Impact of early stages of CKD with and without proteinuria on cardiac remodelling in UK Biobank cohort

Abstract Background Chronic kidney disease (CKD) is an established predictor of left atrial (LA) and left ventricular (LV) morphological and functional changes, which translate into excessive cardiovascular morbidity and mortality. However, a focussed study exploring the impact of early stages of CKD defined as stage 1 (eGFR 90 mL/min per 1.73 m2 + albuminuria) and stage 2 (eGFR 60–89 mL/min per 1.73 m2) with and without proteinuria on cardiac magnetic resonance (CMR) parameters is lacking. Purpose In this study, we analysed CMR structural and functional changes in participants with early stages of CKD in the UK Biobank population. Methods 41,095 participants from the UK Biobank imaging study were categorised into CKD stages. We calculated eGFR using the CKD-EPI 2021 equation and proteinuria was ascertained by the urinary protein creatinine ratio (defined as 30mg/mmol). We sought associations between CKD stages (exposure) and CMR parameters: LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), LV ejection fraction (LVEF), LV global functional index (LVGFI), LV myocardial contractile function (LVMCF), LV mass (LVM), LV mass-to-volume ratio (LVMVR), LV global longitudinal strain (GLS), LV global radial strain (GRS), LV global circumferential strain (GCS), LA maximum volume and left atrial emptying fraction. In the multivariable regression model, we adjusted for covariates including age, sex, ethnicity, height, body mass index, hypertension, diabetes, smoking status, and hyperlipidaemia Results Among the participants, 26,779 (65.1%) had normal kidney function, 2,787 (6.8%) stage 1 CKD, 10,534 (25.6%) stage 2 CKD without proteinuria, 689 (1.7%) stage 2 CKD with proteinuria, 241 (0.6%) CKD stage 3A (eGFR 59-45mL/min per 1.73 m2) without proteinuria, 28 (0.1%) stage 3A with proteinuria and 37 (0.1%) with more advanced CKD defined as stages 3B and above. Approximately 8 years after characterisation of CKD stages these participants underwent CMR. Using adjusted multivariable regression models setting normal kidney function as the reference group, the presence of proteinuria in stage 3 CKD was associated with smaller LV volume, lower LVM and more impaired LV function (LVSV beta=-11ml, 95% confidence interval (CI): -5 to -16ml and GLS beta=0.9%, 95% CI: 0.2 to 1.7%). Conclusions This study highlights the relationship between proteinuria in the early stages of CKD and cardiac remodelling patterns using CMR. CKD sub-characterisation with presence or absence of proteinuria should be considered for risk stratification.Figure 1