Altered renal elimination of organic anions in rats with chronic renal failure

Adriana Mónica Torres1, Myriam Mac Laughlin, Angélica Muller

  • 1Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Argentina. adtorres@fbioyf.unr.edu.ar

Insights

Chronic renal failure (CRF) in rats reduced organic anion transporter 1 (OAT1) expression and Na-K-ATPase activity, impairing p-aminohippurate (PAH) excretion. OAT3 expression remained unchanged, suggesting OAT1

Area of Science:

  • Nephrology
  • Renal Physiology
  • Pharmacokinetics

Background:

  • Chronic renal failure (CRF) involves glomerular and tubular damage.
  • Organic anion renal transporter expression in CRF is poorly understood.

Purpose of the Study:

  • Investigate organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) expression in experimental CRF.
  • Determine their role in p-aminohippurate (PAH) pharmacokinetics and renal excretion.

Main Methods:

  • Created experimental CRF in rats via 5/6 nephrectomy.
  • Compared CRF rats to sham-operated controls six months post-surgery.
  • Measured systolic blood pressure, plasma creatinine, PAH handling, OAT1/OAT3 expression, and Na-K-ATPase activity.

Main Results:

  • CRF rats exhibited elevated blood pressure and creatinine.
  • A significant decrease in PAH filtered, secreted, and excreted loads, and systemic clearance was observed in CRF rats.
  • Renal OAT1 expression and Na-K-ATPase activity were reduced in CRF rats, while OAT3 expression showed no significant change.

Conclusions:

  • Reduced OAT1 expression and Na-K-ATPase activity in CRF rats contribute to the diminished PAH secretion.
  • The impaired PAH excretion in CRF is linked to decreased filtered and secreted loads, primarily due to OAT1 downregulation.

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