Emilie Cornec-Le Gall1, Marie-Pierre Audrézet2, Eric Renaudineau3, Maryvonne Hourmant4, Christophe Charasse5, Eric Michez6, Thierry Frouget7, Cécile Vigneau7, Jacques Dantal4, Pascale Siohan8, Hélène Longuet9, Philippe Gatault9, Laure Ecotière10, Frank Bridoux10, Lise Mandart6, Catherine Hanrotel-Saliou11, Corina Stanescu5, Pascale Depraetre12, Sophie Gie13, Michiel Massad14, Aude Kersalé11, Guillaume Séret15, Jean-François Augusto16, Philippe Saliou17, Sandrine Maestri18, Jian-Min Chen19, Peter C Harris20, Claude Férec21, Yannick Le Meur22. 1. 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. 2. 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. 3. Service de Néphrologie, Centre Hospitalier Broussais, Saint Malo, France. 4. Service de Néphrologie-Immunologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France. 5. Service de Néphrologie, Centre Hospitalier Yves Le Foll, Saint Brieuc, France. 6. Service de Néphrologie, Centre Hospitalier de Bretagne Atlantique, Vannes, France. 7. Service de Néphrologie, Centre Hospitalier Universitaire Pontchaillou, Rennes, France. 8. Service de Néphrologie, Centre Hospitalier de Cornouaille, Quimper, France. 9. Service de Néphrologie, Centre Hospitalier Universitaire de Tours, Tours, France. 10. Service de Néphrologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France. 11. Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest, Brest, France. 12. AUB Santé, Brest, France. 13. AUB Santé, Rennes, France. 14. Service de Néphrologie, Centre Hospitalier de Centre Bretagne, Pontivy, France. 15. Echo, expansion des centres d'hémodialyse de l'Ouest, Le Mans, France. 16. Service de Néphrologie, Centre Hospitalier Universitaire de Angers, France. 17. 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. 18. Laboratoire de Génétique et Génomique Fonctionnelle et Biotechnologies, Centre Hospitalier Régional Universitaire de Brest, Brest, France. 19. 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. 20. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. 21. 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. 22. Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest, Brest, France; Université européenne de Bretagne, Université de Bretagne Occidentale, Brest, France.
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. STUDY DESIGN: Case series, January 2010 to March 2016. SETTINGS & PARTICIPANTS: 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. OUTCOMES: 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. LIMITATIONS: 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.
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. STUDY DESIGN: Case series, January 2010 to March 2016. SETTINGS & PARTICIPANTS: 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. OUTCOMES: 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). PKD2patients 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. LIMITATIONS: 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.
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