Cold Preflush of Porcine Kidney Grafts Prior to Normothermic Machine Perfusion Aggravates Ischemia Reperfusion Injury

Fabry, Gregor; Doorschodt, Benedict M.; Grzanna, Tim; Elliott, Aaron; Stollenwerk, André; Tolba, René; Rossaint, Rolf; Berne, Christian

doi:10.1038/s41598-019-50101-7

Cited by 11 publications

(9 citation statements)

References 23 publications

(32 reference statements)

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“…During NMP, 11.2 mL/h of a nutrient solution comprised of Nutriflex ® peri (B. Braun, Melsungen, Germany), Cernevit (Baxter, Unterschleißheim, Germany) and insulin (Insuman Rapid, Sanofi-Aventi, Frankfurt a.M., Germany) was added to all groups, as previously described by our group [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation

et al. 2022

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Normothermic machine perfusion (NMP) of kidneys in combination with an optimized perfusate composition may increase donor organ preservation quality, especially in the case of marginal donor grafts. Optimization of currently employed perfusates is still a subject of present research. Due to the advantages of being cell-free, easy to store, and having minimal antigenicity, hemoglobin-based oxygen carriers, such as HBOC-301 (Oxyglobin®, Hemoglobin Oxygen Therapeutics LLC, Souderton, PA, USA), offer an alternative to the commonly used perfusates based on packed red blood cells (pRBC). As previously described, using HBOC results in formation of methemoglobin (metHb) as an adverse effect, inducing hypoxic conditions during the perfusion. As a potential counterpart to metHb formation, the application of the antioxidant ascorbic acid (VitC) is of high interest. Therefore, this study was conducted in four experimental groups, to compare the effect of NMP with (1) HBOC or (3) pRBC, and additionally examine a beneficial effect of VitC in both groups (2) HBOC + VitC and (4) pRBC + VitC. All groups were subjected to NMP for 6 h at a pressure of 75 mmHg. Kidneys in the HBOC groups had a significantly lower renal blood flow and increasing intrarenal resistance, with reduced renal function in comparison to the pRBC groups, as demonstrated by significantly lower creatinine clearance and higher fractional sodium excretion rates. Clinical chemistry markers for tissue damage (LDH, lactate) were higher in the HBOC groups, whereas no significant histological differences were observed. Although the application of VitC decreased oxidative stress levels, it was not able to significantly increase the outcome parameters mentioned above in either group. This study demonstrated that HBOC-301 is inferior to pRBCs in our porcine kidney NMP model, independent of additional VitC administration. Oxidative stress and fragmentation of the hemoglobin polymers could be detected as a possible reason for these results, hence further research, focusing on the use of cell-free oxygen carriers that do not exhibit this complex of issues, is required.

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Section: Methodsmentioning

confidence: 99%

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation

et al. 2022

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“…The determination of

has been performed in numerous preclinical and clinical NMP studies, which have focused on therapeutic strategies [ 35 , 36 , 37 , 38 , 39 , 40 , 41 ], the ideal NMP experimental setup [ 42 , 43 , 44 , 45 , 46 , 47 ], or the performance of NMP compared to other preservation methods [ 48 , 49 , 50 ], among others. In these studies, either Fick’s principle (e.g., [ 35 , 42 ]) or the simplified form, the arteriovenous pO 2 difference without consideration of hemoglobin concentration (e.g., [ 37 , 39 ]), served as the basis for

calculation.…”

Section: Discussionmentioning

confidence: 99%

Preoperative Function Assessment of Ex Vivo Kidneys with Supervised Machine Learning Based on Blood and Urine Markers Measured during Normothermic Machine Perfusion

Markgraf

Malberg

2022

Biomedicines

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Establishing an objective quality assessment of an organ prior to transplantation can help prevent unnecessary discard of the organ and reduce the probability of functional failure. In this regard, normothermic machine perfusion (NMP) offers new possibilities for organ evaluation. However, to date, few studies have addressed the identification of markers and analytical tools to determine graft quality. In this study, function and injury markers were measured in blood and urine during NMP of 26 porcine kidneys and correlated with ex vivo inulin clearance behavior. Significant differentiation of kidneys according to their function could be achieved by oxygen consumption, oxygen delivery, renal blood flow, arterial pressure, intrarenal resistance, kidney temperature, relative urea concentration, and urine production. In addition, classifications were accomplished with supervised learning methods and histological analysis to predict renal function ex vivo. Classificators (support vector machines, k-nearest-neighbor, logistic regression and naive bayes) based on relevant markers in urine and blood achieved 75% and 83% accuracy in the validation and test set, respectively. A correlation between histological damage and function could not be detected. The measurement of blood and urine markers provides information of preoperative renal quality, which can used in future to establish an objective quality assessment.

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“… 40 , 47 , 48 The precise role of a brief NMP resuscitation in clinical use has not been solidly established yet, and we await the results of the multicenter randomized clinical kidney trial in the United Kingdom. 49 Alternatively, in a different experimental NMP model, Fabry et al 50 recently demonstrated good outcomes when avoiding cold preflush before NMP, and thus going directly from nephrectomy to NMP. These results are interesting, yet controversial, as removal of blood and organ cooling is clinical practice and is thought to be fundamental in organ preservation.…”

Section: Discussionmentioning

confidence: 99%

Improved Normothermic Machine Perfusion After Short Oxygenated Hypothermic Machine Perfusion of Ischemically Injured Porcine Kidneys

Lignell

Lohmann

Rozenberg

et al. 2021

Transplantation Direct

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Background. In an era where global kidney shortage has pushed the field of transplantation towards using more marginal donors, modified kidney preservation techniques are currently being reviewed. Some techniques require further optimization before implementation in full scale transplantation studies. Using a porcine donation after circulatory death kidney model, we investigated whether initial kidney hemodynamics improved during normothermic machine perfusion if this was preceded by a short period of oxygenated hypothermic machine perfusion (oxHMP) rather than static cold storage (SCS). Methods. Kidneys subjected to 75 minutes of warm ischemia were randomly assigned to either SCS (n = 4) or SCS + oxHMP (n = 4), with a total cold storage time of 240 minutes. Cold preservation was followed by 120 minutes of normothermic machine perfusion with continuous measurement of hemodynamic parameters and renal function. Results. oxHMP preserved kidneys maintained significantly lower renal resistance throughout the normothermic machine perfusion period compared to SCS kidneys (P < 0.001), reaching lowest levels at 60 minutes with means of 0.71 ± 0.35 mm Hg/mL/min/100 g (SCS) and 0.45 ± 0.15 mm Hg/mL/min/100 g (oxHMP). Accordingly, the oxHMP group had a higher mean renal blood flow versus SCS kidneys (P < 0.001). oxHMP kidneys had higher oxygen consumption during normothermic machine perfusion compared to SCS preserved kidneys (P < 0.001). Creatinine clearance remained similar between groups (P = 0.665). Conclusions. Preceding oxHMP significantly improved initial normothermic machine perfusion hemodynamics and increased total oxygen consumption. With the long period of warm ischemia, immediate kidney function was not observed, reflected by the findings of low creatinine clearance in both groups.

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Cold Preflush of Porcine Kidney Grafts Prior to Normothermic Machine Perfusion Aggravates Ischemia Reperfusion Injury

Cited by 11 publications

References 23 publications

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation

Preoperative Function Assessment of Ex Vivo Kidneys with Supervised Machine Learning Based on Blood and Urine Markers Measured during Normothermic Machine Perfusion

Improved Normothermic Machine Perfusion After Short Oxygenated Hypothermic Machine Perfusion of Ischemically Injured Porcine Kidneys

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