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Soc. Open Sci."],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:p>\n                    The kidneys are crucial for maintaining Mg\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis. Along the proximal tubule and thick ascending limb, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    is reabsorbed paracellularly, while along the distal convoluted tubule (DCT), Mg\n                    <jats:sup>2+<\/jats:sup>\n                    is reabsorbed transcellularly via transient receptor potential melastatin 6 (TRPM6). TRPM6 and other renal transporter expressions are regulated by sex hormones. To investigate renal Mg\n                    <jats:sup>2<\/jats:sup>\n                    handling, we have developed sex-specific computational models of electrolyte transport along rat superficial nephron. Model simulations indicated that along the proximal tubule and thick ascending limb, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    and Na\n                    <jats:sup>+<\/jats:sup>\n                    transport occur parallelly, but they are dissociated along the DCT. In addition, our models predicted higher paracellular Mg\n                    <jats:sup>2+<\/jats:sup>\n                    permeability in females to attain similar cortical thick ascending limb fractional Mg\n                    <jats:sup>2+<\/jats:sup>\n                    reabsorption in both sexes. Furthermore, DCT fractional Mg\n                    <jats:sup>2+<\/jats:sup>\n                    reabsorption is higher in females than in males, allowing females to better fine-tune Mg\n                    <jats:sup>2+<\/jats:sup>\n                    excretion. We validated our models by simulating the administration of three classes of diuretics. The model predicted significantly increased, marginally increased and significantly decreased Mg\n                    <jats:sup>2+<\/jats:sup>\n                    excretions for loop, thiazide and K-sparing diuretics, respectively, aligning with experimental findings. The models can be used to conduct\n                    <jats:italic>in silico<\/jats:italic>\n                    studies on kidney adaptations to Mg\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis alterations during conditions such as pregnancy, diabetes and chronic kidney disease.\n                  <\/jats:p>","DOI":"10.1098\/rsos.231484","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T04:05:28Z","timestamp":1710907528000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["How the kidney regulates magnesium: a modelling study"],"prefix":"10.1098","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-4176","authenticated-orcid":true,"given":"Pritha","family":"Dutta","sequence":"first","affiliation":[{"name":"Department of Applied Mathematics, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shervin","family":"Hakimi","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita T.","family":"Layton","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada"},{"name":"Department of Biology, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada"},{"name":"Cheriton School of Computer Science, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada"},{"name":"School of Pharmacology, University of Waterloo , Waterloo, Ontario N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/102.5.616"},{"key":"e_1_3_7_3_2","volume-title":"Brenner and Rector\u2019s The Kidney E-Book","author":"Taal MW","year":"2011","unstructured":"Taal MW , Chertow GM , Marsden PA , Skorecki K , Alan S , Brenner BM . 2011 Brenner and Rector\u2019s The Kidney E-Book. 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