Focus Topic: Left Atrial Mechanics and Remodeling
Clinical Investigations
Left Atrial Structural and Functional Response in Kidney Transplant Recipients Treated With Mesenchymal Stromal Cell Therapy and Early Tacrolimus Withdrawal

https://doi.org/10.1016/j.echo.2022.10.022Get rights and content

Highlights

  • MSC therapy combined with CNIs withdrawal was tested in kidney transplant recipients.

  • MSC therapy prevented an increase in LAVImin.

  • There were no differences in the changes of LAVImax.

  • MSC strategy was also associated with a benefit in LA functional parameters.

  • Minimal LA volume and LA function are sensitive markers of LA reverse remodeling.

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Section snippets

Study Design and Population

In this echocardiographic subanalysis of the TRITON trial (NCT03398681),2 patients who underwent transthoracic echocardiography with speckle-tracking analysis at 4 and 24 weeks post-transplantation were included. In brief, the TRITON trial was a 24-week randomized, prospective, single-center clinical study investigating the combination of MSC therapy and early tacrolimus withdrawal as a novel immunosuppressive strategy after kidney transplantation.2 A total of 70 recipients of a first renal

Results

Of 70 patients initially enrolled in the trial, 13 subjects were excluded due to abnormal MSC growth (n = 4), contraindication for MSC therapy during the COVID-19 pandemic (n = 1), impossibility of obtaining a baseline renal biopsy (n = 3), withdrawal of the informed consent (n = 4), and contraindication for prednisone usage (n = 1). Therefore, the study population was composed by 57 patients, which were randomly assigned to the MSC group (n = 29) or control group (n = 28). Transthoracic

Discussion

The present study showed that MSC therapy combined with early discontinuation of CNIs prevents progressive LA dilation and dysfunction in recipients of kidney transplantation compared with a tacrolimus-based regimen. Notably, LAVImin and LA reservoir strain emerged as more sensitive markers of LA reverse remodeling in comparison to LAVImax.

Patients with CKD as well as kidney transplant recipients are at increased risk of cardiovascular disease.11 Current immunosuppressive treatments,

Conclusion

The combination of MSC therapy and early CNIs withdrawal may prevent LA structural and functional remodeling in the first 6 months after kidney transplantation compared with a standard tacrolimus regimen. The early response of LAVImin and LA reservoir strain in patients treated by MSC strategy supports their value as more sensitive markers of LA reverse remodeling compared with LAVImax.

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    Conflicts of Interest: The Department of Cardiology, Heart Lung Center, Leiden University Medical Center, received research grants from Abbott Vascular, Bayer, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare, and Edwards Lifesciences. J.B. received speaker fees from Abbott Vascular and Edwards Lifesciences. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare and a research grant from Alnylam and has been on the Medical Advisory Board of Philips Ultrasound. V.D. received speaker fees from Abbott Vascular, Medtronic, Edwards Lifesciences, MSD, and GE Healthcare. The remaining authors have nothing to disclose in relation to this paper.

    Thomas H. Marwick, MD, PhD, MPH, served as guest editor for this report.

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