N epsilon-(carboxymethyl)lysine in blood from maintenance hemodialysis patients may contribute to dialysis-related amyloidosis.
BACKGROUND
Recent studies demonstrated not only that advanced glycation end product could be found in amyloid tissue from patient with dialysis related amyloidosis, but also that amyloid beta2-microglobulin was modified with N(epsilon)-(carboxymethyl)lysine (CML). We wanted to determine if CML could be a biomarker in these patients.


METHODS
To raise polyclonal anti-carboxymethyllysine antibody, human serum albumin was carboxymethylated by glyoxylic acid and was immunized to rabbits as antigen. Carboxymethyllysine-hemoglobin (CML-Hb) levels were measured 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 hemodialysis patients (N = 70), 6.39 +/- 3.43 nmol CML/mg Hb in diabetic hemodialysis patient (N = 21), and 3.13 +/- 0.88 nmol CML/mg Hb in 47 healthy volunteers. For clinical signs of dialysis-related amyloidosis, 70 nondiabetic hemodialysis patients were scored according Gejyo's criteria. The CML-Hb levels in patients with a high amyloid score as well as a low amyloid score were significantly higher than in patients with negative amyloid score (8.89 +/- 3.53 nmol CMLmg Hb, 7.28 +/- 2.32 nmol CML/mg Hb vs. 5.11 +/- 2.09 nmol CML/mg Hb, P < 0.001, P < 0.05). Furthermore, the CML-Hb levels correlated significantly with serum values of the methylguanidine over creatinine ratio and hyaluronate.


CONCLUSIONS
We suggest that CML-Hb is increased in blood from patients on maintenance hemodialysis and is thus a potential biomarker of oxidative damage in these patients. Moreover, CML-modification of protein may play a pathogenic role in the development of dialysis related amyloidosis.
Motomiya
Y
Y
Suiyukai Clinic, Kashihara, Nara, Japan.
Oyama
N
N
Iwamoto
H
H
Uchimura
T
T
Maruyama
I
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000097:blood* / Q000209:etiology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002349:Carpal Tunnel Syndrome / Q000097:blood / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008760:Methylguanidine / Q000097:blood; D008875:Middle Aged; D011817:Rabbits; D006435:Renal Dialysis / Q000009:adverse effects*; D013122:Spinal Diseases / Q000097:blood / Q000209:etiology; D001613:beta 2-Microglobulin / Q000378:metabolism
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D006454:Hemoglobins; D001613:beta 2-Microglobulin; D008760:Methylguanidine; C048496:N(6)-carboxymethyllysine; D008239:Lysine