyelonephritis
  notes: >-
    Acute parenchymal kidney infection; most cases resolve with prompt
    antibiotics.
  evidence:
  - reference: PMID:38020186
    reference_title: >-
      Temporal changes in incidence of hospital-diagnosed acute pyelonephritis:
      A 19-year population-based Danish cohort study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      which may lead to sepsis, acute kidney injury, kidney scarring, chronic
      kidney disease, and death
    explanation: >-
      Frames acute pyelonephritis as the starting point of a progression that
      can reach sepsis, scarring, and CKD.
- phase: Emphysematous pyelonephritis
  notes: >-
    Gas-forming necrotizing infection, chiefly in diabetic or obstructed
    patients.
  evidence:
  - reference: PMID:42221797
    reference_title: >-
      Clinical spectrum, outcome and impact of nephrectomy in critically-ill
      adult patients with emphysematous pyelonephritis: the PYELEMPHY
      observational retrospective multicenter Study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Emphysematous pyelonephritis (EPN) is a rare, life-threatening necrotizing
      urinary tract infection marked by gas formation in the renal parenchyma
      and perirenal tissues.
    explanation: >-
      Defines emphysematous pyelonephritis as a severe necrotizing stage of
      upper-tract infection.
- phase: Urosepsis and septic shock
  notes: >-
    Bacteremic spread with systemic sepsis; mortality is high once septic shock
    develops.
  evidence:
  - reference: PMID:42417339
    reference_title: >-
      '[Treatment, outcomes, and management strategy for purulent
      pyelonephritis: a systematic review and meta-analysis. Part II].'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      in patients with septic shock, mortality reached 20-30%
    explanation: >-
      Documents the high mortality of the septic-shock stage of severe
      pyelonephritis.
- phase: Renal scarring and chronic kidney disease
  notes: >-
    Delayed or severe infection leaves permanent scars that can progress to
    hypertension and chronic kidney disease.
  evidence:
  - reference: PMID:27748543
    reference_title: >-
      Delayed treatment of the first febrile urinary tract infection in early
      childhood increased the risk of renal scarring.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Delay in treatment initiation of 72 hours or more was a risk factor for
      permanent renal scars after the first episode of febrile UTI.
    explanation: >-
      Links delayed treatment to the permanent-scarring sequela of acute
      pyelonephritis.
treatments:
- name: Culture-guided fluoroquinolone antimicrobial therapy
  description: >-
    Community-acquired acute pyelonephritis is treated with an antibiotic
    active against the cultured uropathogen and tailored to susceptibility
    results and local resistance; ciprofloxacin is an oral fluoroquinolone
    option when the isolate is susceptible and patient factors permit it.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Antibiotic Therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: Ciprofloxacin
      term:
        id: NCIT:C375
        label: Ciprofloxacin
  target_mechanisms:
  - target: Renal Parenchymal Bacterial Expansion
    treatment_effect: INHIBITS
    description: >-
      Susceptibility-guided antimicrobial therapy kills or suppresses the
      proliferating renal uropathogen population.
  - target: Acute Tubulointerstitial Inflammation
    treatment_effect: INHIBITS
    description: >-
      Bacterial eradication removes the trigger for ongoing neutrophilic
      tubulointerstitial inflammation.
  evidence:
  - reference: PMID:22726802
    reference_title: >-
      Ciprofloxacin for 7 days versus 14 days in women with acute
      pyelonephritis: a randomised, open-label and double-blind,
      placebo-controlled, non-inferiority trial.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Short-term clinical cure occurred in 71 (97%) patients treated with
      ciprofloxacin for 7 days and 80 (96%) treated for 14 days
    explanation: >-
      Supports ciprofloxacin as an effective oral antibiotic in a randomized
      duration trial of women with community-acquired acute pyelonephritis.
- name: Intravenous third-generation cephalosporin (ceftriaxone)
  description: >-
    Hospitalized or febrile acute pyelonephritis in hemodynamically stable
    patients is commonly treated empirically with an intravenous
    third-generation cephalosporin such as ceftriaxone.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Antibiotic Therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: Ceftriaxone
      term:
        id: NCIT:C62020
        label: Ceftriaxone
  target_mechanisms:
  - target: Renal Parenchymal Bacterial Expansion
    treatment_effect: INHIBITS
    description: >-
      Broad-spectrum beta-lactam therapy suppresses the proliferating renal
      uropathogen population.
  evidence:
  - reference: PMID:42417339
    reference_title: >-
      '[Treatment, outcomes, and management strategy for purulent
      pyelonephritis: a systematic review and meta-analysis. Part II].'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Empirical regimens included third-generation cephalosporins (ceftriaxone)
      in hemodynamically stable patients
    explanation: >-
      Supports ceftriaxone as a standard empirical regimen for purulent/severe
      pyelonephritis in stable patients.
- name: Ceftazidime-avibactam
  description: >-
    For complicated or resistant (including ESBL-producing) infection,
    ceftazidime-avibactam is a carbapenem-sparing option that was non-inferior
    to doripenem for complicated UTI including acute pyelonephritis in a Phase 3
    program.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Antibiotic Therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
    therapeutic_agent:
    - preferred_term: ceftazidime-avibactam
      term:
        id: NCIT:C127836
        label: Ceftazidime/Avibactam Sodium
  target_mechanisms:
  - target: Renal Parenchymal Bacterial Expansion
    treatment_effect: INHIBITS
    description: >-
      The ceftazidime-avibactam combination restores beta-lactam activity
      against resistant uropathogens and suppresses renal bacterial expansion.
  evidence:
  - reference: PMID:27313268
    reference_title: >-
      Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated
      Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a
      Phase 3 Randomized Trial Program.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Ceftazidime-avibactam was highly effective for the empiric treatment of
      cUTI (including acute pyelonephritis), and may offer an alternative to
      carbapenems in this setting.
    explanation: >-
      Phase 3 RCT evidence supporting ceftazidime-avibactam for complicated UTI
      including acute pyelonephritis.
- name: Source control (decompression and drainage)
  description: >-
    When obstruction or an abscess is present, antibiotics alone are
    insufficient: urgent decompression (nephrostomy or ureteral stent) and
    percutaneous drainage of large abscesses are required, with nephrectomy
    reserved for fulminant disease.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: urinary tract decompression and drainage
    term:
      id: NCIT:C15329
      label: Surgical Procedure
  target_mechanisms:
  - target: Renal Parenchymal Bacterial Expansion
    treatment_effect: INHIBITS
    description: >-
      Relieving obstruction and draining pus removes the stasis and
      focus that sustain renal bacterial expansion.
  evidence:
  - reference: PMID:42417339
    reference_title: >-
      '[Treatment, outcomes, and management strategy for purulent
      pyelonephritis: a systematic review and meta-analysis. Part II].'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In cases of urinary tract obstruction, urgent decompression with
      nephrostomy or ureteral stenting was mandatory and led to improvement in
      >90% of cases.
    explanation: >-
      Supports obstruction decompression as a required source-control
      intervention in severe pyelonephritis.
animal_models:
- name: Murine transurethral ascending UTI/pyelonephritis model (C3H/HeN)
  species: Mouse
  genotype: C3H/HeN wild-type, transurethral UPEC inoculation
  publication: PMID:33513212
  description: >-
    Transurethral UPEC inoculation of C3H/HeN mice reproduces ascending kidney
    infection and is the workhorse model for bacterial and host determinants of
    pyelonephritis.
  modeled_mechanisms:
  - target: Renal Parenchymal Bacterial Expansion
    relationship: RECAPITULATES
    fidelity: MODERATE
    model_scale: TISSUE
    description: >-
      FimH-dependent UPEC adhesion and renal colonisation are reproduced in the
      C3H/HeN ascending-infection model.
    limitations: >-
      Mice lack a direct IL-8/CXCL8 ortholog (functional homologs are used) and
      differ in urinary-tract anatomy, so the human chemokine-driven neutrophil
      axis and polymorphism spectrum are only partially captured.
    evidence:
    - reference: PMID:33513212
      reference_title: >-
        A host receptor enables type 1 pilus-mediated pathogenesis of
        Escherichia coli pyelonephritis.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Bacterial mutants lacking the type 1 pilus adhesin (FimH) were unable to
        establish kidney infection in male C3H/HeN mice.
      explanation: >-
        The C3H/HeN model recapitulates FimH-dependent renal colonisation
        underlying parenchymal bacterial expansion.
review_notes: >-
  Duplicate preflight found no exact MONDO:0003529 or exact acute-pyelonephritis
  standalone entry in ignored-inclusive kb/disorders, stubs, research, history,
  .github, and docs searches. Local and origin/main matches were confined to
  Familial_Vesicoureteral_Reflux, which models acute pyelonephritis as a
  reflux-mediated consequence; all-state GitHub PR and issue matches were the
  same merged Familial VUR work, not duplicate standalone curation.
📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Review round 1: wire pathograph, add host-susceptibility genetics, risk factors, epidemiology, progression, diagnosis, animal model and treatments · 2026-10-20T04:56:18Z · View source

Addressed the ai4c-reviewer CHANGES_REQUESTED review. Findings 1/3/4/5/6/7 (blocking+important): added downstream edges from Acute Tubulointerstitial Inflammation to Fever/Flank pain/Sepsis (0/3 -> 3/4 connected); bound Pyuria HP:0012085 (report had mislabeled HP:0032453) with PMID:27313268 enrolment definition; dropped circular frequency:FREQUENT on Fever/Flank pain; gave Sepsis evidence (PMID:38020186) and dropped its unsourced frequency; removed quote_role:BACKGROUND from the two case-definition items; dropped GO:0007155 cell adhesion/INCREASED (it described bacterial FimH binding, not a host process). Finding 2 (under-consumption): added genetic SUSCEPTIBILITY loci IRF3/CXCL8/CXCR1 (PMID:20886096/21042230/11817650), environmental risk factors diabetes/obstruction/pregnancy via influences_mechanisms PREDISPOSES (PMID:42221797/41274602), Danish-registry incidence prevalence (PMID:38020186), a four-phase progression (clearing NO_PROGRESSION), a light diagnosis block (urine culture + DMSA), the C3H/HeN murine ascending-infection animal model with modeled_mechanisms, and treatments ceftriaxone, ceftazidime-avibactam (Phase 3 RCT PMID:27313268) and surgical source control. The report's NCIT codes for ceftazidime-avibactam (C120207) and ceftriaxone (C287) were hallucinated and corrected to C127836/C62020 by OAK lookup. Skipped suggestion 8 (conforms_to a topoisomerase module needs a drug-target node this host-response entry does not model) and 9 (StatPearls, explicitly optional). Moved the DR-provenance narration out of notes:. Validated: validate, validate-terms, count-verified-snippets 29/29, validate-disorders, check-causal-targets, check-coarse-phenotypes, check-snippet-grading, gene-activity-grounding, prose-figure-audit, check-reference-titles all pass.

OpenScientist ▸
1. Disease Information
openscientist-autonomous 45 citations 2026-09-30T03:08:45.338528

1. Disease Information

Definition. Acute pyelonephritis is an acute suppurative bacterial infection of the renal parenchyma, tubules, and renal pelvis (upper urinary tract), typically arising by ascent of uropathogens from the bladder. It sits at the severe end of the UTI spectrum, above asymptomatic bacteriuria (ASB) and lower-tract cystitis. It is a form of "complicated" or "febrile" UTI when accompanied by systemic signs.

Key identifiers.

Resource Identifier
MONDO MONDO:0003529 (acute pyelonephritis)
MeSH Pyelonephritis (D011704); Pyelonephritis, Xanthogranulomatous (D058489)
ICD-10 N10 (Acute tubulo-interstitial nephritis / acute pyelonephritis); O23.x for pregnancy-associated
ICD-11 GB51 (Acute pyelonephritis)
SNOMED CT 45816000 (Pyelonephritis); acute pyelonephritis subtype
OMIM / Orphanet Not a Mendelian disorder; no dedicated OMIM phenotype MIM. Host susceptibility loci exist (see §4). Not an Orphanet rare disease per se.

Synonyms / alternative names. Acute infective tubulo-interstitial nephritis; upper urinary tract infection; acute febrile UTI; ascending pyelonephritis. Variant/related entities: emphysematous pyelonephritis (EPN), xanthogranulomatous pyelonephritis (XGP), acute lobar nephronia / acute focal bacterial nephritis (ALN/AFBN), pyonephrosis, and perinephric abscess.

Data provenance. Evidence in this report is drawn from aggregated disease-level resources — population registries (e.g., a 19-year Danish cohort), prospective clinical cohorts, randomized controlled trials, systematic reviews/meta-analyses, and mechanistic model-organism and in-vitro studies — supplemented by EHR-derived cohort studies. It is not derived from a single individual patient.

2. Etiology

Primary cause — infectious. APN is overwhelmingly bacterial and ascending. Uropathogenic E. coli (UPEC) is the dominant pathogen. In a US prospective study (2013–2014) of adults with culture-confirmed APN, E. coli grew in 86.9% (453/521) of cases (PMID: 27532362). Other uropathogens include Klebsiella pneumoniae, Proteus mirabilis (associated with struvite/staghorn calculi and XGP), Enterococcus, Pseudomonas, and, in specific contexts, Staphylococcus saprophyticus and Candida. Hematogenous seeding (e.g., Staphylococcus aureus) is a less common alternative route.

Risk factors.

Environmental / clinical (host): - Female sex — short urethra and perineal proximity favor ascent. Strong female predominance across all age strata (PMID: 38020186). - Pregnancy — ureteral dilation, urinary stasis, and ASB markedly raise ascending-infection risk (PMID: 41274602). - Diabetes mellitus — the dominant risk factor for necrotizing/emphysematous forms (63–76% of EPN series) (PMID: 42221797, PMID: 41836219). - Urinary obstruction / stones — present in ~46% of severe EPN (PMID: 42221797); staghorn calculi underlie XGP. - Vesicoureteral reflux (VUR) and bladder-bowel dysfunction (BBD) — key pediatric risk factors and drivers of scarring (PMID: 35928985). - Infancy/early childhood, instrumentation/catheterization, immunosuppression, prior UTI, and sexual activity.

Genetic (host susceptibility — not causal Mendelian): - IRF3 promoter polymorphisms associated with symptomatic kidney infection vs asymptomatic carriage (PMID: 20886096). - IL-8 / CXCL8 rs4073 (−251A>T) associated with pediatric parenchymal renal infection (PMID: 21042230). - Low CXCR1 expression predisposes to pyelonephritis and scarring (PMID: 11817650).

Protective factors. Intact innate immunity (functional TLR4→IRF3 and IL-8/CXCR1 neutrophil axis); urinary neutrophil extracellular traps (NETs) that block ascension (PMID: 39321268); adequate hydration/urine flow; absence of obstruction; and, for recurrence, vaginal estrogen in postmenopausal women and prophylactic strategies (§13). No well-established protective germline variant is defined; conceptually, "high" innate-signaling genotypes are protective.

Gene–environment interactions. Host genotype modulates the environmental exposure (bacterial colonization): the same UPEC exposure yields ASB in hosts with robust IRF3/IL-8/CXCR1 signaling but ascending symptomatic pyelonephritis in hosts with attenuated signaling. Diabetes (environmental/metabolic) interacts with tissue susceptibility to produce necrotizing EPN. Androgen status interacts with macrophage polarization to modulate post-infection scarring (PMID: 32849562).

3. Phenotypes

Phenotype Type Suggested HPO Frequency / notes
Fever Symptom/sign HP:0001945 Very frequent; hallmark of "febrile UTI"
Flank / loin pain Symptom HP:0030157 (flank pain) Frequent; often unilateral
Costovertebral angle tenderness Clinical sign — Characteristic exam finding
Dysuria / urinary frequency / urgency Symptom HP:0100518 (dysuria) Common (lower-tract overlap)
Nausea and vomiting Symptom HP:0002018 / HP:0002013 Common, especially children
Pyuria (leukocyturia) Lab abnormality HP:0032453 (pyuria) Near-universal; basis of leukocyte-esterase/NET dipstick (PMID: 39321268)
Bacteriuria Lab abnormality HP:0012461 (bacteriuria) Defining; ≥10⁵ CFU/mL
Leukocytosis / elevated CRP, PCT Lab abnormality HP:0001974 (leukocytosis) Systemic inflammation; PCT/uNGAL predict severity/scarring
Hematuria Lab/sign HP:0000790 Variable
Sepsis / septic shock Clinical complication HP:0100806 (sepsis) ~72% septic shock in ICU EPN cohort (PMID: 42221797)
Renal scarring Structural sequela HP:0000800 region / scarring Long-term; DMSA-defined

Onset / severity / progression. Onset is acute (hours to a few days). Age of onset is bimodal: high in infancy (especially girls), then predominant in reproductive-age women, with a further rise in the elderly. Severity is variable — from outpatient-manageable uncomplicated APN to fulminant urosepsis. Course is typically self-limited with treatment, but delayed therapy (>72 h) increases permanent scarring (PMID: 27748543).

Quality-of-life impact. Acute APN causes marked short-term morbidity (hospitalization, pain, fever, work loss). Recurrent UTI/pyelonephritis substantially impairs quality of life and drives major antibiotic use (PMID: 42225392). Post-pyelonephritic scarring can progress to hypertension and CKD, with lasting functional impact.

4. Genetic / Molecular Information

APN has no causal Mendelian gene; it is a multifactorial infectious disease with host susceptibility loci that shift the balance between asymptomatic bacteriuria and symptomatic parenchymal infection.

Susceptibility genes / variants (host innate immunity):

Gene (HGNC) Variant / feature Effect Evidence
IRF3 Promoter polymorphism; disease genotype lowers promoter activity Reduced type I IFN/innate signaling → symptomatic kidney infection PMID: 20886096
CXCL8 (IL-8) rs4073 (−251A>T) Altered neutrophil chemokine signaling → parenchymal renal infection in children PMID: 21042230
CXCR1 Low receptor expression Impaired neutrophil clearance → pyelonephritis + scarring PMID: 11817650
TLR4 Signaling capacity Modulates mucosal response (high response → symptomatic; low → ASB) PMID: 21042230

Variant class: regulatory/promoter SNPs and expression-modulating polymorphisms (not protein-truncating). Origin: germline host variants (susceptibility), distinct from the bacterial genome (virulence). Functional consequence: partial loss of innate signaling function predisposing to ascension. In PMID: 21042230, among TLR4/IL-8/CXCR1/CXCR2 SNPs tested in children with APN/ALN (VUR excluded), "only IL-8 (rs4073, −251A>T) showed significant differences in genotype and allele frequency between the control and APN or ALN cases."

Bacterial "virulence genotype." Disease is strongly shaped by the pathogen genome: fim (type 1 pili/FimH), pap (P-fimbriae), hly (α-hemolysin), and siderophore systems. ESBL genes (e.g., blaCTX-M) and fluoroquinolone-resistance determinants convert treatable disease into refractory disease (PMID: 27532362); ST131-H30Rx clones carry virulence factors linked to recurrence (PMID: 40926251).

Modifier genes / epigenetics / chromosomal abnormalities. Androgen-responsive pathways modify macrophage polarization and scarring (PMID: 32849562). No disease-specific DNA-methylation signature or recurrent chromosomal abnormality is established for APN; CAKUT (congenital anomalies of kidney/urinary tract) predispose anatomically but did not explain the observed incidence rise (PMID: 38020186).

5. Environmental Information

  • Infectious agents (NCBI Taxonomy): Escherichia coli (txid562) — dominant; Klebsiella pneumoniae (txid573); Proteus mirabilis (txid584); Enterococcus faecalis (txid1351); Pseudomonas aeruginosa (txid287); Candida spp. (fungal, in diabetics/instrumented patients).
  • Environmental/metabolic factors: Diabetes mellitus and hyperglycemia (tissue substrate for gas-forming necrotizing EPN); urinary catheters/instrumentation (nosocomial exposure); obstruction/stones (stasis).
  • Lifestyle factors: Sexual activity, spermicide/diaphragm use, inadequate fluid intake, and delayed voiding increase lower-UTI and ascension risk. Increased fluid intake benefits those with low baseline intake (PMID: 42225392).
  • Occupational/toxin exposures: No specific occupational toxin is causally linked; APN is infection-driven.

6. Mechanism / Pathophysiology

Ordered causal chain (initiating lesion → clinical manifestation)

  1. Periurethral/fecal UPEC colonization of the introitus/urethra leads to bladder colonization (ascending route).
  2. Bladder UPEC express type 1 pili (FimH) and P-fimbriae (PapG); FimH binds mannosylated desmoglein-2 (DSG2) on renal epithelium and P-fimbriae bind uroepithelial glycosphingolipids, which results in adhesion and ascent up the ureter to the renal pelvis and collecting ducts (demonstrated in C3H/HeN mice; FimH⁻ mutants cannot establish kidney infection) (PMID: 33513212).
  3. Adhesion and bacterial products (LPS, hemolysin) activate TLR4 on tubular/uroepithelial cells, which leads to IRF3-dependent innate signaling and IL-8/CXCL8 secretion (branch point A) (PMID: 20886096, PMID: 21042230).
  4. IL-8 engaging CXCR1 on neutrophils results in massive neutrophil recruitment across the uroepithelium into the parenchyma and urine — the decisive effector step (PMID: 11817650).
  5. Branch A — effective clearance: Neutrophils phagocytose bacteria, release granules/ROS, and form NETs (also present in healthy urine), which results in bacterial containment → asymptomatic bacteriuria or resolution and a positive leukocyte dipstick (PMID: 39321268, PMID: 42524556).
  6. Branch B — defective clearance (low CXCR1, IRF3/IL-8 risk genotypes): impaired neutrophil recruitment/function leads to parenchymal bacterial proliferation, abscess formation, and symptomatic acute pyelonephritis (PMID: 11817650, PMID: 20886096).
  7. Persistent/dysregulated neutrophil activation results in collateral tissue injury via ROS, proteases, S100A8/A9, and NET-associated mediators, which leads to tubulointerstitial damage (double-edged effector) (PMID: 42524556).
  8. Injury plus androgen-influenced polarization of activin-A–producing macrophages leads to fibrogenic remodeling and permanent renal scarring (post-pyelonephritic scarring) — inferred from mouse models (PMID: 32849562, PMID: 42524556).
  9. In diabetic/obstructed hosts (branch C), high tissue glucose and impaired perfusion result in gas-forming necrotizing infection = emphysematous pyelonephritis, which leads to sepsis/septic shock and, without source control, death (PMID: 42221797).
  10. Systemically, bacteremia and cytokine release result in SIRS/urosepsis; scarring over time leads to hypertension and chronic kidney disease (PMID: 40022942).

Detail by category

  • Molecular pathways: TLR4 → MyD88/TRIF → IRF3 (type I IFN) and NF-κB → IL-8/CXCL8; IL-8–CXCR1/CXCR2 chemotaxis. (Reactome: Toll-like receptor cascades; KEGG hsa04620.)
  • Cellular processes: Innate inflammation, neutrophil chemotaxis/phagocytosis, NETosis, ROS burst, apoptosis/necrosis of tubular cells, macrophage polarization, fibrosis.
  • Protein dysfunction: Bacterial FimH lectin domain gains pathogenic function by binding host DSG2; a mannose-binding-pocket mutation abolishes binding (PMID: 33513212). Host risk = reduced IRF3 promoter activity / low CXCR1.
  • Immune involvement: Predominantly innate (neutrophils, macrophages, epithelial sensing). Not autoimmune.
  • Tissue-damage mechanisms: Oxidative stress (ROS), protease-mediated injury, NET-associated cytotoxicity, ischemia (obstruction), necrosis, and fibrogenesis.
  • Molecular profiling: Biomarkers up in disease include NGAL/LCN2, procalcitonin, CRP, and S100A8/A9 (calprotectin). NGAL is itself a bacteriostatic (iron-sequestering) innate effector.

Suggested ontology terms. GO biological process: neutrophil chemotaxis (GO:0030593), defense response to bacterium (GO:0042742), Toll-like receptor signaling pathway (GO:0002224), neutrophil extracellular trap formation (GO:0140494), response to lipopolysaccharide (GO:0032496). CL cell types: neutrophil (CL:0000775), macrophage (CL:0000235), kidney collecting duct epithelial cell (CL:1000454), renal proximal tubule epithelial cell (CL:1000838). CHEBI: reactive oxygen species (CHEBI:26523), lipopolysaccharide (CHEBI:16412).

7. Anatomical Structures Affected

  • Primary organ: Kidney (UBERON:0002113) — specifically renal parenchyma/cortex (UBERON:0001225), renal medulla (UBERON:0000362), renal pelvis (UBERON:0001224), and collecting duct (UBERON:0001232), the principal site of FimH–DSG2 adhesion.
  • Secondary/complications: Perinephric space (perinephric abscess), ureter (UBERON:0000056), bladder (UBERON:0001255, source), bloodstream (bacteremia/urosepsis). Long-term secondary organ: systemic (sepsis), progression to CKD.
  • Body systems: Renal/urinary system (primary); cardiovascular/immune (sepsis); reproductive/obstetric (pregnancy-associated).
  • Tissues/cells: Tubular and collecting-duct epithelial cells (targets); infiltrating neutrophils (CL:0000775) and macrophages (CL:0000235). Tissue type: epithelial and tubulointerstitial.
  • Subcellular: Bacterial engagement at the apical plasma membrane (GO:0016324) of tubular epithelium; intracellular bacterial communities; neutrophil azurophil granules and NADPH-oxidase-driven ROS; NET chromatin extrusion (extracellular region, GO:0005576).
  • Localization / laterality: Often unilateral (single kidney/segment), can be bilateral; EPN commonly affects one kidney with contralateral involvement possible; acute lobar nephronia is focal/segmental.

8. Temporal Development

  • Onset: Acute to subacute (hours–days). Age of onset bimodal — infancy and reproductive-age adulthood, with elderly resurgence.
  • Progression/stages: Uncomplicated APN → (if untreated/host-vulnerable) → acute lobar nephronia → renal/perinephric abscess → emphysematous pyelonephritis → urosepsis. Chronic sequela: post-pyelonephritic scarring → CKD.
  • Course/duration: Typically self-limited with antibiotics over 7–14 days; delay >72 h predicts permanent scarring (PMID: 27748543). Recurrence is common in the presence of unresolved predisposing factors (obstruction, VUR, diabetes).
  • Critical intervention window: Prompt antibiotics (ideally within hours to <72 h) and, when obstruction is present, urgent decompression (nephrostomy/stent). Early nephrectomy (≤24 h) improves survival in fulminant EPN (PMID: 42221797).

9. Inheritance and Population

Epidemiology. In a 19-year Danish population-based cohort (66,937 APN episodes in 57,162 patients; ICD-10), the incidence roughly doubled over 2000–2018 (PMID: 38020186):

Group 2000 (per 100,000/yr) 2018 (per 100,000/yr)
Women 6.8 15.4
Men 2.7 4.5
Infant girls 7.4 64.8
Infant boys 17.1 52.5

Direct quote: "the incidence increased from 6.8 … to 15.4 … in women and from 2.7 … to 4.5 … in men" and "Among infants, the rate rose from 7.4 … to 64.8 … in girls and from 17.1 … to 52.5 … in boys" (PMID: 38020186). The rise was driven largely by young children and not explained by increasing CAKUT prevalence. In US surveillance, pyelonephritis accounted for 19.9% of invasive E. coli infections; APN affects ~250,000 US patients annually (PMID: 41627814, PMID: 32849562).

Inheritance. Not a monogenic disorder — no Mendelian inheritance pattern, penetrance, anticipation, founder effect, or carrier frequency applies. Susceptibility is multifactorial/polygenic, mediated by innate-immunity variants (IRF3, IL-8/rs4073, CXCR1) plus anatomic/metabolic risk.

Demographics. Strong female predominance across ages; infant male predominance in the neonatal period (before shifting female). Diabetics and pregnant women are over-represented in severe forms. No specific ethnic founder distribution; ESBL/fluoroquinolone-resistant strains show geographic variation (higher ESBL in complicated cases and certain regions).

10. Diagnostics

Laboratory tests. Urinalysis (pyuria, leukocyte esterase, nitrites, hematuria), urine culture with ≥10⁵ CFU/mL and susceptibility testing (essential given resistance), blood cultures in severe/hospitalized cases, CBC (leukocytosis), CRP, and creatinine/eGFR. LOINC: urine culture (630-4); leukocyte esterase (5799-2); nitrite (5802-4).

Biomarkers. - Procalcitonin (PCT): correlates with acute parenchymal involvement on DMSA (8.81 vs 1.7 ng/mL in lesion vs no-lesion, p=0.01) and predicts scarring (cut-off ~1 ng/mL, AUC 0.74), though it cannot replace DMSA (PMID: 23481452, PMID: 19205751, PMID: 27329559). - Urinary NGAL (LCN2): meta-analysis (13 studies) — sensitivity 0.88 (95% CI 0.79–0.94), specificity 0.86 (0.78–0.92) for UTI; for APN sensitivity 0.79, specificity 0.78 (PMID: 39423110). In 321 febrile children uNGAL outperformed CRP/WBC for UTI and APN (AUC 0.860 and 0.780) (PMID: 33091975). uNGAL and PCT are higher in children who later scar (PMID: 40742430).

Imaging. Reserved for complicated/atypical/non-responding cases: renal ultrasound (hydronephrosis, abscess), contrast-enhanced CT (reference for EPN — intrarenal gas; abscess; obstruction), and DMSA (⁹⁹ᵐTc-dimercaptosuccinic acid) scintigraphy — the reference standard for parenchymal involvement and scarring in children (PMID: 27748543, PMID: 16894326). In XGP, CT shows the "bear-paw" sign with staghorn calculus (PMID: 41323310).

Genetic / omics diagnostics. Not indicated for routine diagnosis (APN is not a monogenic disease). Research-level host-susceptibility genotyping (IRF3, IL-8 rs4073, CXCR1) and pathogen whole-genome sequencing (virulence/resistance profiling, e.g., ST131-H30Rx) are used in studies, not clinical care (PMID: 40926251).

Clinical criteria & differential diagnosis. Diagnosis is clinical (fever + flank pain + CVA tenderness) plus pyuria/bacteriuria and positive culture; IDSA criteria used for pregnancy studies. Differentials: cystitis (no systemic/CVA signs), nephrolithiasis/renal colic, PID/STIs (co-occur in sexually active women — evaluate for cervical motion tenderness) (PMID: 40360224), ovarian vein thrombophlebitis (postpartum fever) (PMID: 42402563), appendicitis, and, in mass-forming XGP, renal cell/squamous carcinoma (PMID: 33282610).

Screening. In pregnancy, screen for ASB with urine culture (see §13) (PMID: 39349024).

11. Outcome / Prognosis

Mortality. Uncomplicated APN has low mortality with prompt therapy. Severe/complicated forms are dangerous: in critically ill EPN, ICU mortality ~15%, with higher SAPS II independently predicting 90-day mortality (HR 1.08/point, 95% CI 1.05–1.12) and early nephrectomy associated with lower mortality (HR 0.18, 95% CI 0.04–0.90, p=0.037) (PMID: 42221797). In purulent pyelonephritis meta-analysis, overall mortality ~5.8% (342/5912), rising to 20–30% with septic shock (PMID: 42417339). In invasive E. coli infection surveillance, 7.9% died (PMID: 41627814).

Morbidity / complications. Urosepsis/septic shock, renal and perinephric abscess, emphysematous pyelonephritis, pyonephrosis, acute kidney injury, and permanent renal scarring → hypertension and CKD progression. UTI requiring hospital admission accelerates eGFR decline in CKD patients and is a potentially modifiable CKD-progression factor (PMID: 40022942). In pregnancy, APN is linked to preterm birth and low birth weight (PMID: 41274602, PMID: 41684314).

Prognostic factors. Delay to treatment >72 h (scarring), VUR presence/grade, diabetes, obstruction, septic shock, pre-existing CKD, thrombocytopenia, and dialysis need. Prognostic biomarkers: elevated PCT and uNGAL predict acute parenchymal lesions and later scarring (PMID: 27748543, PMID: 40742430).

12. Treatment

Pharmacotherapy (empirical then culture-directed).

Setting Agents NCIT (suggested) Evidence
Uncomplicated APN (outpatient) Fluoroquinolone (ciprofloxacin/levofloxacin); TMP-SMX if susceptible Ciprofloxacin C376; Levofloxacin C1637 7 days non-inferior to 14 days (PMID: 22726802)
Hospitalized / febrile UTI 3rd-gen cephalosporin (ceftriaxone) IV ± aminoglycoside; oral step-down Ceftriaxone C287 SPILF guidelines (PMID: 42314979)
Complicated / ESBL / resistant Carbapenem; ceftazidime-avibactam (carbapenem-sparing); piperacillin-tazobactam Ceftazidime-Avibactam C120207 Non-inferior to doripenem (PMID: 27313268)
Uncomplicated (oral, ESBL) Pivmecillinam, fosfomycin, nitrofurantoin (lower-tract) Nitrofurantoin C61854 (PMID: 42130306)
Pregnancy Cephalosporins (cefixime), IV for pyelonephritis — (PMID: 39349024, PMID: 39563593)

Duration. Landmark RCT: ciprofloxacin 500 mg BID × 7 days is clinically and bacteriologically non-inferior to 14 days in women with community-acquired APN (248 randomized) (PMID: 22726802). In children, ≤7-day and oral courses may not increase recurrence versus longer/parenteral therapy (PMID: 42803594).

Resistance context. Empirical therapy is constrained by resistance: fluoroquinolone resistance 6.3% (uncomplicated) vs 19.9% (complicated) and ESBL production 2.6% vs 12.2%, with 34.5% of ESBL cases community-acquired and most ESBL/FQ-resistant cases initially treated with inactive drugs (PMID: 27532362). ST131-H30Rx ESBL clones drive recurrence (PMID: 40926251).

Surgical / interventional. Urgent decompression (percutaneous nephrostomy or ureteral stent) for obstruction; percutaneous drainage for abscesses >3–5 cm (avoids open surgery in 80–90%); nephrectomy for fulminant EPN/XGP; XGP may sometimes be managed with kidney-preserving therapy in non-septic patients (PMID: 42417339, PMID: 26889137).

Supportive care. IV fluids, antipyretics/analgesia, vasopressors and ICU care for septic shock; glycemic control in diabetics.

Experimental / precision approaches. FimH mannoside inhibitors (e.g., FIM1033) attenuate bacterial loads in pyelonephritis models — an anti-adhesion, non-antibiotic strategy (PMID: 33513212).

13. Prevention

Primary prevention. - Pregnancy screen-and-treat of ASB — cornerstone: "During pregnancy, there is increased risk of ascending urinary tract infection (UTI) resulting in pyelonephritis and associated preterm delivery and low birth weight" (PMID: 41274602); "Screening for ASB with a urine culture is required during pregnancy, and a positive culture is treated for 5 to 7 days with culture-specific antibiotics" (PMID: 39349024). ASB is common (e.g., 29% culture-positive, 72% asymptomatic in a tertiary cohort) (PMID: 42516470); risk-factor-based selective screening is emerging to balance stewardship (PMID: 41274602). - Hydration, voiding hygiene, glycemic control, and source control of stones/obstruction.

Recurrence prevention (non-antibiotic, RCT-supported). - Sublingual vaccine MV140 — "Immunoprophylaxis with the sublingual vaccine MV140 significantly reduced recurrence compared with placebo, with 56–58% of women remaining UTI free in a large RCT" (PMID: 42133003). - Methenamine hippurate — "non-inferior to daily antibiotic prophylaxis in preventing rUTIs" (PMID: 42133003); supported alongside cranberry and (postmenopausal) vaginal estrogen in an overview of 27 systematic reviews, while probiotics/D-mannose/vaccines need stronger evidence (PMID: 42225392). - Vaginal estrogen in postmenopausal women.

Antibiotic prophylaxis in VUR (children). The RIVUR RCT (>600 children) showed long-term antimicrobial prophylaxis reduced UTI recurrence by 50% (overall NNT ~10) (PMID: 35928985, PMID: 38244067). Re-analysis identified high-benefit subgroups (NNT ≤5): grade IV VUR and children with bladder-bowel dysfunction, especially with febrile index UTI (PMID: 37693511).

Secondary/tertiary prevention. Prompt treatment (<72 h) to prevent scarring; DMSA/imaging follow-up; management of obstruction/diabetes to prevent EPN and CKD progression.

14. Other Species / Natural Disease

  • Taxonomy affected: Humans (NCBI:txid9606) primarily; naturally occurring ascending bacterial pyelonephritis also affects companion animals — dogs (Canis lupus familiaris, txid9615) and cats (Felis catus, txid9685) — and livestock (cattle, pigs), typically from ascending E. coli/Proteus/Enterococcus UTIs, obstruction, or stones.
  • Comparative pathology: Mechanisms are conserved — ascending uropathogen infection, obstruction/stasis predisposition, and neutrophil-mediated parenchymal injury. Veterinary relevance is significant in small-animal medicine (pyelonephritis as a cause of renal failure).
  • Orthologous host genes (NCBI Gene): mouse Irf3 (54131), Tlr4 (21898; human TLR4 7099), functional chemokine homologs (mouse Cxcl1/2 for human CXCL8 3576), Cxcr1, and Dsg2 (mouse 13511; human DSG2 1829).
  • Transmission / zoonosis: UPEC strains overlap between humans and animals/food (foodborne extraintestinal E. coli reservoirs), but APN itself is not classically person-to-person transmissible.

15. Model Organisms

  • Mouse (murine) ascending UTI/pyelonephritis models are the workhorse: transurethral UPEC inoculation in C3H/HeN and related strains reproduces ascending kidney infection, abscesses, and scarring.
  • Genetic models: Irf3⁻/⁻ mice show "a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice," directly modeling the human IRF3 susceptibility axis (PMID: 20886096). CXCR1/IL-8-axis and TLR4 models recapitulate the ASB-vs-pyelonephritis dichotomy (PMID: 11817650).
  • Mechanistic/receptor models: FimH⁻ UPEC mutants fail to colonize the kidney; DSG2 identified as the renal FimH receptor via CRISPR screen in collecting-duct cells; mannoside FIM1033 attenuates loads — establishing druggable anti-adhesion targets (PMID: 33513212).
  • Scarring/sex-difference models: androgen-influenced activin-A macrophage polarization drives post-pyelonephritic scarring; sex differences in kidney bacterial community dynamics are modeled in mice (PMID: 32849562, PMID: 33468577).
  • In vitro / cellular: Renal collecting-duct epithelial cell lines and CRISPR screens (FimH–DSG2 receptor identification); primary neutrophil functional assays (NET formation, ROS).
  • Phenotype recapitulation & limitations: Mouse models faithfully reproduce ascension, neutrophil-dependent clearance, abscess/scarring, and adhesin dependence. Limitations: interspecies differences in chemokine biology (mice lack a direct IL-8/CXCL8 ortholog; functional homologs used), urinary-tract anatomy, and the human polymorphism spectrum; EPN (diabetes-driven, gas-forming) is less commonly modeled.
  • Resources: MGI (mouse), plus UPEC strain collections; models used to study innate immunity, virulence, scarring, and anti-adhesion/vaccine therapeutics.

Mechanistic Model / Interpretation

 UPEC colonization (introitus -> bladder)
      |  FimH->DSG2 ; P-fimbriae->glycosphingolipid   [PMID 33513212]
      v
 Ascension to renal pelvis / collecting duct
      |  LPS/adhesins -> TLR4
      v
 Epithelial innate sensing -> IRF3 + NF-kB -> IL-8 (CXCL8)    [PMID 20886096, 21042230]
      |  IL-8 -> CXCR1 on neutrophils
      v
 NEUTROPHIL RECRUITMENT (decisive effector)                  [PMID 11817650]
|------------- Branch A: robust axis --------------|
|  phagocytosis, ROS, NETs -> clearance            |-> ASB / resolution  [PMID 39321268]
|                                                  |
|------------- Branch B: weak axis ----------------|
   (low CXCR1; IRF3/IL-8 rs4073 risk genotype)     |-> ACUTE PYELONEPHRITIS
      |  parenchymal proliferation, abscess        |
      v                                             |
   Dysregulated neutrophil injury (ROS, proteases,          |
   S100A8/A9, NETs) + androgen-macrophage activin-A         |-> RENAL SCARRING -> HTN/CKD
      |                                    [PMID 42524556, 32849562, 40022942]
      v
   Branch C (diabetes/obstruction): gas-forming necrosis    -> EMPHYSEMATOUS PN -> SEPSIS/DEATH
                                            [PMID 42221797]

The unifying theme is that APN is a disease of the host–pathogen interface: an identical UPEC exposure yields divergent outcomes (silent carriage vs destructive parenchymal infection vs necrotizing sepsis) depending on host innate-signaling genotype, anatomy (VUR/obstruction), and metabolic state (diabetes/pregnancy). This explains why therapy is not only antimicrobial but also directed at source control (decompression, drainage, nephrectomy) and why prevention targets the modifiable environmental inputs (ASB in pregnancy, obstruction, recurrence). Neutrophils are the pivotal, double-edged effector — indispensable for clearance yet responsible for the scarring that links acute infection to chronic kidney disease.

Evidence Base

PMID Contribution Type
20886096 IRF3-dependent innate resistance; human promoter polymorphism → symptomatic kidney infection Mouse + human genetics
11817650 Neutrophils as critical effectors; CXCR1/IL-8 dysfunction → pyelonephritis + scarring Review/mechanism
21042230 IL-8 rs4073 associates with pediatric parenchymal renal infection Human genetics
33513212 DSG2 as renal FimH receptor; FimH mannoside FIM1033 therapy Mouse + in vitro
39321268 Urinary NETs protect against ascension; basis of leukocyte dipstick Human + mouse
42524556 Neutrophil double-edged role; effector molecules of injury/fibrosis Review
32849562 Androgen–activin-A macrophage polarization → scarring; ~250k US cases/yr Mouse
27532362 US resistance rates (FQ, ESBL) in APN; E. coli 86.9% Prospective cohort
42221797 EPN ICU cohort; diabetes/shock/obstruction; early nephrectomy benefit Multicenter cohort
38020186 Population incidence doubling; sex/infant distribution Registry cohort
22726802 7 vs 14 day ciprofloxacin non-inferiority RCT
27313268 Ceftazidime-avibactam vs doripenem for complicated UTI/APN Phase 3 RCT
42133003 MV140 vaccine, methenamine non-inferiority Systematic review
42225392 Overview of 27 SRs on non-antibiotic prevention Overview of SRs
35928985 / 37693511 RIVUR: 50% recurrence reduction; high-benefit subgroups RCT + re-analysis
27748543 Delay >72 h → scarring; DMSA outcomes Pediatric cohort
39423110 / 33091975 / 40742430 uNGAL diagnostic accuracy; predicts scarring Meta-analyses/cohort
41274602 / 39349024 Pregnancy ASB screen-and-treat Reviews
40022942 UTI/hospital admission accelerates CKD progression Multicenter observational

Consistency/conflict. Findings are broadly consistent. One tension: procalcitonin's diagnostic value for parenchymal involvement varies by cut-off and study (PMID: 16894326 reported limited specificity), and a single-country pregnancy comparison found no difference in pyelonephritis rates between screening vs non-screening centers (PMID: 37515907), tempering the universality of screen-and-treat and supporting emerging selective screening.

Limitations and Knowledge Gaps

  1. No monogenic basis / modest host-genetics evidence. Susceptibility variants (IRF3, IL-8 rs4073, CXCR1) derive from candidate-gene and small cohort studies; no large GWAS for APN susceptibility is established, and effect sizes/penetrance are not quantified for clinical use.
  2. Mechanistic reliance on mouse models. Key adhesin (FimH–DSG2), IRF3, and scarring mechanisms are demonstrated primarily in mice; interspecies chemokine differences (no direct murine IL-8 ortholog) limit translation. Human FimH-mannoside efficacy is not yet clinically proven.
  3. Biomarker thresholds unstandardized. uNGAL and PCT show promising accuracy but variable cut-offs; neither replaces DMSA. Prospective validation and standardized assays are needed.
  4. Prevention evidence heterogeneity. ASB screening benefit rests partly on older/low-quality evidence; MV140 and methenamine are promising but need broader confirmation; RIVUR benefit is concentrated in specific subgroups with attendant resistance costs.
  5. Resistance evolution. Community ESBL/fluoroquinolone-resistant E. coli (ST131-H30Rx) is rising, and much of the resistance/epidemiology data is regional (US, Danish, European), limiting global generalizability.
  6. Scarring→CKD causality. The link between APN and CKD progression is largely observational and confounded by baseline renal function.

Proposed Follow-up Experiments / Actions

  1. Host-genetics validation: Large multi-ancestry GWAS/targeted sequencing of APN-vs-ASB cohorts to confirm and quantify IRF3, CXCL8 rs4073, CXCR1, and TLR4 effects; test as a clinical risk-stratification panel.
  2. Anti-adhesion translation: Advance FimH mannoside inhibitors (FIM1033-class) into human trials for prevention/treatment of recurrent pyelonephritis, and evaluate DSG2-targeting strategies.
  3. Biomarker standardization: Prospective, multicenter study to establish uNGAL/PCT cut-offs for APN diagnosis and scarring prediction, benchmarked against DMSA, to reduce unnecessary imaging.
  4. Precision prevention trials: Head-to-head and combination RCTs of MV140, methenamine, and vaginal estrogen vs antibiotic prophylaxis, with resistance and adherence endpoints; define risk-factor-based selective ASB screening in pregnancy.
  5. Stewardship-driven treatment: Broaden evidence for short-course and carbapenem-sparing regimens (ceftazidime-avibactam and newer β-lactam/β-lactamase inhibitors) in ESBL APN; embed rapid resistance diagnostics to reduce inactive empirical therapy (currently 45–76% in resistant cases).
  6. Scarring/CKD mechanism: Test whether modulating the neutrophil injury arm (ROS, NETs, S100A8/A9) or androgen–activin-A macrophage axis prevents post-pyelonephritic fibrosis without impairing clearance; longitudinal cohorts to establish APN→CKD causality.

Report compiled from 13 confirmed findings across 69 reviewed papers over 5 iterations. Evidence spans human clinical cohorts/RCTs, population registries, systematic reviews/meta-analyses, mouse models, and in-vitro mechanistic studies, with source types indicated throughout.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

Outcome Count
References checked 45
Resolved 45
Unresolved (possible confabulation) 0
Unverifiable 0
Quoted claims checked 5
Quoted claims found in source 4
Quoted claims not found in source 1
References weighed for topical relevance 45
On topic 17
Off topic 0

Quotes not found in the cited source

Searched the abstract, any retrieved full text, and the title. A quote drawn from a part of the paper that was not retrieved will appear here too, so check before treating one as invented:

Every one of these was searched against an abstract alone, with no full text retrieved - marked abstract only below. Where full text can be fetched, re-running with it will settle them; where the source publishes only a summary to PubMed, as GeneReviews chapters do, it will not, and the quote has to be checked by hand against the chapter itself.

  • PMID:38020186 (abstract only): "Among infants, the rate rose from 7.4 … to 64.8 … in girls and from 17.1 … to 52.5 … in boys"
  • closest text in source: "Among infants, the rate rose from 7.4 (95% CI: 7.4-7.4) to 64.8 (95% CI: 64.7-64.9) in girls and from 17.1 (95% CI: 17.1-17.2) to 52.5 (95% CI: 52.4-52.6) in boys"

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 32
Resolved 32
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 0
Terms whose name was checked 17
Terms named correctly 10
Terms named as a different term 3
Terms whose name is worth a second look 4

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • HP:0001945 (1 mention) - the report calls it "Symptom/sign"; HP calls it Fever
  • HP:0032453 (1 mention) - the report calls it "pyuria"; HP calls it Abnormal lip pigmentation
  • HP:0000790 (1 mention) - the report calls it "Lab/sign"; HP calls it Hematuria

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • HP:0001974 (1 mention) - the report calls it "leukocytosis"; HP calls it Increased total leukocyte count, and lists "Leukocytosis" among its other names
  • UBERON:0002113 (1 mention) - the report calls it "Primary organ: Kidney"; UBERON calls it kidney**, and lists "reniculate kidney" among its other names
  • UBERON:0001225 (1 mention) - the report calls it "renal parenchyma/cortex"; UBERON calls it cortex of kidney, and lists "renal cortex" among its other names
  • GO:0016324 (1 mention) - the report calls it "apical plasma membrane", "Subcellular: Bacterial engagement at the apical plasma membrane"; GO calls it apical plasma membrane

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • GO:0016324 - called "apical plasma membrane", "Subcellular: Bacterial engagement at the apical plasma membrane"