Short-term Effects of Tolvaptan in Individuals With Autosomal Dominant Polycystic Kidney Disease at Various Levels of Kidney Function

Am J Kidney Dis. 2015 Jun;65(6):833-41. doi: 10.1053/j.ajkd.2014.11.010. Epub 2015 Jan 15.


Background: A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance≥60mL/min. The aim of our study was to determine whether the renal hemodynamic effects and pharmacodynamic efficacy of tolvaptan in ADPKD are dependent on GFR.

Study design: Clinical trial with comparisons before and after treatment.

Setting & participants: Patients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting.

Intervention: Participants were studied at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120mg/d in weeks 1, 2, and 3, respectively).

Outcomes: Change in markers for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine volume, and plasma copeptin) and kidney injury (TKV and kidney injury biomarkers).

Measurements: GFR was measured by (125)I-iothalamate clearance; TKV, by magnetic resonance imaging; biomarker excretion, by enzyme-linked immunosorbent assay; and osmolality, by freezing point depression.

Results: In 27 participants (52% men; aged 46±10 years; mGFR, 69±39mL/min; TKV, 2.15 [IQR, 1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and free-water clearance and a decrease in urine osmolality, TKV, and kidney injury marker excretion. Changes in urine volume and osmolality with treatment were less in participants with lower baseline mGFRs (both P<0.01). However, change in fractional free-water clearance was greater at lower baseline mGFRs (P=0.001), suggesting that participants with decreased GFRs responded more to tolvaptan per functioning nephron.

Limitations: Limited sample size, no control group.

Conclusions: In patients with ADPKD with decreased kidney function, response to tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for fractional free-water clearance. This latter finding suggests that patients with ADPKD with lower GFRs might benefit from long-term treatment with tolvaptan, as has been observed for patients with preserved GFRs.

Keywords: Autosomal dominant polycystic kidney disease (ADPKD); disease progression; drug efficacy; glomerular filtration rate (GFR); kidney function; tolvaptan; vasopressin V(2) receptor antagonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / metabolism
  • Adult
  • Antidiuretic Hormone Receptor Antagonists / therapeutic use*
  • Benzazepines / therapeutic use*
  • Biomarkers / metabolism
  • Cohort Studies
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glomerular Filtration Rate*
  • Glycopeptides / blood
  • Humans
  • Kidney / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size
  • Osmolar Concentration
  • Polycystic Kidney, Autosomal Dominant / complications
  • Polycystic Kidney, Autosomal Dominant / drug therapy*
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Prospective Studies
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / etiology
  • Renal Insufficiency, Chronic / metabolism
  • Severity of Illness Index
  • Tolvaptan
  • Treatment Outcome


  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Biomarkers
  • Glycopeptides
  • copeptins
  • Tolvaptan