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Efficacy of tolvaptan on advanced chronic kidney disease with heart failure: a randomized controlled trial

Shiro Komiya1,2, Mari Katsumata3, Moe Ozawa1,2

  • 1Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Clinical and Experimental Nephrology
|April 26, 2022
PubMed

Insights

Adding tolvaptan (TLV) to furosemide (FUR) significantly increased urine volume in advanced chronic kidney disease (CKD) patients. This combination therapy demonstrated improved renal function and safety compared to increasing FUR dosage alone.

Area of Science:

  • Nephrology
  • Pharmacology
  • Internal Medicine

Background:

  • Patients with chronic kidney disease (CKD) and fluid overload often require diuretic therapy.
  • Furosemide (FUR) is a common diuretic, but its efficacy can be limited in advanced CKD.
  • The addition of tolvaptan (TLV) has been suggested to enhance diuretic effects, but its utility in advanced CKD with heart failure remains unclear.

Purpose of the Study:

  • To evaluate the efficacy and safety of adding tolvaptan (TLV) to furosemide (FUR) in patients with advanced chronic kidney disease (CKD) and fluid overload.
  • To compare the effects of TLV plus standard FUR dosage versus an increased FUR dosage on urine volume and renal function.

Main Methods:

  • An open-label, parallel-group randomized trial involving 33 patients with CKD stage G3-G5 and fluid overload despite adequate FUR.
  • Patients received either 15 mg/day TLV plus their original FUR dose or an increased FUR dose (100 mg/day over previous) for 7 days.
  • Outcomes measured included changes in urine volume, serum creatinine, serum sodium, and incidence of worsening renal function (WRF).

Main Results:

  • The TLV group showed a significantly greater increase in urine volume (637 ml) compared to the FUR group (119 ml).
  • The incidence of worsening renal function (WRF) was significantly lower in the TLV group (18.8%) versus the FUR group (58.8%).
  • Serum creatinine increased only in the FUR group, and serum sodium decreased significantly in the FUR group but not in the TLV group.

Conclusions:

  • Adding tolvaptan (TLV) to furosemide (FUR) is effective in increasing urine volume in advanced CKD patients with fluid overload.
  • This combination therapy offers improved renal function and safety compared to escalating FUR dosage alone.
  • Efficacy and safety of TLV were more pronounced in patients with higher baseline urine osmolality and lower serum sodium.
Abstract

Keywords:
Chronic kidney diseaseFurosemideHeart failureTolvaptanUrine osmolalityWorsening renal function

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