Profound mishandling of protein glycation degradation products in uremia and dialysis

• Published in: Journal of the American Society of Nephrology Vol. 16; no. 5; pp. 1471 - 1485
• Main Authors: AGALOU, Stamatina, AHMED, Naila, BABAEI-JADIDI, Roya, DAWNAY, Anne, THORNALLEY, Paul J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-05-2005
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Chemokine CCL2 - blood; Dialysis Solutions - metabolism; Emergency and intensive care: renal failure. Dialysis management; Female; Glycation End Products, Advanced - blood; Glycation End Products, Advanced - chemistry; Glycation End Products, Advanced - urine; Glycosylation; Humans; Intensive care medicine; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - therapy; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nitrogen - metabolism; Oxidation-Reduction; Peritoneal Dialysis; Renal Dialysis; Renal failure; Severity of Illness Index; Transforming Growth Factor beta - blood; Uremia - metabolism; Uremia - therapy; Kidney disease; Human; Nephrology; Urinary system disease; Terminal stage; Glycation; Protein; Urology; Extrarenal dialysis; Chronic; Treatment; Renal failure; Dialysis; Uremia; Degradation product
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2004080635

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.