Redox-Active Iron Released During Machine Perfusion Predicts Viability of Ischemically Injured Deceased Donor Kidneys

Abstract

Redox-active iron, catalyzing the generation of reactive oxygen species, has been implicated in experimental renal ischemia-reperfusion injury. However, in clinical transplantation, it is unknown whether redoxactive iron is involved in the pathophysiology of ischemic injury of non-heart-beating (NHB) donor kidneys. We measured redox-active iron concentrations in perfusate samples of 231 deceased donor kidneys that were preserved by machine pulsatile perfusion at our institution between May 1998 and November 2002 using the bleomycin detectable iron assay. During machine pulsatile perfusion, redox-active iron was released into the preservation solution. Ischemically injured NHB donor kidneys had significantly higher perfusate redox-active iron concentrations than heartbeating (HB) donor kidneys that were not subjected to warm ischemia (3.9 ± 1.1 vs. 2.8 ± 1.0 lmol/L, p = 0.001). Moreover, redox-active iron concentration was an independent predictor of post-transplant graft viability (odds ratio 1.68, p = 0.01) and added predictive value to currently available donor and graft characteristics. This was particularly evident in uncontrolled NHB donor kidneys for which there is the greatest uncertainty about transplant outcomes. Therefore, perfusate redox-active iron concentration shows promise as a novel viability marker of NHB donor kidneys.

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).…”

Non-heartbeating donation of kidneys for transplantation

“…40 This parameter independently predicts viability of ischemically injured kidneys, particularly those from NHB donors. 41 Especially when used in combination, viability markers are an important means of deciding which donated organs to use for transplantation. (The value of a pretransplantation renal biopsy as a tool to assess viability is controversial; in kidneys from elderly NHB donors, severe arteriosclerosis seems to have an adverse effect on graft survival and GFR.…”

Characterization of the perfusate proteome of human donor kidneys

“…28 We have previously reported that higher concentrations of redox-active iron in the renal preservation solution are associated with increased risk of primary non-function in clinical kidney transplantation. 5 Since lower levels of haptoglobin will lead to higher levels of free haemoglobin -containing redox-active iron in its haeme group -our current findings have biological plausibility and fit into an established theoretical framework. Although we were able to identify almost 50% of the spots picked from the Sypro Ruby-stained gel, the identity of the other differentially expressed protein spots unfortunately could not be identified by MALDI-TOF/TOF, or by additional attempts using electrospray ionization tandem mass spectrometry.…”