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Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study

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Abstract
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, >= 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.
Keywords
fetuin-A, dialysis, hyperphosphataemia, pleiotropic effects, CORONARY-ARTERY CALCIFICATION, P-CRESOL, HEMODIALYSIS-PATIENTS, CHRONIC KIDNEY-DISEASE, sevelamer hydrochloride, FETUIN-A, NORMAL SERUM, VASCULAR CALCIFICATION, INDOXYL SULFATE, CALCIUM, PROGRESSION

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Chicago
Brandenburg, Vincent Matthias, Georg Schlieper, Nicole Heussen, Stefan Holzmann, Birgit Busch, Pieter Evenepoel, Raymond Vanholder, et al. 2010. “Serological Cardiovascular and Mortality Risk Predictors in Dialysis Patients Receiving Sevelamer: a Prospective Study.” Nephrology Dialysis Transplantation 25 (8): 2672–2679.
APA
Brandenburg, V. M., Schlieper, G., Heussen, N., Holzmann, S., Busch, B., Evenepoel, P., Vanholder, R., et al. (2010). Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. NEPHROLOGY DIALYSIS TRANSPLANTATION, 25(8), 2672–2679.
Vancouver
1.
Brandenburg VM, Schlieper G, Heussen N, Holzmann S, Busch B, Evenepoel P, et al. Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. NEPHROLOGY DIALYSIS TRANSPLANTATION. 2010;25(8):2672–9.
MLA
Brandenburg, Vincent Matthias, Georg Schlieper, Nicole Heussen, et al. “Serological Cardiovascular and Mortality Risk Predictors in Dialysis Patients Receiving Sevelamer: a Prospective Study.” NEPHROLOGY DIALYSIS TRANSPLANTATION 25.8 (2010): 2672–2679. Print.
@article{1068832,
  abstract     = {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, {\textrangle}= 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.},
  author       = {Brandenburg, Vincent Matthias and Schlieper, Georg and Heussen, Nicole and Holzmann, Stefan and Busch, Birgit and Evenepoel, Pieter and Vanholder, Raymond and Meijers, Bj{\"o}rn and Meert, Natalie and Fassbender, Walter J and Floege, J{\"u}rgen and Jahnen-Dechent, Willi and Ketteler, Markus},
  issn         = {0931-0509},
  journal      = {NEPHROLOGY DIALYSIS TRANSPLANTATION},
  keyword      = {fetuin-A,dialysis,hyperphosphataemia,pleiotropic effects,CORONARY-ARTERY CALCIFICATION,P-CRESOL,HEMODIALYSIS-PATIENTS,CHRONIC KIDNEY-DISEASE,sevelamer hydrochloride,FETUIN-A,NORMAL SERUM,VASCULAR CALCIFICATION,INDOXYL SULFATE,CALCIUM,PROGRESSION},
  language     = {eng},
  number       = {8},
  pages        = {2672--2679},
  title        = {Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study},
  url          = {http://dx.doi.org/10.1093/ndt/gfq053},
  volume       = {25},
  year         = {2010},
}

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