Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study.
BACKGROUND
Cardiovascular morbidity and mortality are massively increased in patients with chronic kidney disease (CKD). Sevelamer hydrochloride has been shown to attenuate cardiovascular calcifications in CKD and end-stage renal disease (ESRD) patients. We assessed how sevelamer hydrochloride influences the evolution of serum fetuin-A and other serological factors predicting cardiovascular outcome and survival in haemodialysis patients.


METHODS
Fifty-seven prevalent haemodialysis patients were included in a three-phase prospective interventional trial (A-B-A design; 8 weeks per phase). Sevelamer was only administered in the middle phase of the study. Within the other two phases, >or=90% of the patients received calcium acetate for phosphate binding. Detailed time courses of serum biochemistries were analysed in order to obtain detailed insight into the influence of sevelamer upon CKD-mineral and bone disorder (MBD) parameters as well as serum fetuin-A, fibroblast growth factor 23 (FGF23) and uraemic toxin levels [uric acid, indoxyl sulphate, hippuric acid, indole acetic acid, p-cresol and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF)].


RESULTS
Forty-one patients finished the three prospective study phases (intention-to-treat analysis). After treatment with sevelamer, serum fetuin-A significantly increased (+21%), showing a delayed increase outlasting the third (non-sevelamer) study period. Total and low-density lipoprotein (LDL) cholesterol levels, as well as serum calcium, decreased significantly. The opposite occurred with albumin, C-reactive protein and intact parathyroid hormone (iPTH). FGF23, uric acid, indoxyl sulphate, hippuric acid, indole acetic acid, CMPF and serum phosphate did not change significantly during sevelamer treatment. In contrast, in parallel to sevelamer treatment, there was a significant rise in serum P-cresol.


CONCLUSIONS
In haemodialysis patients, treatment with sevelamer over 8 weeks was associated with a delayed yet long-lasting increase in serum fetuin-A levels. Increasing the serum level of fetuin-A, a negative acute-phase protein and systemic calcification inhibitor, might be one of the potential anti-calcification mechanisms of sevelamer. Since we failed to detect a decrease in systemic inflammation and uraemic toxins, the exact mechanisms by which sevelamer treatment affects serum fetuin-A remain to be determined.
Brandenburg
Vincent Matthias
VM
Department of Nephrology, University Hospital of the RWTH Aachen, Pauwelsstase 30, Aachen, Germany. vincent.brandenburg@post.rwth-aachen.de
Schlieper
Georg
G
Heussen
Nicole
N
Holzmann
Stefan
S
Busch
Birgit
B
Evenepoel
Pieter
P
Vanholder
Raymond
R
Meijers
Björn
B
Meert
Natalie
N
Fassbender
Walter J
WJ
Floege
Jürgen
J
Jahnen-Dechent
Willi
W
Ketteler
Markus
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality* / Q000517:prevention & control; D002614:Chelating Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D002908:Chronic Disease; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D007674:Kidney Diseases / Q000628:therapy*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*; D012189:Retrospective Studies; D012307:Risk Factors; D000069603:Sevelamer; D015996:Survival Rate; D055815:Young Adult; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001798:Blood Proteins; D002614:Chelating Agents; D008078:Cholesterol, LDL; C000717427:FGF23 protein, human; D011073:Polyamines; D060749:alpha-2-HS-Glycoprotein; D000089703:Fibroblast Growth Factor-23; D002097:C-Reactive Protein; D000069603:Sevelamer; D002118:Calcium