Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, Canada.
Department of Biology, Cheriton School of Computer Science, and School of Pharmacology, University of Waterloo, Waterloo, Ontario, Canada.
Am J Physiol Renal Physiol. 2024 Jul 1;327(1):F77-F90. doi: 10.1152/ajprenal.00001.2024. Epub 2024 May 9.
Pregnancy is associated with elevated demand of most nutrients, with many trace elements and minerals critical for the development of fetus. In particular, calcium (Ca) and magnesium (Mg) are essential for cellular function, and their deficiency can lead to impaired fetal growth. A key contributor to the homeostasis of these ions is the kidney, which in a pregnant rat undergoes major changes in morphology, hemodynamics, and molecular structure. The goal of this study is to unravel the functional implications of these pregnancy-induced changes in renal handling of Ca and Mg, two cations that are essential in a healthy pregnancy. To achieve that goal, we developed computational models of electrolyte and water transport along the nephrons of a rat in mid and late pregnancy. Model simulations reveal a substantial increase in the reabsorption of Mg along the proximal tubules and thick ascending limbs. In contrast, the reabsorption of Ca is increased in the proximal tubules but decreased in the thick ascending limbs, due to the lower transepithelial concentration gradient of Ca along the latter. Despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of Ca and Mg in pregnancy. Furthermore, we conducted simulations of hypocalcemia and hypomagnesemia. We found that hypocalcemia lowers Ca excretion substantially more than Mg excretion, with this effect being more pronounced in virgin rats than in pregnant ones. Conversely, hypomagnesemia reduces the excretion of Mg and Ca to more similar degrees. These differences can be explained by the greater sensitivity of the calcium-sensing receptor (CaSR) to Ca compared with Mg. A growing fetus' demands of minerals, notably calcium and magnesium, necessitate adaptations in pregnancy. In particular, the kidney undergoes major changes in morphology, hemodynamics, and molecular structure. This computational modeling study provides insights into how these pregnancy-induced renal adaptation impact calcium and magnesium transport along different nephron segments. Model simulations indicate that, despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of calcium and magnesium in pregnancy.
妊娠伴随着大多数营养物质需求的增加，许多微量元素和矿物质对胎儿的发育至关重要。特别是钙（Ca）和镁（Mg）对细胞功能至关重要，其缺乏可导致胎儿生长受损。维持这些离子的体内平衡的关键因素是肾脏，在妊娠大鼠中，肾脏的形态、血液动力学和分子结构发生重大变化。本研究的目的是揭示这些妊娠引起的肾脏对 Ca 和 Mg 处理的功能影响，Ca 和 Mg 是健康妊娠所必需的两种阳离子。为了实现这一目标，我们开发了妊娠中期和晚期大鼠肾脏各段离子和水转运的计算模型。模型模拟表明，在近曲小管和升支粗段，Mg 的重吸收显著增加。相反，由于后者跨上皮 Ca 浓度梯度较低，Ca 的重吸收在近曲小管增加，但在升支粗段减少。尽管转运能力增强，但肾小球滤过率的显著增加导致妊娠时 Ca 和 Mg 的尿排泄增加。此外，我们还进行了低钙血症和低镁血症的模拟。我们发现低钙血症使 Ca 的排泄大大减少，而使 Mg 的排泄减少，这种效应在处女大鼠中比在妊娠大鼠中更为明显。相反，低镁血症使 Mg 和 Ca 的排泄减少到更相似的程度。这些差异可以用钙敏感受体（CaSR）对 Ca 的敏感性比对 Mg 的敏感性更大来解释。胎儿对矿物质的需求不断增加，尤其是钙和镁，这需要在妊娠期间进行适应性改变。特别是肾脏在形态、血液动力学和分子结构方面发生重大变化。这项计算建模研究提供了深入了解这些妊娠引起的肾脏适应如何影响不同肾单位段的钙和镁转运的见解。模型模拟表明，尽管转运能力增强，但肾小球滤过率的显著增加导致妊娠时 Ca 和 Mg 的尿排泄增加。
