Combined therapy with cinacalcet and low doses of vitamin D sterols in patients with moderate to severe secondary hyperparathyroidism

Denver Nephrologists, Denver, CO 80230, USA.
Nephrology Dialysis Transplantation (Impact Factor: 3.49). 07/2008; 23(7):2311-8. DOI: 10.1093/ndt/gfn026
Source: PubMed

ABSTRACT Adequate control of all four KDOQI biochemical targets for chronic kidney disease, bone and mineral disorder (CKD-MBD), which include parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and Ca x P, remains difficult and is accomplished in <6% of patients receiving haemodialysis. The objective of the current study was to determine whether treatment with cinacalcet combined with low doses of vitamin D sterols improves control of both PTH and Ca x P among haemodialysis patients with secondary hyperparathyroidism (sHPT).
This multicentre, open-label study enrolled haemodialysis subjects (N = 444) with moderate to severe sHPT (mean serum biPTH > 160-430 pg/mL) (approximately iPTH 300-800 pg/mL or ng/L). Cinacalcet was titrated sequentially (30-180 mg/day) during an 8-week dose-titration phase to achieve biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L) and efficacy was assessed over 8 weeks. At week 2 of the study, subjects receiving vitamin D sterols had doses reduced to the equivalent of 2 mcg of paricalcitol three times a week or 6 mcg/week. Among the efficacy endpoints were the proportion of subjects with mean biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L), with mean Ca x P <or=55 mg(2)/dL(2) (4.4 mmol(2)/L(2)) and with both simultaneously during the assessment phase.
The majority of subjects (n = 375) reached the assessment phase of the study and were included in efficacy analyses; 39 subjects withdrew due to adverse events. Sixty-two percent of subjects achieved the biPTH target, 83% achieved the Ca x P target and 54% reached both targets. Treatment reduced biPTH by 35% (P < 0.0001), calcium by 11% (P < 0.0001), phosphorus by 7% (P < 0.0001) and Ca x P by 17% (P < 0.0001). The proportion of subjects with values for biPTH, for Ca x P and for both biPTH and Ca x P within the target range during the assessment phase did not differ between subjects who received cinacalcet together with vitamin D sterols, and those who received cinacalcet alone.
Among subjects with moderate to severe sHPT undergoing haemodialysis, combined therapy with cinacalcet and low doses of vitamin D sterols improved achievement of the biochemical targets for CKD-MBD recommended by the KDOQI guidelines.

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    ABSTRACT: Mineral and bone disorders, including secondary hyperparathyroidism, are common in chronic kidney disease and contribute to increased mortality. Traditional therapy to control these disorders involves using phosphate binders and vitamin D sterols, but achieving appropriate results has proved difficult. The availability of calcimimetics has provided a new weapon in the arsenal to treat mineral and bone disorders. Initial clinical trials examined the use of cinacalcet in hemodialysis patients with secondary hyperparathyroidism and showed reductions in parathyroid hormone, calcium, phosphorus and calcium × phosphorus product. More recent clinical trials have attempted to show how these reductions aid in achieving specific K/DOQI goals. Additional studies have examined the use of cinacalcet in the treatment of mineral and bone disorders in CKD patients not yet on dialysis. This review summarizes recent literature regarding the use of calcimimetics in the treatment of CKD patients with mineral and bone disorders and the achievement of K/DOQI goals.
    Kidney 07/2009; 18(4):175-179. DOI:10.1007/s00596-009-0095-0
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    ABSTRACT: Dados de vários ensaios clínicos recentes reafirmam a eficácia do tratamento com cinacalcete para controlar o nível plasmático do PTH em pacientes em diálise com hiperparatireoidismo secundário estabelecido. Em contraste com resultados relatados inicialmente, a partir de estudos onde cinacalcete era usado junto com doses relativamente altas e constantes de vitamina D ou derivados, achados recentes mostram que os níveis plasmáticos de PTH podem ser efetivamente reduzidos quando essa droga é administrada em associação a doses mais baixas de vitamina D ou derivados. Em comparação ao tratamento convencional com vitamina D ou derivados, os níveis séricos de cálcio e fósforo são mais bem controlados com esta abordagem terapêutica e uma maior proporção de pacientes pode alcançar concentrações séricas de cálcio e fósforo e valores do produto Ca x P dentro das faixas recomendadas pelas diretrizes atuais. Entretanto, ensaios clínicos prospectivos adicionais são necessários para determinar se o uso de cinacalcete em pacientes em diálise com hiperparatireoidismo secundário afeta outras variáveis importantes e clinicamente relevantes como, por exemplo, a morfologia do osso, a massa e/ou a densidade óssea, a taxa de fraturas e a necessidade de paratireoidectomia. Descritores: Calcimiméticos. Hiperparatireoidismo secundário. Ensaios clínicos. ABSTRACT Data from several recent clinical trials reaffirm the efficacy of treatment with cinacalcet for controlling plasma PTH levels among dialysis patients with estab- lished secondary HPT. In contrast to results reported previously from studies where cinacalcet was used together with relatively large but constant doses of vitamin D sterols, plasma PTH levels can be reduced effectively during treatment with cinacalcet among patients receiving lower doses of vitamin D sterols. Compared to conventional treatment with vitamin D sterols, serum calcium and phosphorus levels are better controlled with this therapeutic approach, and a larger proportion of patients are able to achieve serum calcium and phosphorus concentrations and values for Ca x P with the ranges rec- ommended in current practice guidelines. Additional prospective clinical trials are needed, however, to determine whether the use of cinacalcet among dial- ysis patients with secondary HPT affects other important and clinically relevant outcomes such bone morphology, bone mass and/or bone density, skeletal fracture rates, and the need for parathyroidectomy.
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