title: PKD2-Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis.
abstract: BACKGROUND
  PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort.
  
  
  METHODS
  Case series, January 2010 to March 2016.
  
  
  METHODS
  Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease.
  
  
  RESULTS
  Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate.
  
  
  RESULTS
  The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54-0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10-3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%-14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%-81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n=36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD.
  
  
  CONCLUSIONS
  Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers.
  
  
  CONCLUSIONS
  Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out.
authors.affiliation: Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest, Brest, France; Université européenne de Bretagne, Université de Bretagne Occidentale, Brest, France; Institut National de la Santé et de la Recherche Médicale, Unité 1078, Brest, France; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. Electronic address: emilie.cornec-legall@chu-brest.fr.
authors.forename: Emilie
authors.initials: E
authors.lastname: Cornec-Le Gall
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1078, Brest, France; Laboratoire de Génétique et Génomique Fonctionnelle et Biotechnologies, Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Audrézet
authors.affiliation: Service de Néphrologie, Centre Hospitalier Broussais, Saint Malo, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Renaudineau
authors.affiliation: Service de Néphrologie-Immunologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Hourmant
authors.affiliation: Service de Néphrologie, Centre Hospitalier Yves Le Foll, Saint Brieuc, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Charasse
authors.affiliation: Service de Néphrologie, Centre Hospitalier de Bretagne Atlantique, Vannes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Michez
authors.affiliation: Service de Néphrologie, Centre Hospitalier Universitaire Pontchaillou, Rennes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frouget
authors.affiliation: Service de Néphrologie, Centre Hospitalier Universitaire Pontchaillou, Rennes, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Vigneau
authors.affiliation: Service de Néphrologie-Immunologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
authors.affiliation: Service de Néphrologie, Centre Hospitalier de Cornouaille, Quimper, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Siohan
authors.affiliation: Service de Néphrologie, Centre Hospitalier Universitaire de Tours, Tours, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Longuet
authors.affiliation: Service de Néphrologie, Centre Hospitalier Universitaire de Tours, Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gatault
authors.affiliation: Service de Néphrologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Ecotière
authors.affiliation: Service de Néphrologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bridoux
authors.affiliation: Service de Néphrologie, Centre Hospitalier de Bretagne Atlantique, Vannes, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Mandart
authors.affiliation: Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hanrotel-Saliou
authors.affiliation: Service de Néphrologie, Centre Hospitalier Yves Le Foll, Saint Brieuc, France.
authors.forename: Corina
authors.initials: C
authors.lastname: Stanescu
authors.affiliation: AUB Santé, Brest, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Depraetre
authors.affiliation: AUB Santé, Rennes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gie
authors.affiliation: Service de Néphrologie, Centre Hospitalier de Centre Bretagne, Pontivy, France.
authors.forename: Michiel
authors.initials: M
authors.lastname: Massad
authors.affiliation: Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Kersalé
authors.affiliation: Echo, expansion des centres d'hémodialyse de l'Ouest, Le Mans, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Séret
authors.affiliation: Service de Néphrologie, Centre Hospitalier Universitaire de Angers, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Augusto
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1078, Brest, France; Laboratoire d'Hygiène et de Santé Publique, Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saliou
authors.affiliation: Laboratoire de Génétique et Génomique Fonctionnelle et Biotechnologies, Centre Hospitalier Régional Universitaire de Brest, Brest, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Maestri
authors.affiliation: Université européenne de Bretagne, Université de Bretagne Occidentale, Brest, France; Institut National de la Santé et de la Recherche Médicale, Unité 1078, Brest, France; Etablissement Français du Sang (EFS) Bretagne, Brest, France.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Chen
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.affiliation: Université européenne de Bretagne, Université de Bretagne Occidentale, Brest, France; Institut National de la Santé et de la Recherche Médicale, Unité 1078, Brest, France; Laboratoire de Génétique et Génomique Fonctionnelle et Biotechnologies, Centre Hospitalier Régional Universitaire de Brest, Brest, France; Etablissement Français du Sang (EFS) Bretagne, Brest, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
authors.affiliation: Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest, Brest, France; Université européenne de Bretagne, Université de Bretagne Occidentale, Brest, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Meur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000209:etiology; D050396:TRPP Cation Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D050396:TRPP Cation Channels
keywords: Autosomal dominant polycystic kidney disease (ADPKD); PKD2; case series; disease progression; disease severity; end-stage renal disease (ESRD); genetic prevalence; genetics; kidney function; mutation detection; mutation spectrum; prognosis; renal survival; sequencing