Abstract Background and Aims Volume status, congestion and endothelial activation/injury were found to play a role in GFR decline and CKD progression. This pilot study aimed to determine whether the plasma markers of endothelial injury and activation as well as markers of fluid overload could serve as independent predictors for dialysis initiation in stable patients with CKD 4 and 5 and preserved EF. Method This prospective study was conducted from March 2019 to March 2022 and enrolled consecutive patients with GFR <30ml/min/1.72 m2 and preserved LVEF. Plasma levels of angiopoietin (Ang)-2, Vascular Endothelial Growth Factor-C (VEGF-C), Vascular Cell Adhesion Molecule-1 (VCAM-1), Copeptin (CPP), beta-trace protein (BTP), brain natriuretic peptide (BNP), cardiac troponin I (cTnI) were measured (Quantikine ELISA;R&D Systems Inc, Minneapolis, MN). Clinical markers of congestion were also recorded: lung US (B-lines), bioimpedance (ECV/ICV), echocardiography with global longitudinal strain (GLS), pulse wave velocity (PWV). Study outcome was need to initiate dialysis during 24-months follow-up. Results We analyzed a total of 105 patients with mean eGFR 21,3 ml/min/1.73m. The median age at enrollment was 52 (+/-14.8) years and 65% of the patients were male; 79% were hypertensive and 24% were diabetic. A positive correlation between concentration of Ang-2 and VCAM-1 and BTP was observed. Ang-2 concentration correlated positively with BNP, TnT, sCr, e/e’, ECV/ICV. Over a follow-up period of 24 months, the deterioration of renal function was observed in 47 patients (58%), 31 (38%) presented stable or ameliorated renal function and 24 on maintenance dialysis formed a control group. In Kaplan-Meier analysis significant impact of Ang-2 on renal survival (Figure) was found. Namely, 72% of patients with Ang-2 concentrations below the median (3.15 ng/ml) survived without dialysis for two years, compared to 42% of those with Ang-2 concentrations above the median. Such impact was not observed for GFR, VCAM, CCP, VEGF-C, BTP. Conclusion Endothelial activation, quantified by plasma levels of Ang-2 may play an important role in GFR decline and need for dialysis initiation in patients with CKD 4 and 5.