Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias

FUNDAMENTO: A redução da frequência cardíaca (FC) na angiografia por tomografia das artérias coronarianas (ATCCor) é fundamental para a qualidade de imagem. A eficácia dos bloqueadores de cálcio como alternativas para pacientes com contraindicações aos betabloqueadores não foi definida. OBJETIVOS: Comparar a eficácia na redução da FC e variabilidade RR do metoprolol e diltiazem na ATCCor. MÉTODOS: Estudo prospectivo, randomizado, aberto, incluiu pacientes com indicação clínica de ATCCor, em ritmo sinusal, com FC>70bpm e sem uso de agentes que interferissem com a FC. Cinquenta pacientes foram randomizados para grupos: metoprolol IV 5-15 mg ou até FC≤60 bpm(M), e diltiazem IV 0,25-0,60mg/kg ou até FC≤60 bpm (D). Pressão arterial (PA) e FC foram aferidas na condição basal, 1min, 3min e 5min após agentes, na aquisição e após ATCCor. RESULTADOS: A redução da FC em valores absolutos foi maior no grupo M que no grupo D (1, 3, 5min, aquisição e pós-exame). A redução percentual da FC foi significativamente maior no grupo M apenas no 1 min e 3 min após início dos agentes. Não houve diferença no 5 min, durante a aquisição e após exame. A variabilidade RR percentual do grupo D foi estatisticamente menor do que a do grupo M durante a aquisição (variabilidade RR/ FC média da aquisição). Um único caso de BAV, 2:1 Mobitz I, revertido espontaneamente ocorreu (grupo D). CONCLUSÃO: Concluímos que o diltiazem é uma alternativa eficaz e segura aos betabloqueadores na redução da FC na realização de angiografia por tomografia computadorizada das artérias coronarianas. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)

Gene expression profiles displayed by peripheral blood mononuclear cells from patients with type 2 diabetes mellitus focusing on biological processes implicated on the pathogenesis of the disease

Patients with type 2 diabetes mellitus (T2DM) exhibit insulin resistance associated with obesity and inflammatory response, besides an increased level of oxidative DNA damage as a consequence of the hyperglycemic condition and the generation of reactive oxygen species (ROS). In order to provide information on the mechanisms involved in the pathophysiology of T2DM, we analyzed the transcriptional expression patterns exhibited by peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic subjects, by investigating several biological processes: inflammatory and immune responses, responses to oxidative stress and hypoxia, fatty acid processing, and DNA repair. PBMCs were obtained from 20 T2DM patients and eight non-diabetic subjects. Total RNA was hybridized to Agilent whole human genome 4x44K one-color oligo-microarray. Microarray data were analyzed using the GeneSpring GX 11.0 software (Agilent). We used BRB-ArrayTools software (gene set analysis - GSA) to investigate significant gene sets and the Genomica tool to study a possible influence of clinical features on gene expression profiles. We showed that PBMCs from T2DM patients presented significant changes in gene expression, exhibiting 1320 differentially expressed genes compared to the control group. A great number of genes were involved in biological processes implicated in the pathogenesis of T2DM. Among the genes with high fold-change values, the up-regulated ones were associated with fatty acid metabolism and protection against lipid-induced oxidative stress, while the down-regulated ones were implicated in the suppression of pro-inflammatory cytokines production and DNA repair. Moreover, we identified two significant signaling pathways: adipocytokine, related to insulin resistance; and ceramide, related to oxidative stress and induction of apoptosis. In addition, expression profiles were not influenced by patient features, such as age, gender, obesity, pre/post-menopause age, neuropathy, glycemia, and HbA(1c) percentage. Hence, by studying expression profiles of PBMCs, we provided quantitative and qualitative differences and similarities between T2DM patients and non-diabetic individuals, contributing with new perspectives for a better understanding of the disease. (C) 2012 Elsevier B.V. All rights reserved.

CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients

Diabet. Med. 29, e55e61 (2012) Abstract Aims The CYBA C242T polymorphism has been associated with cardiovascular phenotypes such as hypertension and atherosclerosis, but available data are conflicting. This report investigated the impact of this variant on hypertension and metabolic determinants of cardiovascular risk in a large Brazilian sample. Methods We cross-sectionally evaluated 1856 subjects (826 normotensive subjects and 1030 hypertensive patients) by clinical history, anthropometry, laboratory analysis and genotyping of the CYBA C242T polymorphism. Results Genotype frequencies in the whole population were consistent with the HardyWeinberg equilibrium and genotype distributions were not different between hypertensive and normotensive subjects. Hypertensive patients with the CC genotype presented lower fasting plasma glucose levels (5.9 +/- 0.1 vs. 6.2 +/- 0.1 mmol/l, P = 0.020) and waist circumference (94.5 +/- 0.6 vs. 96.3 +/- 0.6 cm, P = 0.028) than CT + TT ones. Similarly, the prevalence of diabetes mellitus and obesity was also lower in hypertensive patients carrying the CC genotype (16% vs. 21%, P = 0.041; 36% vs. 43%, P = 0.029, respectively). In addition, multiple and logistic regression analysis demonstrated that the CYBA C242T polymorphism was associated with glucose levels, waist circumference, obesity and diabetes mellitus in hypertensive patients independently of potential confounders. Conversely, in normotensive subjects, no significant difference in studied variables was detected between the genotype groups. Conclusions These data suggest that the T allele of the CYBA C242T polymorphism may be used as a marker for adverse metabolic features in Brazilian subjects with systemic hypertension.

Fibronectin glycation increases IGF-I induced proliferation of human aortic smooth muscle cells

The advanced glycation end products, namely AGEs, contribute to long-termed complications of diabetes mellitus, including macroangiopathy, where smooth muscle cells (SMC) proliferation stimulated by platelet-derived growth factor (PDGF) isoforms and insulin-like growth factor-I (IGF-I) plays an important role. The objective of the present study was to investigate the effect of an AGE-modified extracellular matrix protein on IGF-I induced SMC proliferation and on the IGF-I-IGF binding protein 4 (IGFBP-4) axis under basal conditions and after stimulation with PDGF-BB. IGF-I resulted in significantly higher thymidine incorporation in SMC seeded on AGE-modified fibronectin (AGE-FN) in comparison to cells seeded on fibronectin (FN). This augmented proliferation could not be accounted for by increased expression of IGF-IR, by decreased secretion of IGFBP-4, a binding protein that inhibits IGF-I mitogenic effects or by increased IGF-IR autophosphorylation. PDGF-BB did not modulate IGF-IR and IGFBP-4 mRNA expression in any of the substrata, however, this growth factor elicited opposite effects on the IGFBP-4 content in the conditioned media, increasing it in cells plated on FN and diminishing it in cells plated on AGE-FN. These findings suggest that one mechanism by which AGE-modified proteins is involved in the pathogenesis of diabetes-associated atherosclerosis might be by increasing SMC susceptibility to IGF-I mitogenic effects.

Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population

The present study aimed to investigate the association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with primary open angle glaucoma (POAG). We conducted a case-control study that included 90 patients with POAG and 127 healthy controls whose blood samples were genotyped for the functional polymorphisms T-786C and Glu298Asp of the eNOS gene by Taqman fluorescent allelic discrimination assay. The T-786C polymorphism was significantly associated as a risk factor for POAG among women (OR: 228; 95% CI: 1.11 to 4.70, p = 0.024) and marginally associated to the risk of POAG in the patients >= 52 years of age at diagnosis (OR: 2.11; 95% CI: 0.98 to 4.55, p = 0,055). However, these results was not confirmed after adjustments for gender, age, self-declared skin color, tobacco smoking and eNOS genotypes by multivariate logistic regression model (OR: 2.08; 95% CI: 0.87 to 5.01, p = 0.101 and OR: 2.20; 95% CI: 0.95 to 5.12, p = 0.067, respectively). The haplotype CG of T-786C and Glu298Asp showed a borderline association with risk of POAG in the overall analysis (OR: 1.76; 95% CI: 0.98 to 3.14, p = 0.055) and among women (OR: 2.02; 95% CI: 0.98 to 4.16, p = 0.052). Furthermore, the CG haplotype was significantly associated with the development of POAG for the age at diagnosis group >= 52 years (OR: 3.48; 95% CI: 1.54 to 7.84, p = 0.002). We suggested that haplotypes of the polymorphisms T-786C and Glu298Asp of eNOS may interact with gender and age in modulating the risk of POAG. (C) 2012 Elsevier B.V. All rights reserved.

Left ventricular thrombus attenuation characterization in cardiac computed tomography angiography

BACKGROUND: Because of their similar visual appearance, differentiation of left ventricular thrombotic material and myocardial wall can be difficult in contrast-enhanced coronary computed tomography (CT) angiography. OBJECTIVE: We identified typical thrombi attenuation of left ventricular thrombi with the use of CT measurement. METHODS: Over a time period of 6 years; we retrospectively identified 31 patients who showed a left ventricular thrombus in CT angiography datasets. Patients underwent routine contrast cardiac CT to investigate coronary artery disease. CT attenuation of each thrombus was assessed in the 4-chamber view. CT densities were also determined in the ascending aorta, left ventricle, and myocardial wall both in the mid-septal and mid-lateral segments. The mean CT attenuation of thrombi and the difference between attenuation in thrombi, left ventricular cavity, and myocardial wall were determined. The ratio of attenuation values in thrombus versus aorta and myocardium versus aorta were also determined. RESULTS: Mean (+/- SD) CT attenuation of all left ventricular thrombi in 31 patients was 43.2 +/- 15.3 HU (range, 25-80 HU). Mean CT densities of septal and lateral myocardial wall were 102.9 +/- 23.1 HU (range, 63-155 HU) and 99.3 +/- 28.7 HU (range, 72-191 HU), respectively, and were thus significantly higher than the CT attenuation of thrombi (P < 0.001). A threshold of 65 HU yielded a sensitivity, specificity, and positive and negative predictive values of 94%, 97%, 94%, and 97%, respectively, to differentiate thrombus from the myocardial wall. The mean ratio between CT attenuation of thrombus and CT attenuation within the ascending aorta was 0.11 +/- 0.05 (range, 0.04-0.23), which was significantly lower compared with the mean ratio between CT attenuation of the myocardial wall and the CT attenuation within the ascending aorta. CONCLUSION: CT attenuation within left ventricular thrombi was significantly lower than myocardial attenuation in CT angiography datasets. Assessment of CT attenuation may contribute to the differentiation of thrombi. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved.

Validation of the Short-Version of Rose Angina Questionnaire in Brazil

Background: Stable angina pectoris is a serious condition with few epidemiological studies in Brazil. Objective: To validate the short-version of the Rose angina questionnaire in Brazilian Portuguese for its implementation in surveys and longitudinal studies. Methods: A total of 116 consecutive patients from an outpatient clinic without prior myocardial infarction and/or coronary revascularization were enrolled for application of three questions of the Rose angina questionnaire addressing chest pain after exertion. We used the treadmill test as the gold standard with the Ellestad protocol. Results: The short-version of the Rose angina questionnaire of the 116 subjects submitted to the exercise treadmill test disclosed 89.7% of accuracy, 25% of sensitivity, 92.0% of specificity, 10.0% of positive predictive value, 97.2% of negative predictive value, and 3.1 of positive likelihood ratio and 0.82 of negative likelihood ratio. Conclusion: The Portuguese version with three items of the Rose angina questionnaire is suitable for epidemiological purposes. (Arq Bras Cardiol 2012; 99(5): 1056-1059)

Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with C-14-cholesteryl ester and H-3-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14 C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the H-3-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling.

Effects of anabolic androgenic steroids on chylomicron metabolism

Objective: To evaluate the effects of anabolic androgenic steroids (AAS) on chylomicron metabolism. Methods: An artificial lipid emulsion labeled with radioactive cholesteryl ester (CE) and triglycerides (TG) mimicking chylomicrons was intravenously injected into individuals who regularly weight trained and made regular use of AAS (WT + AAS group), normolipidemic sedentary individuals (SDT group) and individuals who also regularly weight trained but did not use AAS (WT group). Fractional clearance rates (FCR) were determined by compartmental analysis for emulsion plasma decay curves. Results: FCR-CE for the WT + AAS group was reduced (0.0073 +/- 0.0079 min(-1), 0.0155 +/- 0.0100 min(-1), 0.0149 +/- 0.0160 min(-1), respectively; p<0.05), FCR-TG was similar for both the WT and SDT groups. HDL-C plasma concentrations were lower in the WT + AAS group when compared to the WT and SDT groups (22 +/- 13; 41 +/- 38 +/- 13 mg/dL, respectively; p<0.001). Hepatic triglyceride lipase activity was greater in the WT + AAS group when compared to the WT and SDT groups (7243 +/- 1822; 3898 +/- 1232; 2058 +/- 749, respectively; p<0.001). However, no difference was observed for lipoprotein lipase activity. Conclusions: Data strongly suggest that AAS may reduce the removal from the plasma of chylomicron remnants, which are known atherogenic factors. (C) 2012 Elsevier Inc. All rights reserved.

Rest left ventricular function and contractile reserve by dobutamine stress echocardiography in peripartum cardiomyopathy

Aims: To assess whether contractile reserve during dobutamine stress echocardiography (DSE) can predict left ventricular functional recovery in patients with peripartum cardiomyopathy and to assess myocardial fibrosis by magnetic resonance imaging (MRI) in these patients. Methods: Nine patients with peripartum cardiomyopathy were enrolled. All patients underwent DSE and were followed for six months, when a rest Doppler echocardiogram was repeated. MRI was also performed at the beginning of follow-up to identify myocardial fibrosis. Results: Mean age was 29 +/- 7.9 years and mean left ventricular ejection fraction at baseline was 39.4 +/- 8.6% (range 24-49%). Eight of the nine patients showed left ventricular functional recovery with mean ejection fraction at follow-up of 57.1 +/- 13.8%. The ejection fraction response to DSE did not predict recovery at follow-up. On the other hand, left ventricular ejection fraction at baseline correlated with ejection fraction at follow-up. Mild fibrosis was detected in only one patient. Conclusion: Left ventricular ejection fraction at baseline was a predictor of left ventricular functional recovery in patients with peripartum cardiomyopathy. Dobutamine stress echocardiography at presentation of the disease did not predict recovery at follow-up. Myocardial fibrosis appeared to be uncommon in this cardiomyopathy. (C) 2011 Sociedade Portuguesa de Cardiologia Published by Elsevier Espana, S.L. All rights reserved.

Exercise training restores the endothelial progenitor cells number and function in hypertension: implications for angiogenesis

Objectives: Aerobic exercise training has been established as an important nonpharmacological treatment for hypertension. We investigated whether the number and function of endothelial progenitor cells (EPCs) are restored after exercise training, potentially contributing to neovascularization in hypertension. Methods: Twelve-week-old male spontaneously hypertensive rats (SHRs, n = 14) and Wistar Kyoto (WKY, n = 14) rats were assigned to four groups: SHR; trained SHR (SHR-T); WKY; and trained WKY. Exercise training consisted of 10 weeks of swimming. EPC number and function, as well as the vascular endothelial growth factor (VEGF), nitrotyrosine and nitrite concentration in peripheral blood were quantified by fluorescence-activated cell sorter analysis (CD34+/Flk1+ cells), colony-forming unit assay, ELISA and nitric oxide (NO) analyzer, respectively. Soleus capillary/fiber ratio and protein expression of VEGF and endothelial NO synthase (eNOS) by western blot were assessed. Results: Exercise training was effective in reducing blood pressure in SHR-T accompanied by resting bradycardia, an increase in exercise tolerance, peak oxygen uptake (VO2) and citrate synthase activity. In response to hypertension, the amount of peripheral blood-EPC and number of colonies were decreased in comparison with control levels. In contrast, exercise training normalized the EPC levels and function in SHR-T accompanied by an increase in VEGF and NO levels. In addition, oxidative stress levels were normalized in SHR-T. Similar results were found in the number and function of bone marrow EPC. Exercise training repaired the peripheral capillary rarefaction in hypertension by a signaling pathway VEGF/eNOS-dependent in SHR-T. Moreover, improvement in EPC was significantly related to angiogenesis. Conclusion: Our data show that exercise training repairs the impairment of EPC in hypertension, which could be associated with peripheral revascularization, suggesting a mechanism for its potential therapeutic: application in vascular diseases.

Association between diet and polymorphisms in individuals with statin-controlled dyslipidaemia grouped according to oxidative stress biomarkers

The objective of this study was to investigate whether differences in diet and in single-nucleotide polymorphisms (SNPs) found in paraoxonase-1 (PON-1), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) genes, are associated with oxidative stress biomarkers and consequently with susceptibility of low-density cholesterol (LDL) to oxidation. A multivariate approach was applied to a group of 55 patients according to three biomarkers: plasma antioxidant activity, malondialdehyde and oxidized LDL (oxLDL) concentrations. Individuals classified in Cluster III showed the worst prognoses in terms of antioxidant activity and oxidative status. Individuals classified in Cluster I presented the lowest oxidative status, while individuals grouped in Cluster II presented the highest levels of antioxidant activity. No difference in nutrient intake was observed among the clusters. Significantly higher gamma- and delta-tocopherol concentrations were observed in those individuals with the highest levels of antioxidant activity. No single linear regression was statistically significant, suggesting that mutant alleles of the SNPs selected did not contribute to the differences observed in oxidative stress response. Although not statistically significant, the p value of the APO E coefficient for oxLDL response was 0.096, indicating that patients who carry the TT allele of the APO E gene tend to present lower plasma oxLDL concentrations. Therefore, the differences in oxidative stress levels observed in this study could not be attributed to diet or to the variant alleles of PON-1, CETP, HMGCR or APO E. This data supports the influence of gamma-tocopherol and delta-tocopherol on antioxidant activity, and highlights the need for further studies investigating APO E alleles and LDL oxidation.

MYLIP p.N342S polymorphism is not associated with lipid profile in the Brazilian population

Background: A recent study investigated the MYLIP region in the Mexican population in order to fine-map the actual susceptibility variants of this locus. The p.N342S polymorphism was identified as the underlying functional variant accounting for one of the previous signals of genome-wide association studies and the N342 allele was associated with higher cholesterol concentrations in Mexican dyslipidemic individuals. To date, there is no further evaluation on this genotype-phenotype association in the literature. In this scenario, and because of a possible pharmacotherapeutic target of dyslipidemia, the main aim of this study was to assess the influence of the MYLIP p.N342S polymorphism on lipid profile in Brazilian individuals. Methods: 1295 subjects of the general population and 1425 consecutive patients submitted to coronary angiography were selected. General characteristics, biochemical tests, blood pressures, pulse wave velocity, and coronary artery disease scores were analyzed. Genotypes for the MYLIP rs9370867 (p.N342S, c.G1025A) polymorphism were detected by high resolution melting analysis. Results: No association of the MYLIP rs9370867 genotypes with lipid profile, hemodynamic data, and coronary angiographic data was found. Analysis stratified by hyperlipidemia, gender, and ethnicity was also performed and the sub-groups presented similar results. In both general population and patient samples, the MYLIP rs9370867 polymorphism was differently distributed according to ethnicity. In the general population, subjects carrying GG genotypes had higher systolic blood pressure (BP), diastolic BP, and mean BP values (129.0 +/- 23.3; 84.9 +/- 14.6; 99.5 +/- 16.8 mmHg) compared with subjects carrying AA genotypes (123.7 +/- 19.5; 81.6 +/- 11.8; 95.6 +/- 13.6 mmHg) (p = 0.01; p = 0.02; p = 0.01, respectively), even after adjustment for covariates. However, in analysis stratified by ethnicity, this finding was not found and there is no evidence that the polymorphism influences BP. Conclusion: Our findings indicate that association studies involving this MYLIP variant can present distinct results according to the studied population. In this moment, further studies are needed to reaffirm if the MYLIP p.N342S polymorphism is functional or not, and to identify other functional markers within this gene.

Serum C-reactive protein levels predict neurological outcome after aneurysmal subarachnoid hemorrhage

Objectives: Our aim was to evaluate the relationship between serum C-reactive protein (CRP) levels and the neurological prognosis and development of vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: Eighty-two adult patients with aSAH diagnoses were prospectively evaluated. Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, cranial CT scans, digital subtraction angiography studies and daily neurological examinations were recorded. Serial serum CRP measurements were obtained daily between admission and the tenth day. Glasgow Outcome Scale (GOS) and the modified Rankin Scale (mRS) were used to assess the prognosis. Results: Serum CRP levels were related to severity of aSAH. Patients with lower GCS scores and higher Hunt and Hess and Fisher grades presented statistically significant higher serum CRP levels. Patients with higher serum CRP levels had a less favorable prognosis. Conclusions: Increased serum CRP levels were strongly associated with worse clinical prognosis in this study.

Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy

Chronic kidney diseasemineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-?B ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy. (C) 2012 American Society for Bone and Mineral Research.