Kozeta Miliku1,2,3, Suzanne Vogelezang1,2,3, Oscar H Franco2, Albert Hofman2, Vincent W V Jaddoe1,2,3, Janine F Felix1,2,3. 1. The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. 2. Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. 3. Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Abstract
BACKGROUND: Kidney measures in early life are associated with kidney disease in later life. We hypothesized that these associations are partly explained by common genetic variants that lead to both smaller kidneys with lower kidney function in early childhood and kidney disease in adulthood. METHODS: We examined in a population-based prospective cohort study among 4,119 children the associations of a weighted genetic risk score combining 20 previously identified common genetic variants related to adult eGFRcreat with kidney outcomes in children aged 6.0 years (95% range 5.7-7.8). Childhood kidney outcomes included combined kidney volume, glomerular filtration rate (eGFR) based on creatinine levels, and microalbuminuria based on albumin and creatinine urine levels. RESULTS: We observed that the genetic risk score based on variants related to impaired kidney function in adults was associated with a smaller combined kidney volume (P value 3.0 × 10(-3)) and with a lower eGFR (P value 4.0 × 10(-4)) in children. The genetic risk score was not associated with microalbuminuria. CONCLUSION: Common genetic variants related to impaired kidney function in adults already lead to subclinical changes in childhood kidney outcomes. The well-known associations of kidney measures in early life with kidney disease in later life may at least be partly explained by common genetic variants.
BACKGROUND: Kidney measures in early life are associated with kidney disease in later life. We hypothesized that these associations are partly explained by common genetic variants that lead to both smaller kidneys with lower kidney function in early childhood and kidney disease in adulthood. METHODS: We examined in a population-based prospective cohort study among 4,119 children the associations of a weighted genetic risk score combining 20 previously identified common genetic variants related to adult eGFRcreat with kidney outcomes in children aged 6.0 years (95% range 5.7-7.8). Childhood kidney outcomes included combined kidney volume, glomerular filtration rate (eGFR) based on creatinine levels, and microalbuminuria based on albumin and creatinine urine levels. RESULTS: We observed that the genetic risk score based on variants related to impaired kidney function in adults was associated with a smaller combined kidney volume (P value 3.0 × 10(-3)) and with a lower eGFR (P value 4.0 × 10(-4)) in children. The genetic risk score was not associated with microalbuminuria. CONCLUSION: Common genetic variants related to impaired kidney function in adults already lead to subclinical changes in childhood kidney outcomes. The well-known associations of kidney measures in early life with kidney disease in later life may at least be partly explained by common genetic variants.
Authors: Claudia J Kruithof; Marjolein N Kooijman; Cornelia M van Duijn; Oscar H Franco; Johan C de Jongste; Caroline C W Klaver; Johan P Mackenbach; Henriëtte A Moll; Hein Raat; Edmond H H M Rings; Fernando Rivadeneira; Eric A P Steegers; Henning Tiemeier; Andre G Uitterlinden; Frank C Verhulst; Eppo B Wolvius; Albert Hofman; Vincent W V Jaddoe Journal: Eur J Epidemiol Date: 2014-12-21 Impact factor: 8.082
Authors: Matthias Wuttke; Craig S Wong; Elke Wühl; Daniel Epting; Li Luo; Anselm Hoppmann; Anke Doyon; Yong Li; Betül Sözeri; Daniela Thurn; Martin Helmstädter; Tobias B Huber; Tom D Blydt-Hansen; Albrecht Kramer-Zucker; Otto Mehls; Anette Melk; Uwe Querfeld; Susan L Furth; Bradley A Warady; Franz Schaefer; Anna Köttgen Journal: Nephrol Dial Transplant Date: 2015-09-28 Impact factor: 5.992
Authors: J J Miranda Geelhoed; Veronica E Kleyburg-Linkers; Sonja P E Snijders; Maarten Lequin; Jeroen Nauta; Eric A P Steegers; Albert J van der Heijden; Vincent W V Jaddoe Journal: Pediatr Nephrol Date: 2009-03-12 Impact factor: 3.714