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 journalArticle

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

Fingerprint

Dendrimers
Acute Kidney Injury
Sepsis
Biomarkers
Magnetic Resonance Imaging
Punctures
Kidney
Ligation
Cisplatin
Creatinine
Wounds and Injuries
Azotemia
Gadolinium
Serum
Reperfusion
Early Diagnosis
Ischemia
Anti-Bacterial Agents
Mortality
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice. / Dear, James W.; Kobayashi, Hisataka; Jo, Sang Kyung; Holly, Mikaela K.; Hu, Xuzhen; Yuen, Peter S.T.; Brechbiel, Martin W.; Star, Robert A.

In: Kidney International, Vol. 67, No. 6, 01.01.2005, p. 2159-2167.

Research output: Contribution to journalArticle

Dear, James W. ; Kobayashi, Hisataka ; Jo, Sang Kyung ; Holly, Mikaela K. ; Hu, Xuzhen ; Yuen, Peter S.T. ; Brechbiel, Martin W. ; Star, Robert A. / Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice. In: Kidney International. 2005 ; Vol. 67, No. 6. pp. 2159-2167.
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