BACKGROUND: The aim of the study was to analyze the potential relationship between the diuretic response, the clinical profile and the concentrations of selected biochemical markers and to identify a group of patients who will benefit from a new form of therapy combining standard diuretic therapy with the use of a RenalGuard® system. METHODS: This is a retrospective study of 19 patients (mean age 67 ± 10 years, 95% men) hospitalized due to acute decompensated heart failure (ADHF, NYHA class III-IV, BP 125 ± 14/73 ± 16 mmHg, eGFR 58 ± 24) with persistent overhydration despite standard therapy. A targeted comparative analysis of selected clinical and biochemical parameters was performed to determine the parameters associated with a better diuretic response [good diuretic responders (GDR) group]. RESULTS: The good diuretic responders group had significantly lower levels of creatinine (1.23 ± 0.4 vs. 1.69 ± 0.35, p = 0.025) magnesium 0.70 ± 0.14 vs. 0.83 ± 0.09, p = 0.030) and blood urea nitrogen (BUN, 28 ± 11 vs. 39 ± 10, p = 0.045). Additionally, in GDR group a statistically significant greater ability to dilute urine in the 12th and 24th hour of therapy was found. CONCLUSIONS: The results of the study indicate the potential use of the RenalGuard® system in combination with standard intravenous diuretic therapy for controlled dehydration in the treatment of a selected group of patients with ADHF. It is advisable to identify the detailed mechanisms of GDR and characterize this group of patients more precisely.