Disorders of tubular electrolyte handling

Glycosuria—glucose reabsorption in the proximal tubule is carried out by two different pairs of apical Na+-dependent (SGLT1 and -2) and basolateral Na+-independent (GLUT1 and -2) glucose transporters. Abnormalities in renal glucose transport can be seen in association with other defects of proximal tubular transport. Familial renal glycosuria is a rare autosomal recessive condition caused by mutations in the SGLT2-encoding gene, SLC5A2. Phosphate-handling disorders—the plasma concentration of inorganic phosphate depends on the balance between intestinal absorption, renal excretion, and the internal contribution from bone. Changes of serum phosphate levels can be caused by numerous inherited and acquired conditions. Disorders associated with increased urinary phosphate excretion and low serum phosphate levels produce symptoms that mainly affect the bones: rickets in children and osteomalacia in adults. Magnesium-handling disorders—normal plasma magnesium concentration is achieved by variation of urinary magnesium excretion in response to altered uptake by the intestine. The main site of magnesium absorption is the small bowel, via paracellular simple diffusion at high intraluminal concentrations, and via active transcellular uptake through the magnesium channel TRPM6 at low concentrations. Regulation and fine-tuning of serum magnesium concentration occurs primarily in the kidney. Genetic disorders of magnesium handling include Gitelman’s syndrome. Aminoaciduria and renal Fanconi’s syndrome—most amino acids (except for tryptophan, which is protein bound) are freely filtered by the glomerulus, after which 95 to 99.9% are reabsorbed in the proximal tubules by apical Na+-dependent cotransporters and Na+-independent cotransporters. Aminoaciduria is defined as urinary excretion of more than 5% of the filtered load of an amino acid. Renal Fanconi’s syndrome is characterized by a generalized defect of both Na+-coupled and receptor-mediated proximal tubular transport.