**1. Introduction**

The proportion of end-stage renal disease (ESRD) patients with a failed kidney transplant is increasing each year [1,2]; 25% of patients on the US kidney transplant waiting list have a failed transplant [3] and in the Eurotransplant area, the number of patients being re-waitlisted after returning to dialysis steadily ranges between 17.9% and 18.9% [4].

Morbidity and mortality for patients with a failed kidney transplant on dialysis is high; there is a two- to three-fold risk of death compared to patients with a functioning graft and a median recipient survival after graft failure of three years [3,5]. This increased mortality [6] relates to higher rates of cardiovascular, neoplastic and infective events, in which the burden of immunosuppressive therapy is no longer counterbalanced by the benefits of a working kidney transplant [7]. The single modifiable factor which has the greatest impact on recipient survival in this group is the time to re-transplantation [6]; however, the suboptimal outcome of repeated kidney re-transplantation has generated increasing debate regarding the overall managemen<sup>t</sup> and resource allocation within this subgroup. Nevertheless, previous reports have shown that there is a significative survival benefit after repeat deceased donor kidney transplantation over remaining on the waiting list, due to significative improvement in better immunological screening, crossmatching, HLA matching, post-operative managemen<sup>t</sup> and immunosuppression protocols [8], although the overall outcome remains impaired by an inferior survival compared to first kidney transplant recipients [9].

Yet, other fundamental outcome drivers, for example the impact of a high-quality living donor graft, have not been fully investigated in the peculiar context of repeated kidney transplantation.

One of the primary advantages in fact of receiving a kidney from a living donor is that the organ is generally healthier and more resistant to the occurrence and extension of the subsequent ischaemic reperfusion injury. To become eligible, living donors undergo full screening of their kidney function, tissue and immunological compatibility with the recipient and a comprehensive overall physical health check. This is in contrast with grafts retrieved from deceased donors, where already the stress and the damage related to the death of the individual determine a systemic storm summing up to the usual longer time in cold storage to allow retrieval and transfer between di fferent teams and hospitals. All together, these factors can temporarily reduce and potentially compromise the organ function irreversibly [10].

The incidence of delayed graft function in kidneys from deceased donors varies, but is overall as high as 30%; it might also take weeks before the recipient is fully dialysis independent [11,12], thus the recipients are more exposed and vulnerable in the post-operative period. Conversely, kidneys from living donors tend to function immediately, reducing the risk of hospitalisation and renal replacement therapy after transplant to less than 4% [13] and setting in this way the recipient for the best short- and long-term outcome.

Why is it so important an immediate graft function? As stated above, the more complex the procedure, the higher the likelihood of the prolonged ischaemic insult and the resultant impact on challenging recipients. Previously failed grafts, a long history of comorbidities, side e ffects of long-term immunosuppression and previous surgical interventions are common characteristics in the repeated kidney transplant population, leading to significant immunological and technical challenges.

Intuitively, it might initially seem sensible to withdraw immunosuppression in patients after graft failure to reduce the risk of cardiovascular, neoplastic and infective complications. However, for those who are fit for a subsequent transplant, this commonly results in a high degree of sensitisation to HLA, namely the production of donor-specific HLA antibodies (DSA) and other panel-reactive antibodies (PRAs) [14]. This reduces access to compatible donors and may result in an extremely prolonged wait for transplantation, with the associated morbidity and mortality [15]. This increased waiting time might also have a worse synergistic e ffect with the often extended ischemic time, due to the technical challenges associated with re-transplantation, namely adhesions from previous surgery, di fficulties accessing the iliac vasculature or earlier manipulation of the bladder to establish the ureterovesical anastomosis [16].

The aim of this study is to analyse the experience of repeated kidney transplantation in our institution over 50 years, with a focus on outcomes in recipients of first, second and third/fourth kidney transplants and factors which impact these outcomes.
