Kidney Week

Abstract: TH-OR071

Renoprotection by Long-Term Low-Dose Tolvaptan for Congestive Heart Failure Is Pronounced in Hyponatremia

Session Information

• Fluid and Electrolytes: Clinical Resesearch
  November 07, 2019 | Location: 144, Walter E. Washington Convention Center
  Abstract Time: 05:06 PM - 05:18 PM

Category: Fluid and Electrolytes

• 902 Fluid and Electrolytes: Clinical

Authors

• Oka, Tatsufumi, Osaka University Graduate School of Medicine, Suita, Japan

Tatsufumi Oka, MD

• Hamano, Takayuki, Osaka University Graduate School of Medicine, Suita, Japan

Takayuki Hamano,

• Doi, Yohei, Osaka University Graduate School of Medicine, Suita, Japan

Yohei Doi,

• Yamaguchi, Satoshi, Osaka University Graduate School of Medicine, Suita, Japan

Satoshi Yamaguchi,

• Sakaguchi, Yusuke, Osaka University Graduate School of Medicine, Suita, Japan

Yusuke Sakaguchi,

• Matsui, Isao, Osaka University Graduate School of Medicine, Suita, Japan

Isao Matsui,

• Isaka, Yoshitaka, Osaka University Graduate School of Medicine, Suita, Japan

Yoshitaka Isaka,

Background

Reportedly, tolvaptan (TLV), a selective vasopressin V2-receptor antagonist, did not lead to 1-year renoprotection in congestive heart failure (CHF), when its dose was set to be 30 mg/day. We aimed to examine the effects of its lower-dose therapy on long-term renal outcome in CHF.

Methods

In this retrospective cohort study, we enrolled hospitalized patients with acute decompensated heart failure (ADHF) in an educational hospital. TLV users were defined as patients receiving flexible doses of TLV for at least consecutive 180 days or those who continued TLV therapy until death, renal replacement therapy, implantation of a ventricular assist device, or heart transplantation, even if duration of the therapy was less than 180 days. We compared estimated glomerular filtration rate (eGFR) trajectories between TLV users and never-users, using multivariable mixed effects models with time-dependent eGFR as a dependent variable. We explored effect modification by baseline serum sodium levels for the relationship between TLV therapy and annualized eGFR slope, using a multivariable fractional polynomial interaction algorithm.

Results

Of total 584 patients, 78 TLV users were found. The median TLV dose, baseline B-type natriuretic peptide (BNP), and eGFR were 7.5 mg/day, 243 pg/mL, and 54 mL/min/1.73m², respectively. TLV users had higher eGFR trajectories than never-users (P <0.01) during a median follow-up period of 66 weeks (Figure 1). Additional adjustment for time-dependent BNP levels, ADHF hospitalization, and the number of loop diuretics' dose reductions extinguished the difference in eGFR. In hyponatremic patients, renoprotection by TLV was pronounced in terms of eGFR slope (p_interaction =0.02) (Figure 2). This effect modification was extinguished when the analysis was restricted to patients without subsequent cardiac events or those receiving a stable dose of loop diuretics.

Conclusion

Long-term therapy of low-dose TLV is renoprotective in patients with CHF, in particular, hyponatremic patients, possibly by dose sparing in loop diuretics and improvement of CHF.