The optimal immunosuppressive (IS) withdrawal strategy after kidney allograft failure remains unclear. This study evaluated the effects of prolonged calcineurin inhibitor (CNI) therapy on HLA sensitization, graft intolerance syndrome (GIS), and key clinical outcomes.

We conducted a prospective cohort study involving 90 adult patients with kidney allograft failure who were candidates for re-transplantation. Patients were divided into two groups: Rapid withdrawal group (discontinuation of all IS except low-dose prednisolone) and Prolonged CNI Group (maintenance of CNI for six months plus low-dose prednisolone). Outcomes assessed over a 12-month follow-up period included HLA sensitization, defined as an increase in calculated panel reactive antibody (cPRA) and the development of de novo donor-specific antibodies (dnDSA), GIS incidence, re-transplantation, hospitalization rates, and mortality.

No significant differences were observed between the groups regarding HLA sensitization one-year postgraft failure. A composite outcome of cPRA increase, dnDSA, and GIS did not differ between the groups. When evaluated separately, GIS occurred less frequently in the Prolonged CNI Group (4.8% vs. 23%; p = 0.015). Patients who continued CNI maintained better residual kidney function at 6 months (800 vs. 200 mL, p = 0.001) and experienced lower all-cause hospitalization rates (12% vs. 30%, p = 0.036), with comparable retransplantation and mortality rates. Graft removal and higher HLA mismatches were independently linked to increased sensitization at 12 months.

Prolonged CNI therapy for six months postallograft loss did not prevent HLA sensitization but reduced the incidence of GIS and preserved residual kidney function without increasing hospitalization or mortality.

The optimal management of immunosuppressive therapy (IT) after kidney allograft failure (KAF) remains controversial. Although maintaining IT may reduce HLA-sensitization and improve access to retransplantation, it may also increase the rate of immunosuppression-related complications. The overall impact on patient mortality is unknown. The main objective of this study was to compare the evolution of HLA-sensitization 6 months after KAF according to IT management.

Individual clinical and health care data were extracted from the French national end-stage kidney disease registry (Renal Epidemiology and Information Network [REIN]) and the French National Health Data system (SNDS), respectively. Patients aged > 18 years returning to dialysis after KAF between January 2008 and December 2019 in Lorraine were included. Patients were classified into two groups, IT continuation or IT discontinuation. HLA-sensitization was defined as an increase in incompatible graft rate (IGR) between KAF and 6 months post-KAF (change to a higher predefined category (0%-5%), (5%-20%), (20%-50%), (50%-85%), (85%-95%), (95%-98%), (98%-100%)). Secondary outcome was patient survival according to IT management.

A total of 121 patients were included, 35 (29%) of whom continued IT. HLA-sensitization after KAF tended to be higher in the "IT discontinuation" group (57% vs. 38% in the "IT continuation" group, p = .07). In multivariate analysis, IT continuation was associated with a lower increase in IGR (OR .37, 95% CI [.14; .93]). IT management was not associated with patient mortality.

Continuation of IT after KAF was associated with less change in IGR and was not associated with excess mortality.

In March 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a virtual Controversies Conference to address the important but rarely examined phase during which the kidney transplant is failing or has failed. In addition to discussing the definition of a failing allograft, 4 broad areas were considered in the context of a declining functioning graft: prognosis and kidney failure trajectory; immunosuppression strategies; management of medical and psychological complications, and patient factors; and choice of kidney replacement therapy or supportive care following graft loss. Identifying and paying special attention to individuals with failing allografts was felt to be important in order to prepare patients psychologically, manage immunosuppression, address complications, prepare for dialysis and/or retransplantation, and transition to supportive care. Accurate prognostication tools, although not yet widely available, were embraced as necessary to define allograft survival trajectories and the likelihood of allograft failure. The decision of whether to withdraw or continue immunosuppression after allograft failure was deemed to be based most appropriately on risk-benefit analysis and likelihood of retransplantation within a few months. Psychological preparation and support was identified as a critical factor in patient adjustment to graft failure, as was early communication. Several models of care were noted that enabled a medically supportive transition back to dialysis or retransplantation. Emphasis was placed on the importance of dialysis-access readiness before initiation of dialysis, in order to avoid use of central venous catheters. The centrality of the patient to all management decisions and discussions was deemed to be paramount. Patient "activation," which can be defined as engaged agency, was seen as the most effective way to achieve success. Unresolved controversies, gaps in knowledge, and areas for research were also stressed in the conference deliberations.

Patients with failed renal allografts have associated increased morbidity and mortality. The individualization of immunosuppression taper is the key element in managing these patients to avoid graft intolerance and sensitization while balancing the risk of continued immunosuppression. Most patients with uncomplicated chronic allograft failure do not require allograft nephrectomy (AN), and there is no clear evidence that it improves outcomes. The AN procedure is associated with variable morbidity and mortality. It is reserved mainly for early technical graft failure or in symptomatic cases associated with allograft infection, malignancy, or graft intolerance syndrome. It may also be considered in those who cannot tolerate immunosuppression and are at high risk for graft intolerance. AN has been associated with an increased risk of sensitization due to inflammatory response from surgery, immunosuppression withdrawal with allograft failure, and retained endovascular tissue. Although it is presumed that for-cause AN after transplant failure is associated with sensitization, it remains unclear whether elective AN in patients who remain on immunotherapy may prevent sensitization. The current practice of immunosuppression taper has not been shown to prevent sensitization or increase infection risk, but current literature is limited by selection bias and the absence of medication adherence data. We discuss the management of failed allografts based on retransplant candidacy, wait times, risk of graft intolerance syndrome, and immunosuppression side effects. Many unanswered questions remain, and future prospective randomized trials are needed to help guide evidence-based management.

The impact of immunosuppressive therapy (IS) strategies after kidney transplant failure (KTF) on potential future new grafts is poorly established. We assessed the potential benefit of calcineurin inhibitor (CNI)-based IS maintenance throughout the dialysis period on the outcome of the second kidney transplant (KT). We identified 407 patients who underwent a second KT between January 2008 and December 2018 at four French KT centers. Inverse probability of treatment weighting was used to control for potential confounding. We included 205 patients with similar baseline characteristics at KTF: a total of 53 received at least CNIs on the retransplant day (G-CNI), and 152 did not receive any IS (G-STOP). On the retransplant date, G-STOP patients experienced a longer pretransplant dialysis time, were more often hyperimmunized, and underwent more expanded-criteria donor KTs than G-CNI patients. During the second KT follow-up period, rejection episodes were similar in both groups. The 10-year survival rates without death and dialysis were 98.7% and 59.5% in G-CNI and G-STOP patients, respectively. In the multivariable analysis, CNI-based IS maintenance was associated with better survival (hazard ratio: 0.08; 95% confidence interval: 0.01-0.58, p = 0.01). CNI-based IS maintenance throughout the dialysis period after KTF may improve retransplantation outcomes.

Prolonged immunosuppression after dialysis start has been assumed to reduce sensitization, need for graft nephrectomy, and to favor re-transplantation. In contrast, immunosuppression is considered to increase the risk of mortality, infection, and malignancy. We aimed to assess the evidence regarding superiority of early or late withdrawal of maintenance immunosuppression post renal transplant failure.

A literature search of the PubMed, WOS, Ovid, and Scopus databases was conducted. Combined relative risks, (RRs), mean differences, and 95% confidence intervals (CIs) were calculated by using a random-effect model.

Ten studies involving 1187 patients with kidney transplant failure were included. No difference could be detected between patients with early withdrawal of  immunosuppressive drugs (≤ 3 months) or prolonged immunosuppressive treatment (> 3 months) regarding mortality (95% CI 0.91-2.28), panel reactive antibodies (PRAs) (95% CI - 0.75-30.10), re-transplantation rate (95% CI 0.55-1.35), infectious episodes (95% CI 0.67, 1.17), cancer (95% CI 0.26-1.54), and graft nephrectomy (95% CI 0.82-1.63). Similarly, no difference was found between immunosuppressive drug withdrawal over < 6 or ≥ 6 months regarding mortality (95% CI 0.16, 2.89), re-transplantation rate (95% CI 0.85-1.55), cancer (95% CI 0.37-1.63), and allograft nephrectomy (95% CI 0.87-4.33).

Prolonged maintenance immunosuppression post kidney transplant failure is not associated with increased risk of mortality, infection, or malignancy, or reduced risk of sensitization or allograft nephrectomy compared with early withdrawal.

Early (<14 days) renal transplant vein thrombosis posttransplant (eRVTPT) is a rare but threatening complication. We aimed to assess eRVTPT management and the rate of functional renal transplantation. Of 11,172 adult patients who had undergone transplantation between 01/1997 and 12/2020 at 6 French centres, we identified 176 patients with eRVTPT (1.6%): 16 intraoperative (Group 1, G1) and 160 postoperative (Group 2, G2). All but one patient received surgical management. Patients in group G2 had at least one imaging test for diagnostic confirmation (N = 157, 98%). During the operative management of the G2 group, transplantectomy for graft necrosis was performed immediately in 59.1% of cases. In both groups, either of two techniques was preferred, namely, thrombectomy by renal venotomy or thrombectomy + venous anastomosis repair, with no difference in the functional graft rate (FGR) at hospital discharge (p = NS). The FGR was 62.5% in G1 and 8.1% in G2 (p < 0.001). Numerous complications occurred during the initial hospitalization: 38 patients had a postoperative infection (21.6%), 5 experienced haemorrhagic shock (2.8%), 29 exhibited a haematoma (16.5%), and 97 (55.1%) received a blood transfusion. Five patients died (2.8%). Our study confirms the very poor prognosis of early renal graft venous thrombosis.