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

Abstract

Maternal undernutrition (MUN) 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 mo 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 sexes 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 sexes demonstrated reduced vasodilation in response to ACh, indicative of reduced nitric oxide bioavailability and endothelial dysfunction. ELISA and immunofluorescence analysis revealed a significant increase of circulating reactive oxygen species and NADPH oxidase type 4 (NOX4) expression in both LBW sexes, although these increases were more pronounced in males. Although more effective in males, chronic tempol treatment did improve all observed pathologies in both sexes of LBW mice. Chronic NOX4 inhibition with GKT137831 was more effective than tempol in preventing pathologies in LBW males. In conclusion, despite some minor differences, LBW female and male adults have a reduced nephron endowment comparable with progressive renal and vascular dysfunction, which is associated with increased oxidative stress and subsequent endothelial dysfunction. Tempol treatment and/or NOX4 inhibition attenuates renal and vascular dysfunction in LBW adults.

Effects of intrauterine growth restriction during late pregnancy on the ovine fetal renal function and antioxidant capacity

“…Maternal, fetal, and childhood nutrition are crucial contributors to these programming effects in kidney (Luyckx & Brenner, 2015). In this study, the IUGR fetal kidney weight and kidney growth rate were decreased with the decrease of maternal food intake, which was consistent with the results of Abdulmahdi et al (2018). Glomerulus and renal tubules are the main components of nephron (Zohdi et al, 2012).…”

Investigation of some Heavy Metals on Parameter of Blood and Oxidative Enzyme in CKD in Iraq-Al-Qadisiyah

“…That's agreement with previous studies [27]. The results elucidated a significant increase in AchE for hemodialysis patients (8.468±0.058 Mg\dl) compared with control (1.599±0.0047 Mg\dl) and for non-hemodialysis patients 2.941±0.041 Mg\dl) compared with control for old patient (40_60) age group according the table (2), these results were in agreement with [28]. Additional oxidative stress affects the aetiology of renal failure and CKD as well as its start, development, and progression [25]., being some of the main factors contributing to associated CVDs and higher mortality in CKD patients [25], proved heavy metals that impacts antioxidant enzymes in severe CKD patients [25].…”

Individual and Environmental Factors Associated with Proteinuria in Korean Children: A Multilevel Analysis

“…Mechanisms underlying the association of air pollution with renal function have been explained as inflammation and endothelial dysfunction by transition metals induced in reactive oxygen species [62,63]. Accordingly, oxidative stress and subsequent endocardial dysfunction affect the glomerular filtration rate (GFR) [64,65]. Moreover, the prevalence of proteinuria was associated with the level of PM 10 in this study.…”