Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• American journal of kidney diseases, 2015-06, Vol.65 (6), p.833-841

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 ≥ 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 by125 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.