#3258 Immunosuppression management after kidney transplant failure and its impact on sensitization: where do we stand in 2025? A systematic review with meta-analysis

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Abstract Background and Aims Kidney transplant (KT) recipients who return to dialysis face significant challenges in accessing a second transplant due to HLA sensitization. Although it is recognized that immunosuppression (IS) management after graft failure (KTF) can influence the sensitization status, there are no strong evidence-based guidelines, leading to widely variable clinical practices. This systematic review with meta-analysis aims to evaluate the impact of different IS withdrawal strategies after kidney transplant failure on HLA sensitization. Method We systematically reviewed prospective and retrospective cohort studies assessing the impact of prolonged or earlier IS withdrawal strategies on the following outcomes after graft failure: HLA sensitization (including the development of de novo DSA and average cPRA values or cPRA variation rate) and graft nephrectomy or embolization rates. We conducted a comprehensive search across Medline, Embase, and Cochrane Library and used the ROBINS-I scale to assess the risk of bias. The results were synthesized in a meta-analysis, and combined odds ratios and weighted mean differences were calculated using a random-effects model. The protocol for this meta-analysis was registered within PROSPERO (CRD42024496706). Results From 8008 citations, we identified 12 studies involving 1346 patients that fulfilled the eligibility criteria. Most of these studies were retrospective (n = 11), single-center (n = 10) cohorts and exhibited moderate to serious risk of bias. In all studies, the IS regimens in the prolonged withdrawal group involved maintaining more than one immunosuppressant for at least three months after graft failure. Five studies comprising 600 patients reported post-KTF cPRA absolute values; three studies comprising 316 patients reported cPRA variation rates; four studies comprising 498 patients reported de novo DSA occurrence, and nine studies comprising 1112 patients reported graft nephrectomy or embolization rates. Earlier IS withdrawal was significantly associated with decreased odds of cPRA maintenance (OR 0.22, 95% CI 0.05–0.96) and increased odds of graft nephrectomy or embolization (OR 2.13, 95% CI 1.39–3.26). While earlier IS withdrawal also favored a higher occurrence of de novo DSA (OR 2.41, 95% CI 0.43–13.46) and a higher absolute cPRA value (md +0.87, 95% CI −0.45–2.2), neither of these findings reached statistical significance. Conclusion While prolonged IS withdrawal did not prevent the development of de novo DSA or lower cPRA values, it appeared to have a role in preserving the sensitization status of KT recipients returning to dialysis. Efforts were made to minimize heterogeneity among the included studies, particularly regarding the IS regimens compared and the methods and timing of HLA evaluation. Nonetheless, some heterogeneity remained, which may limit the generalizability of our findings. Importantly, the protective effect of prolonged IS withdrawal against graft intolerance syndrome was consistently observed across studies. This study also underscores the lack of multicenter and prospective research on this increasingly relevant topic, as the number of hypersensitized patients with previous graft failures on transplant waiting lists continues to grow.

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