RESUMO
The recent availability of cinacalcet has provided a possible alternative to parathyroidectomy in kidney transplant patients with persistent hyperparathyroidism, but its effect on bone mass density (BMD) is unknown. From our database containing 163 kidney transplants performed at our center from 1999 to 2007, we compared recipients who received cinacalcet for persistent hypercalcemia and hyperparathyroidism following renal transplantation (n = 8) with up to two other posttransplant patients matched for age, sex, race, and graft function (n = 15). The outcome of the study was BMD changes from baseline to 12, 24, and 36 months post-renal transplantation. Repeated-measures mixed model was used to assess the difference of BMD change between two groups. Cinacalcet therapy was started at a median of 9 (range = 1 to 24) months posttransplant with a mean dose 56 ± 29 mg/d (mean duration = 1.6; range = 1 to 2.1 years). Cinacalcet therapy was associated with significant reduction of serum calcium compared to control. Cinacalcet therapy was associated with greater BMD increase at the hip over the 36-month posttransplant period. Cinacalcet was well tolerated. Our results suggest that cinacalcet may have a small but favorable effect on bone density following kidney transplantation.
Assuntos
Densidade Óssea/efeitos dos fármacos , Calcimiméticos/uso terapêutico , Hipercalcemia/tratamento farmacológico , Hiperparatireoidismo Secundário/tratamento farmacológico , Transplante de Rim/efeitos adversos , Naftalenos/uso terapêutico , Absorciometria de Fóton , Adulto , Ossos do Braço/diagnóstico por imagem , Ossos do Braço/efeitos dos fármacos , Biomarcadores/sangue , Calcimiméticos/efeitos adversos , Cálcio/sangue , Estudos de Casos e Controles , Cinacalcete , Feminino , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/efeitos dos fármacos , Humanos , Hipercalcemia/sangue , Hipercalcemia/diagnóstico por imagem , Hipercalcemia/etiologia , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/diagnóstico por imagem , Hiperparatireoidismo Secundário/etiologia , Masculino , Pessoa de Meia-Idade , Naftalenos/efeitos adversos , National Institutes of Health (U.S.) , Estudos Retrospectivos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Surface immunoglobulin (sIg)-mediated stimulation of B lymphocytes induces a tyrosine kinase-dependent sequence of events leading to rapid and large elevations in intracellular ionized calcium ([Ca2+]i). These early biochemical events do not necessarily lead to proliferation of B cells, however, and conversely, the absence of or inhibition of these events does not necessarily prevent cellular proliferation. We now show by digital image analysis of single B cells that conditions which lead to B cell proliferation are associated with low-level but persistent sustained or cyclic elevations in [Ca2+]i. In marked contrast, early and nonsustained elevations in [Ca2+]i are induced in B cells by stimuli that lead to G1 transition but fail to progress to DNA synthesis. Thus, when B cells were stimulated with mitogenic and nonmitogenic anti-IgD antibodies, both of which induce entry of cells into G1 and early calcium transients of comparable magnitude, persistent low-level calcium elevations were only detected in cells stimulated with the mitogenic antibody. Furthermore, persistent calcium elevations were also seen when B cells were stimulated with a multivalent dextran-anti-Ig conjugate which induced very high levels of B cell proliferation in the absence of detectable phosphatidylinositol 4,5-biphosphate hydrolysis or elevations in [Ca2+]i as detected by flow cytometry. Finally, B cells from X-linked B cell-defective mice, which do not proliferate in response to anti-Ig antibody, show marked and early increases in [Ca2+]i, but do not show persistent calcium elevations. These data suggest that the rapid and large increases of [Ca2+]i seen in lymphocytes within seconds after antigen receptor ligation may be associated with entry in G1, whereas low-level but persistent elevations may be the hallmark of a cell destined to synthesize DNA.