Should I Stay or Should I Go? The Role of Allograft Nephrectomy (2023)

Despite substantial improvements in long-term kidney transplant outcomes, many recipients will experience late allograft failure. Unfortunately, transplant recipients returning to dialysis experience a range of negative health outcomes, with reduced quality of life measures and an increased risk of death.1,2 Hospitalization and mortality related to infection are significantly increased, raising important questions about the management of immunosuppressive therapy in this patient group. In the current issue, Budhiraja et al3 provide a comprehensive review of the evidence supporting immunosuppression modification after kidney transplant failure, as well as the closely related question of whether to perform an allograft nephrectomy (AN). It is common clinical practice to reduce immunosuppression after kidney transplant failure, which makes sense with the aim of reducing infection, malignancy, and metabolic risk. However, as reported by the authors, there is very limited evidence to guide clinicians in which immunosuppressive agents to reduce, or how rapidly, and potential harm from reducing immunosuppression too fast. Withdrawal of effective immunosuppression in patients who are eligible for retransplantation increases sensitization,4 potentially impeding access to transplantation. This is particularly important in the era of virtual crossmatching, as immunosuppression reduction in patients with an allograft in situ could increase the potential for de novo HLA antibody formation in the interval between HLA antibody assessments. In addition, immunosuppression withdrawal may accelerate the decline in residual kidney function, increasing the burden of kidney replacement therapy by requiring more stringent fluid restriction or increased dialysis. Some patients may develop an allograft-intolerance syndrome, a form of rejection typically characterized by tenderness of the allograft, fever, systemic inflammation, and anemia.5,6 In some circumstances, there is a strong rationale for considering AN. This includes situations where the allograft has failed within days or weeks due to a technical complication or severe rejection, after the development of a donor-derived malignancy within the transplant, or in recipients with an allograft-intolerance syndrome that is refractory to immunosuppression. For patients with >1 previous transplant, AN may be required to create space for a future allograft. If there is a history of infectious complications or malignancy, or if the waiting time before retransplantation is expected to be prolonged, AN may be attractive with the aim of more rapid and complete withdrawal of immunosuppression. The perceived advantages of AN must be balanced against the risks, not least the significant potential to trigger (or at least reveal) sensitization to the previous transplant, thereby reducing access to a future allograft.4,7 It remains unclear whether the dominant role of AN in promoting sensitization is through priming the immune system in the context of inflammation from the procedure itself, or whether AN amplifies the level of HLA antibodies that were previously adsorbed by the allograft. Persistent hypotension is an occasional complication after AN, presumably as a consequence of hyporeninemia in patients with little or no residual functional kidney tissue.8 AN also exposes patients to perioperative surgical and anesthetic complications. The authors delineate the surgical advantages and disadvantages of AN; however, the surgical risks of AN should be thoughtfully approached and are not insignificant. Typically, poor operative visualization of discrete anatomic planes requires a subcapsular approach to nephrectomy in long-standing grafts. To mitigate the operative hurdles caused by dense adhesions, minimally invasive approaches have been employed as noted by the authors. There should be a low threshold for surgical drain placement, as postoperative hematomas are frequent in the nephrectomy bed and can lead to infectious complications, including arterial stump mycotic pseudoaneurysms and rarely, life-threatening iliac artery rupture. Additionally, an intraperitoneal approach to gain vascular control at the outset of AN can help minimize bleeding complications. Finally, for those with multiple previous transplants and severe recipient vascular disease, AN can be helpful as the graft stumps can be used as targets for implantation. In the absence of high-quality evidence to guide clinicians, decisions about immunosuppression management following transplant failure should be individualized, taking into account the recipient’s individual health status and goals. In patients who are not medically suitable for another transplant, cautious reduction in immunosuppression is reasonable, with monitoring for symptoms of allograft-intolerance syndrome. If retransplantation is likely within a reasonably short timeframe, then immunosuppression should be maintained at a level intended to minimize de novo sensitization. The role of AN remains controversial. When there are significant complications secondary to immunosuppression or an anticipated long waiting period for another transplant, AN with subsequent immunosuppression withdrawal may be appropriate, albeit with a risk of increased sensitization and loss of any residual kidney function. Further research will hopefully clarify the optimal strategies for managing immunosuppression after kidney transplant failure and the role of AN. Until then, these complex decisions require careful deliberation by the patient, their family, and their medical team.