Kidney transplantation is the gold standard treatment for end-stage kidney disease (ESKD), offering substantial improvements in both survival and quality of life compared with dialysis [1, 2]. However, the burden of ESKD continues to grow. In the United States alone, more than 808,000 people are living with ESKD [3]. The transplant waitlist continues to expand, with 90,323 patients listed in 2024, underscoring the critical importance of optimising graft outcomes and extending the longevity of transplanted kidneys [4–6].

Outcomes after transplantation are influenced by multiple donor and recipient factors, including age, donor pathway, HLA matching, sensitisation, and organ quality [7, 8]. Among perioperative factors, cold ischaemic time (CIT) is well established as a determinant of graft function and survival [9–12].

Vascular anastomosis time (AT), also referred to as the second warm ischaemic time (SWIT), has similarly been assumed to exert an influence, but has been comparatively under-investigated, and represents the interval from removal of the kidney from ice, until reperfusion in the recipient. It has been acknowledged as a modifiable risk factor, with prolongation of this interval contributing to ischemia-reperfusion injury that drives inflammatory cascades, interstitial fibrosis and tubular atrophy (IFTA), and ultimately reduces graft viability [8, 13–18]. The clinical manifestation of this injury is delayed graft function (DGF), often requiring dialysis within the first seven days after transplantation [13–15]. Beyond early graft dysfunction, longer SWIT are also associated with longer hospital stays, increased use of renal replacement therapy, and greater reliance on diagnostic resources such as imaging and biopsy, all of which compound the burden on patients and health systems [14].

The first study to explicitly link SWIT to kidney transplant outcomes was published as recently as 2015 [8]. Since then, only a limited number of retrospective cohorts have examined this association, and no systematic review has yet synthesised the available evidence despite the critical role SWIT has on outcomes. As SWIT is a modifiable surgical factor, clarifying its effect is of direct clinical relevance. To address this, we conducted a systematic review to evaluate its association with delayed graft function, one and five-year graft survival, and patient survival in adult kidney transplant recipients.

The systematic review was conducted in adherence with the Preferred Items for Systematic Reviews (PRISMA) checklist and was registered with PROSPERO (CRD42024549222) in 2024 [16, 17].

A total of 9 retrospective cohort studies were included in the systematic review, with a total combined data spread of 155, 523 patients across two continents of North America and Europe. The PRISMA flow chart is outlined in Figure 1.

This review is, to our knowledge, the first systematic synthesis of vascular AT and kidney transplant outcomes across donor types. In the studies involved, prolonged AT was associated with higher rates of DGF across all donor types, and as expected the lowest incidence was seen in living donor grafts, intermediate rates in donation after brain death, and the highest rates in donation after circulatory death. In the studies involved, shorter AT, particularly under 30 min, were associated with superior graft survival, whereas both one-year and five-year graft survival declined once this interval was exceeded. Impacts on patient survival were less clear.

These findings support the interpretation that AT, DGF, and graft survival are best understood as a connected pathway rather than independent outcomes. Prolonged AT consistently increased the risk of DGF, and poorer long-term graft survival was observed in the same cohorts. Because DGF itself is a well-recognised predictor of graft loss, it is plausible that the adverse impact of prolonged AT on survival is mediated in part through its effect on early graft function. This biological plausibility is consistent with the known mechanisms of ischemia-reperfusion injury and lends coherence to the observed clinical outcomes [15].

The modifiability of vascular AT highlights its potential as a risk factor that could be improved through revised surgical techniques and guidelines. Current clinical guidelines from the Transplantation Society of Australia and New Zealand (TSANZ) do not specify an optimal vascular AT but emphasize the importance of minimising cold ischemic time [27]. Additionally, the guidelines highlight strong evidence that a short ischemic time may improve transplant outcomes, recommending that kidneys be transplanted as quickly as possible to mitigate prolonged cold ischemia [27]. However, various factors influencing vascular AT must be considered when promoting speed and precision. These include anatomical complexities (e.g., multiple renal arteries/veins, right-sided kidney grafts), recipient and donor characteristics (BMI, depth, and Age) [8, 28–30]. This emphasizes the need to recognize AT as a modifiable risk factor and incorporate its optimization into surgical planning within the transplant community and has impacts on transplant surgical training, as well as the introduction of robotic kidney transplantation more broadly.

Importantly, AT is not solely a function of surgical technique or efficiency, but also reflects surgical complexity. Prolonged AT commonly occurs in technically challenging scenarios, including ipsilateral re-transplantation, difficult iliac vessel exposure, high recipient BMI, deep iliac fossae, and the presence of calcified vessels, to name but a few [31]. In such cases, prolonged AT may be unavoidable and appropriate to ensure technical precision and haemostatic security. Accordingly, AT may act a s a surrogate marker of procedural complexity rather than an independent causal factor of poor transplant outcomes.

Cold ischaemic time is a well-established independent predictor of graft outcomes and is biologically distinct from AT [9, 11]. While AT and CIT are temporally separate, they are likely biologically synergistic. Prolonged AT may be particularly injurious in kidneys already exposed to extended cold storage, as warm re-ischemia following prolonged hypothermia may amplify ischemia reperfusion injury. This potential interaction, however, is beyond the scope of this review but remains a hypothetical, though clinically plausible mechanism, warranting prospective evaluation.

The feasibility of achieving AT below 30 min also warrants consideration. Registry based data suggests that a substantial proportion of deceased donor transplants exceed this threshold, particularly in DCD cohorts [8, 19, 20]. Short AT is most achievable in living donor cohorts, and straightforward deceased donor cases. Thresholds used across studies in this review, were arbitrary and heterogenous, and no evidence-based cut-off for “safe” AT currently exists.

These findings support viewing AT as a modifiable intra-operative factor with meaningful consequences for both early graft function and long-term graft durability. Minimisation can be encouraged through thorough preparation at the pre-operative briefing, with clear allocation of roles, readiness of instruments, and vascular exposure achieved before removal of the kidney from ice. Further, recording AT as a routine peri-operative quality measure would allow teams to monitor performance and provide constructive feedback. Workflow can also be streamlined, for example, by using a two-surgeon approach where possible and by preparing sutures or clamps in advance so that periods of non-productive time are reduced. An alternative approach would be to incorporate active methods of insulating and/or cooling the graft during anastomoses, to ameliorate the negative impacts of rapid graft rewarming and warm ischemia during this interval.

Several limitations must be recognised in this review, however. Important covariates such as cold ischaemic time, first warm ischemia, multiplicity of vessels, side of graft, recipient body mass index, machine perfusion, and centre or era effects were not consistently adjusted for. We also could not conduct formal meta-analyses and sensitivity analyses given significant differences in donor populations between different studies, variable use and reporting of technologies such as machine perfusion, and variable/inconsistent reporting of all relevant study outcomes stratified by AT thresholds and donor types.

Despite these limitations, the review has notable strengths. It is, to our knowledge, the first systematic review to focus specifically on vascular AT in kidney transplantation. Large and contemporary cohorts were included, stratified by donor type, and the overall risk of bias was low, with eight of the nine studies assessed as good quality. Taken together, this synthesis provides a structured overview of the available evidence and highlights areas where prospective research with standardised definitions and reporting would add the most value.

This systematic review identified studies that found an inverse relationship between AT and graft survival. A shorter AT was associated with a superior immediate graft function, and 1-year and 5-year graft survival, across all types of donor recipients. Currently, there are no guidelines that define the significance of maintaining a short AT for optimal graft function and survival. This systematic review aims to inform the transplant community on the importance of maintaining a short AT, where possible, to provide the most optimal outcome post-operatively.