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

Wendy E. Boertien, Esther Meijer, Paul E. de Jong, Gert J. ter Horst, Remco J. Renken, Eric J. van der Jagt, Peter Kappert, John Ouyang, Gerwin E. Engels, Willem van Oeveren, Joachim Struck, Frank S. Czerwiec, Dorothee Oberdhan, Holly B. Krasa, Ron T. Gansevoort*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

48 Citaten (Scopus)

Samenvatting

Background: A recent study showed that tolvaptan, a vasopressin V-2 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 >= 60 mL/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 120 mg/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 +/- 39 mL/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. (C) 2015 by the National Kidney Foundation, Inc.

Originele taal-2English
Pagina's (van-tot)833-841
Aantal pagina's9
TijdschriftAmerican Journal of Kidney Diseases
Volume65
Nummer van het tijdschrift6
DOI's
StatusPublished - jun-2015

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