Detection of inflammation following renal ischemia by magnetic resonance imaging.
BACKGROUND
Determining the disease culprits in human acute renal failure (ARF) has been difficult because of the paucity of renal biopsies and the lack of noninvasive methods to determine the location or cause of renal injury. Recently, ultrasmall superparamagnetic iron oxide (USPIO) particles have been used to detect inflammation in animal models. Therefore, we tested if USPIO enhanced magnetic resonance imaging (MRI) could detect inflammation in ischemic ARF in rats.


METHODS
Rats were subjected to 40 or 60 minutes of bilateral ischemia or injected with mercuric chloride. MR images were obtained before and 24 hours after USPIO injection, and the signal intensity decrease in the outer medulla was measured. Cells containing iron particles were identified by iron staining and transmission electron microscopy (TEM). Leukocytes were identified by ED-1 and chloracetate esterase staining.


RESULTS
Injection of USPIO particles caused a black band to appear in the outer medulla at 48, 72, and 120 hours after ischemia. This band was not detected in normal animals, 24 hours after ischemia, or 48 hours after mercuric chloride injection. The signal intensity change in the outer medulla correlated with serum creatinine and the number of iron particle containing cells. Most infiltrating cells were macrophages, and iron particles were present inside lysosomes of macrophages. USPIO injection did not alter renal function in normal or ischemic animals.


CONCLUSIONS
USPIO-enhanced MRI could detect inflammation noninvasively from 48 hours after 40 or 60 minutes of renal ischemia in rats. This method might be useful to understand the pathogenesis of human ARF and to evaluate the effectiveness of anti-inflammatory agents.
Jo
Sang-Kyung
SK
Renal Diagnostics and Therapeutics Unit, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hu
Xuzhen
X
Kobayashi
Hisataka
H
Lizak
Martin
M
Miyaji
Takehiko
T
Koretsky
Alan
A
Star
Robert A
RA
D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007501:Iron / Q000494:pharmacology; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D009393:Nephritis / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D013997:Time Factors
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide