title: Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy.
abstract: Alport syndrome inevitably leads to end-stage renal disease and there are no therapies known to improve outcome. Here we determined whether angiotensin-converting enzyme inhibitors can delay time to dialysis and improve life expectancy in three generations of Alport families. Patients were categorized by renal function at the initiation of therapy and included 33 with hematuria or microalbuminuria, 115 with proteinuria, 26 with impaired renal function, and 109 untreated relatives. Patients were followed for a period whose mean duration exceeded two decades. Untreated relatives started dialysis at a median age of 22 years. Treatment of those with impaired renal function significantly delayed dialysis to a median age of 25, while treatment of those with proteinuria delayed dialysis to a median age of 40. Significantly, no patient with hematuria or microalbuminuria advanced to renal failure so far. Sibling pairs confirmed these results, showing that earlier therapy in younger patients significantly delayed dialysis by 13 years compared to later or no therapy in older siblings. Therapy significantly improved life expectancy beyond the median age of 55 years of the no-treatment cohort. Thus, Alport syndrome is treatable with angiotensin-converting enzyme inhibition to delay renal failure and therapy improves life expectancy in a time-dependent manner. This supports the need for early diagnosis and early nephroprotective therapy in oligosymptomatic patients.
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany. gross.oliver@med.uni-goettingen.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Gross
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Anders
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoppe
authors.forename: Bodo
authors.initials: B
authors.lastname: Beck
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tönshoff
authors.forename: Britta
authors.initials: B
authors.lastname: Höcker
authors.forename: Simone
authors.initials: S
authors.lastname: Wygoda
authors.forename: Jochen H H
authors.initials: JH
authors.lastname: Ehrich
authors.forename: Lars
authors.initials: L
authors.lastname: Pape
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Müller-Wiefel
authors.forename: Peter
authors.initials: P
authors.lastname: Hoyer
authors.forename: Bertrand
authors.initials: B
authors.lastname: Knebelmann
authors.forename: Yves
authors.initials: Y
authors.lastname: Pirson
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grunfeld
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
authors.forename: Laurence
authors.initials: L
authors.lastname: Heidet
authors.forename: Said
authors.initials: S
authors.lastname: Lebbah
authors.forename: Roser
authors.initials: R
authors.lastname: Torra
authors.forename: Tim
authors.initials: T
authors.lastname: Friede
authors.forename: Katharina
authors.initials: K
authors.lastname: Lange
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
authors.forename: Manfred
authors.initials: M
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology; D008017:Life Expectancy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000188:drug therapy* / Q000503:physiopathology; D051437:Renal Insufficiency / Q000401:mortality* / Q000517:prevention & control* / Q000628:therapy; D017582:Renal Replacement Therapy; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors