Adult hypertension and kidney disease: the role of fetal programming.
Hypertension (HTN) and chronic kidney disease are highly prevalent diseases that tend to occur more frequently among disadvantaged populations, in whom prenatal care also tends to be poor. More and more evidence is emerging highlighting the important role of fetal programming in the development of adult disease, suggesting a possible common pathophysiologic denominator in the development of these disorders. Epidemiologic evidence accumulated over the past 2 decades has demonstrated an association between low birth weight and subsequent adult HTN, diabetes, and cardiovascular disease. More recently, a similar association has been found with chronic kidney disease. Animal studies and indirect evidence from human studies support the hypothesis that low birth weight, as a marker of adverse intrauterine circumstances, is associated with a congenital deficit in nephron number. The precise mechanism of the reduction in nephron number has not been established, but several hypotheses have been put forward, including changes in DNA methylation, increased apoptosis in the developing kidney, alterations in renal renin-angiotensin system activity, and increased fetal glucocorticoid exposure. A reduction in nephron number is associated with compensatory glomerular hypertrophy and an increased susceptibility to renal disease progression. HTN in low birth weight individuals also appears to be mediated in part through a reduction in nephron number. Increased awareness of the implications of low birth weight and inadequate prenatal care should lead to public health policies that may have long-term benefits in curbing the epidemics of HTN, diabetes, and kidney disease in generations to come.
Zandi-Nejad
Kambiz
K
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. kzandinejad@partners.org
Luyckx
Valerie A
VA
Brenner
Barry M
BM
D000818:Animals; D002908:Chronic Disease; D005333:Fetus / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000473:pathology; D016030:Kidney Transplantation; D009399:Nephrons / Q000473:pathology; D016896:Treatment Outcome