title: Mitomycin-induced hemolytic uremic kidney. An experimental model in the rat.
abstract: Hemolytic uremic syndrome (HUS) reported in some patients treated for cancer with mitomycin is of unknown pathogenesis, and evidence implicating mitomycin is inconclusive. To determine whether mitomycin can induce direct renal damage, left kidneys in Lewis rats were perfused with mitomycin (60-4000 micrograms). Control rats received perfusions of saline only. Renal tissue was examined from 1 hour up to 1 month later. In 29 of 31 rats left renal disease developed: in 9 (mitomycin, 1000-4000 micrograms), severe cortical infarction; in 20 (mitomycin, 60-500 micrograms), lesions indistinguishable from human HUS. Glomerular endothelial damage was the earliest detectable abnormality, followed by platelet accumulation and later capillary wall splitting typical of microangiopathy. Some kidneys had interlobular artery necrosis and thrombosis. Right kidneys were normal. In no rats in the control group (10) did HUS develop. Thus, mitomycin directly produced renal lesions indistinguishable from human HUS, which suggested a mechanism for injury seen in mitomycin-treated patients and provided a new model of HUS.
mesh_terms: D000818:Animals; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008937:Mitomycins / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D008937:Mitomycins