Over the past decade, the pool of patients with terminal chronic heart failure continuously expands because of better treatment modalities of acute ischemic heart failure and progress in the medical treatment of chronic congestive heart failure. As a result, there is an increasing number of patients eligible for heart transplant (HTx), who are older and with more comorbidities like impaired renal function. Consequently, early identification of high-risk HTx recipients is crucial to prevent severe renal complications. The report by Lutz et al1 in this issue of Transplantation presents a potential road map for how an organ perfusion device could be beneficially implemented into routine clinical practice not only for HTx but also for transplantation of other nonrenal organs to preserve renal function. In general, the cause of renal dysfunction after HTx is multifactorial during the different transplant phases, with a close correlation between acute kidney injury at the time of HTx and existing or developing chronic kidney disease (CKD). Both acute kidney injury in the first y and CKD are associated with poorer patient survival. Among HTx recipients, the 5-y cumulative incidence of CKD is between 10% and 50%. Without doubt, calcineurin inhibitors (CNIs) are the most important contributors to end-stage renal disease in the long term, which has an incidence of up to 20% of HTx survivors within 10 y.2 Therefore, the arising enigma in heart-kidney transplantation (HKT) is to identify pre-HTx patients with predominantly hemodynamically mediated renal failure, which may resolve spontaneously (or not) after successful HTx. Such decisions require a correct assessment of the type of cardiorenal syndrome and a profound knowledge of the complexity of perioperative care with all medical treatments and interventions needed to offer best therapeutic options to these high-risk patients. This demands a close interdisciplinary work-up between HTx and kidney transplant (KTx) physicians (Figure 1).FIGURE 1.: Proposal for an algorithm for HTx recipients with impaired renal function based on an interdisciplinary work-up between HTx and KTx physicians to preserve kidney function after HTx alone, after sHKTx, or sequential HTx and KTx. For sHKTx, the proposed use of ex vivo hypothermic kidney perfusion by Lutz et al in this issue seems to be favorable. CNI, calcineurin inhibitor; ECP, extracorporal photophoresis; ESRD, end-stage renal disease; HTx, heart transplantation; ISHLT, International Society of Heart and Lung Transplantation; KaOO, Kidney after Other Organs; KTx, kidney transplantation; sHKTx, simultaneous HTx and KTx.In the case of potential renal recovery posttransplant, the recipient will benefit from renal-sparing immunosuppressive regimens using induction therapy (eg, antithymocyte globulin) to delay CNI initiation to avoid vasoconstrictive renal effects and subsequent renal toxicity.3 In the early and midterm follow-up period, post-HTx CNI minimization or even CNI-withdrawal immunosuppressive regimens based on the mammalian target of rapamycin inhibitor everolimus should be applied to protect renal function as successfully shown in randomized controlled trials.2,4 Notably, it should be kept in mind that CNI-free patients have a higher risk of biopsy-proven acute cellular rejection, which is mainly of low histological grade and without hemodynamic compromise. Unfortunately, other CNI-free regimens involving the costimulatory cell blockage (eg, belatacept or iscalimab), which are established or were studied after KTx, are still off-label use after HTx or were terminated in the development phase because of ineffectiveness, respectively. Recently, however, results from a large European trial show that the application of extracorporeal photopheresis after HTx to the addition of standard immunosuppression allows prevention of cellular and humoral rejection while reducing CNI exposure.5 Thus, extracorporeal photopheresis could be an adjunctive tool for renal protection. If no resolution of renal failure is expected pre-HTx, which is seldom compared with resolution, the options are simultaneous HKTx (sHKTx) or a sequential HTx and KTx (Figure 1). Depending on country-specific regulations, patients with severely impaired renal function or dialysis dependence before HTx can undergo sHKTx. Although the survival of these patients is better with sHKTx than with HTx alone,6 1 in 5 KTx will fail within the first 3 mo after sHKTx,7 which is considerably higher than with KTx alone. This is mainly caused by 2 factors: (1) prolonged cold ischemic time of the kidney, which will only be implanted after HTx, and (2) hemodynamic instability because of primary or secondary graft dysfunction after HTx that infringes optimum perfusion conditions of a transplanted kidney. Given the overall shortage of organs, it is paramount to minimize these organ losses and to implement device strategies that lead to proper function of both heart and kidney. By using hypothermic nonoxygenated machine perfusion, like the one described by Lutz et al1 in this issue of Transplantation, the transplantation of heart and kidney can be split into 2 separate operations occurring several hours to more than a day apart. This window allows for hemodynamic stabilization of the HTx patient in the intensive care unit, whereas the kidney can be maintained on the perfusion set-up without accumulating unperfused cold storage time.8 KTx with optimized hemodynamic and coagulation status of the recipient then follows, which reduces the risk of renal hypoperfusion and hence further damage, that is, delayed graft function, sensibilization, reduced long-term outcome, and potentially primary nonfunction of the graft. In case the intended sHKTx recipient is still not hemodynamically stable, the machine perfusion preserved kidney can be allocated to a backup recipient, without the disadvantage of a critically prolonged unperfused cold ischemic time (Figure 1). As an established concept for sHKTx, the organ-sharing organization Eurotransplant offers the Kidney after Other Organs (KaOO) program to all registered HTx recipients who are on dialysis pretransplant.9 If kidney function does not recover 90 d after HTx, the KaOO program prioritizes the HTx recipient for an urgent KTx (receiving 500 bonus points on the waiting list, similar to a high-urgency kidney patient). However, KaOO also entails that the HTx recipient will have to dialyze for 3 mo plus the time until a suitable kidney offer is found after HTx, which gives the patient a considerable disadvantageous dialysis vintage.10 Additionally, this strategy will lead to transplantation of organs from 2 different donors, thereby increasing immunological challenges and sensibilization. Further innovative and pioneering research with organ perfusion strategies like the one described by Lutz et al will have to show their benefits for combined organ transplantation. Complimentary to sHKTx or sequential HTx and KTx, the ultimate goal for HTx and KTx physicians should be to prevent and minimize the development of CKD and/or end-stage renal disease in HTx patients by using individualized renal protective immunosuppressive therapeutic regimens.
Search from 250 M+ research papersSearch from 250 M+ research papers
Just Published
Apr 20, 2024
Yunxi Cui + 8
Open Access