Donor pre‐treatment in clinical kidney transplantation: a critical appraisal

Abstract

Kidney transplantation represents one of the medical achievements of the 20th century. However, its continued success is limited by the increasing shortage of donor grafts. As a result, more kidney grafts from marginal donors are being considered for transplantation, with concomitantly more initial graft injury and limited organ and patient survival. This has led to an increased need for interventions aiming to optimize and preserve graft quality. Interventions within the donor may protect against ischemia/reperfusion injury, and therefore, donor pre-treatment is a promising strategy to increase graft function and survival. During the last decade, diverse donor pre-treatment interventions have been explored in animal studies. Moreover, the first human trials concerning donor pre-treatment in kidney transplantation have provided encouraging results. Unfortunately, it remains difficult to determine how and where to intervene in the multifactorial and complex processes that affect the donor kidney. Moreover, ethical matters play a critical role in donor interventions, and pre-treatment should principally not have any potentially unfavorable effects on other organs to be transplanted or on the living donor. This review provides an overview of promising therapeutical strategies for donor pre-treatment in kidney transplantation and discusses the clinical trials that have been conducted thus far.

Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

“…1 The donor organ undergoes a number of injurious insults prior to, and during the early post-operative phase that are thought to contribute to the later development of chronic rejection. 2, 3 One such insult is ischemia reperfusion injury (IRI). 4 IRI is an unavoidable complication in the process of cardiac transplantation, with the donor heart rendered ischemic for prolonged periods prior to implantation into the recipient and subsequent reperfusion.…”

Optimized donor management and organ preservation before kidney transplantation

“…Hence, the establishment of institutional review boards and ethic committees with specialist transplantation expertise is advisable to determine the consent process subject to the risk of intervention and to decide whether the recipient needs to give informed consent . Additionally, a safety monitoring board is reasonable, as it can guard each study subject enrolled within the clinical trial .…”

“…In line with the danger hypothesis, this would attenuate the vicious circle of injury and increased immunogenicity after transplantation . Experimental studies highlight the benefits of this approach, but well designed clinical trials studying donor pretreatment are sparse . Trials should ideally assess the results of kidney transplantation by hard outcome data such as patient and graft survival, but can also consider early parameters such as DGF, biopsy‐proven acute rejection (BPAR), and evolution of graft function.…”

Strategies to optimize kidney recovery and preservation in transplantation: specific aspects in pediatric transplantation

“…DBD management includes the treatment of hypertension during the Cushing phenomenon, followed by cardiovascular support with treatment of hypotension [22], and maintenance of adequate intravascular volume (as sustained hypotension is observed in 53 % of brain dead children) [23], avoiding hydroxyethyl starch [24]. In 2009, Schnuelle et al suggested that hemodynamic support by dopamine could improve kidney graft function [25].…”

“…In 2009, Schnuelle et al suggested that hemodynamic support by dopamine could improve kidney graft function [25]. Hormone replacement with methylprednisolone, vasopressin (as diabetes insipidus is observed in 78 % of DBD children) [23] and thyroid hormone (to reduce vasopressor requirement) [25] is a widely used therapy, but controversial in the USA [22,26]. Several studies were unable to find any major effects of donor management on graft quality.…”