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Low birth weight associated renal and vascular impairment
Author(s) -
Ratliff B,
Zullo J,
Barnett C,
Shen M,
Rabadi M,
Nesi L,
Lamba R,
Aldumuahdhi W
Publication year - 2015
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.29.1_supplement.965.2
Subject(s) - renal function , medicine , low birth weight , endocrinology , proinflammatory cytokine , nephron , kidney , offspring , biology , pregnancy , inflammation , genetics
In the United States, 8% of all births are to low birth weight (LBW) neonates, mostly due to maternal malnourishment and preterm delivery. The LBW neonate has a high rate of mortality and morbidity after birth. In experiments, we used a maternal malnourished mouse model to examine the effects of LBW on kidney development and short/long‐term function. Circulating cyto‐/chemokines, renal blood flow, renal developmental gene expression, nephron formation, autophagy, renal function and blood pressure were examined in the LBW offspring. The therapeutic potential of glutamine, methionine and calendula treatment was examined in these animals. LBW male offspring glomerular endowment and survival were reduced by 50%. The LBW neonate experienced attenuated renal blood perfusion by 37%, enhanced circulating proinflammatory cyto‐/chemokines (IL‐1β, IL‐5, IL‐12(p40), IL‐12(p70), IFNγ and GM‐CSF), reduced levels of IL‐10 and VEGF, blunted autophagy, altered expression of critical developmental genes (Wnt9b, Wnt4, Bmp7, FoxD1, Eya1, Sall1 and Fgf8), and a 25% reduction of pre‐nephron structures. Supplementation of methionine and glutamine during nephrogenesis normalized kidney development and function in the LBW neonate. At 2 months post‐birth, LBW mice showed early tubular damage and glomerular abnormalities. At 5 months post‐birth, LBW animals had 10% elevated blood pressure, and elevated serum creatinine and proteinuria. Treatment with calendula improved blood pressure and renal function in the older animals. LBW compromises the kidney and vascular system, enhances circulating proinflammatory cyto‐/chemokines, interferes with normal nephron/glomeruli development and predisposes mice to acute and chronic illness. Effects are improved upon treatment with glutamine, methionine or calendula.