Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background

Abstract

ground. We suggest that initial injury prevention should receive Ischemia-reperfusion injury in renal transplantation is indethe highest priority. pendent of the immunologic background.Background. Adhesion molecule expression is important to early transplant failure. However, whether or not adhesion molecule-facilitated inflammation is antigen-dependent is un-Ischemia-reperfusion injury is an important problem known. We tested this hypothesis. in organ transplantation. Grafts with prolonged cold or Methods. Rat renal grafts were four-hours cold-preserved in University of Wisconsin (UW) solution, transplanted to synwarm ischemia times are more susceptible to short-term geneic or allogeneic recipients, and harvested after 2, 6, 12, 24, or long-term deterioration [1,2]. Clarifying the pathoand 48 hours and after 1 week. The first allogeneic group physiology of ischemia-reperfusion injury and develreceive no immunosuppression; two additional groups received oping new preventive strategies are highly important. either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A In native organs, numerous experimental and clinical (CsA). Renal function and morphology were determined; frozen sections were immunostained for P-selectin, L-selectin, studies showed that ischemia reperfusion constitutes an intercellular adhesion molecule-1 (ICAM-1), vascular cell adacute inflammatory process involving cell surface adhehesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule expression. These molecules are crucial sion molecule-1 (PECAM-1), leukocyte function associated for the recruitment and infiltration of effector cells into molecule-1 (LFA-1), very late antigen-4 (VLA-4), as well as for neutrophils and monocytes. the postischemic tissue [3]. In transplanted organs, the Results. Selectins increased rapidly at 2 hours and quickly same mechanisms are also involved in subsequently inidecreased by 12 hours. While P-selectin was expressed on vastiating the rejection process [4]. However, to what extent culature, L-selectin was found on inflammatory cells. Neutroalloantigen-dependent mechanisms contribute to the iniphil influx and that of LFA-1-positive cells occurred early, tial injury and whether or not ischemia-reperfusion is an peaked between 12 and 24 hours, and paralleled the maximal impairment in renal function. ICAM-1 and PECAM-1 showed alloantigen-independent phenomenon are unclear. Alsimilar kinetics and a diffuse distribution. VCAM-1 increased though numerous studies have addressed antiadhesion more slowly after 12 hours, peaked at 24 hours, and was localstrategies in rodent models of ischemia reperfusion [5,6], ized predominantly on the endothelium of elastic vessels. Bethe sequence in which different cell subsets arrive and tween 24 hours and 1 week, all grafts progressively developed their time course in relationship to ischemia reperfusion dense VLA-4-positive monocytic infiltrates adjacent to vessels expressing VCAM-1. Functional, morphological, and immunohave not been extensively studied. We tested the h...

Histological Alterations Found in the Ureter During Organ Preservation and Early Phases of Renal Transplantation

“…8 The lack of relation to the number of HLA compatibilities suggests that this cellular influx does not seem to involve an immunological phenomena. This is in accordance with the study of Dragun et al who, in the rat, performed renal biopsies after syngeneic and allogeneic renal transplantation with and without immunosuppression and found no significant differences, 11 and with the findings Hoffman et al 7 and Koo et al 8 in postreperfusion renal biopsies in the clinical setting. Cellular vacuolization is known to occur in renal tubular cells after reperfusion 7 and Katz et al 12 considered urothelial vacuolization to be a sign of rejection of the ureter.…”

Hypoxia: The Force that Drives Chronic Kidney Disease

“…53 In addition, many forms of surgery where blood flow is inadvertently or deliberately reduced carry an inherent risk for the development of AKI. [62][63][64][65][66][67][68][69][70] Inadvertent surgical reductions in blood flow can be caused by voluminous blood loss such as often occurs during major hepatic resections. 64,69 Deliberate blood flow reduction is caused by the clamping of major blood vessels such as occurs during organ transplantation, cardiopulmonary bypass, and thoracoabdominal aneurysm surgery.…”

“…64,69 Deliberate blood flow reduction is caused by the clamping of major blood vessels such as occurs during organ transplantation, cardiopulmonary bypass, and thoracoabdominal aneurysm surgery. 63,65,66,70 Meta-analysis, epidemiological, and clinical follow-up studies have all shown a strong correlation between AKI episodes and subsequent development of CKD. [232][233][234][235][236] This correlation is observed even in patients who regained normal renal function after AKI.…”

Postischemic Acute Renal Failure Is Reduced by Short-Term Statin Treatment in a Rat Model

“…Renal ischemia-reperfusion injury is a major cause of acute renal failure (ARF) after major surgery or renal transplantation (1,2). Several experimental ameliorative strategies have been tested (3).…”