title: Serum tryptase concentration and progression to end-stage renal disease.
abstract: BACKGROUND
  Mast cell activation can lead to nonclassical activation of the Renin-Angiotensin-Aldosterone System. However, the relevance of this to human chronic kidney disease is unknown. We assessed the association between serum tryptase, a product of mast cell activation, and progression to end-stage renal disease or mortality in patients with advanced chronic kidney disease. We stratified patients by use of angiotensin-converting enzyme inhibitors/angiotensin receptor II blockers (ACEi/ARB).
  
  
  METHODS
  This was a prospective cohort study of 446 participants recruited into the Renal Impairment in Secondary Care study. Serum tryptase was measured at recruitment by sandwich immunoassay. Cox regression analysis was undertaken to determine variables associated with progression to end-stage renal disease or death.
  
  
  RESULTS
  Serum tryptase concentration was independently associated with progression to end-stage renal disease but not with death. In patients treated with ACEi or ARB, there was a strong independent association between higher tryptase concentrations and progression to end-stage renal disease; when compared to the lowest tertile, tryptase concentrations in the middle and highest tertiles had hazard ratios [HR] of 5·78 (95% confidence interval [CI] 1·19-28·03, P = 0·029) and 6·19 (95% CI 1·49-25·69, P = 0·012), respectively. The other independent risk factors for progression to end-stage renal disease were lower age, male gender, lower estimated glomerular filtration rate and higher urinary albumin creatinine ratio.
  
  
  CONCLUSIONS
  Elevated serum tryptase concentration is an independent prognostic factor for progression to end-stage renal disease in patients with chronic kidney disease who are receiving treatment with an ACEi or ARB.
authors.affiliation: Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.|School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Jesky
authors.affiliation: Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.|School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Stringer
authors.affiliation: Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.|School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Fenton
authors.affiliation: Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Khai Ping
authors.initials: KP
authors.lastname: Ng
authors.affiliation: Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.|School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Punit
authors.initials: P
authors.lastname: Yadav
authors.affiliation: Clinical Immunology Service, University of Birmingham, Birmingham, UK.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ndumbo
authors.affiliation: Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Katerina
authors.initials: K
authors.lastname: McCann
authors.affiliation: Clinical Immunology Service, University of Birmingham, Birmingham, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Plant
authors.affiliation: Renal Unit, Heart of England NHS Foundation Trust, Birmingham, UK.
authors.forename: Indranil
authors.initials: I
authors.lastname: Dasgupta
authors.affiliation: The Binding Site Group Limited, Birmingham, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Harding
authors.affiliation: Clinical Immunology Service, University of Birmingham, Birmingham, UK.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.affiliation: Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Redegeld
authors.affiliation: Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.|School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ferro
authors.affiliation: Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.|School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
mesh_terms: D000367:Age Factors; D000368:Aged; D000419:Albuminuria; D000581:Amidohydrolases / Q000652:urine; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D012084:Renin-Angiotensin System; D012306:Risk; D012307:Risk Factors; D012737:Sex Factors; D053802:Tryptases / Q000097:blood*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D053802:Tryptases; D000581:Amidohydrolases; C019946:creatininase
keywords: Chronic kidney disease; end-stage renal disease; mortality risk; progression of renal failure; risk factors