Markedly elevated levels of plasma advanced glycation end products in patients with liver cirrhosis - amelioration by liver transplantation.
OBJECTIVE
Modification by advanced glycation renders macromolecules susceptible to elimination in the liver via scavenger receptors. Thus, in advanced liver disease an accumulation of advanced glycation end products (AGEs) in circulation might occur, due to the reduction of effective liver mass.


METHODS
Plasma AGE levels (fluorescent AGEs-AGE-Fl and N(epsilon)-carboxymethyllysine - CML) were determined in 51 patients with liver cirrhosis (Ci) and 19 healthy controls. Five patients were followed 36 months after liver transplantation.


RESULTS
In cirrhotic patients, markedly elevated concentrations of AGEs were revealed (AGE-Fl: control, 0.3+/-0.01 x 10(5) AU, Ci: 1.06+/-0.06 x 10(5) AU, P<0.01; CML, control: 431.7+/-16.3 ng/ml, Ci: 647.6+/-258.5, P<0.01). CML levels correlated with the severity of liver disease, as determined by clinical score (r=0.663, P<0.001), albumin level (r=0.704, P<0.001) and monoethylglycinexylide test (r=0.852, P<0.01). Reduced renal function contributed to the rise of CML in proportion to the degree of renal impairment. Liver transplantation resulted in about 50% decline of CML levels within 3 months, while impairment of renal function still persisted, underlying the central role of the liver for AGE removal.


CONCLUSIONS
In liver Ci, hepatic removal of AGEs is impaired. With regard to the toxicity of AGEs, their accumulation could be of pathophysiological relevance.
Sebeková
Katarína
K
Institute of Preventive and Clinical Medicine, Commenius University Medical School, Limbová 14, 833 01, Bratislava, Slovakia. sebekova@upkm.sk
Kupcová
Viera
V
Schinzel
Reinhard
R
Heidland
August
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000601:surgery*; D016031:Liver Transplantation; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D003404:Creatinine; D008239:Lysine