title: Kidney transplantation from non-heart-beating donors after oxygenated low-flow machine perfusion preservation with histidine-tryptophan-ketoglutarate solution.
abstract: The aim of this study was to determine the potential benefit of aerobic machine preservation (MP) with non-colloidal histidine-tryptophan-ketoglutarate (HTK) solution compared with MP with Belzer machine perfusion solution (MPS) and standard cold storage, after marginal kidneys had been obtained from non-heart-beating donors. Cardiac arrest was electrically induced in anaesthetized German landrace pigs (20-25 kg bw). Their kidneys were harvested 40 min thereafter, flushed with HTK by gravity of 100 cm H2O via the renal artery and then stored in HTK for 18 h at 4 degrees C. Other organs were subjected to oxygenated (pO2>500 mmHg) hypothermic pulsatile low-flow machine perfusion with HTK or MP with Belzer MPS at P(max)=40 mmHg, yielding transrenal flow values of 0.2-0.3 ml/min per g with HTK and approximately twice that amount with Belzer MPS. A well-preserved vascular endothelium and intact tubular epithelium were documented by electron microscopy at the end of perfusion preservation in both solutions as well as after cold storage. Concentrations of ATP (in micromoles per gramme) in tissue homogenates at the end of perfusion preservation with HTK were 1.18+/-0.12 vs 0.16+/-0.02 (P<0.05) after simple cold storage and 2.43+/-0.23 after perfusion with Belzer MPS, thus documenting a relevant effect of low-flow perfusion on tissue oxygenation. Viability of the grafts was followed for 1 week after heterotopic transplantation and bilateral nephrectomy in the recipient pigs. Machine perfusion with HTK significantly improved cortical microcirculation upon early reperfusion in vivo, as well as maximal serum levels of urea and creatinine, compared to recipients receiving cold-stored grafts. No differences could be found between MP with HTK or Belzer MPS. In conclusion, provision of oxygen during storage is possible by low-flow perfusion with HTK as with Belzer MPS and apparently improves graft viability after transplantation.
authors.affiliation: Surgical Research Division, University of Bonn, Sigmund Freud Strasse 25, 53127, Bonn, Germany. tminor@uni-bonn.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Minor
authors.forename: Mario
authors.initials: M
authors.lastname: Sitzia
authors.forename: Frank
authors.initials: F
authors.lastname: Dombrowski
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D006323:Heart Arrest; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D016030:Kidney Transplantation; D008353:Mannitol / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010100:Oxygen; D010106:Oxygenators; D010313:Partial Pressure; D010477:Perfusion / Q000295:instrumentation / Q000379:methods*; D011189:Potassium Chloride / Q000494:pharmacology*; D011343:Procaine / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013552:Swine; D014019:Tissue Donors
chemical_list: C039984:Bretschneider cardioplegic solution; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D008353:Mannitol; D011343:Procaine; D000493:Allopurinol; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D011887:Raffinose; D010100:Oxygen