Macrophage infiltration detected at MR imaging in rat kidney allografts: early marker of chronic rejection?
OBJECTIVE
To evaluate detection of iron-loaded macrophages at magnetic resonance (MR) imaging as a noninvasive means to monitor early signs of chronic allograft rejection in the life-supporting Fisher-to-Lewis rat kidney transplantation model.


METHODS
Experiments followed the Swiss federal regulations of animal protection. Male Fisher (n = 37) and Lewis (n = 77) rats were used. After removal of a native recipient kidney and transplantation of a donor kidney, the recipient rat's contralateral kidney was removed. Allografts and control syngeneic grafts comprised, respectively, kidneys from Fisher and Lewis donors transplanted into Lewis rats. Recipients were imaged by using a gradient-echo MR sequence 24 hours after intravenous administration of superparamagnetic iron oxide (SPIO) particles. Biochemical analyses of blood and urine, as well as assessments of Banff scores (reference standard for histologic classification of graft rejection), were performed. Statistical tests used were analysis of variance for multiple comparisons with Bonferroni tests, Mann-Whitney tests, and Pearson correlations with Bonferroni corrections.


RESULTS
A SPIO dose-dependent decrease in cortical MR signal intensity occurred in allografts between 8 and 16 weeks after transplantation. A strong significant negative correlation (P = .005 for 0.3 mL/kg SPIO dose, P = .003 for 1.0 mL/kg SPIO dose) was found between MR signal intensity and Banff scores, which deteriorated over the experimental period. Proteinuria occurred at 16 weeks. Blood and urine creatinine levels remained unchanged up to week 28.


CONCLUSIONS
This MR imaging method is more robust than the usually adopted creatinine clearance method for the detection of early signs of allograft chronic rejection in the Fisher-to-Lewis rat kidney transplantation model.
Beckmann
Nicolau
N
Departments of Discovery Technologies and Transplantation Research, Novartis Institutes for BioMedical Research, Lichtstrasse 35, WSJ-386.2.09, CH-4002 Basel, Switzerland. nicolau.beckmann@novartis.com
Cannet
Catherine
C
Zurbruegg
Stefan
S
Haberthür
Reto
R
Li
Jianping
J
Pally
Charles
C
Bruns
Christian
C
D000818:Animals; D002908:Chronic Disease; D006084:Graft Rejection / Q000175:diagnosis*; D016030:Kidney Transplantation; D008264:Macrophages / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors