Perfusion Techniques in Kidney Allograft Preservation to Reduce Ischemic Reperfusion Injury: A Systematic Review and Meta-Analysis

Abstract

The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.

Keywords: antioxidants; in situ cold preservation; ischemic reperfusion injury; machine perfusion; normothermic regional perfusion; organ preservation; static cold storage.

Figure 1

The process of organ procurement and the potential of implementing normothermic regional perfusion (NRP) and machine perfusion (MP) techniques. Traditionally, organs procured for transplantation are preserved in static cold storage (SCS). Transplanted organs suffer two insults of ischemic injury and oxidative stress: once during procurement and another during implantation. At the time of implantation, ischemic reperfusion injury (IRI) triggers the activation of proteinases, increases the permeability of the mitochondrial membrane, and generates reactive oxygen species. This process further exacerbates oxidative stress, apoptosis, ferroptosis and autophagy. NRP and MP are dynamic perfusion techniques that can reduce oxidative stress and IRI through unique mechanisms. NRP can be applied prior to and during organ procurement, while HMP is used as a mode of organ preservation. Both techniques also hold potential in therapeutic drug delivery and expanding the donor pool (Figure created with www.biorender.com (accessed on 5 April 2024)).

Figure 2

Search results and application of eligibility criteria.

Figure 3

Forest plot for rates of 12 months graft survival between MP and SCS [15,17,24,25,26,27,29,30,31,32,33,34,35,36,38,42,43,44,46,49,50,52,53,54,57].

Figure 4

Forest plot for rates of DGF between MP and SCS [9,15,17,20,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,51,52,53,54,55,56,57,71].

Figure 5

Forest plot for rates of PNF between MP and SCS [15,17,21,22,24,26,27,28,31,32,33,34,35,36,40,43,44,51,52,53,54,57].

Figure 6

Forest plot for mean of length of hospital stay between MP and SCS [15,27,28,31,34,36,37,38,39,40,44,45,49,51,52,57].

Figure 7

Forest plot for post-transplant serum creatinine (mg/dL) between MP and SCS [9,15,17,24,27,28,31,40,41,42,43,44,45,48,49,51,57].

Figure 8

Forest plot for rates (A) acute rejection, (B) delayed graft function, (C) primary non-function, (C) acute rejection, and (D) graft failure within 12 months post-transplant between NRP and ISP [58,59,60,61,62,63,64,65,66,67,68,69,70].

Figure 9

Forest plot for post-transplant eGFR (mL/min/1.73 m²) at (A) 3 months and (B) 12 months between NRP and ISP [59,62,63,64,66,67].