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.

CONCLUSION:

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

• Authors: James W Dear, Hisataka Kobayashi, Sang-Kyung Jo, Mikaela K Holly, Xuzhen Hu, Peter S T Yuen, Martin W Brechbiel, Robert A Star
• Journal: Kidney international (Kidney Int) Vol. 67 Issue 6 Pg. 2159-67 (Jun 2005) ISSN: 0085-2538 [Print] United States
• PMID: 15882259 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Contrast Media
• Gadolinium
• Creatinine

Topics

• Acute Kidney Injury (diagnosis, drug therapy, mortality, pathology)
• Animals
• Biomarkers
• Contrast Media
• Creatinine (blood)
• Female
• Gadolinium
• Image Enhancement
• Magnetic Resonance Imaging (methods)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Prognosis
• Sepsis (complications)