Divalent Cations in Kidney Physiology and Disease

Divalent cations including Ca2+, Mg2+, Fe2+, and Zn2+ play essential roles in a vast array of cellular functions. For example, Ca2+ plays a well-established role as a second messenger, and in the kidney mediates signaling through arginine vasopressin (also known as antidiuretic hormone) and parathyroid hormone. Mg2+ binds nucleic acids, ribosomes, proteins, and membranes, and a small portion of it serves as a cofactor in a variety of critical enzymatic reactions. Fe2+ is an important component of many prosthetic groups such as heme and iron-sulphur clusters. Zn2+ interacts with approximately 10% of all proteins, many of which play critical roles in gene expression, and immune and antioxidative responses. Divalent cations are reabsorbed by the renal epithelia after glomerular filtration to maintain homeostasis, and the channels, transporters or carriers involved have largely been identified.

Perturbations in the intracellular levels of divalent cations or dysregulation of signaling pathways dependent on them are associated with numerous diseases states in the kidney. For example, dysregulation of Ca2+ signaling promotes cyst formation and growth in polycystic kidney disease. Dysfunction of the Ca2+ channel TRPC6 contributes to focal segmental glomerulosclerosis, while TRPV5 dysregulation may contribute to the formation of kidney stones. Lower dietary Mg2+ intake is associated with increased risk of CKD progression, kidney stone formation, and cardiovascular diseases. Dysregulation of Fe2+ and Zn2+ homeostasis has also been associated with kidney injury and progression. Ferroptosis, a form of cell death dependent on Fe2+ contributes to acute kidney injury while Zn2+ may protect against kidney injury though antioxidant activity. Thus, divalent cations play critical roles in determining kidney health and the progression of kidney diseases.

While much progress has been made, many gaps remain in our knowledge of the mechanisms of renal divalent cation handling and the roles of divalent cations in kidney diseases. In particular, compared to other electrolytes such as Na+, K+, and Ca2+, our understanding of Mg2+, Fe2+, Zn2+, and other less studied divalent cations lags in terms of roles in diseases, the availability of research tools and animal models, and overall research efforts. This research topic on “divalent cations in kidney physiology and disease” will serve as a platform for timely publication of new findings, improvements of research tools and models, research summaries, hypotheses, and ideas in the area broadly related to divalent cations and the kidney.

All topics related to divalent cations in kidney physiology and disease are welcome. The types of manuscripts in this research topic include but are not limited to original research, reviews (systemic, regular, and mini), method, and hypothesis and theory. Note that case reports and clinical studies are not permitted. Topics in the following areas are especially encouraged:
- Less commonly studied divalent cations including Fe2+, Zn2+, Cu2+, Co2+, and Mn2+
- Disorders involving disrupted renal divalent cation handling
- Tools and methods in divalent cation research
- Intracellular divalent cation homeostasis
- Roles of divalent cations in polycystic kidney disease, acute kidney injury, chronic kidney disease, and renal mechanisms contributing to hypertension
- Regulation of divalent cation channels, carriers, and transporters
- Physiological regulation of divalent cation reabsorption

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• Data Report
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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: kidney, ckd, aki, channels, transporters, magnesium, divalent cations, reabsorption, nephrocalcinosis, nephrolithiasis, iron, zinc, copper, cobalt, calcium

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