825c1e4e486d9b0049c7d40192d09476 325959.pdf d5921784b120e6e5808ba8b9bb337990896d2918 325959.pdf 2102742dd3ae32e5892479a71577303bb77038b5bdf86d55bd34490e2243bc64 325959.pdf Title: Magnesium Balance in Chronic Kidney Disease: Mineral Metabolism, Immunosuppressive Therapies and Sodium-Glucose Cotransporter 2 Inhibitors Subject: It is now widely recognized that maintaining magnesium (Mg) homeostasis is critical for health, especially in the context of chronic kidney disease (CKD). Patients with CKD commonly develop hyperphosphatemia and secondary hyperparathyroidism, which are controlled by therapies targeting intestinal phosphate absorption and circulating calcium levels or by modulating parathyroid calcium sensing. Notably, Mg supplementation may provide dual benefits by promoting bone formation and maintaining normal mineralization with slightly elevated serum levels. Importantly, low Mg levels are associated with mortality risk in CKD, highlighting the importance of maintaining adequate serum Mg levels in these patients. Particularly, kidney transplant (KT) patients have lower circulating Mg levels, likely due to interactions with immunosuppressive treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown survival benefits in CKD and increased serum Mg levels, suggesting that Mg regulation may contribute to these outcomes. Overall, Mg plays a key role in CKD-associated mineral and bone disorders (CKD-MBD). Thus, understanding the mechanisms underlying the alteration of Mg homeostasis in CKD could improve clinical outcomes. This review summarizes the basic and clinical studies demonstrating (1) the key actions of Mg in CKD-MBD, including secondary hyperparathyroidism and bone abnormalities; (2) the distinctive profile of KT patients for Mg homeostasis; and (3) the interaction between commonly used drugs, such as SGLT2 inhibitors or immunosuppressive treatments, and Mg metabolism, providing a broad understanding of both the key role of Mg in the context of CKD and the treatments that should be considered to manage Mg levels in CKD patients. Keywords: magnesium; chronic kidney disease; CKD-MBD; renal transplant patients; SLGT2 inhibitors Author: Juan Miguel Díaz-Tocados, Maria Jesús Lloret, Juan Diego Domínguez-Coral, Adria Patricia Tinoco Aranda, Leonor Fayos de Arizón, Elisabet Massó Jiménez, Jordi Bover, José Manuel Valdivielso and María Encarnación Rodríguez-Ortiz Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Jun 13 03:59:01 2025 CEST ModDate: Fri Jun 13 04:26:40 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1064001 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWNCSY+URWPalladioL-Roma Type 1 Custom yes yes yes 10 0 GERQUG+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 DENXSM+URWPalladioL-Ital Type 1 Custom yes yes yes 21 0 QDCWHF+EURM10 Type 1 Builtin yes yes yes 47 0 CFIHBN+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 73 0 CFIHCO+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 79 0 CFIHCP+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 85 0 CFIHBN+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 132 0 CFIHCO+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 138 0 CFIHCP+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 144 0 QKZKVH+VnURWPalladioL Type 1 Custom yes yes yes 161 0 QGUKZH+CMSY10 Type 1 Builtin yes yes yes 173 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-02-27 04:51:39 CET RepresentationInformation: 325959.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-02-26 13:29:12 CET Size: 1064001 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 558 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Magnesium and CKD-MBD Destination: section.2 Children: Item: Title: Magnesium and Secondary Hyperparathyroidism Destination: subsection.2.1 Children: Item: Title: Magnesium and Parathyroid Function Destination: subsubsection.2.1.1 Item: Title: Magnesium and Clinical Management of Secondary Hyperparathyroidism Destination: subsubsection.2.1.2 Item: Title: Risk of Hypermagnesemia Destination: subsubsection.2.1.3 Item: Title: Magnesium and Bone Health Destination: subsection.2.2 Item: Title: Magnesium and Bone Homeostasis Destination: subsection.2.3 Item: Title: Magnesium in Renal Transplant Patients Destination: section.3 Item: Title: Magnesium and SGLT2 Inhibitors Destination: section.4 Item: Title: Future Perspectives and Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Magnesium Balance in Chronic Kidney Disease: Mineral Metabolism, Immunosuppressive Therapies and Sodium-Glucose Cotransporter 2 Inhibitors Author: Juan Miguel Díaz-Tocados, Maria Jesús Lloret, Juan Diego Domínguez-Coral, Adria Patricia Tinoco Aranda, Leonor Fayos de Arizón, Elisabet Massó Jiménez, Jordi Bover, José Manuel Valdivielso and María Encarnación Rodríguez-Ortiz Subject: It is now widely recognized that maintaining magnesium (Mg) homeostasis is critical for health, especially in the context of chronic kidney disease (CKD). Patients with CKD commonly develop hyperphosphatemia and secondary hyperparathyroidism, which are controlled by therapies targeting intestinal phosphate absorption and circulating calcium levels or by modulating parathyroid calcium sensing. Notably, Mg supplementation may provide dual benefits by promoting bone formation and maintaining normal mineralization with slightly elevated serum levels. Importantly, low Mg levels are associated with mortality risk in CKD, highlighting the importance of maintaining adequate serum Mg levels in these patients. Particularly, kidney transplant (KT) patients have lower circulating Mg levels, likely due to interactions with immunosuppressive treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown survival benefits in CKD and increased serum Mg levels, suggesting that Mg regulation may contribute to these outcomes. Overall, Mg plays a key role in CKD-associated mineral and bone disorders (CKD-MBD). Thus, understanding the mechanisms underlying the alteration of Mg homeostasis in CKD could improve clinical outcomes. This review summarizes the basic and clinical studies demonstrating (1) the key actions of Mg in CKD-MBD, including secondary hyperparathyroidism and bone abnormalities; (2) the distinctive profile of KT patients for Mg homeostasis; and (3) the interaction between commonly used drugs, such as SGLT2 inhibitors or immunosuppressive treatments, and Mg metabolism, providing a broad understanding of both the key role of Mg in the context of CKD and the treatments that should be considered to manage Mg levels in CKD patients. 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