title: Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model.
abstract: OBJECTIVE
  To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury.
  
  
  METHODS
  Prospective, randomized, placebo-controlled experimental study.
  
  
  METHODS
  University research unit.
  
  
  METHODS
  Twenty-four healthy pigs.
  
  
  METHODS
  The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline.
  
  
  RESULTS
  The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N-acetyl-beta-D-glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups.
  
  
  CONCLUSIONS
  The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response-induced acute kidney injury.
authors.affiliation: Section of Anesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. mlipcsey@eml.cc
authors.forename: Miklós
authors.initials: M
authors.lastname: Lipcsey
authors.forename: Markus
authors.initials: M
authors.lastname: Carlsson
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Lars
authors.initials: L
authors.lastname: Algotsson
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.forename: Agneta
authors.initials: A
authors.lastname: Lukinius
authors.forename: Jan
authors.initials: J
authors.lastname: Sjölin
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D004195:Disease Models, Animal; D004573:Electrolytes / Q000097:blood; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D046529:Microscopy, Electron, Transmission; D013552:Swine; D018746:Systemic Inflammatory Response Syndrome / Q000473:pathology / Q000503:physiopathology*; D014031:Tobramycin / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D055316:Cystatin C; D004573:Electrolytes; D004731:Endotoxins; D003404:Creatinine; D000118:Acetylglucosaminidase; D014031:Tobramycin