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NDT Advance Access originally published online on September 6, 2005
Nephrology Dialysis Transplantation 2006 21(1):23-28; doi:10.1093/ndt/gfi097
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Editorial Comment

Current treatment options in secondary renal hyperparathyroidism

Helmut Reichel

Nephrological Center, Villingen-Schwenningen, Germany

Correspondence and offprint requests to: Prof. Dr H. Reichel, Nephrological Center, Schramberger Str. 28, Villingen-Schwenningen 78054, Germany. Email: helmut.reichel{at}dialyse-schwenningen.de

Keywords: calcimimetics; calcium; calcium–phosphorus product; chronic kidney disease; parathyroid hormone; phosphorus



   Introduction
Top
 Introduction
Treatment targets and objectives
 Conclusions
 References
 
Our view of the clinical problems associated with secondary renal hyperparathyroidism (SHPT) in end-stage renal-disease (ESRD) patients has changed considerably in the last few years. While it formerly was considered primarily a skeletal disorder, recent data show strong associations between renal SHPT and both disturbed bone/mineral metabolism and the development of cardiovascular calcifications, leading to cardiovascular morbidity and patient mortality [1–4]. Therapy for SHPT in ESRD includes active vitamin D metabolites, oral phosphate binders, calcium supplementation and, if pharmacological treatment is unsuccessful, surgical parathyroidectomy (PTx) [5]. However, some therapies to reduce PTH levels can exacerbate mineral imbalances, resulting in undesirable effects, such as hypercalcaemia and further hyperphosphataemia. Recently, a calcimimetic compound, cinacalcet, has been approved for treatment of renal SHPT. Cinacalcet offers a novel therapeutic concept by suppressing PTH synthesis and secretion via manipulation of the activity of the parathyroid calcium-sensing receptor (CaR). Herein, some of the available SHPT therapies will be reviewed.



   Treatment targets and objectives
Top
 Introduction
 Treatment targets and objectives
Conclusions
 References
 
The objectives of SHPT treatment are to achieve and maintain optimal PTH levels, while maintaining controlled serum phosphorus and calcium levels and normal bone turnover rates in order to prevent osseous and particularly, extraosseous complications. Target ranges for intact PTH (iPTH), calcium and phosphorus in renal patients were published recently by the US National Kidney Foundation (NKF) as part of the Kidney Disease Outcomes Quality Initiative (K/DOQITM) [6]. The guidelines suggested for patients with CKD 5 are summarized in Table 1. There is good evidence [7] that the most ‘physiologic’ bone turnover for dialysis patients occurs at a moderately elevated plasma iPTH. Due to the progressive nature of renal SHPT, prophylactic measures to suppress parathyroid function should be instituted early, ideally, before iPTH exceeds the proposed target range. A plasma iPTH ≥600 pg/ml is an independent risk factor for mortality [4], whereas low plasma iPTH is associated with low bone turnover and high calcification scores in haemodialysis patients [8].


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  		Table 1. NKF-K/DOQI treatment targets for the management of iPTH, calcium, phosphorus and Ca x P in patients requiring dialysis. Reproduced from Eknoyan et al. [6]

 
Hyperphosphatemia is a strong risk factor for cardiovascular and overall mortality in dialysis patients [1,2,4]. The risk seems to be elevated when there is a moderate rise of serum phosphorus, and a continuous increase of the mortality risk was noted with further aggravation of hyperphosphataemia [4]. Adequate control of serum phosphorus remains a major clinical problem in ESRD. Despite the availability of phosphate binding agents, about 70% of patients with ESRD still have abnormally high phosphorus levels [1]. Recently, an association between a moderate elevation of serum phosphorus and increased mortality was also shown for patients with chronic kidney disease not on dialysis [9].

Elevated serum calcium is independently associated with increased mortality in dialysis patients [4,10]. Accordingly, the K/DOQI guidelines put emphasis on a relatively low serum calcium target range, but it should be noted that hypocalcaemia or a negative calcium balance, at least in the absence of drugs which suppress PTH secretion, can stimulate PTH release and favour parathyroid hyperplasia and bone demineralisation.

In summary, there is strong evidence that pronounced SHPT, elevated serum phosphorus, and elevated serum calcium are cardiovascular risk factors in ESRD. The deleterious effects of disturbed PTH and mineral metabolism are most likely mediated, at least in part, by favouring the development of cardiovascular calcifications, although clear evidence for a causal relationship is lacking. Calcifications are closely correlated with mortality in dialysis patients [3,11], and their development in ESRD is complex. Divalent ion metabolism, dyslipidaemia, inflammation, imbalances in calcification inhibitors and epidemiological factors can contribute to calcification. Nevertheless, PTH, phosphorus and calcium are modifiable variables, and our therapeutic challenge is the maintenance of those variables within a target range that is potentially most beneficial for our patients (i.e. as proposed by the K/DOQITM guidelines).

Vitamin D and vitamin D analogues
Calcitriol and alfacalcidol have been mainstays of SHPT therapy since the 1980s. Their efficacy and safety have been demonstrated in several studies [12,13]. However, for the benefit of active vitamin D metabolites, there are also some possible risks: (i) rises in serum calcium and/or phosphorus through increases in intestinal calcium and phosphorus absorption; (ii) oversuppression of plasma PTH resulting in reduced bone turnover (adynamic bone) [14] with the concomitant risk of extraosseous calcifications [8]; (iii) development of ‘resistance’ toward active vitamin D metabolites [15,16] in as many as 30% of patients; (iv) pharmacological amounts of vitamin D may have detrimental effects on elastogenesis and inflammation of the arterial wall [17]. In current practice, vitamin D analogue therapy may not always be employed appropriately. In a recent US survey, nearly 34% of vitamin D-treated patients on dialysis had hyperphosphataemia (>6.0 mg/dl) [18].

Considering that hypercalcaemia and hyperphosphataemia often limit therapy with calcitriol, there have been attempts to develop chemically modified vitamin D analogues with fewer hypercalcaemic and hyperphosphataemic side effects. Paricalcitol, a vitamin D2-derived analogue lacking the carbon-19 methylene group, was found in preclinical studies to induce less hypercalcaemia and hyperphosphataemia than calcitriol [19]. Paricalcitol is approved for therapy of SHPT in the US and has recently received European approval. In a recent randomized multicentre study in dialysis patients [20], paricalcitol reduced plasma iPTH somewhat faster than calcitriol, and with fewer sustained episodes of hypercalcaemia. However, in both groups, more than 60% of patients still experienced at least one episode of hypercalcaemia (>11 mg/dl) and/or Ca x P>75 mg2/dl2, in contrast to the available experimental data.

In retrospective studies, paricalcitol-treated patients had a 16% lower mortality rate [21] and fewer hospitalizations [22] than calcitriol-treated patients. However, it is important to note that the duration of dialysis before enrolment in the trial was 90 days longer in the paricalcitol group [21], and treatment data were not collected before the start of the studies. Thus, prospective, randomized studies must be conducted in order to obtain a more accurate assessment of paricalcitol versus calcitriol therapies [23].

Other vitamin D analogues such as doxercalciferol [24] and maxacalcitol [25] are available in some countries for the treatment of renal SHPT. However, none of these agents has been shown to be superior to calcitriol over a prolonged period and none entirely avoids hypercalcaemia or hyperphosphataemia [26].

The replacement of physiological doses of native vitamin D2 or D3 in dialysis patients was recommended recently [6] as some studies have shown an association of hypovitaminosis D with more pronounced SHPT [27,28]. In addition, supplementation of native vitamin D will increase the endogenous capacity to synthesize calcitriol by renal and extrarenal sources [29].

Phosphate binders
In the past, aluminium hydroxide was used to bind ingested phosphate, but its use is now discouraged due to toxic effects caused by aluminium accumulation in tissues including encephalopathy, aluminium-associated osteomalacia, and osteodystrophy [30].

The calcium salts, calcium acetate and calcium carbonate, are most widely used to control hyperphosphataemia. Calcium salts may result in increased serum calcium levels, since 20–30% of ingested calcium is absorbed into the bloodstream [31]. High-dose calcium carbonate therapy (5.5–6.0 g/day) was associated with hypercalcaemia in up to 20% of the patients [32]. It should be noted that based on comparable phosphate binding capacity, less calcium will be absorbed with calcium acetate than with calcium carbonate [33].

The increase in calcium load associated with the long-term use of calcium-containing phosphate binders has created some concern. In light of the potential risk of cardiovascular calcification due to calcium overload [34,35], recommendations of oral high-dose calcium supplementation have been revised to 1–2 g of elemental calcium per day [36]. Now, with the onset of new SHPT therapies that do not lead to increases in serum calcium levels, these recommendations may need reconsideration.

Sevelamer is a calcium- and aluminium-free phosphate binder that has been shown to significantly reduce serum phosphorus and to improve lipid profiles in haemodialysis patients [37]. In a comparative study with calcium-containing phosphate binders, sevelamer limited the progression of coronary artery calcification [38]. It is still under debate as to whether this effect of sevelamer was due to a more restricted calcium uptake or due to its lipid-lowering properties [39]. There is also some debate as to whether sevelamer provides a significant advantage over traditional phosphate binders. In a direct comparison, calcium acetate controlled serum phosphorus more effectively than sevelamer over an 8-week period [40]. A cost–benefit analysis indicated that, in the absence of hypercalcaemia, calcium acetate should remain the treatment of choice for hyperphosphataemia in haemodialysis patients [40]. The question of whether sevelamer can improve survival of chronic dialysis patients is currently addressed in the DCOR study. A press release at the end of July 2005 indicates that in a post-hoc analysis the study shows a significant decrease in mortality over calcium-containing phosphate binders, in patients who completed two or more years of sevelamer treatment, and those who were 65 years of age or older.

Lanthanum carbonate is another aluminium-free, calcium-free phosphate binder that was recently approved in both Europe and the US. It has been shown to reduce serum phosphorus levels in short-term and long-term studies in ESRD patients [41,42]. Animal studies have revealed that there is no evidence for a direct toxic effect of high doses of lanthanum carbonate on bone cells [43]; however, accumulation of lanthanum carbonate into tissues of uraemic animals has been demonstrated [43,44]. An abstract reporting lanthanum carbonate treatment data for up to 3 years has shown good tolerability and no increase in the frequency of adverse events [45].

Calcimimetics
Calcimimetics are a new class of pharmacological compounds with a novel mode of action for the control of PTH. These agents offer the benefit of suppressing PTH release from parathyroid glands without increasing calcium and phosphorus concentrations. Calcimimetics act directly on the parathyroid cells by modulating the activity of the CaR and by increasing its sensitivity to serum calcium, resulting in enhanced signal transduction and suppression of PTH release [46].

Cinacalcet has undergone clinical evaluation and was recently approved for treatment of SHPT in chronic kidney disease patients on dialysis in the USA and Europe. It has been studied in more than 1300 patients across eight Phase II and III trials. The results of the three similar Phase III studies in ESRD patients have been reported recently [47–50]. Patients were randomized to receive placebo or cinacalcet as well as standard care for mineral metabolism management. Standard care consisted of phosphate binders, vitamin D analogues, or both. There was no washout period prior to baseline. The primary endpoint of the studies was the achievement of a mean iPTH level of ≤250 pg/ml [26.5 pmol/l] during the efficacy-assessment phase. In two of the three Phase III studies, 43% of the cinacalcet group (n = 371) reached the primary endpoint of the studies compared with 5% in the control group (n = 370; P<0.001). Serum calcium was reduced by an average of 6.8% (P<0.001) and phosphorus levels by 8.4% (P<0.001) in the cinacalcet group, whereas these values did not change significantly in the control group [49]. Additional analyses also showed that cinacalcet reduced iPTH and Ca x P independent of concomitant vitamin D therapy, dialysis duration, baseline disease severity (as measured by iPTH level) and baseline Ca x P [49]. Data from all three of the Phase III trials show that overall, 41% of cinacalcet-treated patients reached the K/DOQITM target ranges for both for iPTH and Ca x P compared with 6% of patients treated with standard therapy [50]. Data on long-term administration of cinacalcet in a small subset of patients (n = 21) are published in abstract form. The data show that 65% and 60% of patients achieve K/DOQITM targets for iPTH and Ca x P, respectively after 4 years of therapy [51]. There is also already clinical evidence showing that calcimimetics may have the potential to improve some patient outcomes. The effect of cinacalcet on PTx and fractures was analysed in post-hoc analyses of safety data collected from 1184 subjects (697 cinacalcet, 487 placebo) over four similarly designed studies in dialysis patients with plasma iPTH ≥300 pg/ml. Patients receiving cinacalcet underwent PTx significantly less often (0.3 events per 100 subject years vs 4.1 respectively, P = 0.009), had significantly fewer fractures (3.2 events per 100 subject years vs 6.9 respectively, P = 0.04) and a reduced cardiovascular hospitalisation rate (6.9 events per 100 subject years vs 15.0, P = 0.005) compared to patients on placebo [52]. These data, which must be confirmed in longer term analyses, demonstrate the potential of cinacalcet to significantly advance SHPT treatment.

Preliminary data on the impact of cinacalcet on other SHPT therapies are available in abstract form [53], but the exact role of calcimimetics in relation to standard SHPT therapies remains to be established. A treatment algorithm showing how cinacalcet could be used in conjunction with other SHPT therapies is proposed in Figure 1 [54]. This algorithm is designed to take advantage of all available SHPT therapies to best control all metabolic parameters.



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  		Fig. 1. Proposed use of cinacalcet in clinical practice. Reproduced from Cunningham [54], with permission.

 


   Conclusions
Top
 Introduction
 Treatment targets and objectives
 Conclusions
References
 
Since the beginning of dialysis therapy, great progress has been made in the clinical management of SHPT. However, there are significant shortcomings with conventional therapies. The complex pathophysiological relationship between PTH, calcium and phosphorus has often meant that treatments that are effective in controlling one of these parameters have a negative impact on others. Indeed, conventional treatment regimens lead to trade-offs between lowering PTH, and elevating calcium and phosphorus. Current knowledge suggests that this is associated with significant clinical risks for the patient [4]. It is also evident that conventional treatments do not enable physicians to achieve and maintain therapeutic targets as outlined in the K/DOQITM and other guidelines in the majority of their patients [6,55]. Calcimimetics, such as cinacalcet, offer a fundamentally different approach to SHPT therapy. By their ability to lower PTH and concomitantly lower calcium, phosphorus, and Ca x P, calcimimetics represent a significant improvement in treatments available for patients suffering from SHPT.

Conflict of interest statement. None declared.



   References
Top
 Introduction
 Treatment targets and objectives
 Conclusions
 References
 

  1. Block GA, Hulbert S, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998; 31: 607–617[ISI][Medline]
  2. Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001; 12: 2131–2138[Abstract/Free Full Text]
  3. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001; 38: 938–942[Abstract/Free Full Text]
  4. 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: 2208–2218[Abstract/Free Full Text]
  5. Reichel H, Drüeke T, Ritz E. Skeletal disorders. In: Davison AM, Cameron JS, Grunfeld JP, Kerr DNS, Ritz E, Winearls C, eds. Oxford Textbook of Clinical Nephrology. 2nd edition, Oxford: Oxford University Press, 1997: 1954–1981
  6. Eknoyan G, Levin A, Levin NW. Bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003; 42: 1–201[ISI][Medline]
  7. Quarles LD, Lobaugh B, Murphy G. Intact parathyroid hormone overestimates the presence and severity of parathyroid mediated osseous abnormalities in uremia. J Clin Endocrinol Metab 1992; 75: 145–150[Abstract]
  8. London GM, Marty C, Marchais SJ, Guerin AP, Metivier F, deVernejoul MC. Arterial calcification and bone histomorphometry in end-stage renal disease. J Am Soc Nephrol 2004; 15: 1943–1951[Abstract/Free Full Text]
  9. Kestenbaum B, Sampson JN, Rudser KD et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 2005; 16: 520–528[Abstract/Free Full Text]
  10. Young EW, Albert JM, Satayathum S et al. Predictors and consequences of altered mineral metabolism: The dialysis outcomes and practice patterns study. Kidney Int 2005; 67: 1179–1187[CrossRef][ISI][Medline]
  11. Wang AY, Wang M, Woo J et al. Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study. J Am Soc Nephrol 2003; 14: 159–168[Abstract/Free Full Text]
  12. Berl T, Berns AS, Hufer WE et al. 1,25 dihydroxycholecalciferol effects in chronic dialysis. A double-blind controlled study. Ann Intern Med 1978; 88: 774–780[ISI][Medline]
  13. Memmos DE, Eastwood JB, Talner LB et al. Double-blind trial of oral 1,25-dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis. Br Med J (Clin Res Ed) 1981; 282: 1919–1924[Medline]
  14. Hercz G, Pei Y, Greenwood C et al. Aplastic osteodystrophy without aluminum: the role of "suppressed" parathyroid function. Kidney Int 1993; 44: 860–866[ISI][Medline]
  15. Gallieni M, Brancaccio D, Padovese P et al. Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol. Kidney Int 1992; 42: 1191–1198[ISI][Medline]
  16. Quarles LD, Yohay DA, Carroll BA et al. Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. Kidney Int 1994; 45: 1710–1721[ISI][Medline]
  17. Norman PE, Powell JT. Vitamin D shedding light on the development of disease in peripheral arteries. Arteriosler Thromb Vasc Biol 2005; 25: 39–46[Abstract/Free Full Text]
  18. Johnson CA, McCarthy J, Bailie GR, Deane J, Smith S. Analysis of renal bone disease treatment in dialysis patients. Am J Kidney Dis 2002; 39: 1270–1277[CrossRef][ISI][Medline]
  19. Brown AJ, Finch J, Takahashi F, Slatopolsky E. Calcemic activity of 19-Nor-1,25(OH)(2)D(2) decreases with duration of treatment. J Am Soc Nephrol 2000; 11: 2088–2094[Abstract/Free Full Text]
  20. Sprague SM, Llach F, Amdahl M, Taccetta C, Batlle D. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int 2003; 63: 1483–1490[CrossRef][ISI][Medline]
  21. 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; 349: 446–456[Abstract/Free Full Text]
  22. Dobrez DG, Mathes A, Amdahl M, Marx SE, Melnick JZ, Sprague SM. Paricalcitol-treated patients experience improved hospitalization outcomes compared with calcitriol-treated patients in real-world clinical settings. Nephrol Dial Transplant 2004; 19: 1174–1181[Abstract/Free Full Text]
  23. Drueke TB, McCarron DA. Paricalcitol as compared with calcitriol in patients undergoing hemodialysis. N Engl J Med 2003; 349: 496–499[Free Full Text]
  24. Frazao JM, Elangovan L, Maung HM et al. Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism. Am J Kidney Dis 2000; 36: 550–561[Medline]
  25. Hayashi M, Tsuchiya Y, Itaya Y et al. Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients in chronic haemodialysis: a randomized prospective multicentre trial. Nephrol Dial Transplant 2004; 19: 2067–2073[Abstract/Free Full Text]
  26. Drueke TB. Treatment of secondary hyperparathyroidism with vitamin D derivatives and calcimimetics before and after start of dialysis. Nephrol Dial Transplant 2002; 17 [Suppl 11]: 20–22
  27. Bayard F, Bec P, Ton That H, Louvet JP. Plasma 25-hydroxycholecalciferol in chronic renal failure. Eur J Clin Invest 1973; 3: 447–450[Medline]
  28. Ghazali A, Fardellone P, Pruna A et al. Is low plasma 25-(OH)vitamin D a major risk factor for hyperparathyroidism and Looser's zones independent of calcitriol? Kidney Int 1999; 55: 2169–2177[CrossRef][ISI][Medline]
  29. Dusso A, Lopez-Hilker S, Rapp N, Slatopolsky E. Extra-renal production of calcitriol in chronic renal failure. Kidney Int 1988; 34: 368–375[ISI][Medline]
  30. Ott SM. Aluminium-related osteomalacia. Int J Artif Organs 1983; 6: 173–175[Medline]
  31. Emmett M, Sirmon MD, Kirkpatrick WG, Nolan CR, Schmitt GW, Cleveland MB. Calcium acetate control of serum phosphorus in hemodialysis patients. Am J Kidney Dis 1991; 17: 544–550[Medline]
  32. Hercz G, Kraut JA, Andress DA et al. Use of calcium carbonate as a phopsphate binder in dialysis patients. Miner Electrolyte Metab 1986; 12: 314–319[Medline]
  33. Mai ML, Emmett M, Sheikh MS, Santa Ana CA, Schiller L, Fordtran JSl. Calcium acetate, an effective phosphorus binder in patients with renal failure. Kidney Int 1989; 36: 690–695[Medline]
  34. Goodman WG, Goldin J, Kuizon BD et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342: 1478–1483[Abstract/Free Full Text]
  35. Guerin AP, London GM, Marchais SJ, Metivier F. Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 2000; 15: 1014–1021[Abstract/Free Full Text]
  36. Locatelli F, Cannata A, Drueke TB et al. Management of disturbances of calcium and phosphate metabolism in chronic renal insufficiency, with emphasis on the control of hyperphosphataemia. Nephrol Dial Transplant 2002; 17: 723–731[Abstract/Free Full Text]
  37. Chertow GM, Burke SK, Dillon MA, Slatopolsky E. Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients. Nephrol Dial Transplant 1999; 14: 2907–2914[Abstract/Free Full Text]
  38. Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002; 62: 245–252[CrossRef][ISI][Medline]
  39. Coladonato JA, Ritz E. SHPT and its therapy as a cardiovascular risk factor among end-stage renal disease patients. Adv Ren Replace Ther 2002; 9: 193–199[CrossRef][Medline]
  40. Qunibi WY, Hootkins RE, McDowell LL et al. Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE study). Kidney Int 2004; 65: 1914–1926[CrossRef][ISI][Medline]
  41. Hutchison AJ, Speake M, Al Baaj F. Reducing high phosphate levels in patients with chronic renal failure undergoing dialysis: a 4-week, dose-finding, open-label study with lanthanum carbonate. Nephrol Dial Transplant 2004; 19: 1902–1906[Abstract/Free Full Text]
  42. Hutchison AJ, Maes B, Vanwalleghem J et al. Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomised, comparative trial versus calcium carbonate. Nephron Clin Pract 2005; 100: c8–c19[CrossRef][ISI][Medline]
  43. Behets GJ, Dams G, Vercauteren SR et al. Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure? J Am Soc Nephrol 2004; 15: 2219–2228[Abstract/Free Full Text]
  44. Lacour B, Lucas A, Auchere D et al Chronic renal failure is associated with increased tissue deposition of lanthanum after 28 day oral administration. Kidney Int 2005; 67: 1062–1069[CrossRef][ISI][Medline]
  45. Webster I, Gill M. Lanthanum carbonate, a new phosphate binder, is well tolerated over a 3 year period in dialysis patients. EDTA, Lisbon, Portugal, 2004; Abstract SP268
  46. Goodman WG. Calcimimetic agents and secondary hyperparathyroidism: treatment and prevention. Nephrol Dial Transplant 2002; 17: 204–207[Free Full Text]
  47. Quarles LD, Sherrard DJ, Adler S et al. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. J Am Soc Nephrol 2003; 14: 575–583[Abstract/Free Full Text]
  48. Lindberg JS, Moe SM, Goodman WG et al. The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Kidney Int 2003; 63: 248–254[CrossRef][ISI][Medline]
  49. Block GA, Martin KJ, de Francisco AL et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004; 350: 1516–1525[Abstract/Free Full Text]
  50. Moe SM, Chertow GM, Coburn JW et al. Achieving NKF-K/DOQITM bone metabolism and disease treatment goals with cinacalcet HCl. Kidney Int 2005; 67: 760–771[CrossRef][ISI][Medline]
  51. Cunningham J, Urena P, Reichel H et al. Long-term efficacy of cinacalcet in secondary hyperparathyroidism (HPT) of end-stage renal diesease (ESRD). XLII Congress of the ERA-EDTA, 2005; Abstract
  52. Cunningham J, Danese M, Olson K, Klassen P, Chertow G. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture and health-related quality of life in secondary hyperparathyroidism. Kidney Int 2005; in press.
  53. Chertow GM, Corpier C, Zeig S et al. Preliminary results from TARGET: Treatment Strategies to achieve recommended K/DOQITM goals in ESRD patients on Cinacalcet. J Am Soc Nephrol 2004; 15: 863A
  54. Cunningham J. Achieving therapeutic targets in the treatment of secondary hyperparathyoidism. Nephrol Dial Transplant 2004; 19 [Suppl 5]: v9–v14
  55. Cannata-Andia JB, Drueke TB, Cunningham J et al. Clinical algorithms on renal osteodystrophy. Nephrol Dial Transplant 2000; 15 [Suppl 5]: 40–57

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