The influence of warm ischemia elimination on kidney injury during transplantation – clinical and molecular study

Abstract

Kidney surface cooling was used during implantation to assess the effect of warm ischemia elimination on allograft function, histological changes and immune-related gene expression. 23 recipients were randomly assigned to a group operated on with kidney surface cooling during implantation (ice bag technique, IBT group), and the other 23 recipients receiving the contralateral kidney from the same donor were operated on with a standard technique. Three consecutive kidney core biopsies were obtained during the transplantation procedure: after organ recovery, after cold ischemia and after reperfusion. Gene expression levels were determined using low-density arrays (Format 32, TaqMan). The IBT group showed a significantly lower rate of detrimental events (delayed graft function and/or acute rejection, p = 0.015) as well as higher glomerular filtration rate on day 14 (p = 0.026). A greater decrease of MMP9 and LCN2 gene expression was seen in the IBT group during total ischemia (p = 0.003 and p = 0.018). Elimination of second warm ischemia reduced the number of detrimental events after kidney transplantation, and thus had influence on the short-term but not long-term allograft function. Surface cooling of the kidney during vascular anastomosis may reduce some detrimental effects of immune activation resulting from both brain death and ischemia-reperfusion injury.

Haemoadsorption reduces the inflammatory response and improves blood flow during ex vivo renal perfusion in an experimental model

“…Inflammatory mediators play an important role in exacerbating the severity of renal ischaemia reperfusion injury (IRI) [ 7 ]. IRI is a complicated multifactorial process causing damage to the vascular endothelial cells and tubular epithelium due to the production of reactive oxygen species (ROS), upregulation of pro-inflammatory cytokines, recruitment of neutrophils, and complement and platelet activation [ 8 – 10 ]. In transplantation, periods of warm and cold ischaemia exacerbate IRI causing graft dysfunction and reducing graft survival [ 11 , 12 ].…”

Kidney temperature during living donor kidney transplantation is associated with short‐term measured glomerular filtration rate – a prospective study

“…Following the hypothesis of a clinical impact, efforts to keep the kidney temperature low during transplantation could be of relevance. Previous attempts to eliminate WIT2, resulted in lower rates of detrimental events (delayed graft function and/or acute rejection, P = 0.015) in 23 pairs of kidney transplant recipients, randomly assigned for kidney surface cooling during implantation , whereas a study on 134 kidney transplant recipients, randomly assigned for ‘Ice Bag Technique’ kidney cooling, did not find significant differences with regard to occurrence and duration of DGF . The introduction of robotic kidney transplantation provides transplant surgeons with advanced techniques for regional hypothermia.…”

“…Several preventive strategies to reduce the ischaemic damage have been proposed, varying from adjustments of anastomotic techniques to remote ischaemic preconditioning . With the knowledge that a quick rise in kidney graft temperature occurs during the vascular anastomosis, reduction in second warm ischaemia time (WIT2) is one of the strategies to reduce ischaemic damage . These strategies imply that a rushed vascular anastomosis, with rapid kidney rewarming, could have more detrimental effects on graft outcome than a longer vascular anastomosis, in which the kidney graft rewarms slower or is kept at a set low temperature .…”

“…Up to now, the effect of the duration of WIT2 and kidney temperature in this period has not been compared, making the effect of rapid kidney rewarming on short‐term living donor transplant function still uncertain . To establish the association between temperature at an early stage during the vascular anastomosis and short‐term kidney transplant function, a prospective clinical study on living donor kidney transplant temperature was initiated.…”

Review 1: Lung transplant—from donor selection to graft preparation

“…1). This may contribute to acute rejection, primary graft failure, delayed graft failure, as well as other ischaemic complications [105][106][107][108][109], such as biliary strictures [110]. As such, criteria for selecting viable DCD donors must be strict and adhered to, whilst limiting uncontrolled DCD donors and elderly DCD donors with co-morbidities such as hypertension, peripheral vascular disease and diabetes, as well as limiting warm ischaemic time with adjunctive therapies such as ECMO.…”