title: Short-term renal hemodynamic effects of tolvaptan in subjects with autosomal dominant polycystic kidney disease at various stages of chronic kidney disease.
abstract: Vasopressin V2-receptor antagonists may delay disease progression in ADPKD. Trials with V2-receptor antagonists have been performed predominantly in patients with an estimated creatinine clearance of 60 ml/min or more. Here we determined renal hemodynamic effects of the V2-receptor antagonist tolvaptan in 27 patients with ADPKD at various stages of chronic kidney disease: group A: >60, group B: 30-60, and group C: <30 ml/min per 1.73 m(2). Measurements were performed before, after 3 weeks of tolvaptan (up titration to 90/30 mg/day, split dose), and 3 weeks after the last dose of tolvaptan. With tolvaptan, a minor, reversible decrease in GFR ((125)I-iothalamate clearance) was found that reached significance in groups A and B: -7.8 (interquartile range -13.7 to -1.3) and -4.3 (-9.7 to -0.9) ml/min per 1.73 m(2), respectively, but not in group C (GFR decrease -0.7 (-1.1 to 1.5) ml/min/1.73 m(2)). The percentage change in GFR, ERPF ((131)I-hippuran clearance), and filtration fraction with tolvaptan did not differ between the three study groups. No differences between the three study groups were found in other main efficacy variables, besides smaller increases in urine volume in group C during tolvaptan treatment. Tolvaptan was well tolerated, with only two patients withdrawing. Thus, doses of tolvaptan typically used in patients with ADPKD do not produce a difference in renal hemodynamic profile in chronic kidney disease stages 1 through 4, but minor GFR drops may be observed in individual patients.
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Boertien
authors.forename: Esther
authors.initials: E
authors.lastname: Meijer
authors.forename: Paul E
authors.initials: PE
authors.lastname: de Jong
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Frank S
authors.initials: FS
authors.lastname: Czerwiec
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Dorothee
authors.initials: D
authors.lastname: Oberdhan
authors.forename: Susan E
authors.initials: SE
authors.lastname: Shoaf
authors.forename: Holly B
authors.initials: HB
authors.lastname: Krasa
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
mesh_terms: D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017483:Receptors, Vasopressin / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D013997:Time Factors; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D006727:Hormone Antagonists; D017483:Receptors, Vasopressin; D000077602:Tolvaptan; D003404:Creatinine