Molecular mechanisms altering tubular calcium reabsorption
Mallory L Downie1,2, R Todd Alexander3,4,5
1Department of Renal Medicine, University College London, London, UK.
Pediatric Nephrology (Berlin, Germany)
|April 2, 2021
Summary
Understanding kidney calcium reabsorption pathways, including claudins and TRPV5, is key to treating hypercalciuria and kidney stones. This review explains how interventions lower urinary calcium excretion.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Calcium reabsorption in the nephron is crucial for maintaining mineral balance.
- Dysregulation of renal calcium handling can lead to hypercalciuria and kidney stone formation.
- Specific tight junction proteins and ion channels mediate calcium transport along the nephron.
Purpose of the Study:
- To review the molecular mechanisms of renal tubular calcium reabsorption.
- To explain the genetic basis of hypercalciuria and its association with kidney stones.
- To elucidate how dietary and medical interventions impact urinary calcium excretion.
Main Methods:
- Review of existing literature on renal calcium transport pathways.
- Analysis of genetic variations in genes encoding calcium transport proteins.
- Correlation of molecular mechanisms with clinical manifestations of hypercalciuria.
Main Results:
- Calcium reabsorption occurs via paracellular (proximal tubule, thick ascending limb) and transcellular (distal tubule) pathways.
- Claudins (CLDN2, CLDN12, CLDN16, CLDN19, CLDN14), CaSR, TRPV5, calbindin-D28K, PMCA1b, and NCX are key players in renal calcium handling.
- Genetic variations in CLDN14, CASR, and TRPV5 are linked to idiopathic hypercalciuria and nephrolithiasis.
Conclusions:
- Understanding the molecular details of renal calcium reabsorption is essential for managing hypercalciuria.
- Targeting specific proteins and pathways involved in calcium transport offers therapeutic strategies.
- Interventions can effectively modulate urinary calcium excretion by influencing these molecular mechanisms.
Related Concept Videos
01:28Tubular Reabsorption and Secretion
4.6K
Tubular secretion and reabsorption are two critical processes in the nephron tubule of the kidneys. When the fluid filtered from the glomerulus enters the proximal convoluted tubule, it is referred to as filtrate, and its composition changes due to tubular reabsorption and secretion.
Tubular reabsorption is a selective process that starts when the filtrate enters the proximal tubules. It involves substances traveling through the transcellular route (through the tubule cell and peritubular...
Tubular reabsorption is a selective process that starts when the filtrate enters the proximal tubules. It involves substances traveling through the transcellular route (through the tubule cell and peritubular...
4.6K
01:22Physiology of the Genitourinary System II: Tubular Reabsorption and Secretion
507
The kidneys maintain homeostasis through filtration, reabsorption, and secretion. Tubular reabsorption and secretion are crucial in forming urine and regulating electrolytes, water balance, and waste elimination.Tubular Reabsorption and Secretion ProcessesTubular reabsorption is the process that reclaims essential substances such as electrolytes, glucose, amino acids, and water from the glomerular filtrate back into the bloodstream. This is achieved through passive and active transport...
507
01:26Reabsorption and Secretion in the DCT and Collecting Duct
2.2K
The early phase of the DCT manages the reabsorption of approximately 10-15% of filtered water, 5–10% of filtered sodium, and 5–10% of filtered chloride. This process is facilitated by Na+–Cl− symporters in apical membranes and sodium-potassium pumps, as well as Cl− leakage channels in basolateral membranes. The early DCT also stands out as a site where parathyroid hormone (PTH) stimulates calcium reabsorption, depending on the body's requirements.
The distal...
The distal...
2.2K
01:17Reabsorption and Secretion in the Loop of Henle
2.8K
The thick ascending limb of the nephron loop has Na+–K+–2Cl− symporters in the apical membranes of its cells. These symporters simultaneously reclaim one sodium ion, one potassium ion, and two chloride ions from the tubular fluid. Sodium ions are actively transported into the interstitial fluid at the base and sides of the cell, diffusing into the vasa recta. Chloride ions move through leakage channels in the basolateral membrane into the interstitial fluid and then into the...
2.8K
01:22Drug Elimination by Renal Route: Tubular Reabsorption
4.6K
During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the...
4.6K
01:28Antihypertensive Drugs: Potassium-Sparing Diuretics
1.8K
Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
1.8K