Kidney transplantation after oxygenated machine perfusion preservation with Custodiol‐N solution

Custodiol‐N, a new preservation solution, has been shown particularly suitable for hypothermic machine perfusion preservation (HMP) in isolated porcine kidneys. These preliminary results should be confirmed in an actual transplant model in vivo. Kidney function after 21 h of HMP was studied in an autotransplant model using Landrace pigs (25–30 kg; n = 6 per group). Perfusion was performed with oxygenated perfusate, using either Custodiol‐N solution including 50 g/l dextran 40 (CND) or kidney perfusion solution 1 (KPS‐1) as gold standard. Viability of the grafts was followed for 1 week after bilateral nephrectomy in the recipient pigs. HMP with CND resulted in less acute tubular injury, evaluated by levels of fatty acid‐binding protein and better clearance function during the first 24 h after Tx than with KPS‐1 (P < 0.05, resp.). Serum creatinine tended to be lower in the CND group during the whole observation period. Histological tissue scores one week after Tx were similar in both groups. Expression of endothelin‐1 as well as of Toll‐like receptor 4 15 min after reperfusion was lower in the CND group (P < 0.05), suggesting less endothelial stress response. The data provide first in vivo evidence for the suitability of Custodiol‐N as an effective perfusate for renal machine perfusion.

[1]  T. Minor,et al.  New Strategies and Concepts in Organ Preservation , 2014, European Surgical Research.

[2]  T. Minor,et al.  Influence of Oxygen Concentration During Hypothermic Machine Perfusion on Porcine Kidneys From Donation After Circulatory Death , 2014, Transplantation.

[3]  T. Minor,et al.  Subnormothermic machine perfusion for preservation of porcine kidneys in a donation after circulatory death model , 2014, Transplant international : official journal of the European Society for Organ Transplantation.

[4]  O. Celhay,et al.  Benefits of active oxygenation during hypothermic machine perfusion of kidneys in a preclinical model of deceased after cardiac death donors. , 2013, The Journal of surgical research.

[5]  T. Minor,et al.  Role of Pulsatility in Hypothermic Reconditioning of Porcine Kidney Grafts by Machine Perfusion After Cold Storage , 2013, Transplantation.

[6]  T. Minor,et al.  Controlled Oxygenated Rewarming of Cold Stored Liver Grafts by Thermally Graduated Machine Perfusion Prior to Reperfusion , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[7]  G. Franklin,et al.  To pump or not to pump: a comparison of machine perfusion vs cold storage for deceased donor kidney transplantation. , 2013, Journal of the American College of Surgeons.

[8]  T. Minor,et al.  Use of the new preservation solution Custodiol-N supplemented with dextran for hypothermic machine perfusion of the kidney. , 2013, Cryobiology.

[9]  T. Minor,et al.  Hypothermic Reconditioning of Porcine Kidney Grafts by Short-Term Preimplantation Machine Perfusion , 2012, Transplantation.

[10]  N. Pizanis,et al.  A new preservation solution for lung transplantation: evaluation in a porcine transplantation model. , 2012, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[11]  A. Scherag,et al.  Assessment of a chloride‐poor versus a chloride‐containing version of a modified histidine‐tryptophan‐ketoglutarate solution in a rat liver transplantation model , 2011, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[12]  S. Tullius,et al.  Hypothermic kidney preservation: a remembrance of the past in the future? , 2011, Current opinion in organ transplantation.

[13]  Yuzhi Zhang,et al.  Flow Cessation Triggers Endothelial Dysfunction During Organ Cold Storage Conditions: Strategies for Pharmacologic Intervention , 2010, Transplantation.

[14]  G. Garcı́a-Cardeña,et al.  Machine perfusion or cold storage in organ transplantation: indication, mechanisms, and future perspectives , 2010, Transplant international : official journal of the European Society for Organ Transplantation.

[15]  T. Minor,et al.  Use of a new modified HTK solution for machine preservation of marginal liver grafts. , 2010, The Journal of surgical research.

[16]  R. Ploeg,et al.  Machine perfusion or cold storage in deceased-donor kidney transplantation. , 2009, The New England journal of medicine.

[17]  O. Witzke,et al.  78. Custodiol-N—A new, mechanism-based organ preservation solution , 2008 .

[18]  K. Matschke,et al.  80. Development of a new vascular preservation solution , 2008 .

[19]  C. Ince,et al.  Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney , 2008, Molecular medicine.

[20]  H. de Groot,et al.  Improvement of the cold storage of blood vessels with a vascular preservation solution. Study in porcine aortic segments. , 2008, Journal of vascular surgery.

[21]  G. Rakhorst,et al.  Improved Kidney Graft Function After Preservation Using a Novel Hypothermic Machine Perfusion Device , 2007, Annals of surgery.

[22]  R. Ploeg,et al.  Perspectives in Organ Preservation , 2007, Transplantation.

[23]  A. Deussen,et al.  Preclinical evaluation of coronary vascular function after cardioplegia with HTK and different antioxidant additives. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[24]  M. Mangino,et al.  UW Solution for Hypothermic Machine Perfusion of Warm Ischemic Kidneys , 2005, Transplantation.

[25]  T. Minor,et al.  Kidney transplantation from non-heart-beating donors after oxygenated low-flow machine perfusion preservation with histidine–tryptophan–ketoglutarate solution , 2004, Transplant international : official journal of the European Society for Organ Transplantation.

[26]  Matthew S Metcalfe,et al.  A Comparison of Renal Preservation by Cold Storage and Machine Perfusion Using a Porcine Autotransplant Model , 2004, Transplantation.

[27]  H. de Groot,et al.  New Insights into the Cellular and Molecular Mechanisms of Cold Storage Injury , 2004, Journal of Investigative Medicine.

[28]  N. Lloberas,et al.  Promising effects of ischemic preconditioning in renal transplantation. , 2002, Kidney international.

[29]  G. Kootstra,et al.  The cadaveric kidney and the organ shortage – a perspective review , 2001, Clinical transplantation.

[30]  D. Manas,et al.  Early results of a non‐heartbeating donor (NHBD) programme with machine perfusion , 2000, Transplant international : official journal of the European Society for Organ Transplantation.

[31]  T. Minor,et al.  Gaseous oxygen for hypothermic preservation of predamaged liver grafts: fuel to cellular homeostasis or radical tissue alteration? , 2000, Cryobiology.

[32]  S. Kapur,et al.  The influence of pulsatile preservation on renal transplantation in the 1990s. , 2000, Transplantation.

[33]  M. Simonson,et al.  Endothelin up-regulation and localization following renal ischemia and reperfusion. , 1999, Kidney international.

[34]  D. Gjertson,et al.  Transplantation of kidneys from donors whose hearts have stopped beating. , 1998, The New England journal of medicine.

[35]  T. Minor,et al.  Involvement of platelet activating factor in microcirculatory disturbances after global hepatic ischemia. , 1995, The Journal of surgical research.

[36]  M. Brezis,et al.  Determinants of intrarenal oxygenation. II. Hemodynamic effects. , 1994, The American journal of physiology.

[37]  O. Källskog,et al.  Red cell trapping and postischemic renal blood flow. Differences between the cortex, outer and inner medulla. , 1991, Kidney international.

[38]  S. Papson,et al.  “Model” , 1981 .

[39]  F O Belzer,et al.  24-hour and 72-hour preservation of canine kidneys. , 1967, Lancet.

[40]  U. Rauen,et al.  Histidine-induced injury to cultured liver cells, effects of histidine derivatives and of iron chelators , 2006, Cellular and Molecular Life Sciences.

[41]  T. Minor,et al.  Role of the hepatovasculature in free radical mediated reperfusion damage of the liver. , 1993, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes.