Clinical trial NCT01011699: Nicotinamide Versus Sevelamer Hydrochloride on Phosphatemia Control on Chronic Hemodialysed Patients
Official title: Comparison of Nicotinamide and Sevelamer Hydrochloride on Phosphatemia Control on Chronic Hemodialysed Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Renal Failure
Hemodialysis
Keywords: nicotinamide
sevelamer hydrochloride
phosphatemia
cinacalcet
dyslipidemia
vascular calcification
bone mass loss
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2009-11-11
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The comparison between nicotinamide and sevelamer aims to demonstrate, in chronic hemodialysed patients, the non-inferiority of nicotinamide in terms of control of the phosphatemia. Secondary objectives is to compare the two treatments in terms of efficiency in other biological parameters, vascular calcification and bone mass loss and on the clinical and biological tolerance and finally to explore the roles of metabolites of nicotinamide.

Detailed description: This is a multicenter randomized open study with 2 treatment arms (nicotinamide / Sevelamer).

Laboratories who will dose biochemical parameters and PTH, ignore which treatment is received by patients.

The team which will measure bone density and the radiologist or rheumatologist who will appreciate centrally calcification and deformity of the vertebrae, ignore which treatment is received by patients.

Therefore it's a Randomized Prospective Blinded Outcome Endpoint.

Pre-recruitment period (3 to 6 months) with basic medication

* Repletion of vitamin D (p 25 OHD between 30 and 50 ng / ml) (if required by supplementation Dedrogyl weekly by the dialysis nurse)
* Bath dialysis to 1.50 mmol / l calcium (1.75 mmol / l if hemodiafiltration), 32 mmol bicarbonate and 0.5 mmol / l magnesium - Support to provide a dietary protein intake with 1.2 g / kg / d and assessment of contributions of Ca and PO4
* Use of CaCO3 taken with meals rich in phosphorus (morning, noon and evening) without
* In case of hyperkalemia, Calcium Sorbisterit® will preferably be used instead of KAYEXALATE®. This process exposes the worsening effect of hyperphosphatemia increasing calcium malabsorption and therefore the negative calcium balance in renal failure.
* Statin therapy, fibrate or ezetimibe if necessary, but with stable dose

This treatment will be monitored on the following parameters:

* Biochemical weekly Predialytic (midweek): creatinine, urea, PO4, Ca, protein, Na, K, bicarbonate, glucose, uric acid
* Additional monthly balance: PTH intact, Mg, albumin, CRP
* Each 4 months update: lipid profile (fasting or not, but always at the same time, 25 OH D, complete blood count (CBC), AST-ALT, total alkaline phosphatase, gamma-GT, PKC, glycated hemoglobin (HbA1C) )

Recruitment (180 patients):

* Obtaining informed consent
* Perform a bone density by DXA third of the radius (cortical bone), radius ultradistal (trabecular bone), femoral neck bone (mixed), whole body and lumbar spine profile radiography.
* Lumbar and dorsal radiography (frontal and profile) for research and vertebral measurement of aortic calcification by the Framingham score) + pelvis radiography (frontal) and 2 hands radiography (frontal) searching vascular calcification, Looser's streaks and subperiosteal resorption.
* Freezing at -80 ° C (4 tubes of 1 ml of serum)for centralized analysis:PTH, 25 OHD, CTX, PAO. All samples will be sent for laboratory analysis of Biochemistry University Hospital of Amiens at the end of the study.

For this, 10 ml of blood will be collected with a dry tube then centrifuged 15 minutes, 4000-5000 rpm at room temperature within 30 minutes after collection. Then, aliquot 1ml into 4 polypropylene tubes being careful not to take the fibrin.

* Freezing at -80 ° C in a tube of 2.5 ml of plasma to be assayed later the metabolites of nicotinamide. These samples will only be achieved if patients accept and mark the second part of the consent. The tubes are then stored in the biological resource center, CHU Amiens for further research and for an indefinite period.

The nicotinamide metabolites measured in this study will annex the Met2PY (N-methyl-2-pyridone-5-carboxamide), the Met4PY (N-methyl-4-pyridone-3-carboxamide) and NAD (nicotinamide adenine dinucleotide).

6 ml of EDTA whole blood will be collected, then centrifuged 15 minutes, 4000-5000 rpm at room temperature within 30 minutes after collection. Then, 2.5 ml aliquot in 1 polypropylene tube.

* Then a heparinized blood sample of 2.5 ml will be frozen at -80 °C for determination of nicotinamide. All samples will be sent for analysis at CERBA at the end of the study.

Randomization will be done by the minimization technic with stratification factors: center, duration of dialysis and taking lipid lowering therapy. Randomization will be performed remotely via a website.

Follow-up of one year:

* Period titration nicotinamide or sevelamer to control serum phosphorus in 4 weeks, with stable doses of CaCO3
* Increased nicotinamide 500 mg up to 4 tablets: 0-1-0, 0-1-1, 1-1-1, 1-2-1
* Increased sevelamer 800 mg up to 12 tablets: 0-2-2 ; 2-4-4 ; 4-4-4 ; 2-5-5
* Maintenance period of 5 months with assessment of maintenance doses of Renagel (sevelamer) or Nicobion (nicotinamide) or during the last 3 months.
* After these 6 months:
* Freezing -80 ° C, 4 tubes of 1 ml of serum centralized reviews PTH, 25 OHD, CTX, PAO (as mentioned above).
* Freezing -80 ° C in a tube of 2.5 ml of plasma to be assayed later the metabolites of nicotinamide (as mentioned above).
* Freezing -80 ° C with a heparinized blood sample of 2.5 ml for determination of nicotinamide (as mentioned above).
* Second randomization via a website, patients with intact PTH\> 300 pg / ml after 6 months of Nicobion ® and Renagel ®. Randomization 75-150 pg / ml or 150-300 mg / ml will be made by the minimization technic with stratification factors: the center and the type of Hypophosphatemia PTH will be reduced by introducing cinacalcet ® by increments of 30 mg every 3 weeks to 180 mg / day (given with meals 24 hours before the next dialysis). Increase of Cinacalcet ® will be stopped when PTH is \<250 pg / ml for arm 150-300pg/ml or \<125 per arm 75-150 pg / ml.

Once corrected calcemia \<2.25 mmol / l, doses of CaCO3 will be increased; if the maximum tolerable of CaCO3 on the tract map does not prevent hypocalcemia (\<2.10 mmol / l), the calcium bath will be increased to 1.75 mmol / l CaCO3 decreased and, if necessary adjustment of nicotinamide / Sevelamer to maintain PO4 between 1.30 and 1.60 mmol / l.

* During the first 6 months of administration of sevelamer, weekly, monthly and quarterly reports will be done. Regarding PTH assay will be performed, every 3 weeks during the titration of cinacalcet.
* A lumbar and dorsal radiography (frontal and profile), a pelvis radiography (face) and 2 hands radiography (front) will be conducted at the end of follow-up period.
* Bone densitometry will be performed at the end of the study (same camera - same site).
* Case report form: tolerance, serious adverse events, compliance, cardiovascular events (myocardial infarction, PAO, stroke, arteritis, vascular intervention),deaths and fractures during the follow-up study.
* Freezing -80 ° C to 4 tubes of 1 ml of serum centralized reviews PTH, 25 OHD, CTX, PAO at the end of the study (as mentioned above).
* Freezing -80 ° C in a tube of 2.5 ml of plasma to be assayed later the metabolites of nicotinamide at the end of the study (as mentioned above).
* Freezing at -80 ° C with a heparinized blood sample of 2.5 ml for determination of nicotinamide at the end of the study (as mentioned above).

Analytical Methodology

Eligibility criteria: Inclusion Criteria:

* Women or men over 18 years
* Chronic hemodialysis (since more than 3 months)
* Hyperphosphatemia controlled with only CaCO3
* PO4 \> 1,60 mmol/l, PCa \< 2,37 mmol/l
* patient able to understand and sign informed consent form

Exclusion Criteria:

* PTH \< 60 ou \> 800 pg/ml (PTX)
* Aluminium intoxication (aluminium level in blood \> 0,5 µmol/l)
* Score of aortic calcifications ≥ 20 (max 24)
* Characterized intolerance with Renagel and/or Nicobion
* Pregnant woman
* Autoimmune disease
* Patient known to have a bad drug compliance
* Blood tests abnormality (thrombopenia \<150 000, serum albumin \<30g)
* Hepatic tests abnormality
* Transplant probably within 6 months
* Patient who will need transplantation within 6 month
* Patients receiving chemotherapy
* Patients having a loss of dry weight of 3 kg in 3 months or 6 kg in 6 months.

Primary outcomes:
measure: The comparison between nicotinamide and Sevelamer was primarily to demonstrate the noninferiority of nicotinamide in terms of control of the phosphatemia observed during the 4th, 5th and 6th months before to introduce Cinacalcet ®.
timeFrame: 6th months
Secondary outcomes:
measure: To demonstrate noninferiority of nicotinamide in terms of effect on dyslipidemia (evaluated by the ratio LDL / HDL cholesterol), the risk of hypercalcemia (PCa> 2.37 mmol / l) and increase of phospho-calcic product (> 3 , 79 mmol/l).
timeFrame: 6 th months and one year
measure: To evaluate the difference between nicotinamide and sevelamer on vascular calcification
timeFrame: one year
measure: To evaluate the difference between nicotinamide and sevelamer on bone mass loss and fracture risk
timeFrame: one year
measure: Evaluate the percentage of population requiring use of cinacalcet® to control PTH (75-300 pg/ml). Evaluate his benefit on phosphatemia and calcemia control. Prevent the need for surgical PTX, and evaluate the additional cost of treatment by cinacalcet
timeFrame: 6th months
measure: Evaluate roles of metabolites of nicotinamide (efficacy and side effects) through another study
timeFrame: 6th months and one year
measure: Compare the cost-effectiveness ratio of these two treatments
timeFrame: one year
Other outcomes:
Locations:
city: Soissons
country: France
facility: Centre Hospitalier Général
state: Aisne
city: Lisieux
country: France
facility: Centre Hospitalier
state: Calvados
city: Limoges
country: France
facility: ALURAD
state: Limousin
city: Reims
country: France
facility: Centre Hospitalier Universitaire
state: Marne
city: Reims
country: France
facility: Association Régionale Promotion Dialyse à domicile (ARPDD)
state: Marne
city: Hénin-Beaumont
country: France
facility: Association pour le Développement de l'Hémodialyse
state: Nord-Pas de Calais
city: Lille
country: France
facility: Polyclinique de la Louvière
state: Nord
city: Lille
country: France
facility: CHRU
state: Nord
city: Roubaix
country: France
facility: Hôpital Victor Provo
state: Nord
city: Valenciennes
country: France
facility: Centre Hospitalier Général
state: Nord
city: Beauvais
country: France
facility: Centre Hospitalier Général
state: Oise
city: Compiegne
country: France
facility: Clinique Saint Côme
state: Oise
city: Creil
country: France
facility: Centre Hospitalier Général
state: Oise
city: Bois Bernard
country: France
facility: Clinique du Bois Bernard
state: Pas de calais
city: Boulogne sur mer
country: France
facility: Centre Hospitalier
state: Pas de calais
city: Amiens
country: France
facility: Centre Hospital-Universitaire d'Amiens
state: Picardie
city: Rouen
country: France
facility: Clinique de l'Europe
state: Seine maritime
city: Cambrai
country: France
facility: Centre Hospitalier
Study officials:
affiliation: Centre Hospitalier Universitaire, Amiens
name: Albert FOURNIER, Pr
role: STUDY_DIRECTOR
affiliation: Centre Hospitalier Universitaire, Amiens
name: Ziad MASSY, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goldsmith D, Ritz E, Covic A. Vascular calcification: a stiff challenge for the nephrologist: does preventing bone disease cause arterial disease? Kidney Int. 2004 Oct;66(4):1315-33. doi: 10.1111/j.1523-1755.2004.00895.x.
citation: Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol. 1998 Dec;9(12 Suppl):S16-23.
citation: K/DOQI: (Kidney Disease Outcomes Quality Initiative) of the National Kidney Foundation. Am J Kidney Dis suppl 3, october 2003.
citation: Jungers P, Choukroun G, Robino C, Massy ZA, Taupin P, Labrunie M, Man NK, Landais P. Epidemiology of end-stage renal disease in the Ile-de-France area: a prospective study in 1998. Nephrol Dial Transplant. 2000 Dec;15(12):2000-6. doi: 10.1093/ndt/15.12.2000.
citation: Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int. 2003 Mar;63(3):793-808. doi: 10.1046/j.1523-1755.2003.00803.x.
citation: Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003 Jun 14;361(9374):2005-16. doi: 10.1016/s0140-6736(03)13636-7.
citation: London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003 Sep;18(9):1731-40. doi: 10.1093/ndt/gfg414.
citation: 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 Aug;15(8):2208-18. doi: 10.1097/01.ASN.0000133041.27682.A2.
citation: Shahapuni I, Mansour J, Harbouche L, Maouad B, Benyahia M, Rahmouni K, Oprisiu R, Bonne JF, Monge M, El Esper N, Presne C, Moriniere P, Choukroun G, Fournier A. How do calcimimetics fit into the management of parathyroid hormone, calcium, and phosphate disturbances in dialysis patients? Semin Dial. 2005 May-Jun;18(3):226-38. doi: 10.1111/j.1525-139X.2005.18318.x.
citation: Ghazali A, Fardellone P, Pruna A, Atik A, Achard JM, Oprisiu R, Brazier M, Remond A, Moriniere P, Garabedian M, Eastwood J, Fournier A. Is low plasma 25-(OH)vitamin D a major risk factor for hyperparathyroidism and Looser's zones independent of calcitriol? Kidney Int. 1999 Jun;55(6):2169-77. doi: 10.1046/j.1523-1755.1999.00480.x.
citation: Goldsmith DJ, Covic A, Sambrook PA, Ackrill P. Vascular calcification in long-term haemodialysis patients in a single unit: a retrospective analysis. Nephron. 1997;77(1):37-43. doi: 10.1159/000190244.
citation: Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003 Jul 31;349(5):446-56. doi: 10.1056/NEJMoa022536.
citation: Fournier AE, Johnson WJ, Taves DR, Beabout JW, Arnaud CD, Goldsmith RS. Etiology of hyperparathyroidism and bone disease during chronic hemodialysis. I. Association of bone disease with potentially etiologic factors. J Clin Invest. 1971 Mar;50(3):592-8. doi: 10.1172/JCI106529.
citation: Argiles A, Kerr PG, Canaud B, Flavier JL, Mion C. Calcium kinetics and the long-term effects of lowering dialysate calcium concentration. Kidney Int. 1993 Mar;43(3):630-40. doi: 10.1038/ki.1993.92.
citation: Indridason OS, Quarles LD. Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group. Kidney Int. 2000 Jan;57(1):282-92. doi: 10.1046/j.1523-1755.2000.00819.x.
citation: Locatelli F, Covic A, Chazot C, Leunissen K, Luno J, Yaqoob M. Optimal composition of the dialysate, with emphasis on its influence on blood pressure. Nephrol Dial Transplant. 2004 Apr;19(4):785-96. doi: 10.1093/ndt/gfh102.
citation: Chertow GM, Burke SK, Raggi P; Treat to Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002 Jul;62(1):245-52. doi: 10.1046/j.1523-1755.2002.00434.x.
citation: Fournier A, Said S, Ghazali A, Sechet A, Ezaitouni F, Marie A, Westeel PF, Moriniere P, Boudailliez B. The clinical significance of adynamic bone disease in uremia. Adv Nephrol Necker Hosp. 1997;27:131-66. No abstract available.
citation: London GM, Marty C, Marchais SJ, Guerin AP, Metivier F, de Vernejoul MC. Arterial calcifications and bone histomorphometry in end-stage renal disease. J Am Soc Nephrol. 2004 Jul;15(7):1943-51. doi: 10.1097/01.asn.0000129337.50739.48.
citation: Delmez JA, Tindira CA, Windus DW, Norwood KY, Giles KS, Nighswander TL, Slatopolsky E. Calcium acetate as a phosphorus binder in hemodialysis patients. J Am Soc Nephrol. 1992 Jul;3(1):96-102. doi: 10.1681/ASN.V3196.
citation: Ben Hamida F, el Esper I, Compagnon M, Moriniere P, Fournier A. Long-term (6 months) cross-over comparison of calcium acetate with calcium carbonate as phosphate binder. Nephron. 1993;63(3):258-62. doi: 10.1159/000187207.
citation: Yang H, Curinga G, Giachelli CM. Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int. 2004 Dec;66(6):2293-9. doi: 10.1111/j.1523-1755.2004.66015.x.
citation: Porsti I, Fan M, Koobi P, Jolma P, Kalliovalkama J, Vehmas TI, Helin H, Holthofer H, Mervaala E, Nyman T, Tikkanen I. High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure. Kidney Int. 2004 Dec;66(6):2155-66. doi: 10.1111/j.1523-1755.2004.66006.x.
citation: Cozzolino M, Staniforth ME, Liapis H, Finch J, Burke SK, Dusso AS, Slatopolsky E. Sevelamer hydrochloride attenuates kidney and cardiovascular calcifications in long-term experimental uremia. Kidney Int. 2003 Nov;64(5):1653-61. doi: 10.1046/j.1523-1755.2003.00284.x.
citation: Taal MW, Roe S, Masud T, Green D, Porter C, Cassidy MJ. Total hip bone mass predicts survival in chronic hemodialysis patients. Kidney Int. 2003 Mar;63(3):1116-20. doi: 10.1046/j.1523-1755.2003.00837.x.
citation: Parfitt AM. Renal bone disease: a new conceptual framework for the interpretation of bone histomorphometry. Curr Opin Nephrol Hypertens. 2003 Jul;12(4):387-403. doi: 10.1097/00041552-200307000-00007.
citation: Riggs BL, Parfitt AM. Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res. 2005 Feb;20(2):177-84. doi: 10.1359/JBMR.041114. Epub 2004 Nov 16.
citation: Mansour J, Benyahia M, Harbouche L, Presne C, Moriniere P, Fournier A. Calcimetic AMG 073 at 50 and 100 mg per day. Kidney Int. 2003 Dec;64(6):2324-5. doi: 10.1046/j.1523-1755.2003.341_4.x. No abstract available.
citation: Manns B, Stevens L, Miskulin D, Owen WF Jr, Winkelmayer WC, Tonelli M. A systematic review of sevelamer in ESRD and an analysis of its potential economic impact in Canada and the United States. Kidney Int. 2004 Sep;66(3):1239-47. doi: 10.1111/j.1523-1755.2004.00877.x.
citation: Lacour B, Lucas A, Auchere D, Ruellan N, de Serre Patey NM, Drueke TB. Chronic renal failure is associated with increased tissue deposition of lanthanum after 28-day oral administration. Kidney Int. 2005 Mar;67(3):1062-9. doi: 10.1111/j.1523-1755.2005.00171.x.
citation: Takahashi Y, Tanaka A, Nakamura T, Fukuwatari T, Shibata K, Shimada N, Ebihara I, Koide H. Nicotinamide suppresses hyperphosphatemia in hemodialysis patients. Kidney Int. 2004 Mar;65(3):1099-104. doi: 10.1111/j.1523-1755.2004.00482.x.
citation: Renaud H, Atik A, Herve M, Moriniere P, Hocine C, Belbrik S, Fournier A. Evaluation of vascular calcinosis risk factors in patients on chronic hemodialysis: lack of influence of calcium carbonate. Nephron. 1988;48(1):28-32. doi: 10.1159/000184864.
citation: Wanner C, Krane V, Marz W, Olschewski M, Asmus HG, Kramer W, Kuhn KW, Kutemeyer H, Mann JF, Ruf G, Ritz E; Deutsche Diabetes-Dialyse-Studie (4D) Study Group. Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D study): demographic and baseline characteristics. Kidney Blood Press Res. 2004;27(4):259-66. doi: 10.1159/000080241. Epub 2004 Aug 16.
citation: Gale EA, Bingley PJ, Emmett CL, Collier T; European Nicotinamide Diabetes Intervention Trial (ENDIT) Group. European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet. 2004 Mar 20;363(9413):925-31. doi: 10.1016/S0140-6736(04)15786-3.
citation: Moe SM, Chertow GM, Coburn JW, Quarles LD, Goodman WG, Block GA, Drueke TB, Cunningham J, Sherrard DJ, McCary LC, Olson KA, Turner SA, Martin KJ. Achieving NKF-K/DOQI bone metabolism and disease treatment goals with cinacalcet HCl. Kidney Int. 2005 Feb;67(2):760-71. doi: 10.1111/j.1523-1755.2005.67139.x.
citation: Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW. New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis. 1997 Jul 25;132(2):245-50. doi: 10.1016/s0021-9150(97)00106-8.
citation: Wilson PW, Kauppila LI, O'Donnell CJ, Kiel DP, Hannan M, Polak JM, Cupples LA. Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality. Circulation. 2001 Mar 20;103(11):1529-34. doi: 10.1161/01.cir.103.11.1529.
citation: Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O'Donnell CJ, Wilson PW. Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham Heart Study. Calcif Tissue Int. 2001 May;68(5):271-6. doi: 10.1007/BF02390833.
citation: Urena P, Bernard-Poenaru O, Ostertag A, Baudoin C, Cohen-Solal M, Cantor T, de Vernejoul MC. Bone mineral density, biochemical markers and skeletal fractures in haemodialysis patients. Nephrol Dial Transplant. 2003 Nov;18(11):2325-31. doi: 10.1093/ndt/gfg403.
citation: Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993 Sep;8(9):1137-48. doi: 10.1002/jbmr.5650080915.
citation: Grados F, Roux C, de Vernejoul MC, Utard G, Sebert JL, Fardellone P. Comparison of four morphometric definitions and a semiquantitative consensus reading for assessing prevalent vertebral fractures. Osteoporos Int. 2001;12(9):716-22. doi: 10.1007/s001980170046.
citation: Malluche M, Monier-faugère M, wang G, Frazao J, Coburn J, Baker N, McCary LC, Turner JA, Goodman WG: Cinaclacet Hcl reduces bone turn over and bone marrow fibrosa in hemodialysis patients with secondary hyperparathyroidism. ERA XLI congress. AbstractBook Lisboa:P218 (M016), 2004
citation: Dament J,Gill M, Confer S, Jones C, Webster J: The bone kinetics of lanthanum in dialysis patient treated with lanthanum carbonate up to 45 years. J Am Soc Nephrol 15 (Abstract):271A (poster FPO 948), 2004
citation: Malluche M, Faugère MC, Damment SJP, Webster I: No osteomalacia in dialysis patients treated with lanthanum carbonate up to 4.5 years. J Am Soc Nephrol 15 (supplt Abstract):p270A Poster F P0944,2004
citation: De Smet R, Thermote F, Lameire N, Vanholder R: SEVELAMER hydrochloride (Renagel(r)) adsorbs the uremic compounds indoxyl sulfate, indole and p-creso.[Abstract]. J Am Soc Nephrol 15, 2004
citation: Block GA, Martin KJ, de Francisco AL, Turner SA, Avram MM, Suranyi MG, Hercz G, Cunningham J, Abu-Alfa AK, Messa P, Coyne DW, Locatelli F, Cohen RM, Evenepoel P, Moe SM, Fournier A, Braun J, McCary LC, Zani VJ, Olson KA, Drueke TB, Goodman WG. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med. 2004 Apr 8;350(15):1516-25. doi: 10.1056/NEJMoa031633.
citation: Alsheikh-Ali A, Aboujaily HM, Stanek LJ, coll. e: Increases in HDL cholesterol are the strongest predictions of risk reduction in lipid intervention trials. Circulation 111 (suppltIII):813 Abstract 3754,2004