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

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51 Citations (Scopus)

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)2159-2167
Number of pages9
JournalKidney International
Volume67
Issue number6
DOIs
Publication statusPublished - 2005 Jan 1
Externally publishedYes

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Keywords

  • Acute renal failure
  • Dendrimer
  • Ethyl pyruvate
  • Gadolinium
  • MRI
  • Noninvasive
  • Sepsis

ASJC Scopus subject areas

  • Nephrology

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