Prezelin-Reydit Mathilde, Dubois Valérie, Caillard Sophie, Parissiadis Anne, Etienne Isabelle, Hau Françoise, Albano Laetitia, Pourtein Monique, Barrou Benoît, Taupin Jean-Luc, Mariat Christophe, Absi Léna, Vigneau Cécile, Renac Virginie, Guidicelli Gwendaline, Visentin Jonathan, Merville Pierre, Thaunat Olivier, Couzi Lionel
Service de Néphrologie-Transplantation-Dialyse-Aphérèse, Hôpital Pellegrin, CHU de Bordeaux Pellegrin, 33076 Bordeaux, France.
AURAD Aquitaine, 2 allée des demoiselles, 33170 Gradignan, France.
J Clin Med. 2021 May 10;10(9):2032. doi: 10.3390/jcm10092032.
Non-adherence with immunosuppressant medication (MNA) fosters development of de novo donor-specific antibodies (DSA), rejection, and graft failure (GF) in kidney transplant recipients (KTRs). However, there is no simple tool to assess MNA, prospectively. The goal was to monitor MNA and analyze its predictive value for DSA generation, acute rejection and GF.
We enrolled 301 KTRs in a multicentric French study. MNA was assessed prospectively at 3, 6, 12, and 24 months (M) post-KT, using the Morisky scale. We investigated the association between MNA and occurrence of DSA at year 2 post transplantation, using logistic regression models and the association between MNA and rejection or graft failure, using Cox multivariable models.
The initial percentage of MNA patients was 17.7%, increasing to 34.6% at 24 months. Nineteen patients (8.4%) developed DSA 2 to 3 years after KT. After adjustment for recipient age, HLA sensitization, HLA mismatches, and maintenance treatment, MNA was associated neither with DSA occurrence, nor acute rejection. Only cyclosporine use and calcineurin inhibitor (CNI) withdrawal were strongly associated with DSA and rejection. With a median follow-up of 8.9 years, GF occurred in 87 patients (29.0%). After adjustment for recipient and donor age, CNI trough level, DSA, and rejection, MNA was not associated with GF. The only parameters associated with GF were DSA occurrence, and acute rejection.
Prospective serial monitoring of MNA using the Morisky scale does not predict DSA occurrence, rejection or GF in KTRs. In contrast, cyclosporine and CNI withdrawal induce dnDSA and rejection, which lead to GF.
肾移植受者(KTRs)不坚持服用免疫抑制剂(MNA)会促进新的供者特异性抗体(DSA)的产生、排斥反应和移植肾失功(GF)。然而,目前尚无简单的前瞻性评估MNA的工具。本研究旨在监测MNA,并分析其对DSA产生、急性排斥反应和移植肾失功的预测价值。
我们在一项法国多中心研究中纳入了301例KTRs。肾移植术后3、6、12和24个月(M)时,使用Morisky量表对MNA进行前瞻性评估。我们使用逻辑回归模型研究MNA与移植后2年DSA发生之间的关联,并使用Cox多变量模型研究MNA与排斥反应或移植肾失功之间的关联。
MNA患者的初始比例为17.7%,24个月时增至34.6%。19例患者(8.4%)在肾移植后2至3年出现DSA。在对受者年龄、HLA致敏、HLA错配和维持治疗进行调整后,MNA与DSA发生及急性排斥反应均无关联。仅使用环孢素和停用钙调神经磷酸酶抑制剂(CNI)与DSA及排斥反应密切相关。中位随访8.9年,87例患者(29.0%)发生移植肾失功。在对受者和供者年龄、CNI谷浓度、DSA和排斥反应进行调整后,MNA与移植肾失功无关联。与移植肾失功相关的唯一参数是DSA发生和急性排斥反应。
使用Morisky量表对MNA进行前瞻性连续监测不能预测KTRs中DSA的发生、排斥反应或移植肾失功。相反,停用环孢素和CNI会诱导新发DSA和排斥反应,进而导致移植肾失功。