Effects of Delayed Hypothermic Machine Perfusion on Kidney Grafts with a Preliminary Period of Static Cold Storage and a Total Cold Ischemia Time of Over 24 Hours

Abstract

Departmental sources Background: Hypothermic machine perfusion (HMP) appears to exert a reconditioning effect on the ischemic damage of kidney grafts. However, some concerns still remain about its real effectiveness when it is delayed after a preliminary period of static cold storage (SCS) or with prolonged overall cold ischemia time (CIT). Material/Methods: The effect of HMP on hemodynamic, metabolic, histological and ultrastructural features of grafts was investigated in 21 single-kidney grafts treated with a delayed HMP after SCS and with a total CIT of over 24 h. Results: The mean CIT, SCS, and HMP times were 29 h, 12 h, and 18 h, respectively. Longer SCS was associated with higher vascular resistance and lower arterial flow. In the pre-vs. post-HMP comparison, a significant decrease in arterial resistances and increase of flow were recorded. The hemodynamic improvement was independent of HMP duration. The perfused grafts retained some metabolic activity, with a statistically significant decrease of pH, pO2, and glucose levels, and increase of lactates in the perfusion liquid, by the end of HMP. Longer SCS was associated with higher pH and greater pO2 decrease during HMP. Light microscopy and transmission electronic microscopy revealed no significant variations in nuclear, cytoplasmic, or ultrastructural damage. SCS, HMP, and CIT were not identified as risk factor for delayed graft function or rejection. Conclusions: A delayed and extended HMP can recover the graft hemodynamic function, maintain some metabolic activity, and stabilize the accumulated ischemic damage due to a preliminary SCS.

Hypothermic machine perfusion can safely prolong cold ischemia time in deceased donor kidney transplantation. A retrospective analysis on postoperative morbidity and graft function

“…Whether such result was determined by either the relative shortness of preliminary SCS period in the study group or by some reconditioning effect of HMP is still a matter of investigation, as the available data are currently heterogeneous. 6,21 In particular, further clinical studies are needed comparing the outcomes of delayed versus immediate HMP, although we tend to suspect that an immediate HMP may be associated with a greater clinical benefit; 6 thus logistic efforts to support this pretransplant management should be made. Nonetheless, the present findings as well as the pragmatic analysis of previously reported results from large clinical series or randomized trials do actually support the safety of using HMP to extend the CIT time, without any significant additional risk.…”

“…Graft loss was considered either in case of graft nephrectomy or return to dialysis due to graft failure. The immunosuppressive protocol, postoperative management and follow‐up surveillance have been already previously described 6,9,16 …”

“…3,4 Such benefit seems not to vary depending on duration of overall cold ischemia time (CIT), and it has been registered even with CIT over 24 hours, 3,5 thanks to a potential reconditioning effect of HMP. 6 As a matter of fact, HMP seems to recover the graft hemodynamic function, maintain some metabolic activity, and stabilize the accumulated ischemic damage due to a preliminary SCS. 6 However, a significant heterogeneity in the data exists and cold ischemic injury during HMP is still suspected to have a similar magnitude as during SCS.…”

“…6 As a matter of fact, HMP seems to recover the graft hemodynamic function, maintain some metabolic activity, and stabilize the accumulated ischemic damage due to a preliminary SCS. 6 However, a significant heterogeneity in the data exists and cold ischemic injury during HMP is still suspected to have a similar magnitude as during SCS. 7 Thus, several reports still insist on the necessity of limiting CIT to as short as possible.…”

“…Its use is associated with a reduced incidence of delayed graft function (DGF) and improved graft survival, when compared to static cold storage (SCS) 3,4 . Such benefit seems not to vary depending on duration of overall cold ischemia time (CIT), and it has been registered even with CIT over 24 hours, 3,5 thanks to a potential reconditioning effect of HMP 6 . As a matter of fact, HMP seems to recover the graft hemodynamic function, maintain some metabolic activity, and stabilize the accumulated ischemic damage due to a preliminary SCS 6 .…”