Functional relationship of alpha-glutathione S-transferase and glutathione S-transferase activity in machine-preserved non-heart-beating donor kidneys

Kreel, B.K. van; Janssen, Marie P.; Kootstra, G.

doi:10.1111/j.1432-2277.2002.tb00105.x

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…GST is as useful as α-GST; therefore, we have continued to use GST as an enzymatic indicator of damage to the proximal tubular cells of kidneys from NHB donors. 38 Viability markers studied more recently include fatty-acid-binding protein and alanine aminopeptidase. 39 Determining the concentration of these markers has no value in predicting KOOTSTRA AND VAN HEURN MARCH 2007 VOL 3 NO 3 www.nature.com/clinicalpractice/neph post-transplantation renal function over and above viability testing using perfusion flow dynamics and GST.…”

Section: Discussionmentioning

confidence: 99%

Non-heartbeating donation of kidneys for transplantation

Kootstra¹,

Heurn²

2007

Nat Rev Nephrol

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There is a persistent shortage of kidneys available for transplantation. In the early 1980s, therefore, we published the concept of non-heartbeating (NHB) donation; that is, procurement of kidneys from donors whose death has been accompanied by irreversible circulatory arrest. NHB donors are generally categorized using four definitions; category III (awaiting cardiac arrest) and category IV (cardiac arrest while braindead)--or 'controlled'--donors are the most suitable for initiating NHB donation programs. Delayed graft function is associated with use of kidneys from such donors, but has no effect on graft survival in the short or long term. Use of kidneys from category I (dead upon arrival at hospital) and category II (unsuccessfully resuscitated), or 'uncontrolled', donors is likewise associated with delayed graft function, but also with an increased risk of primary nonfunction. Viability testing of donated organs from these sources is a prerequisite for transplantation. Machine preservation parameters and enzyme release measurements help to distinguish viable from nonviable kidneys. The proportion of NHB donor kidneys in the total pool of postmortem kidneys differs considerably between countries. In The Netherlands, the proportion is nearly 50%. This figure is markedly higher than that in the US and Canada, where national programs have now been initiated to increase rates of NHB donation. In the future, warm preservation techniques might facilitate better viability testing, thereby increasing NHB donation from category I and II donors and further reducing the shortage of kidneys available for transplantation.

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Section: Discussionmentioning

confidence: 99%

Non-heartbeating donation of kidneys for transplantation

Kootstra¹,

Heurn²

2007

Nat Rev Nephrol

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“…Perfusate LDH was determined by standard colorimetric assay (Boehringer Mannheim, Almere, The Netherlands). Total GST activity in the perfusate samples was measured as described previously (21). Oxyhemoglobin was identified by absorption spectrum and quantified by absorption at 540 nm.…”

Section: Biochemical Measurementsmentioning

confidence: 99%

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

Vries

Snoeijs

Bonsdorff

et al. 2006

American Journal of Transplantation

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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.

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“…LDH was determined by standard colorimetric assay (Roche Diagnostics, Mannheim, Germany) and total GST activity was measured as described previously. 14 All perfusion characteristics were adjusted for kidney weight.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the perfusate proteome of human donor kidneys

et al. 2013

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Background: Preservation of deceased donor kidneys by hypothermic machine perfusion results in superior transplant outcomes as compared with static cold storage and provides the opportunity to measure biomarkers of cellular injury in perfusate samples. Identification of biomarkers predicting early graft dysfunction so far has met with limited success. Methods: Two-dimensional difference gel electrophoresis and mass spectrometry were used to explore the proteome of perfusate samples from machine-perfused human donor kidneys (N ¼ 18) and to discover novel biomarkers of ischaemic acute kidney injury. Results: Thirty-two protein spots were successfully identified, representing 19 unique proteins that were derived from renal tissue and from residual plasma in the renal microcirculation. Two unidentified protein spots were significantly upregulated, whereas one protein spot -identified as haptoglobin -was significantly down-regulated in the perfusate of ischaemically injured kidneys from donors after cardiac death as compared with kidneys from brain-dead donors who had not suffered warm ischaemic injury. Furthermore, two protein spots were up-regulated in kidneys that never functioned after transplantation, whereas one spot was up-regulated -identified as a1-antitrypsin -in kidneys with delayed graft function. Conclusions: We provide the first description of the renal perfusate proteome and present preliminary evidence of differentially expressed biomarkers in human donor kidneys with different levels of acute ischaemic injury. Their diagnostic value for the selection of marginal kidneys in clinical transplantation should be determined in future studies.

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Functional relationship of alpha-glutathione S-transferase and glutathione S-transferase activity in machine-preserved non-heart-beating donor kidneys

Cited by 5 publications

References 25 publications

Non-heartbeating donation of kidneys for transplantation

Non-heartbeating donation of kidneys for transplantation

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

Characterization of the perfusate proteome of human donor kidneys

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