Gary A. Quamme and Christian de Rouffignac

Department of Medicine, University of British Columbia, Vancouver, BC Canada, and Département de Biologie Cellulaire et Moléculaire, Commissariat á l'Energie Atomique, Centre d'Etudes de Saclay, Gif-Sur-Yvette, France

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Basic mechanisms of magnesium transport in the kidney

3.1. Glomerular filtration
3.2. Proximal tubule
3.3. Loop of henle

3.3.1. Proximal straight tubule
3.3.2. Thin limbs
3.3.3. Thick ascending limb

2.4. Distal tubule

4. Hormonal control of renal magnesium transport

4.1. Proximal tubule
4.2. Loop of henle

4.2.1. Medullary thick ascending limb (mTAL)
4.2.2. Cortical thick ascending limb (cTAL)

3.3. Distal tubule

5. Nonhormonal influences of renal magnesium transport

5.1. Intrinsic control: magnesium-restriction
5.2. Ca2+/Mg2+-sensing: hypercalcemia, hypermagnesemia
5.3. Extracellular fluid volume
5.4. Diuretics:

5.4.1. Osmotic diuretics: glucose, mannitol
5.4.2. Loop diuretics: furosemide
5.4.3. Distal diuretics: amiloride, thiazides

5.5. Metabolic acidosis/alkalosis

5.6. Phosphate depletion

5.7. Potassium depletion

6. Acknowledgement

7. References

1. ABSTRACT

Magnesium is the fourth most abundant cation in the body and the second most common cation in the intracellular fluid. It is the kidney that provides the most sensitive control for magnesium balance. About a 80% of the total serum magnesium is ultrafilterable through the glomerular membrane. In all of the mammalian species studied to date, the proximal tubule of the adult animal reabsorbs only a small fraction, 10-15%, of the filtered magnesium. Unlike the adult proximal convoluted tubule that of young rats (aged 13-15 days) reabsorbs 50-60% of filtered magnesium along the proximal tubule together with sodium, calcium, and water. Micropuncture experiments, in every species studied to date, indicates that a large part (approximately 60%) of the filtered magnesium is reabsorbed in the loop of Henle. Magnesium reabsorption in the loop occurs within the cortical thick ascending limb (cTAL) by passive means driven by the transepithelial voltage through the paracellular pathway. Micropuncture experiments have clearly showed that the superficial distal tubule reabsorbs significant amounts of magnesium. Unlike the thick ascending limb of the loop of Henle, magnesium reabsorption in the distal tubule is transcellular and active in nature. Many hormones and nonhormonal factors influence renal magnesium reabsorption to variable extent in the cTAL and distal tubule. Moreover, nonhormonal factors may have important implications on hormonal controls of renal magnesium conservation. Dietary magnesium restriction leads to renal magnesium conservation with diminished urinary magnesium excretion. Adaptation of magnesium transport with dietary magnesium restriction occurs in both the cTAL and distal tubule. Elevation of plasma magnesium or calcium concentration inhibits magnesium and calcium reabsorption leading to hypermagnesiuria and hypercalciuria. The identification of an extracellular Ca2+ /Mg2+ -sensing receptor located on the peritubular side of cTAL and distal tubule cells explains this phenomenon. Loop diuretics, such as furosemide and bumetanide, diminish salt absorption in the cTAL whereas the distally acting diuretics, amiloride and chlorothiazide stimulate magnesium reabsorption within the distal convoluted tubule. Finally, metabolic acidosis, potassium depletion or phosphate restriction can diminish magnesium reabsorption within the loop and distal tubule. Research in the 90's have greatly contributed to our understanding of renal magnesium handling.