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Proximal tubule: organic anion and cation secretion

Proximal tubule · OAT1/3 OCT2 Probenecid

The late proximal tubule (S2/S3) actively pumps organic anions and cations from peritubular blood into the lumen. This is how most diuretics reach their luminal site of action and how the kidney clears protein-bound drugs that the glomerulus cannot filter.

Traced from the start

  1. Efferent arterioleGlomerular filtration barrier
  2. Proximal tubule: organic anion and cation secretion

Detail

Secretes (anions)
Para-aminohippurate, urate, penicillins, cephalosporins, methotrexate, loop and thiazide diuretics, acetazolamide via basolateral OAT1/OAT3 (exchange with alpha-ketoglutarate)
Secretes (cations)
Creatinine, metformin, cimetidine, trimethoprim, morphine via basolateral OCT2 and apical MATE1/MATE2-K
Marker
PAH clearance approximates effective renal plasma flow (~90% extracted in one pass)
Diuretic dependence
Loop and thiazide diuretics are >95% protein-bound so are barely filtered; they must be secreted here to act from the lumen
Inhibitors
Probenecid blocks OAT (raises penicillin levels, uricosuric); cimetidine, trimethoprim and dolutegravir block OCT2/MATE

When it goes wrong

CKD (retained organic anions compete for OAT), nephrotic syndrome (luminal albumin binds drug) or concurrent NSAIDs

Less loop diuretic reaches the lumen: diuretic resistance requiring higher doses, IV bolus or infusion, or thiazide co-blockade

Trimethoprim, cimetidine or dolutegravir

Serum creatinine rises 10-30% with no true fall in GFR; urea and cystatin C unchanged

Probenecid

Uricosuria (used in gout) but raised plasma penicillin and methotrexate levels

Practise this structure

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