Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice

James W Dear, Hisataka Kobayashi, Sang-Kyung Jo, Mikaela K Holly, Xuzhen Hu, Peter S T Yuen, Martin W Brechbiel, Robert A Star

Research output: Contribution to journalArticlepeer-review

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.

CONCLUSION: Dendrimer-enhanced MRI is a novel biomarker that provides information for the early diagnosis, drug responsiveness, and prognosis of sepsis-induced ARF.

Original languageEnglish
Pages (from-to)2159-67
Number of pages9
JournalKidney International
Volume67
Issue number6
DOIs
Publication statusPublished - Jun 2005

Keywords

  • Acute Kidney Injury
  • Animals
  • Biomarkers
  • Contrast Media
  • Creatinine
  • Female
  • Gadolinium
  • Image Enhancement
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Prognosis
  • Sepsis

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