Cold ischemia in the absence of alloreactivity induces chronic transplant nephropathy through a process mediated by the platelet-activating factor.
BACKGROUND
Ischemia-reperfusion injury is considered a risk factor for the development of chronic transplant nephropathy (CTN) although the mechanisms that mediate its effects have not been completely established. We have previously shown that treatment with a platelet-activating factor (PAF) receptor antagonist (UR12670) protected kidneys from the progression to chronic nephropathy induced by warm ischemia. Here we examine the contribution of cold ischemia to the development of late functional and structural kidney changes in rats subjected to syngeneic renal transplantation and the role of PAF in this chronic nephropathy.


METHODS
Lewis rats were used as kidney donors and recipients, which were transplanted either immediately or after a cold ischemia period of 5 hr. Contralateral nephrectomy was performed on the seventh day after transplantation. Cyclosporine was administered for 15 days after transplantation. Groups were as follows: Sy, immediate transplantation; SyI, transplantation after 5 hr of cold ischemia; SyIUr, transplantation after 5 hr of cold ischemia plus UR12670 from the transplantation day to the end of the study, at 24 weeks. Serum creatinine, creatinine clearance, and proteinuria were determined every 4 weeks. Urinary
Herrero-Fresneda
I
I
Department of Medicine, University of Barcelona, Spain
Torras
J
J
Lloberas
N
N
Riera
M
M
Cruzado
J M
JM
Condom
E
E
Merlos
M
M
Alsina
J
J
Grinyó
J M
JM
D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology* / Q000652:urine; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000139:chemically induced / Q000150:complications* / Q000209:etiology; D013997:Time Factors
D010972:Platelet Activating Factor; D003404:Creatinine