Kidney dysfunction in the low-birth weight murine adult: implications of oxidative stress

Maternal undernutrition during pregnancy leads to low birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 months of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy and a worse survival rate than LBW females. In contrast, both genders experienced a comparable progressive decline in renal vascular density (immunofluorescence analysis), renal blood flow (Laser-Doppler flowmetry analysis), glomerular filtration rate (FITC-sinistrin clearance analysis), and a progressive increase in systemic blood pressure (measured via tail-cuff method). Isolated aortas from both LBW genders demonstrated reduced vasodilation in response to acetylcholine, indicative of reduced nitric oxide bioavailability and endothelial dysfunction. ELISA and i...