Figure 3 - available via license: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
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Death after graft loss. (a) According to age. Kaplan-Meier plots illustrating the cumulative incidence of death in patients according to age at graft loss. Patients with higher age at graft loss have a higher mortality. (b) Relisting and retransplantation. Kaplan-Meier plots illustrating the cumulative incidence of death in patients relisted and transplanted, relisted and not transplanted, or not relisted for repeat kidney transplantation showing the highest mortality among nonrelisted patients. (c) Relisting. Kaplan-Meier plots with landmark at one year, illustrating the cumulative incidence of death in patients relisted or not relisted for repeat kidney transplantation showing a higher mortality among patients not relisted 1 year after transplantation.
Source publication
Background:
The number of patients returning to dialysis after graft failure increases. Surprisingly, little is known about the clinical and immunological outcomes of this cohort.
Methods:
We retrospectively analyzed 254 patients after kidney allograft loss between 1997-2017 and report clinical outcomes such as mortality, relisting, retransplant...
Contexts in source publication
Context 1
... survival depends on age (Fig. 3a). Furthermore, patients who were retransplanted had the best overall survival whereas patients who were not relisted had the highest mortality (P < 0.001; Fig. 3b). The superior overall survival of patients who were relisted was also confirmed in a landmark analysis only including patients who were relisted 1 year after graft loss (Fig. ...
Context 2
... survival depends on age (Fig. 3a). Furthermore, patients who were retransplanted had the best overall survival whereas patients who were not relisted had the highest mortality (P < 0.001; Fig. 3b). The superior overall survival of patients who were relisted was also confirmed in a landmark analysis only including patients who were relisted 1 year after graft loss (Fig. ...
Context 3
... on age (Fig. 3a). Furthermore, patients who were retransplanted had the best overall survival whereas patients who were not relisted had the highest mortality (P < 0.001; Fig. 3b). The superior overall survival of patients who were relisted was also confirmed in a landmark analysis only including patients who were relisted 1 year after graft loss (Fig. ...
Context 4
... median was used as a cutoff for classification dividing the cohort in 118 patients with a PIRCHE-II score ≤70 and 119 patients with a score >70. The occurrence of dnDSA was significantly higher in patients with a PIRCHE-II score >70 (P = 0.001; Fig. 6). We did not find a correlation of the PRICHE-II score and cPRA at the time point of graft loss (Fig. ...
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Objectives
SARS-CoV-2 vaccination is a crucial intervention for infection control; however, the immune response to vaccination in dialysis patients has been reported to be moderate compared with healthy adults. There are few studies available on humoral response in immunised dialysis patients compared with well-matched control group, we conducted a...
Citations
... The Spanish health system guarantees to chronic kidney disease population universal evaluation for KT feasibility as demonstrated by the fact that almost 60% of patients are relisted for second transplantation in our cohort. Similar [13] or lower [14] overall relisting in patients with allograft failure are depicted in other studies. Despite this fact, after the first kidney graft failure, we observed that the probability to receive a second KT is similar to dying. ...
Background
There is lack of information regarding which is the best dialysis technique after kidney transplant (KT) failure. The aim of this study is to compare the effect of kidney replacement therapy modality -peritoneal dialysis (TX-PD-TX), hemodialysis (TX-HD-TX) and preemptive deceased donor retransplantation (TX-TX)- on patient survival and second KT outcomes.
Methods
A retrospective observational study from the Catalan Renal Registry was carried out. We included adult patients with failing of their first KT from 2000 to 2018.
Results
Among 2,045 patients, 1,829 started on HD (89.4%), 168 on PD (8.2%) and 48 (2.4%) received a preemptive KT. Non-inclusion in the KT waiting list and HD were associated with worse patient survival. For patients included in the waiting list, the probability of HLA sensitization and to receive a second KT was similar in HD and PD. 776 patients received a second KT (38%), 656 in TX-HD-TX, 72 in TX-PD-TX and 48 in TX-TX groups. Adjusted mortality after second KT was higher in TX-HD-TX patients compared with TX-TX and TX-PD-TX groups, without differences between TX-TX and TX-PD-TX group. Death-censored second graft survival was similar in all 3 groups.
Conclusions
Our results suggest that after first KT failure, PD is superior to HD in reducing mortality in candidates for a second KT without options for preemptive retransplantation.
... In addition, increased morbidity and inferior outcomes after retransplantation can result from diverse complications such as long waiting times, increased doses of immunosuppressive therapy, increased risk of infections and malignancies, high rates of acute rejection, and delayed graft function. Kidney graft failure is also associated with increasing the average waiting time for transplantation, due to relisting (15). ...
... patients received a second transplant. At 5 years after graft loss, of the 254 patients, 49% had died, 27% were relisted, 14% were on dialysis and not relisted, and only 11% were re-transplanted (15). ...
Conditional marketing authorization (CMA) facilitates timely access to new drugs for illnesses with unmet clinical needs, such as late graft failure after kidney transplantation. Late graft failure remains a serious, burdensome, and life-threatening condition for recipients. This article has been developed from content prepared by members of a working group within the European Society for Organ Transplantation (ESOT) for a Broad Scientific Advice request, submitted by ESOT to the European Medicines Agency (EMA), and reviewed by the EMA in 2020. The article presents the rationale for using surrogate endpoints in clinical trials aiming at improving late graft failure rates, to enable novel kidney transplantation therapies to be considered for CMA and improve access to medicines. The paper also provides background data to illustrate the relationship between primary and surrogate endpoints. Developing surrogate endpoints and a CMA strategy could be particularly beneficial for studies where the use of primary endpoints would yield insufficient statistical power or insufficient indication of long-term benefit following transplantation.
Background: Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely.
Methods: This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and panel reactive anti-HLA antibodies (PRA) were determined at 1, 3, 6 , and 12 months and bi-annually until death, repeat transplantation, or loss to follow-up.
Results: The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, while 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (HR =0.40, 95% CI, 0.17-0.93) and were not at increased risk of hospitalized infection (HR 1.81; 95% CI 0.82 to 4.0) compared to patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II PRA increased from 11% to 27% and 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR 0.81, 95% CI, 0.22-2.94).
Conclusions: Prolonged use of immunosuppressants greater than one year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.
The weight of HLA matching in kidney allocation algorithms, especially in the US, has been devalued in a stepwise fashion, supported by the introduction of modern immunosuppression. The intent was further to reduce the observed ethnic/racial disparity, as data emerged associating HLA matching with decreased access to transplantation for African American patients. In recent years, it has been increasingly recognized that a leading cause of graft loss is chronic antibody mediated rejection attributed to the development of de novo antibodies against mismatched donor HLA expressed on the graft. These antibodies are most frequently against donor HLA-DQ molecules. Beyond their impact on graft survival, generation of de novo donor specific HLA antibodies also leads to increased sensitization as measured by panel reactive antibody metrics. Consequently, access to transplantation for patients returning to the waitlist in need of a second transplant is compromised. Herein, we address the implications of reduced HLA matching policies in kidney allocation. We highlight the observed diminished outcome data, the significant financial burden and the long-term health consequences, and importantly the unintended consequences. We further provide recommendations to examine the impact of donor-recipient HLA class II and specifically HLA-DQα1β1 mismatching, focusing on collection of appropriate data, application of creative simulation approaches, and reconsideration of best practices to reduce inequalities while optimizing patient outcomes.
