Only ESRD was associated with a significant increase in the molecular mass of HSA in vivo. Since this mass increase was very low and much lower than reported for AGE-modified peptides, it may reflect AGE formation on HSA by alpha-oxoaldehydes that accumulate in uremia, rather than modification of albumin by AGE-modified peptides. The molecular mass of HSA in vivo was indicative of a minimal and not a high extent of glycation.

No abstract

Mass spectrometric monitoring of albumin in uremia. disease and other disorders [1]. Successful kidney trans-Background. Advanced glycation end products (AGEs) are plantation decreases the concentrations of uremic toxins, a novel class of uremic toxins. In plasma, they are present whereas dialysis is generally less effective. Few uremic in proteins and also in low molecular mass peptides. AGEtoxins have been identified: They include parathyroid hormodified peptides are thought to bind and modify plasma proteins. Monitoring of the consequent increase in molecular mass mone, ␤ 2 -microglobulin, indoxyl sulfate, potassium, inorof serum albumin may be used in surveillance of the clinical ganic phosphate, and hydrogen ions [1]. Recently, a furmanagement of uremia. ther class of compounds, advanced glycation end products Methods. We investigated molecular mass changes of human (AGEs), have been proposed as uremic toxins [2-5]. serum albumin (HSA) glycated by glucose and methylglyoxal in vitro and of subjects with moderate renal impairment, end-Advanced glycation end products are terminal end-stage stage renal disease (ESRD), ESRD on hemodialysis, and noradducts of protein glycation. Glycation of proteins occurs mal healthy controls by matrix-assisted laser desorption ionizaby the nonenzymatic reaction of saccharide derivatives tion mass spectrometry. with proteins. Glucose and the physiological ␣-oxoalde-Results. Fatty acid-free HSA had a molecular mass of 66,446 Ϯ 114 D. Mean (ϮSD) molecular mass increases were hydes glyoxal, methylglyoxal and 3-deoxyglucosone are HSA minimally glycated by glucose 399 Ϯ 88 D (N ϭ 5, P Ͻ particularly important glycating agents in vivo [6]. Lysine, 0.001), HSA highly glycated by glucose 6780 Ϯ 122 D (N ϭ 5, arginine, and N-terminal amino acid residues are the ma-P Ͻ 0.001), HSA minimally glycated by methylglyoxal 73 Ϯ jor amino acid residues modified. Glucose reacts initially 121 D (N ϭ 5, P Ͼ 0.05), and HSA without fatty acid removal 535 Ϯ 90 D (N ϭ 5, P Ͻ 0.001). For HSA of human subjects,