Different patterns of renal cell killing after warm and cold ischemia.
Kidneys preserved for transplantation surgery sustain injuries caused by cold ischemia during storage. Additionally, kidneys harvested from non-heart-beating donors encounter the stress of warm ischemia. The aim of this study was to determine the specific cell types losing viability after warm and cold ischemia. In warm ischemia studies, the pedicles of left kidneys of Lewis rats were cross-clamped for up to 90 min. In cold ischemia studies, kidneys were flushed with cold University of Wisconsin solution and stored up to 48h at 0-1 degrees C. After warm or cold ischemia, kidneys were perfused via the renal arteries with Krebs-Henseleit bicarbonate (KHB) buffer at 37 degrees C, followed by trypan blue to label the nuclei of nonviable cells. Warm ischemia for 90 min caused renal failure and led to injury of proximal tubular cells, e.g., loss of brush borders, cast formation and trypan blue labeling. Cold ischemia for 48 h also caused renal failure but, unlike warm ischemia, caused trypan blue labeling of glomerular podocytes and peritubular endothelial cells. In warm ischemia-induced injury, electron microscopy showed shedding of microvilli and marked swelling of proximal tubular cells, microvilli and mitochondria. In cold ischemia-induced injury, podocytes were blebbed and swollen, and their pedicels were detached from the basement membrane, but disruption in proximal tubules was milder. In conclusion, warm ischemia triggers injury primarily to proximal tubular cells, whereas cold ischemia damages glomerular podocytes and peritubular endothelial cells in addition to proximal tubules.
Yin
Ming
M
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill 27599-7090, USA.
Currin
Robert T
RT
Peng
Xing-Xi
XX
Mekeel
Harold E
HE
Schoonhoven
Robert
R
Lemasters
John J
JJ
D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects*; D004195:Disease Models, Animal; D006358:Hot Temperature / Q000009:adverse effects*; D007511:Ischemia / Q000150:complications* / Q000473:pathology*; D007668:Kidney / Q000098:blood supply / Q000293:injuries* / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D009336:Necrosis; D009399:Nephrons / Q000098:blood supply / Q000293:injuries / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D051437:Renal Insufficiency / Q000209:etiology* / Q000473:pathology*