Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice.
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.
Dear
James W
JW
Renal Diagnostics and Therapeutics Unit, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kobayashi
Hisataka
H
Jo
Sang-Kyung
SK
Holly
Mikaela K
MK
Hu
Xuzhen
X
Yuen
Peter S T
PS
Brechbiel
Martin W
MW
Star
Robert A
RA
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*
D015415:Biomarkers; D003287:Contrast Media; D005682:Gadolinium; D003404:Creatinine