Tubular Resorption in Kidneys

The formation of urine involves the initial generation of a protein-free ultrafiltrate by the glomerulus, followed by extensive modification as the filtrate passes through the tubular network.
The bulk of the glomerular filtrate is reabsorbed into the peritubular capillaries, with only approximately 0.5% ultimately excreted as urine.

Tubular resorption relies on the vectorial transport of solutes across epithelial cells, utilizing both active transcellular and passive paracellular pathways.
Primary Active Transport: The basolateral Na+/K+-ATPase pump utilizes ATP to transport three Na+ ions out of the cell in exchange for two K+ ions. This establishes a low intracellular Na+ concentration and a cell-negative potential difference.
Secondary Active Transport: Apical transporters utilize the established Na+ electrochemical gradient to drive the reabsorption of other solutes against their concentration gradients, such as glucose via Na+-glucose cotransporters and protons via the Na+/H+ exchanger.
Tertiary Active Transport: Gradients generated by secondary active transport drive the movement of other ions, such as the apical Cl-/base exchanger driven by the gradient created by the Na+/H+ exchanger.
Paracellular Transport: Passive movement of water and solutes occurs between cells across tight junctions, primarily determined by the specific expression of claudin and occludin proteins in each nephron segment.

Nephron Segment	% of Filtered Na+ Reabsorbed	Key Apical Transporters	Major Functions & Solutes Reabsorbed
Proximal Tubule (PT)	60–65%	SGLT-2, SGLT-1, NHE3, NaPi-IIa, NaPi-IIc	Bulk isosmotic reabsorption of water, glucose (100%), amino acids (100%), bicarbonate (~80%), and phosphate.
Thick Ascending Limb (TAL)	25–30%	NKCC2, ROMK	Reabsorption of NaCl without water; generation of lumen-positive voltage driving paracellular Ca2+ and Mg2+ reabsorption.
Distal Convoluted Tubule (DCT)	5–10%	NCC, TRPV5, TRPM6	Active transcellular reabsorption of NaCl, Ca2+, and Mg2+.
Collecting Duct (CD)	1–3%	ENaC, H+-ATPase, AQP2	Fine-tuning of Na+ and K+ balance; AVP-regulated water reabsorption; final urinary acidification.

The proximal tubule reabsorbs approximately 60-80% of the glomerular filtrate in a strictly isosmotic fashion.
Glucose: All filtered glucose is reabsorbed here via a low-affinity/high-capacity transporter (SGLT-2) in the early proximal tubule, and a high-affinity/low-capacity transporter (SGLT-1) in the late proximal tubule. Glucose exits the basolateral membrane via facilitative diffusion using GLUT2 and GLUT1.
Amino Acids: Filtered amino acids are entirely reclaimed via specific Na+-dependent cotransporters on the apical membrane, such as EAAC1 for acidic amino acids, and the rBAT/b0+AT heterodimer for cystine and basic amino acids.
Bicarbonate: Approximately 80% of filtered bicarbonate is reabsorbed. Secreted H+ (via NHE3 and H+-ATPase) combines with filtered HCO3- to form H2CO3. Carbonic anhydrase IV (luminal) and II (intracellular) facilitate its conversion to CO2 and water, and subsequent regeneration into intracellular HCO3- which exits via the basolateral NBC1 cotransporter.
Water: Water freely follows solute reabsorption, primarily facilitated by abundant Aquaporin 1 (AQP1) channels on both apical and basolateral membranes.

Thin Limbs: The thin descending limb is highly permeable to water (via AQP1) but does not actively transport solutes, concentrating the tubular fluid. The thin ascending limb is impermeable to water but highly permeable to NaCl via the CLC-K1 channel.
Thick Ascending Limb (TAL): The TAL is impermeable to water. It reabsorbs 25-30% of filtered NaCl via the apical electroneutral Na-K-2Cl cotransporter (NKCC2).
Potassium is recycled back into the tubular lumen via the apical ROMK channel, generating a lumen-positive electrical potential (+8 to +10 mV).
This positive voltage is the essential driving force for the paracellular reabsorption of divalent cations, particularly Ca2+ and Mg2+, which travel through tight junctions composed of claudin-16 and claudin-19.

DCT: Reabsorbs 5–10% of filtered NaCl via the thiazide-sensitive Na-Cl cotransporter (NCC). It is the primary site for active, transcellular fine-tuning of Mg2+ (via TRPM6 channels) and Ca2+ (via TRPV5 channels).
Cortical Collecting Duct (Principal Cells): Principal cells mediate final Na+ reabsorption via the apical epithelial sodium channel (ENaC), which is stimulated by aldosterone. This creates a lumen-negative potential that drives K+ secretion via ROMK and BK channels.
Water Handling: Under basal conditions, the collecting duct is impermeable to water. In response to hyperosmolality or hypovolemia, Arginine Vasopressin (AVP) binds to basolateral V2 receptors (AVPR2). This triggers a cAMP/PKA signaling cascade, causing the insertion of Aquaporin-2 (AQP2) water channels into the apical membrane, allowing water to be reabsorbed along the hypertonic medullary gradient to concentrate the urine.
Cortical Collecting Duct (Intercalated Cells): Alpha-intercalated cells secrete protons into the lumen via an apical H+-ATPase and reabsorb bicarbonate via the basolateral AE1 (Cl-/HCO3-) exchanger, critical for correcting acidemia. Beta-intercalated cells function inversely, secreting bicarbonate via apical Pendrin to correct alkalemia.