DurgicalDurgical
EN
Open the app

Physiology · Renal, fluids and acid–base

Tubular secretion of organic acids and bases !

  • Mechanism
  • For completeness

The proximal tubule pulls many drugs and wastes out of the blood and dumps them into urine, even those bound to proteins.

Updated 2026-11-01

Also called: OAT and OCT transporters, Drug secretion

See it in 3D: Kidneys

What it is

Besides filtering, the kidney actively secretes organic anions and cations in the straight segment of the proximal tubule. Anions enter the cell from blood via OAT1 and OAT3 and leave into the lumen via MRP2/MRP4 and others; cations enter via OCT2 and leave via MATE in exchange for H⁺. Because secretion takes molecules even when bound to albumin, it clears substances that are barely filtered. Shared transporters mean substances compete with one another: the basis of many interactions.

How it works, step by step

  1. The Na⁺/K⁺-ATPase creates a Na⁺ gradient that keeps α-ketoglutarate high inside the cell.
  2. OAT1/OAT3 swap that α-ketoglutarate for an organic anion from blood: the anion enters against its gradient.
  3. The anion exits into the lumen through apical transporters (MRP2, MRP4, OAT4) and is excreted.
  4. Cations enter via OCT2, helped by the negative cell interior, and leave via MATE1/MATE2-K in exchange for luminal H⁺.
  5. By taking the free fraction, secretion shifts the equilibrium and frees more drug from albumin: it can clear almost all that arrives.
  6. The transporters saturate and are shared: two substances of the same class slow each other down.

The nephron: segments, transporters and diuretics

The nephron: segments, transporters and diuretics CortexOuter medullaInner medulla3006009001200mOsm/kgUrineGlomerulusProximal tubuleDistal tubuleThin descendingThin ascendingThick ascendingCollecting ductJuxtaglomerularapparatusNHE3 · SGLT2Filters ≈ 180 L/dayAQP1Passive NaClNKCC2 · ROMKParacellular Ca²⁺, Mg²⁺NCC · Ca²⁺ (PTH)ENaC · ROMK/BKAQP2 (ADH)α: H⁺-ATPase · β: pendrin

Na⁺ reabsorbed ≈ 65–70%Water reabsorbed ≈ 65–70%

Proximal tubule

  • What it does: Reabsorbs ≈ 65–70% of filtered Na⁺ and water (isosmotically), nearly all glucose and amino acids, ≈ 80% of HCO₃⁻ and most K⁺ and phosphate. Secretes organic acids and bases (many drugs) and makes NH₄⁺ from glutamine.
  • Transporters: NHE3 (Na⁺/H⁺) with carbonic anhydrase; SGLT2 (early segment, ≈ 90% of glucose) and SGLT1; NaPi-2a (phosphate); basolateral Na⁺/K⁺-ATPase.
  • Hormones: Ang II stimulates NHE3 (more Na⁺ and HCO₃⁻: contraction alkalosis); PTH inhibits NaPi-2a (phosphaturia) and activates 1α-hydroxylase (active vitamin D).
  • Drugs: Carbonic anhydrase inhibitors (1), SGLT2 inhibitors (2) and osmotic diuretics (3, with the thin descending limb).
  • Disorders: Fanconi syndrome (loses glucose, amino acids, phosphate and HCO₃⁻); type 2 (proximal) renal tubular acidosis; familial renal glucosuria (SGLT2).
  • Glomerulus and arterioles
  • Proximal tubule
  • Thin descending limb
  • Thin ascending limb
  • Thick ascending limb
  • Distal convoluted tubule
  • Collecting tubule and duct
  • Juxtaglomerular apparatus (macula densa)
  • Cortex
  • Medulla
  • Interstitial osmolality (≈ 300 → 1200 mOsm/kg)
Illustrative schematic drawn by Durgical (a long-loop juxtamedullary nephron); proportions and percentages are approximate and not for clinical decisions.

The two secretory systems

SystemEntry (blood side)Exit (lumen)Examples
Organic anionsOAT1, OAT3MRP2, MRP4, OAT4PAH, penicillins, furosemide, thiazides, methotrexate, NSAIDs, urate
Organic cationsOCT2MATE1, MATE2-KCreatinine, metformin, cimetidine, trimethoprim, dopamine

Clinical notes

  • In CKD, uraemic organic anions build up and compete with diuretics for OATs: less drug reaches the lumen, which looks like diuretic resistance.
  • Uric acid is handled by both reabsorption (URAT1) and secretion; drugs that shift that balance affect gout.
  • A small creatinine rise after starting trimethoprim may reflect blocked secretion rather than kidney damage.

Test yourself

Think of the answer, then tap the question to see it.

Why can PAH clearance approach renal plasma flow when only about 20 % of PAH is filtered?

Proximal OATs secrete almost all PAH left in peritubular plasma: between filtration and secretion, ≈90 % of the PAH delivered is removed.

A patient starts trimethoprim and creatinine rises slightly with no change in urea or urine output. What explains it?

Trimethoprim competes with creatinine for organic-cation secretion (OCT2/MATE): less creatinine is secreted and its level rises with no change in true GFR.

Why do loop diuretics need tubular secretion to work?

They are largely albumin-bound and barely filtered; they reach the lumen of the loop via proximal OATs, and their target (NKCC2) is on the luminal side.

Add to my cards (3)

See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

In Pharmacology

← All of physiology

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 25.6 Tubular Reabsorption (OpenStax (Rice University), 2022); Gout (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 28). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.