title: Tolvaptan and Kidney Pain in Patients With Autosomal Dominant Polycystic Kidney Disease: Secondary Analysis From a Randomized Controlled Trial.
abstract: BACKGROUND
  Kidney pain is a common complication in patients with autosomal dominant polycystic kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on kidney pain in this patient group. Because pain is difficult to measure, the incidence of kidney pain leading to objective medical interventions was used in the present study to assess pain.
  
  
  METHODS
  Secondary analysis from a randomized controlled trial.
  
  
  METHODS
  Patients with ADPKD with preserved kidney function.
  
  
  METHODS
  Tolvaptan or placebo.
  
  
  RESULTS
  Kidney pain events defined by objective medical interventions.
  
  
  METHODS
  Kidney pain events were recorded and independently adjudicated. Incidence of a first kidney pain event was assessed overall and categorized into 5 subgroups according to severity.
  
  
  RESULTS
  Of 1,445 participating patients (48.4% women; mean age, 39±7 [SD] years; mean estimated glomerular filtration rate, 81±22mL/min/1.73m2; median total kidney volume, 1,692 [IQR, 750-7,555] mL), 50.9% reported a history of kidney pain at baseline. History of urinary tract infections, kidney stones, or hematuria (all P<0.001) and female sex (P<0.001) were significantly associated with history of kidney pain. Tolvaptan use resulted in a significantly lower incidence of kidney pain events when compared to placebo: 10.1% versus 16.8% (P<0.001), with a risk reduction of 36% (HR, 0.64; 95% CI, 0.48-0.86). The reduction in pain event incidence by tolvaptan was found in all groups irrespective of pain severity and was independent of predisposing factors (P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, kidney stones, and hematuria when compared to placebo.
  
  
  CONCLUSIONS
  Trial has specific inclusion criteria for total kidney volume and kidney function.
  
  
  CONCLUSIONS
  Tolvaptan decreased the incidence of kidney pain events independent of patient characteristics predisposing for kidney pain and possibly in part due to reductions in ADPKD-related complications.
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Niek F
authors.initials: NF
authors.lastname: Casteleijn
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc, Rockville, MD.
authors.forename: Jaime D
authors.initials: JD
authors.lastname: Blais
authors.affiliation: Division of Nephrology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Arlene B
authors.initials: AB
authors.lastname: Chapman
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc, Rockville, MD.
authors.forename: Frank S
authors.initials: FS
authors.lastname: Czerwiec
authors.affiliation: Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: Department of Urology, Kyorin University School of Medicine, Mitaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Higashihara
authors.affiliation: Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Leliveld
authors.affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc, Rockville, MD.
authors.forename: John
authors.initials: J
authors.lastname: Ouyang
authors.affiliation: Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Perrone
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: r.t.gansevoort@umcg.nl.
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
mesh_terms: D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D008297:Male; D010146:Pain / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control*; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications*; D011446:Prospective Studies; D016037:Single-Blind Method; D013997:Time Factors; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan
keywords: Autosomal dominant polycystic kidney disease (ADPKD); TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) 3:4; acute kidney pain event; analgesic; pain; pain severity; tolvaptan; vasopressin