Proteins that pass through the glomerulus are reabsorbed in the proximal tubule. The glomerulus filters out peptide hormones, small proteins, and small amounts of larger proteins like albumin. Despite this, only a small fraction of proteins actually make it through the glomerulus and enter Bowman's space, resulting in a concentration of about 40 mg/L in the glomerular ultrafiltrate. However, due to the high glomerular filtration rate (GFR), the total amount of filtered protein per day is significant, amounting to 7200 mg/day or 7.2 g/day.

The proximal tubule is responsible for reabsorbing the filtered proteins. This occurs through endocytosis, where intact proteins or partially degraded proteins, facilitated by enzymes on the surface of the proximal tubule cells, are taken up. Once inside the cell, these proteins and peptides are broken down by enzymes into their individual amino acids. The amino acids then leave the cell across the basolateral membrane using transport proteins and are returned to the blood. Under normal circumstances, this reabsorption mechanism effectively retrieves nearly all the filtered proteins, resulting in urine that is essentially free of proteins. However, if the amount of filtered proteins increases, the reabsorption mechanism can become overwhelmed, leading to proteinuria, which is the presence of protein in the urine. If the glomerular filtration barrier to proteins is disrupted, it can result in increased filtration of proteins and subsequently proteinuria, a common occurrence in kidney disease.

The cells of the proximal tubule also play a crucial role in the secretion of organic anions and organic cations into the tubule fluid. This secretion process helps regulate the plasma levels of various xenobiotics (e.g., antibiotics, diuretics, statins, antivirals, antineoplastics, immunosuppressants, neurotransmitters, and NSAIDs) and toxic compounds derived from both endogenous and exogenous sources. Many of these organic anions and cations are end products of metabolism that circulate in the plasma. Since they are often bound to plasma proteins, they are not easily filtered. Consequently, only a small fraction of these potentially toxic substances are eliminated through filtration alone. Therefore, the secretion of organic anions and cations by the proximal tubule, including many toxins from the peritubular capillary into the tubular fluid, helps eliminate these compounds from plasma as it enters the kidneys. It's worth noting that reduced kidney function due to disease severely impairs the urinary excretion of organic anions and cations, leading to increased plasma levels of xenobiotics and the potential accumulation of toxic organic anions and cations.
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.