Renal Normothermic Machine Perfusion:The Road Toward Clinical Implementation of a Promising Pretransplant Organ Assessment Tool

The increased utilization of high-risk renal grafts for transplantation requires optimization of pretransplant organ assessment strategies. Current decision-making methods to accept an organ for transplantation lack overall predictive power and always contain an element of subjectivity. Normothermic machine perfusion (NMP) creates near-physiological conditions, which might facilitate a more objective assessment of organ quality prior to transplantation. NMP is rapidly gaining popularity, with various transplant centers developing their own NMP protocols and renal viability criteria. However, to date, no validated sets of on-pump viability markers exist nor are there unified NMP protocols. This review provides a critical overview of the fundamentals of current renal NMP protocols and proposes a framework to approach further development of ex vivo organ evaluation. We also comment on the potential logistical implications of routine clinical use of NMP, which is a more complex procedure compared to static cold storage or even hypothermic machine perfusion. Supplemental Visual Abstract; http://links.lww.com/TP/C232

Kidney Perfusion as an Organ Quality Assessment Tool—Are We Counting Our Chickens Before They Have Hatched?

The final decision to accept an organ for transplantation remains a subjective one. With “poor organ quality” commonly cited as a major reason for kidney discard, accurate, objective, and reliable quality assessment is essential. In an era of increasingly higher-risk deceased donor kidneys, the catch is to accept those where the risk–benefit scale will tip in the right direction. Currently available assessment tools, such as risk-scores predicting outcome and zero-time biopsy, perform unsatisfactory, and assessment options during static cold storage are limited. Kidney perfusion technologies are finding their way into clinical practice, and they bring a new opportunity to assess kidney graft viability and quality, both in hypothermic and normothermic conditions. We give an overview of the current understanding of kidney viability assessment during ex situ kidney perfusion. A pragmatic framework to approach viability assessment is proposed as an interplay of three different compartments: the nephron, the vascular compartment, and the immune compartment. Although many interesting ways to assess kidney injury and function during perfusion have been proposed, none have reached the stage where they can reliably predict posttransplant outcome. Larger well-designed studies and validation cohorts are needed to provide better guidance

Cytokine release during normothermic kidney perfusion – a scoping review.

This scoping review investigates the currently knowledge on the evolution of perfusate cytokines during normothermic perfusion of pig or human kidneys

Kidney Perfusion as an Organ Quality Assessment Tool-Are We Counting Our Chickens Before They Have Hatched?

The final decision to accept an organ for transplantation remains a subjective one. With "poor organ quality" commonly cited as a major reason for kidney discard, accurate, objective, and reliable quality assessment is essential. In an era of increasingly higher-risk deceased donor kidneys, the catch is to accept those where the risk-benefit scale will tip in the right direction. Currently available assessment tools, such as risk-scores predicting outcome and zero-time biopsy, perform unsatisfactory, and assessment options during static cold storage are limited. Kidney perfusion technologies are finding their way into clinical practice, and they bring a new opportunity to assess kidney graft viability and quality, both in hypothermic and normothermic conditions. We give an overview of the current understanding of kidney viability assessment during ex situ kidney perfusion. A pragmatic framework to approach viability assessment is proposed as an interplay of three different compartments: the nephron, the vascular compartment, and the immune compartment. Although many interesting ways to assess kidney injury and function during perfusion have been proposed, none have reached the stage where they can reliably predict posttransplant outcome. Larger well-designed studies and validation cohorts are needed to provide better guidance.status: publishe

IGL-1 preservation solution in kidney and pancreas transplantation: A systematic review.

We aimed to systematically review published data on the effectiveness of Institut Georges Lopez-1 (IGL-1) as a preservation solution for kidney and pancreas grafts. A systematic literature search of PubMed, Embase, Web of Science, and the Cochrane Library databases was performed. Human studies evaluating the effects of IGL-1 preservation solution in kidney and/or pancreas transplantation were included. Outcome data on kidney and pancreas graft function were extracted. Of 1513 unique articles identified via the search strategy, four articles could be included in the systematic review. Of these, two retrospective studies reported on the outcome of IGL-1 compared to University of Wisconsin (UW) solution in kidney transplantation. These show kidneys preserved in IGL-1 had improved early function (2 weeks post-transplant) compared to UW. Follow-up was limited to 1 year and showed similar graft and patient survival rates when reported. Two case series described acceptable early outcomes (up to 1 month) of simultaneous kidney pancreas transplantation after storage in IGL-1. As only four clinical papers were identified, we widened our search to include four eligible large animal studies. Three compared IGL-1 with UW in pig kidney transplant models with inconclusive or mildly positive results. One pig pancreas transplant study suggested better early outcome with IGL-1 compared to UW. Too few published data are available to allow any firm conclusions to be drawn on the effectiveness of IGL-1 as a preservation solution of kidney and pancreas grafts. The limited available data show satisfactory early outcomes though no medium to long-term outcomes have been described. Further well-designed clinical studies are needed

IGL-1 preservation solution in kidney and pancreas transplantation: A systematic review

We aimed to systematically review published data on the effectiveness of Institut Georges Lopez-1 (IGL-1) as a preservation solution for kidney and pancreas grafts. A systematic literature search of PubMed, Embase, Web of Science, and the Cochrane Library databases was performed. Human studies evaluating the effects of IGL-1 preservation solution in kidney and/or pancreas transplantation were included. Outcome data on kidney and pancreas graft function were extracted. Of 1513 unique articles identified via the search strategy, four articles could be included in the systematic review. Of these, two retrospective studies reported on the outcome of IGL-1 compared to University of Wisconsin (UW) solution in kidney transplantation. These show kidneys preserved in IGL-1 had improved early function (2 weeks post-transplant) compared to UW. Follow-up was limited to 1 year and showed similar graft and patient survival rates when reported. Two case series described acceptable early outcomes (up to 1 month) of simultaneous kidney pancreas transplantation after storage in IGL-1. As only four clinical papers were identified, we widened our search to include four eligible large animal studies. Three compared IGL-1 with UW in pig kidney transplant models with inconclusive or mildly positive results. One pig pancreas transplant study suggested better early outcome with IGL-1 compared to UW. Too few published data are available to allow any firm conclusions to be drawn on the effectiveness of IGL-1 as a preservation solution of kidney and pancreas grafts. The limited available data show satisfactory early outcomes though no medium to long-term outcomes have been described. Further well-designed clinical studies are needed.status: publishe

Differential Cytokine Levels during Normothermic Kidney Perfusion with Whole Blood- or Red Blood Cell-Based Perfusates—Results of a Scoping Review and Experimental Study

The ideal composition of the perfusate for normothermic kidney perfusion is unknown, though the perfusate commonly used to perfuse human kidneys contains leukocyte-depleted packed red blood cells (RBC), as this is believed to prevent excessive inflammation. We performed a systematic search identifying 19 articles reporting on cytokine levels during normothermic pig or human kidney perfusion. Cytokine levels varied widely across the reported studies. No direct comparisons of perfusate cytokines during perfusion with RBC or whole blood were performed, and no data on how these levels are influenced by ischemia are available. Therefore, we compared perfusate IL-6, IL-1β, TNF-α, TGF-β, IL-10, IL-8, and CCL2 levels during 4 h normothermic pig kidney perfusion with a whole blood- or RBC-based perfusate. Kidneys were exposed to either 1 h of warm or 22 h of cold ischemia. We found no evidence of different perfusate cytokine or gene expression levels in whole blood or RBC perfusions. There was no clear evidence to suggest that cytokine concentrations differ between ischemically injured kidneys and controls. In conclusion, pro-inflammatory and anti-inflammatory cytokines and chemokines are detectable in the perfusate and urine of kidneys undergoing normothermic perfusion. It is unclear how cytokine levels change in different ischemic conditions and whether the use of a leukocyte filter plays a role

Tracing metabolites throughout the metabolic network of the isolated perfused kidney: protocol of a scoping review

Protocol of scoping review regarding the use of tracers during isolated kidney perfusion