RESUMO
Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.
Assuntos
Hidroxicolecalciferóis/uso terapêutico , Diálise Renal , Insuficiência Renal Crônica/tratamento farmacológico , Administração Oral , Idoso , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Morte Súbita Cardíaca/prevenção & controle , Feminino , Humanos , Hidroxicolecalciferóis/farmacologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Receptores de Calcitriol/efeitos dos fármacos , Receptores de Calcitriol/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Método Simples-CegoRESUMO
We evaluated the efficacy of technetium-sestamibi ((99m) Tc-MIBI) SPECT/CT for planning parathyroidectomy in cases with primary hyperparathyroidism (pHPT), comparing with planar scintigraphy and ultrasound (US), in an aim to establish the proper surgical strategy according to the preoperative imaging studies. A retrospective review of consecutive 75 pHPT patients who had been operated on was conducted. The results of preoperative imaging modalities and the operative finding were analyzed. Seven cases were found to have multiple hyperplastic glands, and no responsible gland was found in three cases. Four cases underwent only US scan for preoperative imaging. Remaining 61 cases were found to have single adenoma, and were included in the evaluation of localization imaging. US scan, (99m) Tc-MIBI planar scan and (99m) Tc-MIBI SPECT/CT showed accurate localization in 77.0% (47/61), 75.4% (46/61) and 88.5% (46/52) of the evaluable cases, respectively. US and (99m) Tc-MIBI planar scan demonstrated consistent result in 42 cases (68.9%), and those cases showed accurate localization in 90.5% (38/42). When both US and (99m) Tc-MIBI SPECT/CT was consistent, all 37 lesions had been correctly indicated. No clinico-pathological features were suggested to influence in demonstrating the localization, other than only (99m) Tc-MIBI SPECT/CT exhibited 100% sensitivity in ectopic glands. Combination of US and (99m) Tc-MIBI SPECT/CT certainly contributes to the planning of minimally invasive operation in cases with pHPT by indicating correct localization of single adenoma.
Assuntos
Adenoma/cirurgia , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Neoplasias das Paratireoides/cirurgia , Tecnécio Tc 99m Sestamibi , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único , UltrassonografiaRESUMO
BACKGROUND: Unlike the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), n-3-PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to have beneficial effects on inflammation, thrombosis, and cardiovascular disease (CVD). We examined possible alterations in serum PUFA profiles in patients on maintenance hemodialysis therapy and its association with CVD risk. STUDY DESIGN: An observational study including cross-sectional and longitudinal analyses. SETTING & PARTICIPANTS: Single-center study of 517 maintenance hemodialysis patients in an urban area in Japan. PREDICTORS: Serum EPA, DHA, and AA concentrations and EPA:AA, DHA:AA, and (EPA+DHA):AA ratios. OUTCOMES: CVD events, including ischemic heart disease, stroke, peripheral artery disease, pulmonary edema, and valve disease. RESULTS: Hemodialysis patients showed lower (EPA+DHA):AA, EPA:AA, and DHA:AA ratios than 122 controls similar in age and sex. During follow-up, 190 CVD events were recorded. (EPA+DHA):AA ratio was not associated significantly with CVD in unadjusted analysis, but was associated significantly and inversely with CVD in Cox models adjusted for age and other confounding variables, with HRs in the range of 1.71-1.99 in the lowest versus highest quartile of (EPA+DHA):AA ratios. Similarly, EPA:AA and DHA:AA ratios showed inverse associations with CVD, whereas serum EPA, DHA, and AA concentrations were not predictive of CVD. LIMITATIONS: No information for dietary intake, use of dietary supplements, or cell membrane PUFA content. CONCLUSIONS: In hemodialysis patients, serum PUFA profile is unfavorably altered, and the low n-3-PUFA:AA ratios are independent predictors of CVD.
Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Diálise Renal/efeitos adversos , Idoso , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
BACKGROUND: Extracellular magnesium (Mg) accounts for approximately 1% of the total body Mg. Clinically, serum Mg concentration is measured, but it does not necessarily reflect total body Mg status. Although relationships have been reported between reduced Mg and cardiovascular disease in non-dialysis patients, there have been few such studies in hemodialysis patients. It was hypothesized that reduced Mg, as represented by lower Mg concentration in the hair, would be associated with echocardiographic parameters in chronic hemodialysis patients. METHODS AND RESULTS: Hair Mg concentration was measured in 79 male hemodialysis patients using inductively coupled plasma mass spectrometry, and the relationships between hair Mg concentration and echocardiographic parameters were investigated. There was no significant correlation between Mg concentration in the hair and in serum. Hair Mg concentration in the patients with high-left ventricular mass index (LVMI) was significantly lower than that in the low-LVMI patients. Hair Mg concentration correlated significantly and negatively with posterior left ventricular wall thickness, interventricular septum thickness, left ventricular wall thickness (LVWT), and relative wall thickness. Serum Mg concentration, however, did not correlate with any of these echocardiographic parameters. CONCLUSIONS: In hemodialysis patients, hair Mg concentration is a biomarker, independent of serum Mg concentration. Hair Mg, but not serum Mg, was significantly and negatively associated with LVWT. Reduced tissue Mg concentration, as measured in the hair, may be associated with left ventricular hypertrophy in hemodialysis patients.
Assuntos
Cabelo/metabolismo , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Magnésio/metabolismo , Diálise Renal , Idoso , Biomarcadores/metabolismo , Eletrocardiografia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Endocrine and metabolic abnormalities may affect the survival of hemodialysis patients. Serum dehydroepiandrosterone sulfate (DHEA-S), an adrenal androgen with anabolic properties, is known to be lowered in ill patients and predicts poor outcome in the general population and in those with cardiac disease. The aims of this study were to examine a possible change in the DHEA-S level in dialysis patients and its association with survival in this population. METHODS: This was an observational cohort study in 494 prevalent hemodialysis patients (313 men and 181 women) in urban area of Osaka, Japan. The main exposure was the baseline DHEA-S level in December 2004 and the key outcome was all-cause mortality during the subsequent 5 years. Also, DHEA-S levels were compared between the hemodialysis patients and 122 matched healthy controls. RESULTS: The median (inter-quartile range) DHEA-S levels were 771 (447-1351) and 414 (280-659) ng/mL for male and female dialysis patients, respectively, and these values were significantly lower by 40-53% than the healthy control levels. Among the hemodialysis patients, DHEA-S was lower in women, those with older age, pre-existing cardiovascular disease, lower serum albumin and higher C-reactive protein. During the follow-up, we recorded 101 deaths. A low DHEA-S level was a significant predictor of all-cause mortality independent of potential confounders in male, but not in female, hemodialysis patients. CONCLUSIONS: The serum DHEA-S level is decreased in hemodialysis patients and associated with mortality in men. These results support the growing observational evidence that uremia-induced endocrine alterations including decreased sex hormones may be linked to adverse clinical outcomes.
Assuntos
Sulfato de Desidroepiandrosterona/sangue , Diálise Renal/mortalidade , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Desnutrição Proteico-Calórica/sangue , Desnutrição Proteico-Calórica/etiologiaRESUMO
BACKGROUND: Numbers of endothelial progenitor cells (EPC) have been shown to be decreased in subjects with end-stage renal disease (ESRD). It is not clear, however, whether dialysis modality affects circulating EPCs in ESRD subjects. METHODS: We examined the number of circulating EPCs in 67 continuous ambulatory peritoneal dialysis (CAPD) patients and age- and gender-matched 142 haemodialysis (HD) patients, and 78 subjects without chronic kidney disease. Arterial stiffness was analysed as pulse-wave velocity (PWV) for these patients, and their mutual relationship with circulating EPCs was examined. EPCs were measured as CD34(+) CD133(+) CD45(low) VEGFR2(+) cells determined by flow cytometry. RESULTS: The EPC numbers exhibited a strong correlation (R(2) = 0.866) with endothelial-colony forming units on culture assay. The levels of EPCs in HD or CAPD subjects were significantly lower than those in control subjects. Among ESRD subjects, the levels of EPC were significantly higher in CAPD subjects than those in HD subjects. In ESRD subjects, PWV levels tended to be associated with EPCs (Rs = -0.131, P = 0.058). However, the significant relationship between dialysis modality and circulating EPCs was independent of the levels of PWV. The association of circulating EPCs with dialysis modality was significant even after adjusting for other potential confounders, including age, gender, blood pressure, history of cardiovascular diseases, presence of diabetes, blood haemoglobin level and treatments with angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or statin. CONCLUSIONS: CAPD treatment could be a positive regulator of number of circulating EPCs in subjects with ESRD, with the relationship independent of the status of arteriosclerosis.
Assuntos
Células Endoteliais , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua , Diálise Renal , Células-Tronco , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Synchronous associations of Cushing's syndrome (CS) and primary aldosteronism (PA) with multiple adrenocortical adenomas secreting each hormone independently have rarely been reported. Herein, we describe a unique case of PA associated with CS with detailed clinical and pathological investigations. Bilateral adrenal masses with clinical symptoms of CS and PA were found in a 43-year-old woman. Venous sampling demonstrated excess secretion of cortisol, and aldosterone from right, and left tumor, respectively. A bilateral laparoscopic partial adrenalectomy was undergone. The right adrenal tumor (3 cm) was yellow in color with abundant lipofuscin granules, and was composed of both eosinophilic compact cells and clear cells. In situ hybridization showed that both mRNAs for HSD3B2 and CYP17A1 were strongly expressed in the tumor, suggesting cortisol synthesis. Left adrenal tumor (2.4 cm) was golden-yellow in color, and composed of clear cells only. Expression of HSD3B2 and CYP11B mRNAs were observed in the tumor compatible with the aldosterone synthesis. Furthermore, minute nodules were found at the surface of normal-appearing cortex on both sides of the adrenal glands, and the expression of HSD3B2 and CYP11B mRNAs was clearly demonstrated within the nodules, indicating aldosterone synthesis. We diagnosed that the present case had 1) cortisol-producing right adrenocortical adenoma, 2) aldosterone producing left adrenocortical adenoma, and 3) cortical minute nodules with aldosterone production in both adrenal glands compatible with idiopathic adrenal hyperplasia. We reviewed the cases reported, and discussed the significance of the minute nodules in the adrenal cortex, often found in association with the adrenocortical adenoma.
Assuntos
Neoplasias do Córtex Suprarrenal/complicações , Adenoma Adrenocortical/complicações , Síndrome de Cushing/etiologia , Hiperaldosteronismo/etiologia , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/cirurgia , Adulto , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/cirurgia , Feminino , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Progesterona Redutase/metabolismo , Esteroide 11-beta-Hidroxilase/metabolismoRESUMO
OBJECTIVE: Receptor for advanced glycation end-products (RAGE) is involved in diabetic vascular complications. We have recently shown that plasma endogenously secretory RAGE (esRAGE), an alternatively spliced form of RAGE, is closely associated with metabolic syndrome and atherosclerosis. Here, we evaluated if plasma esRAGE is a predictor of cardiovascular mortality in a cohort of 206 (171 nondiabetic) patients with end-stage renal diseases (ESRD). METHODS AND RESULTS: The cohort was followed for a median of 111 months, and 74 deaths including 34 cardiovascular deaths were recorded. Plasma esRAGE was measured at baseline. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly higher in subjects in the lowest tertile of plasma esRAGE than those in the middle or the highest tertile both in all and nondiabetic subjects alone. In all subjects, as compared with the lowest tertile of plasma esRAGE, the hazards ratios for the highest and middle tertile were 0.40 (95% CI, 0.18 to 0.89) and 0.26 (0.10 to 0.66), respectively. The higher risk for lower esRAGE was still significant even after adjusted either with body mass index, hypertension, dyslipidemia and vascular complications, but was confounded by age and diabetes. CONCLUSIONS: Low circulating esRAGE is a predictor for cardiovascular mortality in ESRD patients.
Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Produtos Finais de Glicação Avançada/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Idoso , Doenças Cardiovasculares/diagnóstico , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Feminino , Humanos , Resistência à Insulina , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVE: Hypothyroidism is associated with increased morbidity from cardiovascular disease. The arterial stiffness index beta (stiffness beta) in the common carotid artery (CCA), which is a parameter of arterial stiffening, is known to increase in hypothyroid patients, while normalization of thyroid function for 1 year by levothyroxine (L-T(4)) replacement therapy significantly decreases CCA stiffness beta. Since serum C-reactive protein (CRP) has recently emerged as an independent factor for cardiovascular risk, the present study was designed to examine whether hypothyroidism causes an increase in CRP and whether the serum CRP level is correlated with CCA stiffness beta in hypothyroid patients. PATIENTS AND METHODS: Serum CRP levels and CCA stiffness beta were determined in 46 patients with hypothyroidism and in 46 age- and sex-matched normal control subjects. Thirty-five patients were further monitored for change in CCA stiffness beta during 1 year in the euthyroid state induced by L-T(4) therapy. RESULTS: Baseline CRP and CCA stiffness beta were both significantly higher in hypothyroid patients than in normal controls [1064.6+/-224.3 vs. 602.1+/-43.3 ng/ml (mean+/-SE), p<0.0001; and 9.25+/-0.84 vs. 8.21+/-0.85, p<0.05, respectively]. Baseline CRP was significantly correlated in a positive manner with baseline values of CCA stiffness beta (r=0.683, p<0.0001). In multivariate analysis, baseline CCA stiffness beta was significantly associated with baseline levels of serum CRP (r=0.740, p<0.0001). During 1 year of L-T(4) replacement therapy, significant decrease in stiffness beta (from 9.25+/-0.84 to 8.57+/-0.58, p<0.0001) to the normal levels was found. Moreover, the change in CCA stiffness beta during L-T(4) replacement therapy was significantly and independently associated in a negative fashion with baseline levels of serum CRP (r=-0.696, p=0.0002). CONCLUSIONS: This study suggests that increased serum CRP might have an important independent role in increased arterial stiffening and the measurement of serum CRP is a useful predictor for the degree of improvement of arterial stiffening in hypothyroid patients.
Assuntos
Artérias/fisiopatologia , Proteína C-Reativa/metabolismo , Artéria Carótida Primitiva/fisiopatologia , Hipotireoidismo/fisiopatologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Elasticidade , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores Sexuais , Tiroxina/farmacologiaRESUMO
OBJECTIVE: To investigate the impact of glycemic control during regular hemodialysis on the survival of diabetic patients with chronic kidney disease (CKD) in a longitudinal observational study. RESEARCH DESIGN AND METHODS: A total of 114 diabetic CKD patients on hemodialysis at Inoue Hospital (Suita, Japan) were surveyed from May 1995 to December 2002 (survey period 45.5 +/- 29.3 [means +/- SD] months). All subjects were categorized into three groups by mean HbA(1c) (A1C) level during the 3-month period on hemodialysis preceding entry, as follows: good (A1C <6.5%, 5.7 +/- 0.4%, n = 34), fair (6.5
Assuntos
Glicemia/metabolismo , Nefropatias Diabéticas/terapia , Hemoglobinas Glicadas/análise , Falência Renal Crônica/mortalidade , Causas de Morte , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/mortalidade , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Diálise Renal/mortalidadeRESUMO
Magnesium (Mg) is the second most abundant intracellular cation in human and is involved in numerous biological processes. The kidney and intestinal tract are the principal organs involved in Mg homeostasis. Although calcium (Ca) is considered to be the major regulator of PTH secretion, a number of studies have demonstrated that Mg can modulate PTH secretion in a manner similar to Ca. Especially, it has been suggested that intracellular Mg depletion impairs the ability of the parathyroid to secrete PTH resulting in a fall in the serum PTH levels, and subsequently a fall in the serum Ca concentration.
Assuntos
Hipoparatireoidismo/etiologia , Deficiência de Magnésio/complicações , Humanos , Hipocalcemia/etiologia , Hipoparatireoidismo/fisiopatologia , Magnésio/fisiologia , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/metabolismoRESUMO
OBJECTIVE: While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT)-PCR and immunohistochemistry. RESULTS: FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23. CONCLUSIONS: Serum calcium may regulate circulating FGF-23 levels in PHPT.
Assuntos
Cálcio/farmacologia , Fatores de Crescimento de Fibroblastos/sangue , Hiperparatireoidismo Primário/sangue , Cálcio/sangue , Fator de Crescimento de Fibroblastos 23 , Humanos , Hiperparatireoidismo Primário/cirurgia , Pessoa de Meia-Idade , Glândulas Paratireoides/metabolismo , Paratireoidectomia , Fosfatos/sangue , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We evaluated the relationship between the volume of parathyroid glands estimated by ultrasonography (US) and response of 22-oxa calcitriol (Maxacalcitol, OCT) in patients with secondary hyperparathyroidism (2HPT) to evaluate whether the volume can be a predictor of the OCT response. Eleven institutes participated in this study. Ninety-four patients with advanced 2HPT were enrolled. The volume of the parathyroid glands were estimated by US before and 6 months after OCT treatment. The response of OCT treatment was classified into three groups (Group A: i-PTH < 300 pg/mL; Group B: 300 pg/mL < or = i-PTH < 500 pg/mL; Group C: i-PTH > or = 500 pg/mL). Forty-eight patients were in Group A, 28 patients in Group B, and 18 patients in Group C. The PTH levels at the beginning and 6 months were 458.3-199.1 pg/mL (P < 0.0001) in Group A, 524.6-403.2 pg/mL (P = 0.007) in Group B and 736.7-613.6 pg/mL (ns) in Group C, respectively. The volume of the largest gland in Group B was significantly larger than that in Group A (96.2 vs. 343.2 mm3: P < 0.001). Clinical factors affecting response of OCT was evaluated by logistic regression analysis and only the volume of the largest gland was a significant factor. In the patients whose volume was less than 300 mm3, the OCT response was significantly effective. We conclude that the glandular volume of the largest parathyroid gland estimated by US can be a useful factor to predict the OCT response in patients with moderate or severe renal HPT.
Assuntos
Calcitriol/análogos & derivados , Hiperparatireoidismo Secundário/tratamento farmacológico , Glândulas Paratireoides/diagnóstico por imagem , Calcitriol/uso terapêutico , Distribuição de Qui-Quadrado , Feminino , Humanos , Hiperparatireoidismo Secundário/patologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/efeitos dos fármacos , Diálise Renal , Estatísticas não Paramétricas , Resultado do Tratamento , UltrassonografiaRESUMO
Secondary hyperparathyroidism (SHPT) remains a serious complication in patients with chronic kidney disease, and some patients require parathyroidectomy. The Parathyroid Surgeons' Society of Japan (PSSJ) evaluated parathyroidectomy for SHPT and tertiary hyperparathyroidism (THPT) in Japan. The annual numbers of parathyroidectomies between 2004 and 2013 were evaluated using questionnaires. Since 2010, the PSSJ has registered the patients. In total, 826 patients from 42 institutions were registered. The annual number of parathyroidectomies for SHPT and THPT in Japan increased from 2004 to 2007 and then decreased markedly after 2007, with 296 operations performed in 2013. The number of women and men was almost equal (397/427). Median (interquartile range) age of these patients was 59.0 (24-87) years, the duration of hemodialysis before parathyroidectomy was 10.83 (0.0-38.7) years, and diabetic nephropathy was 87/826 (10.5%). Of these patients 59.6% were treated with cinacalcet at undergoing parathyroidectomy. In 75.3% of patients, a total parathyroidectomy with forearm autograft was performed. In 77.7% of patients, four or more parathyroid glands were removed during the initial operation. The incidences of husky voice and wound hemorrhage were 2.9% and 1.1%, respectively. The number of parathyroidectomies for SHPT in Japan decreased markedly after the introduction of cinacalcet. Based on the evaluation of registered patients, parathyroidectomies have been successfully performed at the institutions participating in the PSSJ.
Assuntos
Cinacalcete/uso terapêutico , Hiperparatireoidismo Secundário , Paratireoidectomia , Complicações Pós-Operatórias/epidemiologia , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Calcimiméticos/uso terapêutico , Feminino , Humanos , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/epidemiologia , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Paratireoidectomia/efeitos adversos , Paratireoidectomia/métodos , Paratireoidectomia/estatística & dados numéricos , Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Recent genetic animal models reveal important roles of platelet P-selectin on progression of atherosclerosis. In the present study, we examine the relation between platelet P-selectin expression and atherosclerotic parameters in 517 subjects. METHODS AND RESULTS: Unrelated subjects (n=517; 235 male and 282 female), including 187 with type 2 diabetes, 184 with hypertension, and 366 with hyperlipidemia, were enrolled in the study. P-selectin expression was determined by whole-blood flow cytometry. Arterial stiffness (stiffness index beta) and arterial wall thickness (intima-media thickness [IMT]) were determined by carotid ultrasound. P-selectin expression was significantly and positively correlated with carotid IMT and stiffness index beta. Multiple regression analyses showed that the association of the percentage of P-selectin-positive platelets with carotid IMT was independent of other clinical factors. Moreover, the percentage of P-selectin-positive platelets was higher in subjects with carotid plaque and was an independent factor associated with occurrence of carotid plaque analyzed by multiple logistic regression analysis. Finally, the percentage of P-selectin-positive platelets was positively associated with age, body mass index, systolic and diastolic blood pressure, and HbA1c and inversely associated with HDL cholesterol. CONCLUSIONS: Platelet P-selectin is independently associated with atherosclerotic arterial wall changes in human subjects.
Assuntos
Plaquetas/metabolismo , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/metabolismo , Selectina-P/biossíntese , Fatores Etários , Plaquetas/patologia , Pressão Sanguínea , Índice de Massa Corporal , Doenças das Artérias Carótidas/epidemiologia , HDL-Colesterol/sangue , Feminino , Citometria de Fluxo , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Selectina-P/análise , Valor Preditivo dos Testes , Análise de Regressão , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , UltrassonografiaRESUMO
CONTEXT: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process. OBJECTIVE: Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro. METHODS: The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies. RESULTS: The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+. CONCLUSIONS: These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells.
Assuntos
Cálcio/farmacologia , Glândulas Paratireoides/efeitos dos fármacos , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/metabolismo , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Humanos , Hiperparatireoidismo Secundário/metabolismo , Glândulas Paratireoides/citologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/isolamento & purificação , Uremia/complicaçõesRESUMO
Cholesteryl ester transfer protein (CETP) is a key regulating factor of lipid metabolism, and the polymorphism of its gene may therefore be a candidate for modulating the lipid parameters, altering the susceptibility to atherosclerosis in type 2 diabetic subjects. In a group of 443 unrelated Japanese patients with type 2 diabetes, we studied the B1B2 polymorphism at the CETP locus, which is detectable with the restriction enzyme TaqI. Patients were separated into three groups according to genotype and compared based on their clinical characteristics, lipid parameters, and macrovascular complications. The B2 allele was associated in a dose-dependent fashion with higher HDL cholesterol and apolipoprotein AI levels, together with lower CETP concentrations. Furthermore, the prevalence of macrovascular complications, such as coronary heart disease, arteriosclerosis obliterans, and cerebral vascular disease, was significantly higher in subjects with the B1B1 genotype. Multiple logistic regression analysis also showed that the B1 allele of CETP genotype was associated with the incidence of these three complications independently of other risk factors. Thus, in type 2 diabetic patients, the B1B2 polymorphism of CETP gene is likely to be a strong genetic predictor of macrovascular complications.
Assuntos
Proteínas de Transporte/genética , Desoxirribonucleases de Sítio Específico do Tipo II , Diabetes Mellitus Tipo 2/genética , Glicoproteínas , Polimorfismo de Fragmento de Restrição , Alelos , Apolipoproteína A-I/sangue , Proteínas de Transferência de Ésteres de Colesterol , HDL-Colesterol/sangue , Angiopatias Diabéticas/genética , Genótipo , Humanos , Japão , Modelos LogísticosRESUMO
Polymorphism of alpha2 integrin (C807T) is shown to be associated with an increased incidence of thrombotic cardiovascular events. However, it is not clear whether this polymorphism is associated with atherosclerotic arterial wall thickening. In this study, we examined the association of C807T polymorphism with arterial wall thickness in 265 control subjects and 272 patients with type 2 diabetes. In all subjects, intima-media thickness of the right carotid artery in the 807TT group (0.649 +/- 0.028 mm [SE]) was significantly (P = 0.0228, Scheffe's F test) less than in the 807CC group (0.767 +/- 0.033). This effect of polymorphism is gene dose dependent (P = 0.0227, ANOVA). The similar association was also observed in patients with diabetes but not in control subjects. Multiple regression analysis in all subjects revealed that the T allele was inversely (beta = -0.095, P = 0.021) associated with intima-media thickness independent of age, HbA(1c), and HDL cholesterol. Finally, an inverse relation between the occurrence of carotid plaque and the T allele was observed in patients with diabetes with an adjusted odds ratio of 0.487 (P = 0.031) in multiple logistic regression analyses. These results suggest that the number of 807T alleles in alpha2 integrin is protective against atherosclerotic arterial wall thickening and the occurrence of plaque in patients with type 2 diabetes.
Assuntos
Antígenos CD/genética , Doenças das Artérias Carótidas/genética , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Feminino , Genótipo , Humanos , Integrina alfa2 , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
Hypothyroidism is associated with increased morbidity from cardiovascular disease, and an increase in serum osteoprotegerin (OPG) has recently been reported to be associated with the severity of coronary heart disease and cardiovascular mortality. The present study was designed to examine whether hypothyroidism causes an increase in serum OPG, and to determine whether levothyroxine (L-T4) replacement therapy might suppress serum OPG levels in hypothyroid patients. Fifty-three hypothyroid patients with chronic thyroiditis and age- and sex-matched normal control subjects were examined for the levels of serum OPG and plasma von Willebrand factor (vWF), a vascular injury marker. Thirty-seven of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T4 replacement therapy. Baseline OPG was significantly higher in hypothyroid patients than in normal controls (4.51 +/- 0.50 vs 3.72 +/- 0.23 pmol/l (mean +/- S.E.); P = 0.0182). In multivariate analysis, baseline OPG was significantly associated with baseline levels of TSH (r = 0.280, P = 0.0162) and vWF (r = 0.626, P < 0.0001). During one year of L-T4 replacement therapy, hypothyroid patients showed a significant decrease in OPG levels from 4.35 +/- 0.51 to 3.48 +/- 0.26 pmol/l (P = 0.0166), a level comparable to normal controls. The change in serum OPG levels during L-T4 replacement therapy was significantly and independently associated in a negative fashion with baseline vWF (r = -0.503, P = 0.0014). This study suggested that the severity of hypothyroidism and vascular injury might have important independent roles in increasing the serum OPG level in hypothyroid patients. Furthermore, it was demonstrated that a sustained euthyroid state might have the potential to decrease the serum OPG level in hypothyroid patients and that the degree of vascular injury in the hypothyroid state is independently associated with a decrease in serum OPG during a 1-year normalization of thyroid function.
Assuntos
Glicoproteínas/sangue , Terapia de Reposição Hormonal , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/sangue , Tiroxina/uso terapêutico , Feminino , Glicoproteínas/antagonistas & inibidores , Humanos , Hipotireoidismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoprotegerina , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores do Fator de Necrose Tumoral , Tireotropina/sangue , Fator de von Willebrand/metabolismoRESUMO
Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.