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Semin Nephrol. 2019 May;39(3):244-255. doi: 10.1016/j.semnephrol.2019.02.002.

Genetic and Developmental Factors in Chronic Kidney Disease Hotspots.

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Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Institute for Biomedical Ethics and History of Medicine, University of Zurich, Zurich, Switzerland. Electronic address:


Chronic kidney disease increasingly is being recognized as an important global public health problem. Interindividual susceptibility to kidney disease is high and likely is dependent on risk modulation through genetics, fetal and early childhood development, environmental circumstances, and comorbidities. Traditionally, the chronic kidney disease burden has been ascribed largely to hypertension and diabetes. Increasingly, evidence is accumulating that nontraditional risk factors may predominate in some regions and populations, contributing to epidemics of kidney disease. Such nontraditional risk factors include environmental exposures, traditional medicines, fetal and maternal factors, infections, kidney stones, and acute kidney injury. Genetic factors may predispose patients to chronic kidney disease in some populations. Chronic kidney disease of unknown origin has its epicenters in Central America and South Asia. Such clustering of CKD may represent either genetic or environmentally driven kidney disease, or combinations of both. Developmental conditions impacting kidney development often are related to poverty and structural factors that persist throughout life. In this article, we explore the possibilities that genetic and developmental factors may be important contributors to the epidemics in these regions and suggest that optimization of factors impacting kidney development hold promise to reduce the risk of kidney disease in future generations.


CKDu; Genetics; birth weight; developmental programming; kidney disease; nephron number

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