NDT Advance Access originally published online on March 19, 2008
Nephrology Dialysis Transplantation 2008 23(6):2102-2103; doi:10.1093/ndt/gfn104
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Time-dependent effect of sevelamerHCl on the cardiovascular system
Correspondence and offprint requests to: E-mail: visavica{at}tin.itWe read with great interest the paper ‘Systematic review of the clinical efficacy and safety of sevelamer in dialysis patients’ by Tonelli and co-workers [1].
Although well written, we only partially agree with the authors’ conclusions. Indeed, our experience corroborates the notion of a significant time-dependent effect of sevelamer on the cardiovascular (CV) system. To our opinion, this represents a plausible explanation for the contradictory results of the RIND [2] and the DCOR study [3] and should be further emphasized.
We observed the effect of sevelamerHCl on cardiovascular morbidity (hospitalization rate and duration) in 16 patients (age: 67.4 ± 11.9 years) on maintenance dialysis (dialysis vintage: 167.4 ± 87.9 months). At study entry, phosphate binder regimen was changed from calcium salts to sevelamerHCl, and CV hospitalization events were collected thereafter for 3 years.
At study completion we noticed a significant reduction in serum calcium, phosphate, calcium x phosphate product and total cholesterol (all P values <0.05) (figure 1a). In contrast, non-significant changes in serum PTH and triglycerides were recorded.
|
More importantly, a graded decrease in the hospitalization rate (P < 0.01) and hospitalization duration (P < 0.001) was noted throughout the study follow-up (figure 1b). Of note, none of the bone mineral or lipid metabolism parameters was significantly associated with the reduction of the hospitalization rate and duration.
Indeed, our experience further supports the time–treatment interaction previously reported by other authors. In a post hoc analysis of the DCOR study, Suki and colleagues showed a significant improvement in survival among patients treated for >2 years with sevelamerHCl as compared to peers treated with calcium salts (RR 0.66; IC 95%: 0.48–0.94; P = 0.02) [4]. Furthermore, as also stated by Tonelli et al. [1], the longer follow-up of the RIND study [2] appears as one of the main factors that explain the apparent discrepancies between the ‘positive’ data from the RIND study [2] and the ‘negative’ data from the DCOR study [3].
In light of these and our experience, it is therefore plausible that to impact CV morbidity and mortality in end-stage renal disease a longer time period of treatment might be recommended. Furthermore, although based on a very small sample size, it appears that the beneficial effects of sevelamerHCl rely on its pleiothropic effects [5] rather than on phosphate control only. However, future studies should confirm our preliminary data.
Conflict of interest statement. None declared.
1Nephrology and Dialysis Units Papardo Hospital, Messina 2Division of Nephrology and Dialysis, University of Messina Italy
References
- Tonelli M, Wiebe N, Culleton B, et al. Systematic review of the clinical efficacy and safety of sevelamer in dialysis patients. Nephrol Dial Transplant (2007) 22:2856–2866.
[Abstract/Free Full Text] - Block GA, Raggi P, Bellasi A, et al. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int (2007) 71:438–441.[CrossRef][Web of Science][Medline]
- Suki WN, Zabaneh R, Cangiano JL, et al. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int (2007) 72:1130–1137.[CrossRef][Web of Science][Medline]
- Suki WN. Dialysis Clinical Outcomes Revisited Investigator: Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients: results of a randomized trial. In: J Ren Nutr (2008) 18(1):91–98.[CrossRef][Web of Science][Medline]
- Evenepoel P. Control of hyperphosphatemia beyond phosphate. Kidney Int (2007) 71:376–379.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||