Proteins filtered by the glomerulus are reabsorbed in the proximal tubule. As mentioned previously, peptide hormones, small proteins, and small amounts of larger proteins such as albumin are filtered by the glomerulus. Overall, only a small percentage of proteins cross the glomerulus and enter Bowman’s space (i.e., the concentration of proteins in the glomerular ultrafiltrate is only ≈ 40 mg/L). However, the total amount of protein filtered per day is significant because the glomerular filtration rate (GFR) is so high:
Equation 34.1
Filtered protein = GFR ×[Protein] in the ultrafiltrate = 7200 mg/day, or 7 2. g/day
Filtered proteins are reabsorbed in the proximal tubule by endocytosis either as intact proteins or after being partially degraded by enzymes on the surface of proximal tubule cells. Once the proteins and peptides are inside the cell, enzymes digest them into their constituent amino acids, which then leave the cell across the basolateral membrane by transport proteins and are returned to the blood. Normally this mechanism reabsorbs virtually all the proteins filtered, and hence the urine is essentially protein free. However, because the mechanism is easily saturated, an increase in filtered proteins can result in proteinuria (appearance of protein in urine). Disruption of the glomerular filtration barrier to proteins increases the filtration of proteins and 610 SECTION7Berne & Levy Physiology • BOX 34.2 Some Organic Cations Secreted by Proximal Tubule • BOX 34.1 Some Organic Anions Secreted by Proximal Tubule cAMP, cGMPBile saltsHippuratesOxalateProstaglandins: PGE2, PGF2α UrateVitamins: ascorbate, folate
AcetazolamideAcyclovirAmoxicillinCaptoprilChlorothiazideFurosemideLosartanPenicillinProbenecidSalicylate (aspirin)HydrochlorothiazideSimvastatinBumetanideNonsteroidal antiinflammatory drugs (NSAIDs): indomethacin cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate.
results in proteinuria, which is frequently seen with kidney disease.
Secretion of Organic Anions and Organic Cations
Cells of the proximal tubule also secrete organic anions and organic cations into the tubule fluid. Secretion of organic anions and cations by the proximal tubule plays a key role in regulating the plasma levels of xenobiotics (e.g., a variety of antibiotics, diuretics, statins, antivirals, antineoplastics, immunosuppressants, neurotransmitters, and nonsteroidal antiinflammatory drugs [NSAIDs]) and toxic compounds derived from endogenous and exogenous sources. Many of the organic anions and cations (
Boxes 34.1 34.2 ) secreted by the proximal tubule are end products of metabolism that circulate in plasma. Many of these organic compounds are bound to plasma proteins and thus are not readily filtered. Therefore only a small fraction of these potentially toxic substances are eliminated from the body by excretion resulting from filtration alone. Thus secretion of organic anions and cations, including many toxins from the peritubular capillary into the tubular fluid, promote elimination of these compounds from plasma entering the kidneys. Hence these substances are removed from plasma by both filtration and secretion. It is important to note that when kidney function is reduced by disease, urinary excretion of organic anions and cations is severely reduced, which can lead to increased plasma levels of xenobiotics and potentially toxic accumulation of organic anions and cations.