#4703 IMPACT OF THE EARLY STAGES OF CKD WITH AND WITHOUT PROTEINURIA ON CARDIOVASCULAR OUTCOMES IN THE UK BIOBANK COHORT

Abstract Background and Aims Chronic kidney disease (CKD) is an established predictor of cardiovascular disease. However, the relationship between cardiovascular disease and the 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, is lacking. In this study, we explored the incidence of major adverse cardiovascular events (MACE), heart failure (HF) and all-cause mortality of participants with early stages of CKD in the UK Biobank population. Method 456,015 participants from the UK Biobank 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 demonstrated the survival probability of adverse outcomes using unadjusted Kaplan-Meier curves and performed an adjusted Cox proportional hazard analysis to include MACE, HF, MACE and HF and all-cause mortality across CKD stages. Results Among the participants (mean age ± standard deviation, 56.5 ± 8.1 years) 282,121 (61.9%) had normal kidney function, 33,582 (7.4%) stage 1 CKD, 121,358 (26.6%) stage 2 CKD without proteinuria, 10,788 (2.4%) stage 2 CKD with proteinuria, 4,654 (1.0%) CKD stage 3A (eGFR 59-45mL/min per 1.73 m2) without proteinuria, 1034 (0.2%) stage 3A with proteinuria and 1,478 (0.3%) with more advanced CKD defined as stages 3B and above. Using Cox regression setting normal kidney function as the reference group, with the exception of stage 2 CKD without proteinuria; there was a progressive increase in the hazard ratio (HR) in all other stages of CKD with respect to MACE, HF, MACE and HF (Figure 1). Significantly, stage 2 CKD without proteinuria was associated with a lower incidence of adverse events than stage 1 CKD and had a comparable prognosis to normal renal function. There was a statistically significant association between stage 2 with proteinuria and MACE (HR 1.33, CI: 1.26 – 1.41), which was comparable to stage 3A without proteinuria (HR 1.32, CI: 1.22 – 1.42). Preliminary analysis of the ongoing cardiac magnetic resonance imaging (cMRI) data from this cohort shows similar progressive changes, apart from stage 2 CKD without proteinuria. Conclusion The presence of proteinuria in patients with mild CKD is a significant risk factor for MACE, HF, cMRI changes and all-cause mortality independent of age, sex, ethnicity, height, BMI, hypertension, diabetes, smoking status, and hyperlipidaemia. We recommend that in order to better risk stratify patients for prognostication and early treatment, stage 2 CKD should be considered as a significant cardiovascular risk only in the presence of proteinuria.