title: Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice.
abstract: BACKGROUND
  Acute renal failure (ARF) induced by sepsis has a high mortality. In an aged mouse model of sepsis-induced ARF we have previously shown that renal injury occurs before serum creatinine is elevated. Development of a noninvasive biomarker that could diagnose renal dysfunction early in sepsis and monitor the response to therapy would be very valuable.
  
  
  METHODS
  We performed magnetic resonance imaging (MRI) with gadolinium-based G4 dendrimer intravenous contrast in a fluid- and antibiotic-treated cecal ligation and puncture (CLP) sepsis model in aged mice. Imaging was also performed in a mouse volume depletion model and in models of ARF induced by ischemia/reperfusion (I/R) and cisplatin.
  
  
  RESULTS
  Twenty hours post-CLP, aged mice had a distinct pattern of renal injury using dendrimer-enhanced MRI. This pattern was different from renal injury induced by either cisplatin or I/R. Prerenal azotemia induced by volume depletion was distinguished from sepsis by dendrimer-enhanced MRI. Dendrimer-enhanced MRI detected renal dysfunction 6 hours post-CLP, a time when serum creatinine was still normal. Ethyl pyruvate reversed the renal dysfunction detected by dendrimer-enhanced MRI at 20 hours, but not at 6 hours post-CLP. The appearance of renal dysfunction on dendrimer-enhanced MRI at 6 hours post-CLP predicted the length of survival.
  
  
  CONCLUSIONS
  Dendrimer-enhanced MRI is a novel biomarker that provides information for the early diagnosis, drug responsiveness, and prognosis of sepsis-induced ARF.
authors.affiliation: Renal Diagnostics and Therapeutics Unit, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Dear
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
authors.forename: Mikaela K
authors.initials: MK
authors.lastname: Holly
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Hu
authors.forename: Peter S T
authors.initials: PS
authors.lastname: Yuen
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D000818:Animals; D015415:Biomarkers; D003287:Contrast Media; D003404:Creatinine / Q000097:blood; D005260:Female; D005682:Gadolinium; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011379:Prognosis; D018805:Sepsis / Q000150:complications*
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D005682:Gadolinium; D003404:Creatinine