Meucci Maria Chiara, Reinders Marlies E J, Groeneweg Koen E, Bezstarosti Suzanne, Marsan Nina Ajmone, Bax Jeroen J, De Fijter Johan W, Delgado Victoria
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands; Erasmus MC Transplant Institute, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
J Am Soc Echocardiogr. 2023 Feb;36(2):172-179. doi: 10.1016/j.echo.2022.10.022. Epub 2022 Nov 5.
Autologous bone marrow-derived mesenchymal stromal cell (MSC) therapy and withdrawal of calcineurin inhibitors (CNIs) has been shown to improve systemic blood pressure control and left ventricular hypertrophy regression in kidney transplant recipients. In the current subanalysis, we aimed to evaluate the impact of this novel immunosuppressive regimen on the longitudinal changes of left atrial (LA) structure and function after kidney transplantation.
Kidney transplant recipients randomized to MSC therapy-infused at weeks 6 and 7 after transplantation, with complete discontinuation at week 8 of tacrolimus (MSC group)-or standard tacrolimus dose (control group) were evaluated with transthoracic echocardiography at weeks 4 and 24 after kidney transplantation. The changes in echocardiographic parameters were compared between the randomization arms using an analysis of covariance model adjusted for baseline variable.
Fifty-four participants (MSC therapy = 27; tacrolimus therapy = 27) were included. There was no significant interaction between the allocated treatment and the changes of indexed maximal LA volume (LAVImax) over the study period. Conversely, between 4 and 24 weeks post-transplantation, an increase in indexed minimal LA volume (LAVImin) was observed in control subjects, while it remained unchanged in the MSC group, leading to a significant difference between groups (P = .021). Additionally, patients treated with MSC therapy showed a benefit in LA function, assessed by a significant interaction between changes in LA emptying fraction and LA reservoir strain and the randomization arm (P = .012 and P = .027, respectively).
The combination of MSC therapy and CNIs withdrawal prevents progressive LA dilation and dysfunction in the first 6 months after kidney transplantation. LAVImin and LA reservoir strain may be more sensitive markers of LA reverse remodeling, compared with LAVImax.
自体骨髓间充质基质细胞（MSC）疗法及停用钙调神经磷酸酶抑制剂（CNIs）已被证明可改善肾移植受者的全身血压控制及左心室肥厚消退情况。在本次亚组分析中，我们旨在评估这种新型免疫抑制方案对肾移植后左心房（LA）结构和功能纵向变化的影响。
将肾移植受者随机分为两组，一组在移植后第6周和第7周输注MSC疗法，并在第8周完全停用他克莫司（MSC组），另一组采用标准他克莫司剂量（对照组）。在肾移植后第4周和第24周，通过经胸超声心动图对两组患者进行评估。使用针对基线变量调整的协方差分析模型比较随机分组组间超声心动图参数的变化。
纳入54名参与者（MSC疗法组 = 27名；他克莫司疗法组 = 27名）。在研究期间，分配的治疗与指数化最大LA容积（LAVImax）变化之间无显著交互作用。相反，在移植后4至24周，对照组患者的指数化最小LA容积（LAVImin）增加，而MSC组则保持不变，导致两组间存在显著差异（P = 0.021）。此外，接受MSC疗法治疗的患者在LA功能方面表现出益处，通过LA排空分数变化与LA储备应变变化与随机分组之间的显著交互作用评估（分别为P = 0.012和P = 0.027）。
MSC疗法与停用CNIs相结合可预防肾移植后前6个月LA的渐进性扩张和功能障碍。与LAVImax相比，LAVImin和LA储备应变可能是LA逆向重构更敏感的标志物。
