Abstract

The primary focus of this thesis was the use of the spiny mouse to model birth asphyxia-induced neonatal Acute Kidney Injury (AKI). Understanding what effect birth asphyxia has on the neonatal kidney at a molecular, structural and functional level, determining if deficits persist into adulthood, and the potential for intervention using maternal creatine supplementation, were important goals. The work in this thesis also characterised maternal creatine homeostasis during late pregnancy, to assess the potential role of creatine as a cellular energy buffer in the placenta, fetus and maternal tissues during gestation. Finally, studies in this thesis assessed the effects of maternal dietary creatine supplementation from mid-gestation on maternal weight gain, kidney function, and maternal de novo creatine synthesis, to establish if maternal dietary creatine supplementation is safe for the mother, an imperative first step before creatine can be considered further as a treatment to prevent the adverse outcomes of birth asphyxia in pregnant women. Results reported in this thesis provide evidence to this point and allow evaluation for the further development of a creatine treatment regime that could be applied in many obstetric populations.

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