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Published ahead of print on March 30, 2005
J Am Soc Nephrol 16: 1471-1485, 2005
© 2005 American Society of Nephrology
doi: 10.1681/ASN.2004080635

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Clinical Dialysis

Profound Mishandling of Protein Glycation Degradation Products in Uremia and Dialysis

Stamatina Agalou*, Naila Ahmed*, Roya Babaei-Jadidi*, Anne Dawnay{dagger} and Paul J. Thornalley*

* Department of Biological Sciences, University of Essex, Colchester, Essex; {dagger} Renal Research Laboratory, St. Bartholomew’s and The Royal London School of Medicine and Dentistry, St. Bartholomew’s Hospital, London, United Kingdom

Address correspondence to: Dr. Paul J. Thornalley, Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK. Phone/Fax: +44-1206-873010; thorp{at}essex.ac.uk

Received for publication August 4, 2004. Accepted for publication February 16, 2005.

The aim of this study was to define the severe deficits of protein glycation adduct clearance in chronic renal failure and elimination in peritoneal dialysis (PD) and hemodialysis (HD) therapy using a liquid chromatography-triple quadrupole mass spectrometric detection method. Physiologic proteolysis of proteins damaged by glycation, oxidation, and nitration forms protein glycation, oxidation, and nitration free adducts that are released into plasma for urinary excretion. Inefficient elimination of these free adducts in uremia may lead to their accumulation. Patients with mild uremic chronic renal failure had plasma glycation free adduct concentrations increased up to five-fold associated with a decline in renal clearance. In patients with ESRD, plasma glycation free adducts were increased up to 18-fold on PD and up to 40-fold on HD. Glycation free adduct concentrations in peritoneal dialysate increased over 2- to 12-h dwell time, exceeding the plasma levels markedly. Plasma glycation free adducts equilibrated rapidly with dialysate of HD patients, with both plasma and dialysate concentrations decreasing during a 4-h dialysis session. It is concluded that there are severe deficits of protein glycation free adduct clearance in chronic renal failure and in ESRD on PD and HD therapy.




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