Lanthanum carbonate for the treatment of hyperphosphatemia in CKD 5D: multicenter, double blind, randomized, controlled trial in mainland China

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• 作者：Jing Xu (1)
  Yi-Xiang Zhang (1)
  Xue-Qing Yu (2)
  Zhi-Hong Liu (3)
  Li-Ning Wang (4)
  Jiang-Hua Chen (5)
  Ya-Ping Fan (6)
  Zhao-Hui Ni (7)
  Mei Wang (8)
  Fa-Huan Yuan (9)
  Guo-Hua Ding (10)
  Xiang-Mei Chen (11)
  Ai-Ping Zhang (12)
  Chang-Lin Mei (1)
  
• 关键词：Lanthanum carbonate ; Hyperphosphatemia ; Chronic kidney disease 5D ; Hemodialysis ; Continuous ambulatory peritoneal dialysis (CAPD)
• 刊名：BMC Nephrology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：14
• 期：1
• 全文大小：270KB
• 参考文献：1. Tonelli M, Pannu N, Manns B: Oral phosphate binders in patients with kidney failure. / N Engl J Med 2010, 362:1312-324. CrossRef
  2. Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL: Serum phosphate levels and mortality risk among people with chronic kidney disease. / J Am Soc Nephrol 2005, 16:520-28. CrossRef
  3. Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, Robinson BM, Port FK: Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). / Am J Kidney Dis 2008, 52:519-30. CrossRef
  4. Melamed ML, Eustace JA, Plantinga L, Jaar BG, Fink NE, Coresh J, Klag MJ, Powe NR: Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study. / Kidney Int 2006, 70:351-57. CrossRef
  5. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. / J Am Soc Nephrol 2004, 15:2208-218. CrossRef
  6. Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK: Association of elevated serum PO(4), Ca × PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. / J Am Soc Nephrol 2001, 12:2131-138.
  7. Young EW, Akiba T, Albert JM, McCarthy JT, Kerr PG, Mendelssohn DC, Jadoul M: Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). / Am J Kidney Dis 2004, 44:34-8. CrossRef
  8. Block GA, Hulbert-Shearon TE, Levin NW, Port FK: Association of serum phosphorus and calcium × phosphate product with mortality risk in chronic hemodialysis patients: a national study. / Am J Kidney Dis 1998, 31:607-17. CrossRef
  9. National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. / Am J Kidney Dis 2003, 42:S1-S202.
  10. Isakova T, Gutiérrez OM, Chang Y, Shah A, Tamez H, Smith K, Thadhani R, Wolf M: Phosphorus binders and survival on hemodialysis. / J Am Soc Nephrol 2009, 20:388-96. CrossRef
  11. Hutchison AJ: Oral phosphate binders. / Kidney Int 2009, 75:906-14. CrossRef
  12. Schaefer K, Umlauf E, von Herrath D: Reduced risk of hypercalcemia for hemodialysis patients by administering calcitriol at night. / Am J Kidney Dis 1992, 19:460-64.
  13. Miller JE, Kovesdy CP, Norris KC, Mehrotra R, Nissenson AR, Kopple JD, Kalantar-Zadeh K: Association of cumulatively low or high serum calcium levels with mortality in long-term hemodialysis patients. / Am J Nephrol 2010, 32:403-13. CrossRef
  14. Navaneethan SD, Palmer SC, Craig JC, Elder GJ, Strippoli GF: Benefits and harms of phosphate binders in CKD: a systematic review of randomized controlled trials. / Am J Kidney Dis 2009, 54:619-37. CrossRef
  15. Jamal SA, Fitchett D, Lok CE, Mendelssohn DC, Tsuyuki RT: The effects of calcium-based versus non-calcium-based phosphate binders on mortality among patients with chronic kidney disease: a meta-analysis. / Nephrol Dial Transplant 2009, 24:3168-174. CrossRef
  16. Joy MS, Finn WF: LAM-302 Study Group: Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia. / Am J Kidney Dis 2003, 42:96-07. CrossRef
  17. Chiang SS, Chen JB, Yang WC: Lanthanum carbonate (Fosrenol) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease. / Clin Nephrol 2005, 63:461-70.
  18. Shigematsu T: Lanthanum Carbonate Research Group: Lanthanum carbonate effectively controls serum phosphate without affecting serum calcium levels in patients undergoing hemodialysis. / Ther Apher Dial 2008, 12:55-1. CrossRef
  19. Shigematsu T: Lanthanum Carbonate Group: Multicenter prospective randomized, double-blind comparative study between lanthanum carbonate and calcium carbonate as phosphate binders in Japanese hemodialysis patients with hyperphosphatemia. / Clin Nephrol 2008, 70:404-10.
  20. Al-Baaj F, Speake M, Hutchison AJ: Control of serum phosphate by oral lanthanum carbonate in patients undergoing haemodialysis and continuous ambulatory peritoneal dialysis in a short-term, placebo-controlled study. / Nephrol Dial Transplant 2005, 20:775-82. CrossRef
  21. Xu J, Mao ZG, Kong M, Hu LH, Ye CY, Xu CG, Rong S, Sun LJ, Wu J, Dai B, Chen DP, Zhu YX, Zhang YX, Zhang YQ, Zhao XZ, Mei CL: Scientific publications in nephrology and urology journals from Chinese authors in East Asia: a 10-year survey of the literature. / PLoS One 2011, 6:e14781. CrossRef
  22. International conference on harmonization of technical requirements for registration of pharmaceuticals for human use: / ICH Harmonised tripartite guideline. Statistical principles for clinical trials E9. Current Step 4 version. 1998.
  23. D’Amico G: Opportunities for a chronic disease outreach program in China. / Kidney Int 2005, 68:S46-S48. CrossRef
  24. Zhu C: Launch of the health-care reform plan in China. / Lancet 2009, 373:1322-324. CrossRef
  25. Martin P, Wang P, Robinson A, Poole L, Dragone J, Smyth M, Pratt R: Comparison of dietary phosphate absorption after single doses of lanthanum carbonate and sevelamer carbonate in healthy volunteers: a balance study. / Am J Kidney Dis 2011, 57:700-06. CrossRef
  26. Daugirdas JT, Finn WF, Emmett M, Chertow GM: Frequent Hemodialysis Network Trial Group: Frequent Hemodialysis Network Trial Group. The phosphate binder equivalent dose. / Semin Dial 2011, 24:41-9. CrossRef
  27. Sprague SM: A comparative review of the efficacy and safety of established phosphate binders: calcium, sevelamer, and lanthanum carbonate. / Curr Med Res Opin 2007, 23:3167-175. CrossRef
  28. Joy MS, Kshirsagar A, Candiani C, Brooks T, Hudson JQ: Lanthanum carbonate. / Ann Pharmacother 2006, 40:234-40. CrossRef
  29. Damment SJ, Pennick M: Clinical pharmacokinetics of the phosphate binder lanthanum carbonate. / Clin Pharmacokinet 2008, 47:553-63. CrossRef
  30. Sprague SM, Abboud H, Qiu P, Dauphin M, Zhang P, Finn W: Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial. / Clin J Am Soc Nephrol 2009, 4:178-85. CrossRef
  31. Finn WF, Joy MS, Hladik G: Lanthanum Study Group: Efficacy and safety of lanthanum carbonate for reduction of serum phosphorus in patients with chronic renal failure receiving hemodialysis. / Clin Nephrol 2004, 62:193-01.
  32. Malluche HH, Siami GA, Swanepoel C, Wang GH, Mawad H, Confer S, Smith M, Pratt RD, Monier-Faugere MC: SPD405-07 Lanthanum Carbonate Study: SPD405-07 Lanthanum Carbonate Study Group. Improvements in renal osteodystrophy in patients treated with lanthanum carbonate for two years. / Clin Nephrol 2008, 70:284-95.
  33. D'Haese PC, Spasovski GB, Sikole A, Hutchison A, Freemont TJ, Sulkova S, Swanepoel C, Pejanovic S, Djukanovic L, Balducci A, Coen G, Sulowicz W, Ferreira A, Torres A, Curic S, Popovic M, Dimkovic N, De Broe ME: A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. / Kidney Int Suppl 2003, 85:S73-S78. CrossRef
  34. Hutchison AJ, Barnett ME, Krause R, Kwan JT, Siami GA: SPD405-09 Lanthanum Study Group: SPD405-09 Lanthanum Study Group. Long-term efficacy and safety profile of lanthanum carbonate: results for up to 6 years of treatment. / Nephron Clin Pract 2008, 110:c15-c23. CrossRef
  35. Altmann P, Barnett ME, Finn WF: SPD405-07 Lanthanum Carbonate Study Group. Cognitive function in stage 5 chronic kidney disease patients on hemodialysis: no adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy. / Kidney Int 2007, 71:252-59. CrossRef
  36. Toussaint ND, Lau KK, Polkinghorne KR, Kerr PG: Attenuation of aortic calcification with lanthanum carbonate versus calcium-based phosphate binders in haemodialysis: a pilot randomized controlled trial. / Nephrology 2011, 16:290-98. CrossRef
  37. Neven E, Dams G, Postnov A, Chen B, De Clerck N, De Broe ME, D'Haese PC, Persy V: Adequate phosphate binding with lanthanum carbonate attenuates arterial calcification in chronic renal failure rats. / Nephrol Dial Transplant 2009, 24:1790-799. CrossRef
  38. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/29/prepub
  
• 作者单位：Jing Xu (1)
  Yi-Xiang Zhang (1)
  Xue-Qing Yu (2)
  Zhi-Hong Liu (3)
  Li-Ning Wang (4)
  Jiang-Hua Chen (5)
  Ya-Ping Fan (6)
  Zhao-Hui Ni (7)
  Mei Wang (8)
  Fa-Huan Yuan (9)
  Guo-Hua Ding (10)
  Xiang-Mei Chen (11)
  Ai-Ping Zhang (12)
  Chang-Lin Mei (1)
  
  1. Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China
  2. Department of Nephrology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  3. Department of Nephrology, Institute of Kidney Disease of the Chinese People’s Liberation Army, Jingling Hospital, Nanjing University School of Medicine, Nanjing, China
  4. Department of Nephrology, First Affiliated Hospital of China Medical University, Shenyang, China
  5. Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  6. Department of Nephrology, Affiliated Hospital of Nantong Medical College, Jiangsu, China
  7. Renal Division, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
  8. Department of Nephrology, People’s Hospital of Peking University, Beijing, China
  9. Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
  10. Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
  11. Chinese PLA Institute of Nephrology, Chinese PLA General Hospital and Military Medical Postgraduate College, Beijing, China
  12. Department of Nephrology, General Hospital of Jinan Military Command, Jinan, Shandong, China
  

文摘

Background Serum phosphorus control is critical for chronic kidney disease (CKD) 5D patients. Currently, clinical profile for an oral phosphorus binder in the mainland Chinese population is not available. Objective To establish the efficacy, safety, and tolerability of lanthanum carbonate in CKD 5D patients. Design Multicenter, randomized, double blind, placebo-controlled study. A central randomization center used computer generated tables to allocate treatments. Setting Twelve tertiary teaching hospitals and medical university affiliated hospitals in mainland China. Participants Overall, 258 hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) adult patients were enrolled. Intervention After a 0--week washout period and a 4-week lanthanum carbonate dose-titration period, 230 patients were randomized 1:1 to receive lanthanum carbonate (1500 mg-3000 mg) or placebo for a further 4-week maintenance phase. Main outcome measures Efficacy and safety of lanthanum carbonate to achieve and maintain target serum phosphorus concentrations were assessed. Results In the titration phase, serum phosphorus concentrations of all patients decreased significantly. About three-fifths achieved target levels without significantly disturbing serum calcium levels. At the end of the maintenance period, the mean difference in serum phosphorus was significantly different between the lanthanum carbonate and placebo-treated groups (0.63±0.62 mmol/L vs. 0.15±0.52 mmol/L, P < 0.001). The drug-related adverse effects were mild and mostly gastrointestinal in nature. Conclusion Lanthanum carbonate is an efficacious and well-tolerated oral phosphate binder with a mild AE profile in hemodialysis and CAPD patients. This agent may provide an alternative for the treatment of hyperphosphatemia in CKD 5D patients in mainland China. Trial registration No. ChiCTR-TRC-10000817