A new alloantigen-independent control for chronic allograft nephropathy rat models.
BACKGROUND
Isografts are used as controls in many transplant experiments. Our laboratory and others have noticed histological changes in control isograft groups of rats similar to allograft groups, suggesting alloantigen-independent factors contributing to chronic allograft nephropathy. However, the isograft model as a nonalloantigen control is flawed because of the potential of unrecognized minor antigen differences between rats. We designed a study using autografts to isolate alloantigen-independent factors in the rat renal transplant allograft model.


METHODS
Male Lewis rats weighing 150-250 g underwent a procedure designed to mimic the injury of renal transplant, in which the left kidney was perfused with cold University of Wisconsin solution and subjected to similar cold and warm ischemic times as Lewis isograft rats undergoing renal transplanation.


RESULTS
Six autograft rats were compared to five isograft and three single nephrectomy rats. Autograft rats showed normal kidney function according to serum BUN, Cr, and urinary protein. At 360 days, four of six autografts displayed normal renal parenchymal histology, whereas the remaining two autografts displayed histological changes scored as Banff acute rejection 1a and 1b. At sacrifice time, four of five isografts showed histological changes scored as Banff chronic rejection 1 and the single nephrectomy group showed normal histology in the remaining native kidney.


CONCLUSIONS
Our data demonstrate that the chronic nephropathy observed in the isograft cannot be completely freed from suspicion of immunological origin. We propose that the autograft model for rat renal transplant research is a better nonimmunologic control than the isograft model for chronic allograft nephropathy.
Chang
Seong-Hwan
SH
Department of Surgery, Division of Transplant Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0254, USA.
Park
Hwon-Kyum
HK
Eryilmaz
Ramazan
R
Bu
Dawen
D
Stone
James J
JJ
Massey
Davis
D
Riley
Roger S
RS
Fisher
Robert A
RA
D000818:Animals; D006084:Graft Rejection / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D007668:Kidney / Q000098:blood supply; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D023421:Models, Animal; D009392:Nephrectomy / Q000009:adverse effects; D019188:Organ Preservation Solutions / Q000009:adverse effects; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications
D007519:Isoantigens; D019188:Organ Preservation Solutions