title: Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?
abstract: Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called "developmental programming" or "developmental origins of health and disease" (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.|Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.affiliation: Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. chien_ning_hsu@hotmail.com.|School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chien_ning_hsu@hotmail.com.
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Hsu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D012084:Renin-Angiotensin System; D012737:Sex Factors; D015222:Sodium Channels / Q000378:metabolism; D013564:Sympathetic Nervous System; D059467:Transcriptome
chemical_list: D005938:Glucocorticoids; D015222:Sodium Channels
keywords: Epigenetic regulation; chronic kidney disease; congenital anomalies of the kidney and urinary tract (CAKUT); developmental origins of health and disease (DOHaD); nephron endowment; oxidative stress; renin-angiotensin system; sex differences; sodium transporter; transcriptome