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Direct micropuncture evidence that matrix extracellular phosphoglycoprotein inhibits proximal tubular phosphate

David G Shirley1, Nuno J R Faria, Robert J Unwin

  • 1Centre for Nephrology, University College London Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK. david.shirley@ucl.ac.uk

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|May 18, 2010
PubMed
Abstract

Insights

Matrix extracellular phosphoglycoprotein (MEPE) increases phosphate excretion by reducing reabsorption in the proximal tubule. This study confirms MEPE's phosphaturic effect and its action site in the nephron.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Matrix extracellular phosphoglycoprotein (MEPE) is a potential phosphatonin.
  • Previous studies indicated MEPE has phosphaturic effects in rats.
  • The precise site of MEPE action within the nephron was previously unconfirmed.

Purpose of the Study:

  • To investigate the effect of MEPE on phosphate reabsorption directly within the proximal tubule.
  • To confirm the phosphaturic role of MEPE and identify its nephron site of action.

Main Methods:

  • Micropuncture collections were performed on late proximal convoluted tubules in anesthetized rats.
  • The direct effect of MEPE on proximal tubule phosphate reabsorption was assessed.
  • Phosphate concentration ratios and filtered phosphate fractions were measured.

Main Results:

  • MEPE did not affect glomerular filtration rate or single-nephron filtration rate.
  • MEPE significantly increased phosphate excretion.
  • The proximal tubular fluid to plasma phosphate concentration ratio (TF/P(Pi)) increased from 0.49 to 0.68.
  • The fraction of filtered phosphate reaching the late proximal tubule (FD(Pi)) increased from 0.20 to 0.33.

Conclusions:

  • The phosphaturic effect of MEPE is confirmed.
  • MEPE's action primarily involves reduced phosphate reabsorption in the proximal convoluted tubule.
  • These findings align with MEPE-induced reductions in apically located NaPT2a.

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