Figure 1.

Urinary biomarkers for ALS derived from normal kidney function. Urine is a rich source of candidate ALS biomarkers, whose solute content is determined by the size and charge of components passing through the nephrons. The functional unit of the kidney is the nephron that consists of the glomerulus, which filters blood, and the renal tubule, which reabsorbs necessary components back into the blood. These components include salts like sodium chloride (NaCl), potassium (K⁺) and chloride (Cl⁻) ions. Hydrogen (H⁺), ammonia (NH₃⁺) and bicarbonate (HCO₃⁻) are among other ions that are reabsorbed, alongside glucose, amino acids, vitamins and urea. All the blood metabolites and proteins less than 20 kDa in size pass through the nephron and into the urine. Most proteins of 20–50 kDa size are excreted, while only some 50–70 kDa proteins, especially cationic proteins, are excreted. Most proteins larger than 60–70 kDa are actively transported back into blood at the proximal convoluted tubule. Levels of other urinary components such as salts and urea are determined by their active and passive transport along the tubule, while most vesicles found in urine are derived from the urogenital system.