N-EPSILON-(CARBOXYMETHYL)LYSINE IN BLOOD FROM MAINTENANCE HEMODIALYSIS-PATIENTS MAY CONTRIBUTE TO DIALYSIS-RELATED AMYLOIDOSIS

Background. Recent studies demonstrated not only that advanced glycati on end product could be found in amyloid tissue from patient with dial ysis related amyloidosis, but also that amyloid beta 2-microglobulin w as modified with N-epsilon-(carboxymethyl)lysine (CML). We wanted to d etermine if CML could be a biomarker in these patients. Methods. To ra ise polyclonal anti-carboxymethyllysine antibody, human serum albumin was carboxymethylated by glyoxylic acid and was immunized to rabbits a s antigen. Carboxymethyllysine-hemoglobin (CML-Hb) levels were measure d by the dot blotting method using this antibody. Results. The levels of CML-Hb were 6.68 +/- 3.10 nmol CML/mg Hb in nondiabetic hemodialysi s patients (N = 70), 6.39 +/- 3.33 nmol CML/mg Hb in diabetic hemodial ysis patient (N = 21), and 3.13 +/- 0.88 nmol CML/mg Hb in 47 healthy volunteers. For clinical signs of dialysis-related amyloidosis, 70 non diabetic hemodialysis patients were scored according Gejyos criteria. The CML-Hb levels in patients with a high amyloid score as well as a l ow amyloid score were significantly higher than in patients with negat ive amyloid score (8.89 +/- 3.53 nmol CML/mg Hb, 7.28 +/- 2.32 nmol CM L/mg Hb vs. 5.11 +/- 2.09 nmol CML/mg Hb, P < 0.001, P < 0.05). Furthe rmore, the CML-Hb levels correlated significantly with serum values of the methylguanidine over creatinine ratio and hyaluronate. Conclusion s. We suggest that CML-Hb is increased in blood from patients on maint enance hemodialysis and is thus a potential biomarker of oxidative dam age in these patients. Moreover, CML-modification of protein may play a pathogenic role in the development of dialysis related amyloidosis.