Glutathione S-Transferase Iso-Enzymes in Perfusate From Pumped Kidneys Are Associated With Delayed Graft Function.

Abstract

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multicenter study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.28) and 1.33 (1.02-1.72), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

Donor Hemodynamics as a Predictor of Outcomes After Kidney Transplantation From Donors After Cardiac Death

“…Further research is warranted to investigate associations between donor hemodynamic profiles and processes contributing to organ injury. Investigation of associations between renal perfusate biomarkers and donor hemodynamics is a logical direction for future research (26)(27)(28)(29). Although our findings indicate that certain parameters may be associated with inferior outcomes, it is unlikely that any one hemodynamic measure will be sufficient to describe relevant physiological changes (eg, donors with the same AUCSBP could have radically different SBP trajectories).…”

A systematic review to identify whether perfusate biomarkers produced during hypothermic machine perfusion can predict graft outcomes in kidney transplantation

“…In this pioneering work, Cho et al established a statistically significant correlation between GST (previously known as ligandin) levels at the end of perfusion and the development of acute tubular necrosis defined as the need of one haemodialysis session in the first three days post-transplantation. GST levels increased throughout perfusion in all the included studies and they were associated with DGF in 7/10 articles three of which were 'good' quality studies with two (Moers et al [7] and Hall et al [9]) demonstrating a significant association after multivariable analysis. However, the strength of the association of GST levels and DGF was less convincing and the different isoforms and assays used meant that direct comparison of values between studies was not possible.…”

Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function

“…HMP continuously flushes the kidney with cold preservation solution (perfusate) to provide nutrients, to carry away toxic metabolites and to reduce lactic acid build‐up ; however, there are conflicting reports regarding the ability of biomarkers in perfusate to assess kidney quality and to predict graft outcomes . Our group recently demonstrated the utility of perfusate glutathione S‐transferase (GST) isoenzymes for predicting DGF , no large studies are focused on more novel biomarkers of kidney ischemia–reperfusion injury in perfusate. HMP also generates real‐time pump parameter measurements that include perfusion pressure, perfusion flow and renal resistance, which may reflect the effects of continued ischemia on the kidney.…”