title: Impact of antibiotic treatment intensity on long-term sepsis-associated kidney injury in a polymicrobial peritoneal contamination and infection model.
abstract: OBJECTIVE
  Long-term kidney affections after sepsis are poorly understood. Animal models for investigating kidney damage in the late phase of disease progression are limited. The aim of this study was to investigate the impact of two antibiotic regimes on persistence of kidney injury after peritonitis.
  
  
  METHODS
  Kidney damage was investigated 65 days after polymicrobial peritoneal contamination and infection (PCI) sepsis induction in C57BL/6 mice. Short-term antibiotic therapy (STA, 4 days) was compared to long-term (LTA, 10 days) treatment using plasma creatinine, plasma and urine neutrophil gelatinase-associated lipocalin (NGAL), urine albumin/creatinine ratio and renal histology.
  
  
  RESULTS
  Sepsis resulted in mortality rates of 68.2% (STA) and 61.0% (LTA). Surviving STA animals showed the most pronounced kidney damage indicated by significantly elevated levels of creatinine and acute tubular damage (ATD), whereas NGAL was significantly increased in LTA survivors only. A creatinine level above 0.3 mg/dl was used to define kidney injury, found in 21.4% of STA animals and 7.8% of LTA animals. While animals with kidney injury demonstrated significantly higher ATD scores and persistent tubular damage, no significant differences were found for plasma or urine NGAL levels or urine albumin/creatinine ratios.
  
  
  CONCLUSIONS
  Prolonged antibiotic treatment reduced the rate of ongoing peritonitis-induced kidney injury in a C57BL/6 mouse model. Plasma or urine NGAL levels were not able to identify animals with or without persistent kidney injury. The kidney injury after the PCI mouse model represents prototypic clinical findings and should be used for further studies investigating disease mechanisms.
authors: Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors: Gordon P
authors: GP
authors: Otto
authors: Benedikt
authors: B
authors: Grünwald
authors: Christian
authors: C
authors: Geis
authors: Susanne
authors: S
authors: Köthe
authors: Jorge
authors: J
authors: Hurtado-Oliveros
authors: Ha-Yeun
authors: HY
authors: Chung
authors: Michael
authors: M
authors: Ekaney
authors: Clemens L
authors: CL
authors: Bockmeyer
authors: Maik
authors: M
authors: Sossdorf
authors: Martin
authors: M
authors: Busch
authors: Ralf A
authors: RA
authors: Claus
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000382:microbiology / Q000473:pathology; D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D015415:Biomarkers / Q000378:metabolism; D060085:Coinfection / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D015513:Oncogene Proteins / Q000378:metabolism; D010529:Peritoneal Cavity / Q000382:microbiology*; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D015415:Biomarkers; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse