Secondary hyperparathyroidism is a common complication in patients with end-stage renal disease. It has been associated with increased cardiovascular events and mortality. Traditional therapy has been based on vitamin D analogs and phosphate binders; but these therapies often do not control secondary hyperparathyroidism, particularly in peritoneal dialysis patients for whom phosphate clearances are limited and intravenous vitamin D is impractical. Cinacalcet, a calcimimetic, suppresses parathormone secretion by interacting with the calcium-sensing receptor on the surface of parathyroid gland cells. The resulting suppression of parathyroid hormone secretion produces a reduction in serum phosphate level and CaxPO4 product. The present paper reviews the efficacy of cinacalcet in the management of secondary hyperparathyroidism in peritoneal dialysis patients.
BlockG.A., KlassenP.S., LazarusJ.M., OfsthunN., LowrieE.G., ChertowG.M.Mineral metabolism, mortality, and morbidity in maintenance hemodialysis.J Am Soc Nephrol2004; 15: 2208–18.
2.
GaneshS.K., StackA.G., LevinN.W., Hulbert–ShearonT., PortF.K.Association of elevated serum PO4, Ca x PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients.J Am Soc Nephrol2001; 12: 2131–8.
3.
MoeS.M.Vascular calcification and renal osteodystrophy relationship in chronic kidney disease.Eur J Clin Invest2006; 36(Suppl 2): 51–62.
AchingerS.G., AyusJ.C.Left ventricular hypertrophy: is hyperphosphatemia among dialysis patients a risk factor?J Am Soc Nephrol2006; 17(Suppl 3): S255–61.
6.
Fernandez–FresnedoG., RodrigoE., de FranciscoA.L., de CastroS.S., CastañedaO., AriasM.Role of pulse pressure on cardiovascular risk in chronic kidney disease patients.J Am Soc Nephrol2006; 17(Suppl 3): S246–9.
7.
AyusJ.C., MizaniM.R., AchingerS.G., ThadhaniR., GoA.S., LeeS.Effects of short daily versus conventional hemodialysis on left ventricular hypertrophy and inflammatory markers: a prospective, controlled study.J Am Soc Nephrol2005; 16: 2778–88.
8.
YoungE.W., AkibaT., AlbertJ.M., McCarthyJ.T., KerrP.G., MendelssohnD.C.Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Am J Kidney Dis2004; 44: S34–8.
9.
WangA.Y., WooJ., SeaM.M., LawM.C., LuiS.F., LiP.K.Hyperphosphatemia in Chinese peritoneal dialysis patients with and without residual kidney function: what are the implications?Am J Kidney Dis2004; 43: 712–20.
10.
JuergensenP., ErasJ., McClureB., KligerA.S., FinkelsteinF.O.The impact of various cycling regimens on phosphorus removal in chronic peritoneal dialysis patients.Int J Artif Organs2005; 28: 1219–23.
11.
MoeS.M., CunninghamJ., BommerJ., AdlerS., RosanskyS.J., Urena–TorresP.Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl.Nephrol Dial Transplant2005; 20: 2186–93.
12.
BlockG.A., MartinK.J., de FranciscoA.L., TurnerS.A., AvramM.M., SuranyiM.G.Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.N Engl J Med2004; 350: 1516–25.
13.
SpiegelD.M., CaseyL., BellS., ParkerM., ChoncholM.Achieving targets for bone and mineral metabolism: the impact of cinacalcet HCl in clinical practice.Hemodial Int2006; 10(Suppl 2): S24–7.
14.
MoeS.M., ChertowG.M., CoburnJ.W., QuarlesL.D., GoodmanW.G., BlockG.A.Achieving NKF–K/DOQI bone metabolism and disease treatment goals with cinacalcet HCl.Kidney Int2005; 67: 760–71.
15.
Gal–MoscoviciA., SpragueS.M.The role of calcimimetics in chronic kidney disease.Kidney Int Suppl2006; 104: S68–72.
16.
GoodmanW.G.Calcimimetic agents and secondary hyperparathyroidism: rationale for use and results from clinical trials.Pediatr Nephrol2003; 18: 1206–10.
17.
CostaA.F., dos ReisL.M., RibeiroM.C., MoysésR.M., JorgettiV.Effects of calcitriol on parathyroid function and on bone remodelling in secondary hyperparathyroidism.Nephrol Dial Transplant2003; 18: 743–9.
18.
GallieniM., BrancaccioD., PadoveseP., RollaD., BedaniP., ColantonioG.Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol.Kidney Int1992; 42: 1191–8.
19.
MartinK.J., GonzálezE.A., GellensM., HammL.L., AbboudH., LindbergJ.19-nor-1-alpha-25-Dihydroxyvitamin D2 (paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis.J Am Soc Nephrol1998; 9: 1427–32.
20.
TentoriF., HuntW.C., StidleyC.A., RohrscheibM.R., BedrickE.J., MeyerK.B. for Medical Directors of Dialysis Clinic Inc. Mortality risk among hemodialysis patients receiving different vitamin D analogs.Kidney Int2006; 70: 1858–65.
21.
DorschO.Use of cinacalcet in a patient on long-term dialysis with end-stage renal failure and refractory secondary hyperparathyroidism.Nephrol Dial Transplant2007; 22: 637–40.
22.
CozzolinoM., GallieniM., BrancaccioD., ArcidiaconoT., BianchiG., VezzoliG.Vitamin D retains an important role in the pathogenesis and management of secondary hyperparathyroidism in chronic renal failure.J Nephrol2006; 19: 566–77.
23.
QuarlesL.D., YohayD.A., CarrollB.A., SpritzerC.E., MindaS.A., BartholomayD.Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD.Kidney Int1994; 45: 1710–21.
24.
CollotonM., ShatzenE., MillerG., Stehman–BreenC., WadaM., LaceyD.Cinacalcet HCl attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism.Kidney Int2005; 67: 467–76.
25.
MizobuchiM., HatamuraI., OgataH., SajiF., UdaS., ShiizakiK.Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency.J Am Soc Nephrol2004; 15: 2579–87.
26.
LopezI., Aguilera–TejeroE., MendozaF.J., AlmadenY., PerezJ., MartinD.Calcimimetic R-568 decreases extra-osseous calcifications in uremic rats treated with calcitriol.J Am Soc Nephrol2006; 17: 795–804.
27.
de FranciscoA.L., PiñeraC., PalomarR., AriasM.Impact of treatment with calcimimetics on hyperparathyroidism and vascular mineralization.J Am Soc Nephrol2006; 17(Suppl 3): S281–5.
28.
CunninghamJ., DaneseM., OlsonK., KlassenP., ChertowG.M.Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism.Kidney Int2005; 68: 1793–800.
29.
LindbergJ.S., CulletonB., WongG., BorahM.F., ClarkR.V., ShapiroW.B.Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study.J Am Soc Nephrol2005; 16: 800–7.
30.
BillaV., ZhongA., BargmanJ., VasS., WongP.Y., OreopoulosD.G.High prevalence of hyperparathyroidism among peritoneal dialysis patients: a review of 176 patients.Perit Dial Int2000; 20: 315–21.
31.
SherrardD.J., HerczG., PeiY., MaloneyN.A., GreenwoodC., ManuelA.The spectrum of bone disease in end-stage renal failure—an evolving disorder.Kidney Int1993; 43: 436–42.
32.
ColadonatoJ.A.Control of hyperphosphatemia among patients with ESRD.J Am Soc Nephrol2005; 16(Suppl 2): S107–14.
33.
SzczechL.A.The impact of calcimimetic agents on the use of different classes of phosphate binders: results of recent clinical trials.Kidney Int Suppl2004; 90: S46–8.
34.
RashidG., BernheimJ., GreenJ., BenchetritS.Parathyroid hormone stimulates the endothelial nitric oxide synthase through protein kinase A and C pathways.Nephrol Dial Transplant2007; 22: 2831–7.
35.
Kalantar–ZadehK., KuwaeN., RegidorD.L., KovesdyC.P., KilpatrickR.D., ShinabergerC.S.Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients.Kidney Int2006; 70: 771–80.
36.
TengM., WolfM., OfsthunM.N., LazarusJ.M., HernánM.A., CamargoC.A.Jr.Activated injectable vitamin D and hemodialysis survival: a historical cohort study.J Am Soc Nephrol2005; 16: 1115–25.
37.
CurhanG.Fooling the parathyroid gland—will there be health benefits?N Engl J Med2004; 350: 1565–7.
