Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation

Abstract

Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24-h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short-term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.

Normothermic Ex Vivo Kidney Perfusion Following Static Cold Storage—Brief, Intermediate, or Prolonged Perfusion for Optimal Renal Graft Reconditioning?

“…In former studies, we demonstrated feasibility and safety in heart-beating donor pig kidney transplantation (17) and superiority of NEVKP over SCS in DCD kidney transplantation (18). In a follow-up study, superior outcomes were demonstrated for continuous NEVKP with near complete exclusion of hypothermia versus brief NEVKP following SCS (14). The present study investigated how different time periods of NEVKP following hypothermic storage affect the posttransplant outcomes.…”

“…During NEVKP kidneys demonstrated physiologic perfusion characteristics As previously described (14), the initial arterial pressure for NEVKP was set to 75 mmHg, and the venous pressure to 0-3 mmHg by height regulation of the venous reservoir. After rewarming of the graft, the arterial pressure dropped to 65 mmHg and was kept at this level (Figure 2A).…”

“…Clinical studies reported results from brief normothermic perfusions of 1 h at the end of the SCS preservation period (8,9,31) or in between two periods of SCS (32). Previous porcine studies indicated that minimizing SCS, either by reduction of storage time itself (33), or by replacing SCS with NEVKP, improves outcome after transplantation (14). However, the impact of various times of NEVKP after SCS had not been investigated.…”

“…Sequential biopsies taken during NEVKP would be necessary to investigate molecular mechanisms. To prevent bleeding and to not compromise posttransplant outcomes, similar to former studies (14), biopsies were only taken at the end of follow-up at pod 8. Follow-up studies, specifically designed to further explore mechanisms and investigate changes in gene and protein expression, need to be conducted.…”

The future of marginal kidney repair in the context of normothermic machine perfusion

“…Current studies have focused on determining the ideal time for perfusion in addition to deciding about an optimal perfusate composition. Although Hosgood et al are currently running a clinical trial investigating the effects of 1 hour periods of NMP prior to transplantation, Kaths et al have shown in a porcine experimental model that prolonged periods of NMP can further improve the reconditioning effect 24, 45, 46. To properly assess the efficacy of a therapeutic treatment, like extended perfusion, more comprehensive diagnostic tools must come to fruition.…”