Early-Life Course Socioeconomic Factors and Chronic Kidney Disease Patrick D. Brophy, David A. Shoham, The CKD Life Course Group, Jennifer R. Charlton, J. Bryan Carmody, Kimberly J. Reidy, Lyndsay Harshman, Jeffrey Segar, and David Askenazi Kidney failure or ESRD affects approximately 650,000 Americans, whereas the number with earlier stages of CKD is much higher. Although CKD and ESRD are usually associated with adulthood, it is likely that the initial stages of CKD begin early in life. Many of these pathways are associated with low birth weight and disadvantaged socioeconomic status (SES) in childhood, trans- lating childhood risk into later-life CKD and kidney failure. Social factors are thought to be fundamental causes of disease. Although the relationship between adult SES and CKD has been well established, the role of early childhood SES for CKD risk remains obscure. This review provides a rationale for examining the association between early-life SES and CKD. By collect- ing data on early-life SES and CKD, the interaction with other periods in the life course could also be studied, allowing for ex- amination of whether SES trajectories (eg, poverty followed by affluence) or cumulative burden (eg, poverty at multiple time points) are more relevant to lifetime CKD risk. Q 2015 by the National Kidney Foundation, Inc. All rights reserved. Key Words: Chronic kidney disease, Socioeconomic status, Health disparities, Life course, Epidemiology Introduction Kidney failure or ESRD affects approximately 650,000 Amer- icans, whereas the number with earlier stages of CKD is much higher. 1 The health-related costs of ESRD exceed 28 billion dollars per year, adding economic burden to the human toll from this disease. 2-4 Although CKD and ESRD are usually associated with adulthood, it is likely that the initial stages of CKD begin early in life. 2-4 Infants and children who develop CKD are at significant risk for associated health problems beyond those directly attributable to kidney disease as they have not completed their physiological or intellectual maturity. 4 The risk factors and natural history for CKD progression in in- fants and children are not well understood. 4 Currently, North American and European investigators are moni- toring childhood cohorts of patients with CKD to better un- derstand the natural progression and treatment of CKD and to identify significant risk factors for patients at risk for developing progressive CKD. 4-7 This review focuses on the early-life determinants of CKD, with an emphasis on pathophysiological mechanisms. Many of these path- ways are associated with low birth weight and disadvan- taged socioeconomic status (SES) in childhood, translating childhood risk into later-life CKD and kidney failure. Social factors are thought to be “fundamental causes” of disease because they constrain health-promoting behaviors and access to resources. 8 Social class and SES may be defined in a number of manners including education, income, occu- pation, and composite measures such as neighborhood disadvantage. 9 The importance of SES in the initiation and progression of CKD has been noted in several populations including the United States, 10 Canada, 11 and Australia, 12 although socioeconomically disadvantaged groups in the United States may be at greater risk than those in other developed countries. 13 Although numerous studies have examined the association between adult SES and CKD, 14-24 few have examined the contribution of early-life socioeconomic determinants of CKD. 25,26 Nevertheless, given extant pathophysiological evidence, it is likely that socioeconomic determinants begin to influence kidney health and disease during gestation. The life-course perspective essentially reflects the study of long-term protective and risk factor effects of physical and social exposures from gestation through to adult life, which may be applied to kidney disease. It incorporates studies based on cross-generational and individual biological, behavioral, psychosocial, and environmental determi- nants. 27 Three life course models have been proposed as gen- eral paradigms for how socioeconomic factors may influence development and adult disease: (1) the critical periods model, which emphasizes particular time points, such as early childhood, as most important in disease development; (2) the trajectory model, which posits that early and later life factors interact with one another to confer disease risk; and (3) the cumulative model, whereby all periods in the life course contribute to disease development and progression. 28 From Pediatric Nephrology, University of Iowa Children’s Hospital; Depart- ment of Public Health Sciences, Loyola University Chicago, Maywood, IL; Divi- sion of Nephrology, Department of Pediatrics, University of Virginia, Charlottesville, VA; Pediatric Nephrology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Pediatrics, University of Iowa Chil- dren’s Hospital, Iowa City, IA; Neonatology, University of Iowa Children’s Hos- pital, Iowa City, IA; Department of Pediatric Nephrology, University of Alabama at Birmingham, Birmingham, AL; and the Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, IL. An earlier version of this manuscript was presented at the Life Course Research Network meeting in Washington, DC, in February 2013. Financial Disclosure: The authors declare that they have no relevant finan- cial interests. Address correspondence to Patrick Brophy, MD, Pediatric Nephrology, Uni- versity of Iowa Children’s Hospital. E-mail: patrick-brophy@uiowa.edu Ó 2015 by the National Kidney Foundation, Inc. All rights reserved. 1548-5595/$36.00 http://dx.doi.org/10.1053/j.ackd.2014.06.006 Advances in Chronic Kidney Disease, Vol 22, No 1 (January), 2015: pp 16-23 16