Mathematical Modeling of Kidney Function During Pregnancy

Abstract

During pregnancy major adaptations must occur in the maternal body to be able to support the rapidly developing fetus and placenta. Adaptations occur in almost all tissues and organs. These changes are dynamic, complex, and not fully understood. In particular, due to the altered requirements of an expanded plasma volume and increased electrolyte needs of the fetus and placenta, major adaptations must occur in the kidneys. The goal for this thesis is to investigate the functional implications of the pregnancy-induced adaptations that happen in the kidneys by developing and analyzing computational models. In particular, we first developed pregnancy-specific epithelial transport models of a single nephron in a mid- and late pregnant rat to quantify how individual renal adaptations in morphology, hemodynamics, and transporter activity affect handling of electrolytes and volume along the nephron. Our results predict which transport adaptations are essential for a healthy pregnancy as well as predict transport adaptations that have not been investigated experimentally. We then developed full pregnancy-specific kidney models that include heterogeneity in the nephron populations for a more accurate accounting of whole kidney function during pregnancy. Additionally, we developed models for renal function in a hypertensive female rat to analyze the effects of hypertension as well as hypertension with pregnancy on nephron transport.

Our results suggest that increased Na+ transporter expression along the distal segments in female rats when compared to males may better prepare females for the demands of pregnancy. During pregnancy, it appears that significantly increased activity of distal segment Na+ transporters with increased proximal tubule size are key in ensuring Na+ retention occurs. K+ retention is likely achieved through decreased distal segment K+ secretion as well as increased activity of the K+ pump. Together these changes allow the maternal body to retain sufficient Na+ and K+ for fetal cell function. During hypertension, similar relative changes in transporter activity in males and females results in similar transport properties. Specifically, Na+ load is shifted to the distal segments requiring altered transporter expression to avoid excess natriuresis.