Ceruloplasmin and acute phase protein levels are associated with cardiovascular disease in chronic dialysis patients.
BACKGROUND
The most frequent cause of death in hemodialysis (HD) patients is cardiovascular disease (CVD), and chronic inflammation has been identified as an epidemiologically important risk factor for CVD. Elevated levels of minor acute phase reactants, such as ceruloplasmin (Cp) and transferrin, have been related to an increased cardiovascular risk in the general population, but little information is available regarding dialysis patients. We investigated the correlation between Cp and copper concentration (Cu) with major acute phase reactants such as C-reactive protein (CRP) and interleukin-6 (IL-6) in a population of chronic dialytic patients. Furthermore, we evaluated the relationship between long-lasting acute phase proteins such as Cp and nutritional markers.


METHODS
CRP (Berhing Diagnostic, high sensitivity modified nephelometric technique, detection limit 0.1 mcg/mL), IL-6 (EIA, RD Systems), serum albumin, prealbumin, Cp (Berhing, nephelometric assay), copper (mass spectrometry, Varian) and standard laboratory routine analysis were determined in 75 stable chronic dialysis patients (age 60 +/- 16 yrs; dialytic age 65 +/- 50 months ) starting a midweek dialytic session.


RESULTS
Thirty-seven patients (49%) had clinical signs of cerebrovascular, cardiovascular or peripheral vascular disease. Fifty-one patients (67%) showed biochemical inflammation markers as suggested by elevated CRP levels (mean 12.4 mg/L, SD 11.5) and IL-6 (mean 21.3 pg/mL, SD 19.7) with a positive correlation (r=0.65; p<0.001) between CRP and IL-6. CRP and IL-6 also related negatively to nutritional markers such as albumin and prealbumin (r=-0.42; p<0.01). Cp related significantly to CRP (r=0.4; p<0.001) and IL-6 (r=0.41; p<0.001), and as expected to copper (r=0.96; p<0.001), but not with serum albumin and prealbumin. In a multivariate logistic regression analysis, age (p<0.001), dialytic age (p>0.01), IL-6 (p=0.04) and Cp (p=0.02) were the strongest risk factors for cardio-vascular disease (CVD).


CONCLUSIONS
These data suggest that serum Cp could be useful in monitoring the ""chronic inflamed"" patient and support the suggestion that elevated metalloprotein levels are associated with an increased cardiovascular risk in a population of stable dialysis patients.
Panichi
Vincenzo
V
Dipartimento Medicina Interna, Sezione di Nefrologia, Università di Pisa, Pisa, Italy. vpanichi@med.unipi.it
Taccola
Daniele
D
Rizza
Giovanni Manca
GM
Consani
Cristina
C
Migliori
Massimiliano
M
Filippi
Cristina
C
Paoletti
Sabrina
S
Sidoti
Antonino
A
Borracelli
Donella
D
Panicucci
Erica
E
Giovannini
Luca
L
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology; D002570:Ceruloplasmin / Q000378:metabolism*; D003300:Copper / Q000097:blood; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D000209:Acute-Phase Proteins; D015415:Biomarkers; D015850:Interleukin-6; D003300:Copper; D002097:C-Reactive Protein; D002570:Ceruloplasmin