Hutchison_edit 17/7/07 3:23 pm Page 34
Phosphorus Control
Lanthanum carbonate is highly insoluble and therefore has a low turnover (adynamic bone disease or osteomalacia) at baseline tended to
potential for accumulation compared with aluminium (0.00089% versus show improved bone histology in the lanthanum carbonate group
0.05–0.1% absorption of the oral dose) and does not appear to cross the compared with those in the calcium carbonate group, where low
blood–brain barrier. Also, it has no effect on the absorption of fat-soluble turnover lesions persisted (71% versus 42%, respectively).
43
This finding
vitamins.
40
Lanthanum carbonate has been studied in over 5,000 patients is particularly important in excluding any aluminium-like effect on
in clinical trials before launch. These studies showed good control of osteoblast function. Thus, it appears that the evolution towards low bone
phosphate levels over short- and long-term follow-up (up to six years).
41,42
turnover lesions that is often seen in calcium-treated dialysis patients is
Low serum lanthanum levels were detectable in the majority of patients not seen with lanthanum carbonate. No correlations between bone
(0.1–0.8ng/l). This increase was noted for all doses administered versus lanthanum content, PTH levels or bone histology were found.
44
baseline and levels reached a plateau early in the study, then showed no Lanthanum is priced equally to sevelmer (see Table 2).
further increase. Furthermore, they were not dose-dependent and there
are no reported pathological or toxic consequences associated with the Conclusion
increase in plasma lanthanum concentration. The incidence of adverse Hyperphosphataemia remains one of the major and modifiable risk
events was comparable to the placebo group, and it is reported that they factors for mortality in ESRD patients, and all means at our disposal must
are minimised if taken with – or preferably immediately after – food, and be used to prevent it. However, we must begin to individualise
generally abate with time and continued dosing.
42
phosphate-binder therapy according to bone mineral indices and the
presence of vascular calcification to make the right choice and dose, at
The effects on bone were examined in a large-scale (98 patients) the lowest cost. Indeed, the best phosphate binder is still the one that the
histology-based study: after one year of treatment there was a trend patient will take, so potency and pill burden are perhaps the most
towards improved histology. However, the patients with low bone important considerations from the patient’s perspective. ■
1. Food Standard Agency 2003. Available at: effective phosphorus binder in patients with renal failure, calcium- and aluminium-free phosphate binder, inhibits
http:www.foodstandards.gove.uk/multimedia/pdfs/vitamin Kidney Int, 1898;36:690–95. phosphate absorption in normal volunteers, Nephrol Dial
2003.pdf&e 16. Albaaj F, Hutchison AJ, Hyperphosphataemia in renal dialysis Transplant, 1997;12:1640–44.
2. Rufino M,Bonis ED,Martin M, et al., Is it possible to control patients, Hospital Pharmacy Europe, 2004;13:68–72. 31. Slatoplsky E, Burke SK, Dillon MA, et al., RenaGel, a
hyperphosphataemia with diet, without inducing protein 17. Shaefer K, Scheer J, Asmus G, et al., The treatment of uraemic nonabsorbed calcium and aluminium free phosphate binder,
malnutrion?, Nephrol Dial Transplant, 1998;13 (Suppl. hyperphosphataemia with calcium acetate and calcium lowers serum phosphorus and parathyroid hormone, Kidney Int,
3):65–7. carbonate: a comparative study, Nephrol Dial Transplant, 1999;55:299–307.
3. Dlemez JA, Slatopolsky E, Martin KJ, et al., Minerals, vitamin D, 1991;6:170–75. 32. Wiles BM, Reiner D, Kern M et al., Simultaneous lowering of
and parathyroid hormone in continuous ambulatory peritoneal 18. Schneider HW, Kulbe KD, Weber H, et al., In vitro and in vivo serum phosphate and LDL-cholesterol by sevelamer
dialysis, Kidney Int, 1982;21:862–7. studies with a non-aluminium phosphate binding compound, hydrochloride (RenaGel) in dialysis patients, Clin Nephrol,
4. Zehender C, Gutzwiller JR, Renggli K, Haemodiafiltration: a new Kidney Int Suppl, 1986;18:S120–23. 1998;50:381–6.
treatment option for hyperphosphataemia in haemodialysis 19. Passlick J, Wilhelm M, Busch TH, et al., Calcium alginate, 33. Chertow GM, Burke SK, Raggi P, Sevelamer attenuates the
patients, Clin Nephrol, 1999;52(3):152–9. aluminium free phosphate binder in patients on CAPD, Clin progression of coronary and aortic calcification in haemodialysis
5. Haas T, Hillion D, Dongradi G, Phosphate kinetics in dialysis Nephrol, 1989;32(2):96–100. patients, Kidney Int, 2002;62:245–52.
patients, Nephrol Dial Transplant, 1991;6(Suppl. 2): 20. Bro S, Rasmussen RA, Handberg J, et al., Randomised crossover 34. Albaaj F, Hutchison AJ, Hyperphosphataemia in renal failure:
S108–13. study comparing the phosphate binding efficacy of calcium causes, consequences and current management, Drugs,
6. Charra B, Calemard E, Ruffet M, et al., Survival as an index of ketoglutarate versus calcium carbonate in patients on chronic 2003;63(6):577–96.
adequacy of dialysis, Kidney Int, 1992;41:1286–91. haemodialysis, Am J Kidney Dis, 1998;2:257–62. 35. Macro MP, Muray S, Betriu A, et al., Treatment with sevelamer
7. Kooistra MP, Vos J, Kooman HA, et al., Daily home 21. Riedel E, Hampl H, Steudle V, Calcium-alpha-ketoglutarate decreases bicarbonate levels in haemodialysis patients,
haemodialsis in the Netherlands: effects on metabolic control, administration to malnourished haemodialysis patients improves Nephron, 2002;92:499–500.
haemodynamics and the quality of life, Nephrol Dial Transplant, plasma arginine concentrations, Mineral Electrolytes Metab, 36. Suki W, et al., The DCOR Trial- A prospective Randomised Trial
1998;13:2853–60. 1996;22:119–22. Assessing the impact on Outcomes of Sevellamer in Dialysis
8. Slatopolsky E, Weerts C, Norwood K, et al., Long-term effects 22. National Kidney Foundation: K/DOQI clinical practice guidelines Patients, J Am Soc Nephrol, 2005;16:281A (Abstract).
of calcium carbonate and 2.5 mEq/l calcium dialysate on for bone metabolism and disease in chronic kidney disease, Am 37. Block GA, et al., Mortality effect of coronary calcification and
mineral metabolism, Kidney Int, 1989;36:897–903. J Kidney Dis, 2003;42:1–201. phosphate binder choice in incident hemodialysis patients,
9. Cunningham J, Reduced calcium dialysate in CAPD patients: 23. Jenkins DA, Gouldesborough D, Smith GD, et al., Can low Kidney Int, 2007;71:438–41.
efficacy and limitation, Nephrol Dial Transplant, 1997;12(6): dosage aluminium hydroxide control the plasma phosphate 38. Manns B, Stevens L, Miskulin D, et al., A systematic review of
1223–8. without bone toxicity?, Nephrol Dial Transplant, sevelamer in ESRD and an analysis of its potential economic
10. Bender FH, Bernardini J, Piraino B, Calcium mass transfer with 1989;4:51–6. impact in Canada and the United States, Kidney Int, 2004;66:
dialysate containing 1, 25 and 1, 75 mmol/l calcium in 24. Canterbury JM, Bricker NA, Levey GS, Matabolism of bovine 1239–47.
peritoneal dialysis patients, Am J Kidney Dis, 1992;20(4): parathyroid hormone: immunological and biological 39. Finn WF, Joy MS, Haldick GA, Results of a randomised dose-
367–71. characterstics of fragments generated by liver perfusion, J Clin ranging placebo controlled study of lanthanum carbonate for
11. Hutchison AJ, Freemont AJ, Boulton HF, et al., Low-calcium Invest, 1975;55:1245–52. reduction of serum phosphate in chronic renal failure
dialysis fluids and oral calcium carbonate in CAPD: a method of 25. Parsons V, Baldwin D, Moniz C, et al., Successful control of patients receiving haemodialysis, J Am Soc Nephrol,
controlling hyperphosphataemia whilst minimising aluminium hyperparathyroidism in patients on CAPD using magnesium 1999;10:261A.
exposure and hypercalcaemia, Nephrol Dial Transplant, 1992;7: carbonate and calcium carbonate as phosphate binders, 40 Hutchison AJ, Speake M, Albaaj F, Reducing high phosphate
1219–25. Nephron, 1993;63:79–83. levels in patients with chronic renal failure undergoing dialysis:
12. Weinreich T, Ritz E, Passlick-Deejan J, et al., Long-term 26. Hergesell O, Ritz E, Stabilized polynuclear iron hydroxide is an a 4-week, dose-finding, open-label study with lanthanum
dialysis with low calcium solution (1.0 mmol/l) in CAPD: efficient oral phosphate binder in uraemic patients, Nephrol Dial carbonate, Nephrol Dial Transplant, 2004;19:1902–6.
effects on bone mineral metabolism, Peri Dial Int, Transplant, 1999;14:863–7. 41. Hutchison AJ, et al., Poster presented at the American Society
1996;16:260–68. 27. Spengler K, Follmann H, Boss KS, et al., Cross-linked iron of Nephrology, 2005.
13. Moriniere PH, Roussel A, Tahiri Y, et al., Substitution of dextran is an efficient oral phosphate binder in the rat, Am J 42. Hutchison AJ, Pratt R, Poster presented at the American Society
aluminium hydroxide by high doses of calcium carbonate in Kidney Dis, 1996;11:808–12. of Nephrology, 2005.
patients on chronic haemodialysis: disappearance of 28. Graff L, Burnell D, Reduction of dietary phosphorus absorption 43. D’Haese PC, Spasovsk GB, Sikole A, et al., A multicentre study
hyperaluminaemia and equal control of hyperparathyroidism, by oral phosphorus binders, Res Common Mol Pathol Pharmacol, on the effects of lanthanum carbonate (Fosrenol) and calcium
Proc Eur Dial Transolant Assoc, 1983;19:784–7. 1995;90(3):389–401. carbonate on renal bone disease in dialysis patients, Kidney Int,
14. Slatopolsky E, Weerts C, Lopez-Itilker S, et al., Calcium 29. Takahashi Y, Tanaka A, Nakamura T, et al., Nicotinamide 2003;63(Suppl. 1):S73–8.
carbonate as a phosphate binder in patients with chronic renal suppresses hyperphosphataemia in haemodialysis patients, 44. Albaaj F, Hutchison AJ, Lanthanum Carbonate for the treatment
failure undergoing dialysis, N Eng J Med, 1986;315:157–61. Kidney Int, 2004;65:1099–1104. of hyperphosphataemia in renal failure and dialysis patients,
15. Mai M, Emmett M, Sheikh M, et al., Calcium acetate an 30. Burke SL, Slatopolsky EA, Goldberg DI, RenaGel, a novel Expert Opin Pharmacother, 2005;6(2):319–28.
34 EUROPEAN RENAL DISEASE 2007
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74