Children after kidney transplantation show severe cardiac alterations

Abstract Sudden cardiac death is among the most common causes of death in patients with chronic kidney diseases (CKD) after pediatric kidney transplantation (KTx), but defined diagnostic procedures identifying children at risk are not established. Echocardiographically detectable damage in the context of CKD has been described, but there are few data after KTx in childhood. The aim was to characterize structural and functional cardiac alterations on cardiac MRI (cMRI) and echocardiography in children after KTx and to elucidate the significance of diastolic dysfunction in this special context. 46 KTx recipients (mean age 16.0±3.5 years) and due to missing reference values 46 age- and sex-matched healthy controls were examined with non-contrast cMRI. Native T1 time (nT1), left ventricular mass z-score (LVMIz), ejection fraction (EF), global longitudinal strain (GLS) were measured. KTx recipients underwent comprehensive echocardiography: EF, mitral inflow (E-, A-wave), TDI e', E/e'-ratio, isovolumetric relaxation time (IVRT), pulmonary venous flow (PVFsys, PVFdia), atrial reversal (PVF-AR) and left atrial volume index (LAVI), left ventricular mass z-score (LVMz). Multivariable linear regression analysis (co-variates: age, sex, height) were used to show associations between cMRI and echo parameters. In cMRI KTx recipients had a siginficant higher nT1 than healthy controls (septal: 1198±49ms vs. 1155±23ms, p<0.0001; lateral: 1141±57ms vs. 1109±37ms, p=0.003). In KTx recipients, LVMIz was higher (0.1±1.1g/m2 vs. -0.3±0.7g/m2; p=0.026), GLS was lower than in healthy controls (-19± 2.1% vs. -20.3±2.7%, p=0.01). While based on cMRI 2 patients were diagnosed with left ventricluar hypertrophy (LVH), 11% (n=5) displayed LVH on echo. EF was preserved in all patients. However, in echocardiography, 90% (n=40) of the KTx recipients showed diastolic parameters out of the age-specific normal range (Fig.1) with changes in two or more diastolic parameters in half of the cohort. Associations with septal nT1 on cMRI could be demonstrated for septal E/e´ (ß=8.415, p=0.042), A-wave (ß=1.037, p=0.045), LAVI (ß=3.347, p=0.002) and PVF-AR (ß=2.945, p=0.021); associations with lateral nT1: septal E/e´ (ß=9.590, p=0.045) and LAVI (ß=3.393, p=0.009) (Fig. 2); 7 (15 %) had an elevated nT1 septal, lateral and E/e´ out of the normal range. Young KTx recipients show a high prevalence of diastolic dysfunction with preserved EF. Impaired diastolic function was associated with structural alterations reflecting myocardial fibrosis. Our findings suggest that a large number of children after KTx suffer from heart failure with preserved EF – an entity not yet defined in children but described for adults, in whom it is associated with sudden cardiac death. Further studies are needed to describe the clinical relevance of these findings, which gain explicit importance, as the prognosis of HFpEF in adults is improved by SGLT2i, a treatment option not yet considered in our high-risk patient group.