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Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study.
Nephrol Dial Transplant. 2010 Aug; 25(8):2672-9.ND

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, >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.

Authors+Show Affiliations

Department of Nephrology, University Hospital of the RWTH Aachen, Pauwelsstase 30, Aachen, Germany. vincent.brandenburg@post.rwth-aachen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20172849

Citation

Brandenburg, Vincent Matthias, et al. "Serological Cardiovascular and Mortality Risk Predictors in Dialysis Patients Receiving Sevelamer: a Prospective Study." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 25, no. 8, 2010, pp. 2672-9.
Brandenburg VM, Schlieper G, Heussen N, et al. Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. Nephrol Dial Transplant. 2010;25(8):2672-9.
Brandenburg, V. M., Schlieper, G., Heussen, N., Holzmann, S., Busch, B., Evenepoel, P., Vanholder, R., Meijers, B., Meert, N., Fassbender, W. J., Floege, J., Jahnen-Dechent, W., & Ketteler, M. (2010). Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 25(8), 2672-9. https://doi.org/10.1093/ndt/gfq053
Brandenburg VM, et al. Serological Cardiovascular and Mortality Risk Predictors in Dialysis Patients Receiving Sevelamer: a Prospective Study. Nephrol Dial Transplant. 2010;25(8):2672-9. PubMed PMID: 20172849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. AU - Brandenburg,Vincent Matthias, AU - Schlieper,Georg, AU - Heussen,Nicole, AU - Holzmann,Stefan, AU - Busch,Birgit, AU - Evenepoel,Pieter, AU - Vanholder,Raymond, AU - Meijers,Björn, AU - Meert,Natalie, AU - Fassbender,Walter J, AU - Floege,Jürgen, AU - Jahnen-Dechent,Willi, AU - Ketteler,Markus, Y1 - 2010/02/18/ PY - 2010/2/23/entrez PY - 2010/2/23/pubmed PY - 2010/10/29/medline SP - 2672 EP - 9 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 25 IS - 8 N2 - 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. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/20172849/Serological_cardiovascular_and_mortality_risk_predictors_in_dialysis_patients_receiving_sevelamer:_a_prospective_study_ DB - PRIME DP - Unbound Medicine ER -