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Developmental origins of renal disease: a translational approach
Author(s) -
Ojeda Norma B.,
Intapad Suttira,
Carter Anthony J,
Alexander Barbara T,
Bhatt Abhay
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.910.1
Subject(s) - low birth weight , medicine , aldosterone , leptin , offspring , endocrinology , birth weight , renal function , population , kidney disease , physiology , pregnancy , obesity , biology , genetics , environmental health
Previous studies from my laboratory indicate that low birth weight ( LBW ) is a risk factor for renal disease; however, the exact mechanisms involved are unclear. The objective of this translational study was to determine whether leptin and aldosterone levels at birth are associated with the etiology of renal disease. The clinical protocol used a prospective study in newborns and infants with 1,100 participants form both sexes and all races enrolled at the University of Mississippi. The experimental protocol used a rodent model of LBW induced by placental insufficiency. Human LBW newborns showed an 8‐fold increase in plasma aldosterone and a 2.5‐fold reduction in plasma leptin at birth compared to normal birth weight (NBW) newborns. Glomerular filtration rate ( GFR ) was reduced ( P <0.05) in LBW infants exposed to hypoperfusion between 6 and 12 months of age, with positive correlation with leptin and negative correlation with aldosterone levels at birth. Rodent LBW offspring showed increased aldosterone and decreased leptin levels at birth and reduced GFR when exposed to mild renal ischemia later in life. Perinatal antioxidant treatment in rodents completely abolished aldosterone, leptin and GFR disturbances in LBW offspring. Thus, the parallelisms between human and animal studies suggest that aldosterone and leptin levels at birth are associated with increased susceptibility for renal injury in LBW. Additionally, early interventions may prevent this enhanced susceptibility in the LBW individual; and monitoring of renal function should be indicated in this “at‐risk” population when exposed to hypoperfusion events.