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Advances in kidney transplantation and immunosuppression have resulted in significant improvements in short-term kidney allograft survival but long-term graft survival remains suboptimal. This has led to an increased prevalence of patients with graft loss returning to dialysis and relisted to a subsequent kidney transplant (KT). (1Hickey M. J. Singh G. Lum E. L. Continuation of immunosuppression vs. immunosuppression weaning in potential repeat kidney transplant candidates: a care management perspective. Frontiers in Nephrology. 2023 Jun 7; 31163581Crossref Google Scholar) A major challenge for these patients is HLA sensitization and patients waiting for a retransplant represent the majority of the highly sensitized. (2Tafulo S. Malheiro J. Dias L. Almeida M. Martins L. S. Pedroso S. et al. Eplet-based virtual PRA increases transplant probability in highly-sensitized patients. Transpl Immunol. 2021 Apr 1; 65101362Crossref Scopus (2) Google Scholar) In Portugal, there is a major concern about the growing number of highly sensitized patients waiting for a KT. Patients with a calculated PRA≥98% account for more than 30% of the total list, and 93. 6% of these have a previously failed kidney graft. (2Tafulo S. Malheiro J. Dias L. Almeida M. Martins L. S. Pedroso S. et al. Eplet-based virtual PRA increases transplant probability in highly-sensitized patients. Transpl Immunol. 2021 Apr 1; 65101362Crossref Scopus (2) Google Scholar) Several strategies are being developed to overcome the barrier of sensitization and improve the access to retransplantation in Portugal including a new allocation system that prioritizes HLA matching and a special program for the highly sensitized. However, one of the most complex and controversial decisions arising upon transplant failure, that might significantly impact HLA sensitization, is the appropriate approach for immunosuppression tapering. Maintaining immunosuppressive therapy may preserve residual renal function, prevent graft intolerance syndrome and perhaps allosensitization, but also enhances the risk of infections, metabolic side effects, and malignancy. Unfortunately, there is no consensus on the best approach on immunosuppression management following graft failure, and only the British Transplantation Society has published guidelines. (3UK GUIDELINE FOR THE MANAGEMENT OF THE PATIENT WITH A FAILING KIDNEY TRANSPLANT - British Transplantation Society Internet. cited 2024 Mar 9. Available from: https: //bts. org. uk/uk-guideline-for-the-management-of-the-patient-with-a-failing-kidney-transplant/Google Scholar) Data is scarce, reflecting on different practice patterns among different centers and among different nephrologists within the same hospital. (4Elgenidy A. Shemies R. S. Atef M. Awad A. K. El-Leithy H. H. Helmy M. et al. Revisiting maintenance immunosuppression in patients with renal transplant failure: early weaning of immunosuppression versus prolonged maintenance—systematic review and meta-analysis. J Nephrol Internet. 2023 Mar 1; 36 (cited 2024 Mar 13) (Available from: https: //link. springer. com/article/10. 1007/s40620-022-01458-y): 537-550Crossref Scopus (2) Google Scholar) Considering the impact of the highly sensitized patients in Portugal, we surveyed Portuguese nephrologists' practices on immunosuppression withdrawal post renal graft failure. There are seven kidney transplant centers in Portugal, and in the last 10 years a mean of 465±43. 5 kidney transplants were performed annually, corresponding to a mean rate of kidney transplant per million population of 46. 75±4. 3, one of the highest in Europe. (5https: //ipst. pt/index. php/pt/dados-estatisticos-transplantacao, accessed on the 6th of May 2024Google Scholar, 6https: //www. spnefro. pt/assets/relatorios/tratamentodoencaₜerminal/er2023ᵣegisto. pdf, accessed on the 6th of May 2024Google Scholar). We conducted a national survey of five short questions addressed to a total of 385 Nephrology residents and specialists who practiced in Portugal in 2021, through email distribution by the Portuguese Society of Nephrology. We received a total of 90 responses, 49 participants (54. 4%) were currently working at renal transplant units but all the respondents had experience with IS withdrawal post graft failure. When faced with a patient returning to dialysis after graft loss, all participants immediately discontinued mycophenolate mofetil or equivalent, 66. 7% (n=60) maintained the calcineurin inhibitor and prednisolone, and 33. 3% (n=30) maintained only prednisolone (table 1). Among those who maintain calcineurin inhibitors and steroids, 46. 6% (n=28) wean calcineurin inhibitors within 6 months to 1 year following graft loss, 23% (n=14) discontinue calcineurin inhibitors within 3 to 6 months, and 30% (n=18) discontinue calcineurin inhibitors before the first three months after graft loss. Considering steroids, 36. 7% (N=32) discontinue prednisone after one-year post graft loss, and 64. 3% (N=58) maintain steroids indefinitely or until graft removal or steroid-associated complications. The majority (83. 3%, n=75) agreed that the risk of graft intolerance syndrome is the main factor in deciding to maintain immunosuppression, followed by the possibility of re-transplantation (56. 7%, n=51) and the risk of infection was the major concern to withdrawal (55. 6%, n=50). All the participants agreed that IS withdrawal strategy is an important issue in kidney transplantation that needs further investigation. Table 1Immunosuppression practices among Portuguese NephrologistsImmunosuppression management% (n) Overall approach to graft failureMaintain calcineurin inhibitor and prednisolone66. 7 (60) Maintain only prednisolone33. 3 (30) Calcineurin inhibitor managementWean within 6 months to 1 year46. 6 (28) Discontinue within 3 to 6 months23 (14) Discontinue before the first three months30 (18) Steroid managementDiscontinue prednisone after one year36. 7 (32) Maintain steroids indefinitely or until graft removal or complications64. 3 (58) Factors influencing decisions on maintenance of immunosuppressionRisk of toxic rejection of the graft83. 3 (75) Possibility or re-transplantation56. 7 (51) Risk of infection55. 6 (50) Open table in a new tab In this survey, we confirmed that practices regarding immunosuppression withdrawal vary widely among physicians, reflecting the lack of consensus on this matter. With the increasing numbers of kidney transplant recipients returning to dialysis, questions on immunosuppression management should be prioritized, given its significant clinical implications. Our group is currently performing a prospective study to compare the impact of maintain calcineurin inhibitors for six months versus withdrawal in KT recipients experiencing graft loss and subsequently include it in a meta-analysis. Hopefully, data from this work will help us to improve the care of patients with renal graft loss. Nothing to disclose.
Leal et al. (Sat,) studied this question.