Benefits of active oxygenation during hypothermic machine perfusion of kidneys in a preclinical model of deceased after cardiac death donors

• Published in: The Journal of surgical research Vol. 184; no. 2; pp. 1174 - 1181
• Main Authors: Thuillier, Raphaël, PhD, Allain, Geraldine, MD, Celhay, Olivier, MD, Hebrard, William, MSc, Barrou, Benoit, MD, Badet, Lionel, MD, Leuvenink, Henri, PhD, Hauet, Thierry, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2013; Elsevier
• Subjects: Animals; Aspartate Aminotransferases - blood; Biochemistry, Molecular Biology; Creatinine - blood; DCD; Death; Hypothermia, Induced - methods; Kidney - pathology; Kidney - physiology; Kidney transplantation; Life Sciences; Lipocalins - urine; Machine perfusion; Male; Marginal donors; Models, Animal; Oxygen; Perfusion - methods; Preclinical; Reactive Oxygen Species - administration & dosage; Recovery of Function - physiology; Surgery; Swine; Tissue Donors; Vimentin - metabolism; Oxygen; Marginal donors; Preclinical; DCD; Machine perfusion; Kidney transplantation; marginal donor; machine perfusion; dcd; preclinical; oxygen; kidney transplantation
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2013.04.071

Abstract Background Deceased after cardiac death donors (DCDs) represent a valuable source of organs; however, preventing poor outcome is difficult, even with the use of machine perfusion (MP). It is of paramount importance to improve this method. We proposed to evaluate the benefits of active oxygenation during kidney graft hypothermic MP using a novel perfusion machine: Kidney Assist (KA). Methods We used a pig model of DCD transplantation in Large White pigs. Cold preservation was performed by conventional non-oxygenated MP (KAnoO2 ) or oxygenated MP (KA). Results In the first 2 wk post-transplant, KA grafts displayed a lower serum creatinine peak and a faster return to normal levels compared with KAnoO2 animals, translating into a smaller area under the curve. Urinary neutrophil gelatinase-associated lipocalin levels and serum aspartate amino transferase levels were lower in KA animals compared with the non-oxygenated group. These correlated with better chronic function. Longer follow-up of the animals (3 mo) permitted evaluation of chronic outcome lesions. Interstitial fibrosis was reduced in the KA group, and these kidneys also displayed significantly lower levels of vimentin staining. Further histologic investigation also showed a trend toward decreased chronic inflammation in kidneys preserved with oxygen. Conclusions This new MP system is efficient in preserving DCD kidneys, greatly enhancing the capacity of the graft to withstand preservation stress and improving outcome. Oxygen delivery during preservation is thus valuable for highly damaged organs and offers an important therapeutic tool for transplant teams faced with decreased quality of donor organs.