SP264SIGNIFICANCE OF SERUM SODIUM CONCENTRATION IN THE VERY EARLY TREATMENT PHASE OF CONGESTIVE HEART FAILURE COMPLICATED BY ADVANCED CHRONIC KIDNEY DISEASE: POSTHOC ANALYSIS OF THE K-STAR STUDY

Abstract

Introduction and Aims: The objective of this posthoc analysis was to investigate the clinical significance of pre‐existing hyponatremia (HN) in patients with congestive heart failure (HF) complicated by advanced chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73m2) in the very early treatment phase. Methods: The Kanagawa Aquaresis Investigators Trial of Tolvaptan (TLV) on HF Patients with Renal Impairment (K‐STAR) was a multicenter, open‐labeled, randomized, and controlled prospective clinical study consisting of 81 Japanese patients with congestive HF and residual signs of congestion despite oral furosemide (FUR) treatment (> 40 mg/day). They were randomly assigned to 7‐day treatment with either < 15 mg/day of newly added TLV or < 40 mg/day of increased FUR. Posthoc analysis was conducted for 73 patients, except those for whom some results were not available within 2 days from baseline. We classified these patients into two groups according to their serum sodium level (sNa): HN (sNa < 135 mEq/L, n = 15) and non‐HN (sNa > 135 mEq/L, n = 58). Subsequently, each group was also stratified into two subgroups (increased sNa; inc‐sNa, and decreased sNa; dec‐sNa) according to whether sNa increased in 48 hours after adding on TLV to FUR or increasing FUR. Results: Analysis of baseline characteristics showed that systolic blood pressure (102.6 +/‐ 13.6 vs 117.1 +/‐ 23.0 mmHg, P = 0.023) and fractional excretion of urea (25.9 +/‐ 13.2 vs 38.5 +/‐ 29.1%, P = 0.019) were significantly lower in the HN than non‐HN group. Plasma renin activity (18.5 +/‐ 15.6 vs 4.6 +/‐ 4.4 ng/mL/h, P < 0.001) and the percentage of patients with lung congestion (80.0 vs 74.1%, P = 0.023) were significantly higher in the HN than non‐HN group. The water intake volume was greater in the HN than non‐HN group (910.0 +/‐ 366.5 vs 708.3 +/‐ 309.1 mL/day, P = 0.058). In subgroup analysis, increase in urine volume at 48 hours was smaller in both dec‐sNa subgroups (146.7 +/‐ 683.0 vs 419.3 +/‐ 432.3 mL/day in HN group, P = 0.470; 71.9 +/‐ 315.9 vs 321.5 +/‐ 681.2 mL/day in non‐HN group, P = 0.133). In the HN group, body weight reduction at 48 hours was significantly lower in the dec‐sNa than inc‐sNa subgroup (0.0 +/‐ 0.5 vs ‐1.0 +/‐ 0.9 kg, P = 0.042) and serum creatinine level was significantly higher in the dec‐sNa than inc‐sNa subgroup (3.0 +/‐ 1.0 vs 1.6 +/‐ 0.4 mg/dL, P = 0.014). The mean dose (8.9 vs 7.5 mg/day, P = 0.747) and the percentage of patients (66.7 vs 66.7%, P = 1.000) for newly added TLV were not statistically different between the inc‐sNa and dec‐sNa subgroups. However, the mean total FUR dose was significantly higher in the dec‐sNa than inc‐sNa subgroup (100.0 +/‐ 20.0 vs 56.7 +/‐ 25.3 mg/dL, P = 0.027). Conclusions: In this posthoc study, congestive HF patients with HN tended to have the "wet and cold" profile at baseline. Moreover, the dec‐sNa subgroup in the HN group had worse kidney function and showed lesser urine volume and body weight reduction in the very early treatment phase, regardless of higher doses of FUR[53rd ERA‐EDTA Congress Vienna Austria. Conference Start: 20160521 Conference End: 20160524.]