Contribution of prolonged ischemia and donor age to chronic renal allograft dysfunction.
As a consequence of an advancing discrepancy between supply of suitable grafts and demand from potential recipients, less than optimal organs are increasingly being used. Although clinical studies demonstrate the involvement of various risk factors, including donor age and duration of ischemia on long-term graft outcome, their individual contribution and correlation has not been followed experimentally. After cold ischemic times of 5, 60, and 120 min, kidney allografts of 3-, 12-, and 18-mo-old Fischer 344 donors were transplanted into 3-mo-old Lewis rats. Age-related changes were examined in matched native uninephrectomized controls. Proteinuria and creatinine clearance were determined, and histologic and immunohistologic studies were assessed and quantified at the end of the observation period (20 wk). All grafts functioned satisfactorily with the exception of one graft each from 12- and 18-mo-old donors with prolonged ischemia (120 min). Functional deterioration and structural changes progressed in parallel to increasing donor age and prolonged ischemia. The impact of expanded ischemia was particularly detrimental in grafts from older donor animals. Donor age and duration of ischemia act in a synergistic manner in our model. Brief ischemic times seem of particular relevance when grafts from older donors are being used.
Tullius
Stefan Günther
SG
Department of Surgery, Charité-Virchow Clinic, Berlin, Germany.
Reutzel-Selke
Anja
A
Department of Surgery, Charité-Virchow Clinic, Berlin, Germany.
Egermann
Frank
F
Department of Surgery, Charité-Virchow Clinic, Berlin, Germany.
Nieminen-Kelhä
Melina
M
Department of Surgery, Charité-Virchow Clinic, Berlin, Germany.
Jonas
Sven
S
Department of Surgery, Charité-Virchow Clinic, Berlin, Germany.
Bechstein
Wolf Otto
WO
Department of Surgery, Charité-Virchow Clinic, Berlin, Germany.
Volk
Hans-Dieter
HD
Department of Medical Immunology, Charité-Campus Mitte, Berlin, Germany.
Neuhaus
Peter
P
Department of Surgery, Charité-Virchow Clinic, Berlin, Germany.
D000375:Aging / Q000502:physiology*; D000818:Animals; D000941:Antigens / Q000032:analysis; D003401:Creatine / Q000378:metabolism; D015925:Cryopreservation; D006085:Graft Survival; D007511:Ischemia / Q000601:surgery*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016030:Kidney Transplantation; D008297:Male; D009392:Nephrectomy; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012079:Renal Circulation; D013997:Time Factors; D014019:Tissue Donors
D000941:Antigens; D003401:Creatine