Hypothermic Machine Preservation in Comparison with Static Cold Storage of Kidney Allografts: A Systematic Review and Meta-Analysis

Abstract

Introduction: There is renewed interest in Hypothermic Machine Perfusion (HMP) of kidneys in recent years with the development of a new generation of pumps. However, it remains controversial which method is most beneficial for the transplant recipient. A systematic review of the level of available evidence comparing HMP with SCS and a statistical analysis of the combined data was performed. Methods: A systematic literature search was performed using MEDLINE (1948 to October 2011), EMBASE (1980 to October 2011), the Cochrane Library, the Transplant Library of RCTs from the Centre for Evidence in Transplantation and the International Clinical Trials Registry Platform. Studies were assessed for methodological quality. Summary effects of meta-analysis are presented as Relative Risks (RR) and 95% Confidence Intervals (95%CI). RCTs alone were used for meta-analysis. Results: Nineteen studies met the full inclusion criteria, including 7 RCTs and 12 Non-RCTS with a total of 2,086 kidneys. The overall risk of Delayed Graft Function (DGF) was lower with HMP than with SCS (fixed effects, RR=0.81, 95%CI=0.70-0.92, p< 0.01). DGF was not significantly reduced when results were split into DBD kidneys (fixed effects, RR=0.84, 95%CI=0.68-1.04, p=0.10) and DCD kidneys (fixed effects, RR=0.80, (95%CI=0.62-1.04, p=0.09). There was no evidence that the effect on DGF comparing these two donor types was significantly different (Test of Interaction, p=0.78). There was no difference in the risk of graft loss within the first 12 months (fixed effects, RR=0.86, 95%CI=0.68-1.09, p=0.22) or the rate of Primary Non-Function (PNF) between HMP and SCS kidneys (random effects, RR=1.16, 95%CI=0.46-2.94, p=0.75). Three studies found a faster fall in serum creatinine for HMP preserved kidneys in the first 14 days; however 3 studies found no significant difference in longer term renal function (30-365 days). Rates of acute rejection were equal in 2 studies, although higher following SCS in 1 study. In the 7 studies that reported patient survival there was no relationship between preservation method and this outcome. Conclusion: Data from the included studies shows that HMP reduces DGF compared to SCS. This effect may be the same in both DBD and DCD kidneys. HMP may lead to a quicker reduction in serum creatinine post-op. There was no difference in graft loss in the first 12 months, PNF, long term renal function, acute rejection or patient survival. Figure: Forest plot to show RR of DGF comparing hypothermic machine perfusion (HMP) to static cold storage (SCS) in randomised controlled trials. N= total patients in study arm, n= number of patients with DGF. Summary RR calculated by fixed effects meta-analysis, < 1 Favours HMP. 95%CI=95% confidence interval.Figure: [Forest plot to show relative risk (RR) of DGF.]