Hypothermic machine perfusion is superior to static cold storage in deceased donor kidney transplantation: A meta-analysis.

There remains a lack of consensus on the optimal storage method for deceased donor kidneys. This meta-analysis compares storage with hypothermic machine perfusion (HMP) vs traditional static cold storage (SCS). The Cochrane Kidney and Transplant Specialised Register was searched to identify (quasi-) randomized controlled trials (RCTs) to include in our meta-analysis. PRISMA guidelines were used to perform and write this review. There is high-certainty evidence that HMP reduces the risk of delayed graft function (DGF) when compared to SCS (2138 participants from 14 studies, RR = 0.77; 0.67-0.90, P = .0006). This benefit is significant in both donation following circulatory death (DCD; 772 patients from seven studies, RR = 0.75; 0.64-0.87, P = .0002) and donation following brainstem death (DBD) grafts (971 patients from four studies, RR = 0.78; 0.65-0.93, P = .006). The number of perfusions required to prevent one episode of DGF was 7.26 and 13.60 in DCD and DBD grafts, respectively. There is strong evidence that HMP also improves graft survival in both DBD and DCD grafts, at both 1 and 3 years. Economic analyses suggest HMP is cost-saving at 1 year compared with SCS. Hypothermic machine perfusion is superior to SCS in deceased donor renal transplantation. Direct comparisons with normothermic machine perfusion in RCTs are essential to identify optimal preservation methods in kidney transplantation.

Tingle SJ ，Figueiredo RS ，Moir JA ，Goodfellow M ，Thompson ER ，Ibrahim IK ，Bates L ，Talbot D ，Wilson CH ... -  《-》

Normothermic and hypothermic machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

Kidney transplantation is the optimal treatment for kidney failure. Donation, transport and transplant of kidney grafts leads to significant ischaemia reperfusion injury. Static cold storage (SCS), whereby the kidney is stored on ice after removal from the donor until the time of implantation, represents the simplest preservation method. However, technology is now available to perfuse or "pump" the kidney during the transport phase ("continuous") or at the recipient centre ("end-ischaemic"). This can be done at a variety of temperatures and using different perfusates. The effectiveness of these treatments manifests as improved kidney function post-transplant. To compare machine perfusion (MP) technologies (hypothermic machine perfusion (HMP) and (sub) normothermic machine perfusion (NMP)) with each other and with standard SCS. We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies until 15 June 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. All randomised controlled trials (RCTs) and quasi-RCTs comparing machine perfusion techniques with each other or versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory death (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion. The results of the literature search were screened, and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratios (RR) with 95% confidence intervals (CI). Survival analyses (time-to-event) were performed with the generic inverse variance meta-analysis of hazard ratios (HR). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was the incidence of delayed graft function (DGF). Secondary outcomes included graft survival, incidence of primary non-function (PNF), DGF duration, economic implications, graft function, patient survival and incidence of acute rejection. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twenty-two studies (4007 participants) were included. The risk of bias was generally low across all studies and bias domains. The majority of the evidence compared non-oxygenated HMP with standard SCS (19 studies). The use of non-oxygenated HMP reduces the rate of DGF compared to SCS (16 studies, 3078 participants: RR 0.78, 95% CI 0.69 to 0.88; P < 0.0001; I2 = 31%; high certainty evidence). Subgroup analysis revealed that continuous (from donor hospital to implanting centre) HMP reduces DGF (high certainty evidence). In contrast, this benefit over SCS was not seen when non-oxygenated HMP was not performed continuously (low certainty evidence). Non-oxygenated HMP reduces DGF in both DCD and DBD settings in studies performed in the 'modern era' and when cold ischaemia times (CIT) were short. The number of perfusions required to prevent one episode of DGF was 7.69 and 12.5 in DCD and DBD grafts, respectively. Continuous non-oxygenated HMP versus SCS also improves one-year graft survival (3 studies, 1056 participants: HR 0.46, 0.29 to 0.75; P = 0.002; I2 = 0%; high certainty evidence). Assessing graft survival at maximal follow-up confirmed a benefit of continuous non-oxygenated HMP over SCS (4 studies, 1124 participants (follow-up 1 to 10 years): HR 0.55, 95% CI 0.40 to 0.77; P = 0.0005; I2 = 0%; high certainty evidence). This effect was not seen in studies where HMP was not continuous. The effect of non-oxygenated HMP on our other outcomes (PNF, incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain. Studies performing economic analyses suggest that HMP is either cost-saving (USA and European settings) or cost-effective (Brazil). One study investigated continuous oxygenated HMP versus non-oxygenated HMP (low risk of bias in all domains); the simple addition of oxygen during continuous HMP leads to additional benefits over non-oxygenated HMP in DCD donors (> 50 years), including further improvements in graft survival, improved one-year kidney function, and reduced acute rejection. One large, high-quality study investigated end-ischaemic oxygenated HMP versus SCS and found end-ischaemic oxygenated HMP (median machine perfusion time 4.6 hours) demonstrated no benefit compared to SCS. The impact of longer periods of end-ischaemic HMP is unknown. One study investigated NMP versus SCS (low risk of bias in all domains). One hour of end ischaemic NMP did not improve DGF compared with SCS alone. An indirect comparison revealed that continuous non-oxygenated HMP (the most studied intervention) was associated with improved graft survival compared with end-ischaemic NMP (indirect HR 0.31, 95% CI 0.11 to 0.92; P = 0.03). No studies investigated normothermic regional perfusion (NRP) or included any donors undergoing NRP. Continuous non-oxygenated HMP is superior to SCS in deceased donor kidney transplantation, reducing DGF, improving graft survival and proving cost-effective. This is true for both DBD and DCD kidneys, both short and long CITs, and remains true in the modern era (studies performed after 2008). In DCD donors (> 50 years), the simple addition of oxygen to continuous HMP further improves graft survival, kidney function and acute rejection rate compared to non-oxygenated HMP. Timing of HMP is important, and benefits have not been demonstrated with short periods (median 4.6 hours) of end-ischaemic HMP. End-ischaemic NMP (one hour) does not confer meaningful benefits over SCS alone and is inferior to continuous HMP in an indirect comparison of graft survival. Further studies assessing NMP for viability assessment and therapeutic delivery are warranted and in progress.

Tingle SJ ，Thompson ER ，Figueiredo RS ，Moir JA ，Goodfellow M ，Talbot D ，Wilson CH ... -  《Cochrane Database of Systematic Reviews》

Machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

Tingle SJ ，Figueiredo RS ，Moir JA ，Goodfellow M ，Talbot D ，Wilson CH ... -  《Cochrane Database of Systematic Reviews》

Hypothermic Machine Perfusion Versus Static Cold Storage in Deceased Donor Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Static cold storage (SCS) and hypothermic machine perfusion (HMP) are two primary options for renal allograft preservation. Compared with SCS, HMP decreased the incidence of delayed graft function (DGF) and protected graft function. However, more evidence is still needed to prove the advantages of the HMP. In this study, the outcomes of kidney grafts from the two preservation methods were compared by conducting a systematic review and meta-analysis. Randomized controlled trials (RCTs) comparing the effect of hypothermic machine perfusion and static cold storage in deceased donor kidney transplantation were identified through searches of the MEDLINE, EMBASE, and Cochrane databases between January 1, 1980 and December 30, 2017. The primary endpoints were delayed graft function and graft survival. Secondary endpoints included primary non-function (PNF), graft renal function, duration of DGF, acute rejection, postoperative hospital stay and patient survival. Summary effects were calculated as risk ratio (RR) with 95% confidence interval (CI) or mean difference (MD) with 95% confidence intervals (CI). A total of 13 RCTs were included, including 2048 kidney transplant recipients. The results indicated that compared with SCS, HMP decreased the incidence of DGF (RR 0.78, 95% CI 0.69-0.87, P < 0.0001), and improved the graft survival at 3 years (RR 1.06, 95% CI 1.02-1.11, P = 0.009). There was no significant difference in other endpoints. HMP might be a more desirable method of preservation for kidney grafts. The long-term outcomes of kidney allografts stored by hypothermic machine perfusion still need to be further investigated.

Peng P ，Ding Z ，He Y ，Zhang J ，Wang X ，Yang Z ... -  《-》

Hypothermic Machine Perfusion Results in a Marginal Kidney Transplant Programme.

Hypothermic machine perfusion (HMP) of deceased donor kidneys is associated with a better outcome than static cold storage, predominantly in marginal donors. Nevertheless, there is little evidence supporting whether graft centre of origin and donor category impact HMP results. To identify factors impacting HMP in transplantation from marginal donors. Analysis of prospectively collected cohort data of expanded criteria donor (ECD) and donor after circulatory death (DCD) categories II and III was performed. A total of 214 adult recipients of first kidney transplantation with complete data and a minimum of 6-mo follow-up were included. Delayed graft function (DGF) was defined as the lack of decrease in creatinine level in the first 48h. Graft loss was defined as return to dialysis or creatinine clearance <15ml/min/1.73m2. Univariate and multivariate logistic regression analyses for DGF were constructed to identify independent risk factors. Recipient and graft survival (GS) analyses were conducted by Kaplan-Meier, and univariate and multivariate Cox regression analyses. DGF occurred in 32.8% of imported and 20.5% of local grafts (p=0.059). Only donor category (DCD; odds ratio [OR]: 6.6, p=0.008) and haemodialysis (OR: 3.5, p=0.002) were significantly associated with DGF development. The 1-yr GS rate was 92.5% in the local donor group and 84.3% in the imported donor group (p=0.050). Multivariate analysis by Cox proportional hazards model identified only donor category (hazard ratio [HR] 10.99, p=0.001) and donor age (HR 1.07, p=0.005) as predictive variables for GS. The small sample size of the DCD group diminished the statistical power and did not permit a subgroup analysis to determine the impact of specific DCD category on HMP results. DCD donor category, but not donor centre of origin, impacted DGF development and GS in the HMP of deceased donor kidneys. Currently, the number of donors is insufficient to meet the demand for renal grafts. Expanded criteria for donation after brain death and donation after circulatory death (DCD) programmes have been developed as strategies to minimise this problem. Hypothermic machine perfusion has previously demonstrated its usefulness in expanded criteria donation and DCD preservation. DCD type and donor age increase the risk of graft loss.

Gómez-Dos Santos V ，Ruiz Hernández M ，Burgos-Revilla FJ 《European Urology Focus》