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Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation.
Transplantation. 2017 Apr; 101(4):754-763.T

Abstract

BACKGROUND

Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques, such as normothermic perfusion.

METHODS

We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes of warm ischemia, right kidneys were removed from 30-kg Yorkshire pigs and preserved with 8-hour NEVKP or in 4°C histidine-tryptophan-ketoglutarate solution (SCS), followed by kidney autotransplantation.

RESULTS

Throughout NEVKP, electrolytes and pH values were maintained. Intrarenal resistance decreased over the course of perfusion (0 hour, 1.6 ± 0.51 mm per minute vs 7 hours, 0.34 ± 0.05 mm Hg/mL per minute, P = 0.005). Perfusate lactate concentration also decreased (0 hour, 10.5 ± 0.8 vs 7 hours, 1.4 ± 0.3 mmol/L, P < 0.001). Cellular injury markers lactate dehydrogenase and aspartate aminotransferase were persistently low (lactate dehydrogenase < 100 U/L, below analyzer range; aspartate aminotransferase 0 hour, 15.6 ± 9.3 U/L vs 7 hours, 24.8 ± 14.6 U/L, P = 0.298). After autotransplantation, renal grafts preserved with NEVKP demonstrated lower serum creatinine on days 1 to 7 (P < 0.05) and lower peak values (NEVKP, 5.5 ± 1.7 mg/dL vs SCS, 11.1 ± 2.1 mg/dL, P = 0.002). The creatinine clearance on day 4 was increased in NEVKP-preserved kidneys (NEVKP, 39 ± 6.4 vs SCS, 18 ± 10.6 mL/min; P = 0.012). Serum neutrophil gelatinase-associated lipocalin at day 3 was lower in the NEVKP group (1267 ± 372 vs 2697 ± 1145 ng/mL, P = 0.029).

CONCLUSIONS

Continuous pressure-controlled NEVKP improves renal function in DCD kidney transplantation. Normothermic ex vivo kidney perfusion might help to decrease posttransplant delayed graft function rates and to increase the donor pool.

Authors+Show Affiliations

1 Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. 2 Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. 3 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 4 Department of General, Visceral, and Transplant Surgery, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany. 5 Laboratory Medicine & Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 6 Departments of Surgery (Urology) and Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada. 7 Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 8 Multi Organ Transplant Program, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 9 Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27467537

Citation

Kaths, J Moritz, et al. "Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation." Transplantation, vol. 101, no. 4, 2017, pp. 754-763.
Kaths JM, Echeverri J, Chun YM, et al. Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation. Transplantation. 2017;101(4):754-763.
Kaths, J. M., Echeverri, J., Chun, Y. M., Cen, J. Y., Goldaracena, N., Linares, I., Dingwell, L. S., Yip, P. M., John, R., Bagli, D., Mucsi, I., Ghanekar, A., Grant, D. R., Robinson, L. A., & Selzner, M. (2017). Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation. Transplantation, 101(4), 754-763. https://doi.org/10.1097/TP.0000000000001343
Kaths JM, et al. Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation. Transplantation. 2017;101(4):754-763. PubMed PMID: 27467537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation. AU - Kaths,J Moritz, AU - Echeverri,Juan, AU - Chun,Yi Min, AU - Cen,Jun Yu, AU - Goldaracena,Nicolas, AU - Linares,Ivan, AU - Dingwell,Luke S, AU - Yip,Paul M, AU - John,Rohan, AU - Bagli,Darius, AU - Mucsi,Istvan, AU - Ghanekar,Anand, AU - Grant,David R, AU - Robinson,Lisa A, AU - Selzner,Markus, PY - 2016/7/29/pubmed PY - 2017/5/23/medline PY - 2016/7/29/entrez SP - 754 EP - 763 JF - Transplantation JO - Transplantation VL - 101 IS - 4 N2 - BACKGROUND: Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques, such as normothermic perfusion. METHODS: We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes of warm ischemia, right kidneys were removed from 30-kg Yorkshire pigs and preserved with 8-hour NEVKP or in 4°C histidine-tryptophan-ketoglutarate solution (SCS), followed by kidney autotransplantation. RESULTS: Throughout NEVKP, electrolytes and pH values were maintained. Intrarenal resistance decreased over the course of perfusion (0 hour, 1.6 ± 0.51 mm per minute vs 7 hours, 0.34 ± 0.05 mm Hg/mL per minute, P = 0.005). Perfusate lactate concentration also decreased (0 hour, 10.5 ± 0.8 vs 7 hours, 1.4 ± 0.3 mmol/L, P < 0.001). Cellular injury markers lactate dehydrogenase and aspartate aminotransferase were persistently low (lactate dehydrogenase < 100 U/L, below analyzer range; aspartate aminotransferase 0 hour, 15.6 ± 9.3 U/L vs 7 hours, 24.8 ± 14.6 U/L, P = 0.298). After autotransplantation, renal grafts preserved with NEVKP demonstrated lower serum creatinine on days 1 to 7 (P < 0.05) and lower peak values (NEVKP, 5.5 ± 1.7 mg/dL vs SCS, 11.1 ± 2.1 mg/dL, P = 0.002). The creatinine clearance on day 4 was increased in NEVKP-preserved kidneys (NEVKP, 39 ± 6.4 vs SCS, 18 ± 10.6 mL/min; P = 0.012). Serum neutrophil gelatinase-associated lipocalin at day 3 was lower in the NEVKP group (1267 ± 372 vs 2697 ± 1145 ng/mL, P = 0.029). CONCLUSIONS: Continuous pressure-controlled NEVKP improves renal function in DCD kidney transplantation. Normothermic ex vivo kidney perfusion might help to decrease posttransplant delayed graft function rates and to increase the donor pool. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/27467537/Continuous_Normothermic_Ex_Vivo_Kidney_Perfusion_Improves_Graft_Function_in_Donation_After_Circulatory_Death_Pig_Kidney_Transplantation_ L2 - https://doi.org/10.1097/TP.0000000000001343 DB - PRIME DP - Unbound Medicine ER -