• 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, and Ron T Gansevoort.
• Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
• Am. J. Kidney Dis. 2015 Jun 1;65(6):833-41.

BackgroundA 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 DesignClinical trial with comparisons before and after treatment.Setting & ParticipantsPatients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting.InterventionParticipants 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).OutcomesChange 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).MeasurementsGFR 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.ResultsIn 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.LimitationsLimited sample size, no control group.ConclusionsIn 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.Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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