Donor pretreatment-mediated and cold storage-dependent proximal tubular necrosis--a unique form of acute renal insufficiency.

After a 5-hour period of donor pretreatment with cyclophosphamide (CY) and methylprednisolone (P) (100 mg/kg each), cold storage of pretreated canine renal allografts may cause early and severe postoperative renal insufficiency. This renal insufficiency is mediated by CY metabolites and depends on the number of hours of cold storage, for severe renal insufficiency is not observed after 6 hours of cold storage but is invariably present after cold storage beyond 18 hours. The renal insufficiency is associated with coagulation necrosis of the proximal tubules, particularly the pars recta. Since the repair of ischemia-medicated proximal tubular lesions requires mitotic activity, results suggest that the proximal tubules of donor pretreated kidneys are subjected to a concentration of CY metabolites sufficient to cause an extent of DNA damage that, in the absence of a sufficient time for nuclear repair, inevitably leads to cell death and renal insufficiency when the tubular cells are driven to mitosis by cold storage-mediated ischemia.