Cardiac Allograft Rejection Induces Changes in Nucleocytoplasmic Transport: RANGAP1 as a Potential Non-Invasive Biomarker.

The non-invasive diagnosis of acute cellular rejection (ACR) is a major challenge. We performed a molecular study analyzing the predictive capacity of serum RanGTPase AP1 (RANGAP1) for diagnosing ACR during the first year after heart transplantation (HT). We included the serum samples of 75 consecutive HT patients, extracted after clinical stability, to determine the RANGAP1 levels through ELISA. In addition, various clinical, analytical, and echocardiographic variables, as well as endomyocardial biopsy results, were collected. RANGAP1 levels were higher in patients who developed ACR (median 63.15 ng/mL; (inter-quartile range (IQR), 36.61-105.69) vs. 35.33 ng/mL (IQR, 19.18-64.59); p = 0.02). Receiver operating characteristic (ROC) curve analysis confirmed that RANGAP1 differentiated between patients with and without ACR (area under curve (AUC), 0.70; p = 0.02), and a RANGAP1 level exceeding the cut-off point (≥90 ng/mL) was identified as a risk factor for the development of ACR (OR, 6.8; p = 0.006). Two independent predictors of ACR identified in this study were higher RANGAP1 and N-terminal pro-brain natriuretic peptide levels. The analysis of the ROC curve of the model showed a significant AUC of 0.77, p = 0.001. Our findings suggest that RANGAP1 quantification facilitates risk prediction for the occurrence of ACR and could be considered as a novel non-invasive biomarker of ACR.

Alterations in the Nucleocytoplasmic Transport in Heart Transplant Rejection.

BACKGROUND: Nucleocytoplasmic transport is a crucial process for cell function. Previous studies have observed alterations in different molecules involved in it, relating them to ventricular function. However, there are no published data evaluating possible differences in the expression of these molecules in heart transplantation (HT) recipients. Our objective is to evaluate whether its levels are related to the appearance of cellular rejection (CR) during the first year after HT. METHODS: A prospective clinical cohort that included patients undergoing HT between January 2017 and January 2019 (n = 46). Blood samples for the analysis of importin 5 (IMP5), nucleoporin 153 (Nup153); RAN-GTPaseAP1 (RanGAP1), and sarcoplasmic reticulum calcium ATPase (ATP-aseCaTransp) were collected approximately 2 months post-HT. The levels obtained were correlated with the incidence of at least moderate CR during the first year of follow-up. RESULTS: Results showed that 17.39% of the patients had at least moderate CR during the first year of follow-up. Higher levels of IMP5, Nup153, and RanGAP1 were observed in this group. This difference was statistically significant in the case of Nup153 and RanGAP1 (15.94 ± 14.00 vs 28.62 ± 23.61, P = .048; 21.95 ± 15.97 vs 40.90 ± 27.16, P = .026, respectively); there was an opposite trend in the ATP-aseCaTransp case. CONCLUSION: Patients with at least a moderate degree of CR during follow-up showed higher serum levels of IMP5, Nup153, and RanGAP1. The prognostic usefulness of the determination of these biomarkers and whether their elevation during follow-up would facilitate early, noninvasive identification of patients with CR remains to be clarified.

Impact of Circulatory Assistance in the Early Evolution After Heart Transplantation. Unicentric Experience.

BACKGROUND: Heart transplantation (HT) is the reference treatment for patients with terminal heart failure. In recent years there has been a progressive increase in HT procedures in patients who have a circulatory support (CS). METHODS: This is a retrospective single-center study of 293 consecutive patients who underwent HT from 2009 to 2018, analyzing the evolution of the 2 cohorts: patients with and without CS as a bridge to HT. Baseline and evolutionary clinical data collected following the usual follow-up protocol were recorded, including clinical events observed during the follow-up 1 year after the procedure. RESULTS: The subgroup of patients transplanted with CS showed a higher incidence of primary graft failure, frequent infection, and mortality. A tendency toward lower cardiac allograft vasculopathy was observed in this subgroup. Mechanical ventilation added to the CS resulted in a higher incidence of primary graft failure, infection, and renal dysfunction. The CS variable as a bridge to HT was shown to be predictive of 1-year mortality in both univariate (odds ratio, 1.84; 95% confidence interval, 1.03-3.3; P = .038) and multivariate (odds ratio, 2.1; 95% confidence interval, 1.01-4.3; P = .047) analyses. CONCLUSIONS: In our experience, CS as a bridge to HT results in a higher incidence of primary graft failure, frequent infection, and mortality at 1-year follow-up. Mechanical ventilation added to CS has a clear unfavorable prognostic impact. CS as a bridge to HT was shown to be predictive of 1-year mortality in both univariate and multivariate analyses.