Effect of medium cut-off and high-flux hemodialysis membranes on blood pressure assessed by ambulatory blood pressure monitoring.

BACKGROUND: Hypertension is one of the most critical risk factors for cardiovascular disease, which is the leading cause of death in hemodialysis (HD) patients. Medium cut-off (MCO) membrane increases the clearance of medium molecules, which could improve blood pressure (BP) control. This study aimed to compare the effect of MCO and high-flux hemodialysis membranes on BP assessed by ambulatory blood pressure monitoring (ABPM). METHODS: This is a pre-established secondary analysis of a 28-week, randomized, open-label crossover clinical trial. Patients were randomized to HD with MCO or high-flux membranes over 12 weeks, followed by a 4-week washout period, and then switched to the alternate membrane treatment for 12 weeks. ABPM was started before the HD session and ended at least 24 h later in weeks 1, 12, 16, and 28. RESULTS: 32 patients, 59% male, with a mean age of 52.7 years, and 40% with unknown CKD etiology, were enrolled. The dialysis vintage was 8 years, and more than 70% of the patients had hypertension. Regarding 24-h BP control, morning diastolic BP showed an increase in the high-flux compared to stability in the MCO group (interaction effect, p = 0.039). The adjusted ANOVA models showed no significant difference in the morning BP levels between the groups. Considering only the period of the HD session, patients in the MCO, compared to those in the high-flux membrane group, showed greater BP stability during dialysis, characterized by smaller variation in the pre-post HD systolic and minimum systolic BP (treatment effect, p = 0.039, and p = 0.023, respectively). CONCLUSIONS: MCO membrane seems to have a beneficial effect on morning BP and favors better BP stability during HD sessions.

EFFECT OF HEMODIALYSIS WITH MEDIUM CUT-OFF vs. HIGH-FLUX MEMBRANES ON ENDOTHELIAL FUNCTION OF PATIENTS WITH CHRONIC KIDNEY DISEASE.

BACKGROUND: Endothelial dysfunction (ED) is considered a marker of vascular complications, especially in patients with end-stage kidney disease (ESKD). Inflammation and the uremic state contribute to ED in patients undergoing hemodialysis (HD). Recently, the medium cut-off (MCO) dialysis membrane has been proposed to efficiently remove inflammatory cytokines and large middle-sized uremic toxins, with the potential effect to improve endothelial function. This study aims to compare the effect of dialysis with MCO or high-flux membranes on the endothelial function of patients on chronic HD. METHODS: A prospective, randomized, crossover study in which 32 patients with ESKD were dialyzed for 12 weeks with each membrane, including a 4-week washout period between treatments. Endothelial function was assessed by flow-mediated dilation (FMD) using brachial artery ultrasound at weeks 1, 12, 16, and 28. RESULTS: The population consisted of 59% men, 52.7±13.4 years, 16% non-black, on HD for 8.8 (4.1-15.1) years, 72% with arteriovenous fistula. Hypertension was the most common etiology of CKD and 34% of patients had previous cardiovascular disease. Patients were grouped, regardless of treatment sequence, into MCO or high-flux groups, since no carry-over (p=0.634) or sequence (p=0.998) effects were observed in the FMD assessment. The ANOVA model with repeated measures showed no effects of treatment (p=0.426), time (p=0.972) or interaction (p=0.413) in the comparison of FMD, between the MCO and high flux groups. CONCLUSION: Dialysis performed with MCO, or high-flux membranes had no influence on endothelial function in patients undergoing HD. However, a trend towards increased FMD was observed with the use of the MCO membrane.

Bone density, microarchitecture and estimated strength in stone formers: a cross-sectional HR-pQCT study.

BACKGROUND: Low areal bone mineral density (BMD), increased fracture risk and altered bone remodeling have been described among stone formers (SFs), but the magnitude of these findings differs by age, sex, menopausal status and urinary calcium (uCa). This study aimed to investigate volumetric BMD (vBMD), bone microarchitecture and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in young SFs, irrespective of calciuria, further distinguishing trabecular from cortical compartments. METHODS: HR-pQCT/FEA was performed at the distal tibia (DT) and distal radius (DR) in 106 SFs (57 males and 49 premenopausal females; median age 37 years) and compared with 106 non-SFs (NSFs) retrieved from an existing database, matched for age, sex and body mass index (BMI). Biochemical/hormonal serum and urinary parameters were obtained from SFs. RESULTS: SFs exhibited significantly lower trabecular number (TbN) and higher trabecular separation (TbSp) than NSFs at both anatomical sites and lower cortical porosity in the DR. In a subgroup analysis separated by sex, female SFs presented significantly lower TbvBMD, relative bone volume fraction (BV/TV) and TbN and higher TbSp than NSFs at both sites, while male SFs showed significantly lower stiffness and failure load. Multivariate analysis showed TbN to be independently associated with sex and BMI at both sites and with uCa at the DR. CONCLUSIONS: The present findings suggest that bone disease represents an early event among SFs, associated at least in part with calcium excretion and mainly characterized by trabecular bone microarchitecture impairment, especially among women, but with reduced bone strength parameters in men.

Piezoelectric osteotomy for the placement of titanium implants in rabbits: histomorphometry study.

OBJECTIVE: To evaluate bone remodeling around dental implants inserted into recipient sites prepared using either the piezoelectric or the conventional drilling technique. MATERIAL AND METHODS: Twenty-four male New Zealand white rabbits (4 months, 2.70 kg) received dental implants (3.3 mm diameter and 6 mm length) on the medial surface of the tibia and were divided into 3 groups (n = 8). Group I was euthanized at 7 days; group II, at 14; and group III, at 28 days. Each animal received four implants, two in the right and two in the left tibia (96 implants were installed). Each tibia was operated by the same technique, and there are therefore neighbor's implants installed by different techniques. Histomorphometric parameters were used: the volume occupied by trabecular bone around the implants (BV/TV), media thickness, separation and number of trabeculae around the loops, and the contact area (interface) directly between the bone and implant (BIC). RESULTS: BV/TV was similar for both techniques (P = 0.291). Reduction in trabecular thickness was observed for both techniques (P < 0.05), but then returned to prior levels, with no significant difference between techniques (P = 0.217). Trabecular number increased from day 7 to day 14 (P < 0.001) and remained constant afterward for both techniques. No difference in BIC was observed between techniques on day 28 (P = 0.961). CONCLUSIONS: Piezoelectric osteotomy allowed bone formation for osseointegration of titanium implants, was not associated with bone necrosis, and provided results similar to those of the conventional technique. The piezoelectric technique can be considered a viable alternative in dental implantology.

Bone aluminum accumulation in the current era.

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Renal osteodystrophy and clinical outcomes: a prospective cohort study.

INTRODUCTION: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. METHODS: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. RESULTS: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. CONCLUSION: The incidence of clinical outcomes did not differ between the types of ROD.

Vertebral bone density by quantitative computed tomography mirrors bone structure histomorphometric parameters in hemodialysis patients.

Diagnosing low bone mass is of clinical importance for hemodialysis (HD) patients due to its association with fractures and cardiovascular disease. We investigated whether bone density obtained by quantitative computed tomography (QCT) is associated with the histologically determined bone volume and microarchitecture parameters in HD patients. Twenty-six HD patients were studied. Bone biopsy samples were obtained from the iliac crest and trabecular bone volume, thickness, number and separation were evaluated by histomorphometry. Vertebral trabecular bone density (VTBD) was evaluated by QCT. VTBD correlated positively with trabecular bone volume (r = 0.69, p < 0.001), trabecular thickness (r = 0.45, p = 0.022) and trabecular number (r = 0.62, p < 0.001), and negatively with trabecular separation (r = -0.50, p < 0.01). In the multiple linear regression analysis adjusting for age, gender and diabetes, VTBD remained associated with bone volume by histomorphometry (ß = 0.06; 95 % CI 0.02-0.11; p = 0.006; R² = 0.49). VTBD measured by QCT mirrored bone volume and microarchitecture parameters obtained by histomorphometry in HD patients.

Adipose Tissue Denervation Blunted the Decrease in Bone Formation Promoted by Obesity in Rats.

The impact of obesity upon bone metabolism is controversial since both beneficial or harmful effects have been reported. Bone remodeling is modulated by the central nervous system through cytokines, hormones and neuromodulators. The present study aimed to evaluate the effects evoked by bilateral retroperitoneal white adipose tissue (rWAT) denervation (Dnx) upon bone mineral metabolism and remodeling in an experimental model of obesity in rats. Male Wistar rats were fed during 18 weeks with high-fat diet (HFD) or standard diet (SD) as controls, and rWAT Dnx or Sham surgery was performed at the 14th week. Biochemical and hormonal parameters, bone histomorphometry, rWAT and hypothalamus protein and gene expression were analyzed. The HFD group presented decreased bone formation parameters, increased serum and bone leptin and FGF23, increased serum and hypothalamic neuropeptide Y (NPY) and decreased serum 1,25-dihydroxyvitamin D3 and PTH. After rWAT Dnx, bone markers and histomorphometry showed restoration of bone formation, and serum and hypothalamic NPY decreased, without alteration in leptin levels. The present study shows that the denervation of rWAT improved bone formation in obese rats mediated by a preferential reduction in neurohormonal actions of NPY, emphasizing the relevance of the adipose tissue-brain-bone axis in the control of bone metabolism in obesity.

Risk factors for hypovitaminosis D in nondialyzed chronic kidney disease patients.

BACKGROUND: Hypovitaminosis D is highly prevalent among patients with chronic kidney disease and has been associated with worse outcome even in the earlier stages of the disease. OBJECTIVE: This study aimed to investigate the risk factors for hypovitaminosis D in nondialyzed patients with chronic kidney disease. DESIGN: This cross-sectional study included 120 patients with chronic kidney disease at stages 2 to 5 (62% male, age: 55.4 ± 11.3 year, estimated glomerular filtration rate: 35.1 ± 15 mL/minute, body mass index [BMI]: 27.1 ± 5.2 kg/m(2), 31% diabetics). Serum 25-hydroxivitamin D [25(OH)D] was measured by chemiluminescence. Subjective global assessment, total body fat (dual-energy X-ray absorptiometry), visceral and subcutaneous abdominal fat (computed tomography), and several laboratory parameters were assessed. RESULTS: Insufficiency of 25(OH)D (15 to 30 ng/mL) was observed in 55% and deficiency (<15 ng/mL) in 20% of the patients. Patients with diabetes, BMI ≥30 kg/m(2), and who had the blood collection during the winter or spring had lower levels of 25(OH)D. Serum 25(OH)D correlated inversely with parathyroid hormone, proteinuria, insulin resistance, leptin, and subcutaneous abdominal fat. The risk factors for hypovitaminosis D were diabetes (odds ratio: 3.8; 95% CI: 1.2 to 11.7; P = .022) and BMI ≥30 kg/m(2) (odds ratio: 4.3; 95% CI: 1.2 to 15.3; P = .018). In the logistic regression analysis adjusting for gender, skin color, and season of the year, diabetes and BMI ≥30 kg/m(2) were independently associated with hypovitaminosis D. CONCLUSIONS: Diabetes and obesity were the risk factors for hypovitaminosis D in nondialyzed patients with chronic kidney disease. Effective interventional protocols of vitamin D supplementation taking into account these risk factors are warranted for this population.

Multiple extremity necrosis in fatal calciphylaxis: Case report.

INTRODUCTION: The clinical impact of vascular calcification is well established in the context of cardiovascular morbidity and mortality, but other clinical syndromes, such as calciphylaxis, although less frequent, have a significant impact on chronic kidney disease. METHODS: Case report of a 27-year-old woman, who had complained of bilateral pain in her toes for 3 days, with the presence of small necrotic areas in the referred sites. She had a history of type 1 diabetes (25 years ago), with chronic kidney disease, on peritoneal dialysis, in addition to rheumatoid arthritis. She was admitted to the hospital, which preceded the current condition, due to exacerbation of rheumatoid arthritis, evolving with intracardiac thrombus due to venous catheter complications, when she started using warfarin. Ischemia progressed to her feet, causing the need for bilateral amputations. Her chirodactyls were also affected. Thrombophilia, vasculitis, endocarditis or other embolic sources were investigated and discarded. Her pathology report evidenced skin necrosis and superficial soft parts with recent arterial thrombosis, and Monckeberg's medial calcification. We started treatment with bisphosphonate and sodium thiosulfate, conversion to hemodialysis and replacement of warfarin with unfractionated heparin. Despite all the therapy, the patient died after four months of evolution. DISCUSSION: Calciphylaxis is a rare microvasculature calcification syndrome that results in severe ischemic injuries. It has pathogenesis related to the mineral and bone disorder of chronic kidney disease combined with the imbalance between promoters and inhibitors of vascular calcification, with particular importance to vitamin K antagonism. CONCLUSION: The preventive strategy is fundamental, since the therapy is complex with poorly validated effectiveness.

Cbfa1 expression in vascular smooth muscle cells may be elevated by increased nitric oxide/iNOS.

INTRODUCTION: Vascular calcification is a common complication of chronic kidney disease. Osteoblast differentiation factor (Cbfa1) is present in histologic sections of arteries from patients with end-stage renal disease. Vascular smooth muscle cells (VSMC) can dedifferentiate to osteoblast-like cells, possibly by up-regulation of Cbfa1. There is evidence that the production of nitric oxide (NO) may have an important role in the regulation of osteoblast metabolism. The aim of this study is to evaluate whether increased NO/iNOS expression causes an increase in cbfa1 expression in VSMC. METHODS: VSMC were obtained from renal artery of Wistar male rats, treated for 72 hours with lipopolysaccharide (LPS), ß-glycerophosphate (BGF), a donor of phosphate and aminoguanidine (AG), an inhibitor of iNOS, in the following groups: CTL (control), LPS, BGF, LPS + BGF, and LPS + AG. NO synthesis was determined by chemiluminescence. Cbfa1 and iNOS mRNA expressions were analyzed by RT-PCR, Cbfa1 protein expression by immunohistochemistry and cellular viability by acridine orange. RESULTS: Cbfa1 and iNOS mRNA expressions were higher in LPS and LPS+ BGF vs CTL (p < 0.05), and they were lower in LPS+AG vs LPS (p < 0.05). The Cbfa1 in the groups LPS and LPS+BGF also resulted in a higher value compared to CTL (p < 0.05), and in LPS+AG it was lower compared to LPS (p < 0.05). NO was higher in LPS and LPS+BGF compared to CTL group (p < 0.05) and lower in LPS + AG compared to LPS group (p < 0.05). Cellular viability showed no statistical difference among groups. CONCLUSION: This study showed that increased NO/iNOS expression causes an increase in cbfa1 expression in VSMC.

Renal osteodystrophy and clinical outcomes: data from the Brazilian Registry of Bone Biopsies - REBRABO.

INTRODUCTION: Mineral and bone disorders (MBD) are major complications of chronic kidney disease (CKD)-related adverse outcomes. The Brazilian Registry of Bone Biopsy (REBRABO) is an electronic database that includes renal osteodystrophy (RO) data. We aimed to describe the epidemiological profile of RO in a sample of CKD-MBD Brazilian patients and understand its relationship with outcomes. METHODS: Between August 2015 and March 2018, 260 CKD-MBD stage 3-5D patients who underwent bone biopsy were followed for 12 to 30 months. Clinical-demographic, laboratory, and histological data were analyzed. Bone fractures, hospitalizations, and death were considered the primary outcomes. RESULTS: Osteitis fibrosa, mixed uremic osteodystrophy, adynamic bone disease, osteomalacia, osteoporosis, and aluminum (Al) accumulation were detected in 85, 43, 27, 10, 77, and 65 patients, respectively. The logistic regression showed that dialysis vintage was an independent predictor of osteoporosis (OR: 1.005; CI: 1.001-1.010; p = 0.01). The multivariate logistic regression revealed that hemodialysis treatment (OR: 11.24; CI: 1.227-100; p = 0.03), previous parathyroidectomy (OR: 4.97; CI: 1.422-17.241; p = 0.01), and female gender (OR: 2.88; CI: 1.080-7.679; p = 0.03) were independent predictors of Al accumulation; 115 patients were followed for 21 ± 5 months. There were 56 hospitalizations, 14 deaths, and 7 fractures during follow-up. The COX regression revealed that none of the variable related to the RO/turnover, mineralization and volume (TMV) classification was an independent predictor of the outcomes. CONCLUSION: Hospitalization or death was not influenced by the type of RO, Al accumulation, or TMV classification. An elevated prevalence of osteoporosis and Al accumulation was detected.

Clinical outcomes of incident peritoneal dialysis patients coming from kidney transplantation program: A case-control study.

INTRODUCTION: Brazil ranks second in the absolute number of transplantations in the world. Despite improvements in graft survival, many patients will progress to graft loss and return to dialysis. Concerns exist regarding adverse clinical outcomes in this population when undergone peritoneal dialysis (PD). OBJECTIVE: To compare the occurrence of mortality, technique failure, and peritonitis among incident patients in PD coming from either Tx or pre-dialysis treatment. METHODOLOGY: A retrospective study in which 47 adult patients with Tx failure (Tx group) were matched for age, gender, diabetes mellitus (DM), modality and start year of PD, with 1:1 predialysis patient (nTx group). The Fine-Gray competing risk model was used to analyze mortality and technique failure. RESULTS: Compared to nTx, the Tx group had a lower body mass index, serum potassium, and albumin concentrations. A higher ferritin level, transferrin saturation and the number of patients with positive serology for viral hepatitis were also observed in the Tx group. In the multivariate analysis, patients of the Tx group had 4.4-times higher risk of death (p = 0.007), with infection as the main cause. Technique failure and peritonitis were similar in both groups. CONCLUSION: Previous Tx is a risk factor for mortality but not for technique failure or peritonitis in incident patients on a PD program.

Bone aluminum accumulation in the current era / Acúmulo de alumínio no tecido ósseo na era atual

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Nos últimos anos, evidências do Registro Brasileiro de Biópsia óssea (REBRABO) apontaram uma alta incidência de intoxicação por alumínio (Al) no tecido ósseo de pacientes com DRC em diálise. Essa surpreendente informação parece representar não apenas um acúmulo passivo deste metal, visto que dados prospectivos do REBRABO sugerem que a presença de Al no tecido ósseo pode estar independentemente relacionada a eventos cardiovasculares adversos maiores. Essas informações contrastam com a percepção mundial do controle epidemiológico dessa condição. Neste artigo de opinião, discutimos por que o diagnóstico de acúmulo ósseo de Al não é relatado em outras partes do mundo, e também discutimos uma gama de possibilidades para entender por que nós acreditamos que o acúmulo de Al no tecido ósseo ainda ocorre, não como se apresentava no passado, ou seja, como uma síndrome com sinais e sintomas sistêmicos de intoxicação.

Associated factors related to chronic kidney disease progression in elderly patients.

BACKGROUND: Chronic Kidney Disease (CKD) is a worldwide public health problem. The prevalence of CKD is rising especially in elderly, as consequence of population-ageing related to socioeconomic development and better life expectancy. There are scarce studies evaluating CKD progression and its associated factors in elderly patients. METHODS: This is a retrospective observational study including 340 patients (≥ 65 years old) CKD stages 3a-5 non-dialysis, incidents in an outpatient CKD clinic, followed by 2.1 years. CKD progression was assessed by the slope of eGFR calculated by CKD-EPI and BIS 1 equations. The patients were divided in progressor and non-progressor groups (eGFR slope < or ≥ 0 mL/min/1.73 m2/year, respectively). RESULTS: Kidney function declined in 193 (57%) patients. In this group, the progression rate was -2.83 (-5.1 / -1.1) mL /min /1.73 m2 /year. Compared to non progressor, the progressor patients were younger [72 (69-78) vs. 76 (69-80) years; p = 0.02]; had higher proportion of diabetic nephropathy, higher serum phosphorus [3.8 (3.3-4.1) vs. 3.5 (3.9-4.1) mg/dL; p = 0.04] and proteinuria [0.10 (0-0.9 vs. 0 (0-0.3)] g/L; p = 0.007)] at the admission. In the logistic regression analysis adjusted for gender and eGFR, proteinuria was independently associated with CKD progression [OR (Odds Ratio) (1.83; 95% CI, 1.17-2.86; p < 0.01)]. CONCLUSION: CKD progression was observed in the majority of elderly CKD patients and proteinuria was the most important factor associated to the decline of kidney function in this population.

Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

Effect of spironolactone on the progression of coronary calcification in peritoneal dialysis patients: a pilot study.

INTRODUCTION: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. METHODS: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. RESULTS: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. CONCLUSION: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC.

Association of changes in bone remodeling and coronary calcification in hemodialysis patients: a prospective study.

BACKGROUND: Vascular calcification is common and constitutes a prognostic marker of mortality in the hemodialysis population. Derangements of mineral metabolism may influence its development. The aim of this study is to prospectively evaluate the association between bone remodeling disorders and progression of coronary artery calcification (CAC) in hemodialysis patients. STUDY DESIGN: Cohort study nested within a randomized controlled trial. SETTING & PARTICIPANTS: 64 stable hemodialysis patients. PREDICTOR: Bone-related laboratory parameters and bone histomorphometric characteristics at baseline and after 1 year of follow-up. OUTCOMES: Progression of CAC assessed by means of coronary multislice tomography at baseline and after 1 year of follow-up. Baseline calcification score of 30 Agatston units or greater was defined as calcification. Change in calcification score of 15% or greater was defined as progression. RESULTS: Of 64 patients, 38 (60%) of the patients had CAC and 26 (40%) did not [corrected]. Participants without CAC at baseline were younger (P < 0.001), mainly men (P = 0.03) and nonwhite (P = 0.003), and had lower serum osteoprotegerin levels (P = 0.003) and higher trabecular bone volume (P = 0.001). Age (P = 0.003; beta coefficient = 1.107; 95% confidence interval [CI], 1.036 to 1.183) and trabecular bone volume (P = 0.006; beta coefficient = 0.828; 95% CI, 0.723 to 0.948) were predictors for CAC development. Of 38 participants who had calcification at baseline, 26 (68%) had CAC progression in 1 year. Progressors had lower bone-specific alkaline phosphatase (P = 0.03) and deoxypyridinoline levels (P = 0.02) on follow-up, and low turnover was mainly diagnosed at the 12-month bone biopsy (P = 0.04). Low-turnover bone status at the 12-month bone biopsy was the only independent predictor for CAC progression (P = 0.04; beta coefficient = 4.5; 95% CI, 1.04 to 19.39). According to bone histological examination, nonprogressors with initially high turnover (n = 5) subsequently had decreased bone formation rate (P = 0.03), and those initially with low turnover (n = 7) subsequently had increased bone formation rate (P = 0.003) and osteoid volume (P = 0.001). LIMITATIONS: Relatively small population, absence of patients with severe hyperparathyroidism, short observational period. CONCLUSIONS: Lower trabecular bone volume was associated with CAC development, whereas improvement in bone turnover was associated with lower CAC progression in patients with high- and low-turnover bone disorders. Because CAC is implicated in cardiovascular mortality, bone derangements may constitute a modifiable mortality risk factor in hemodialysis patients.

Phosphate binder impact on bone remodeling and coronary calcification--results from the BRiC study.

BACKGROUND AND AIMS: Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients. This is a prospective study that compares the effects of calcium acetate and sevelamer on coronary calcification (CAC) and bone histology. METHODS: 101 hemodialysis patients were randomized for each phosphate binder and submitted to multislice coronary tomographies and bone biopsies at entry and 12 months. RESULTS: The 71 patients who concluded the study had similar baseline characteristics. On follow-up, the sevelamer group had higher levels of intact parathyroid hormone (498 +/- 352 vs. 326 +/- 236 pg/ml, p = 0.017), bone alkaline phosphatase (38 +/- 24 vs. 28 +/- 15 U/l, p = 0.03) and deoxypyridinoline (135 +/- 107 vs. 89 +/- 71 nmol/l, p = 0.03) and lower LDL cholesterol (74 +/- 21 vs. 91 +/- 28 mg/dl, p = 0.015). Phosphorus (5.8 +/- 1.0 vs. 6 +/- 1.0 mg/dl, p = 0.47) and calcium (1.27 +/- 0.07 vs. 1.23 +/- 0.08 mmol/l, p = 0.68) levels did not differ between groups. CAC progression (35 vs. 24%, p = 0.94) and bone histological diagnosis at baseline and 12 months were similar in both groups. Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption (eroded surface, ES/BS = 9.0 +/- 5.9 vs. 13.1 +/- 9.5%, p = 0.05), whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate (BFR/BS = 0.015 +/- 0.016 vs. 0.062 +/- 0.078, p = 0.003 for calcium and 0.017 +/- 0.016 vs. 0.071 +/- 0.084 microm(3)/microm(2)/day, p = 0.010 for sevelamer). CONCLUSIONS: There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups.

Is there relationship between epicardial fat and cardiovascular parameters in incident kidney transplant patients? A post-hoc analysis.

BACKGROUND: Epicardial fat (EF) has been related to increased cardiovascular risk in chronic kidney disease patients. Kidney transplantation is associated with weight gain, especially within the first 12 months. Recently an association between EF and left ventricular mass (LVM) has been suggested in kidney transplant (KTX) recipients. OBJECTIVE: Evaluate the EF in KTX recipients and its association with cardiovascular parameters in a 12-month follow-up study. METHODS: EF volume was determined using thoracic computed tomography. The EF progressor group (EF gain) was defined by any increment in EF after 12 months. LVM and LVM index were calculated by echocardiography. RESULTS: Ninety-eight incident KTX patients [57% men, 41.2 ± 10.1 years, mean dialysis time prior to transplant of 24 (11-60) months] were analyzed. At baseline and after 12 months, EF was 318.6 (275.2-392.6) ml and 329.5 (271.7-384.8) ml, respectively (p = 0.03). When compared to patients who EF decreased (n = 33), those with EF gain (n = 65) had a greater increase of body mass index, abdominal circumference and blood glucose. These patients also had a lower reduction of LVM index. However in the multivariate analysis, there was no difference in LVM index change between groups (interaction p = 0.565), even after adjustment for hypertension, glucose and coronary calcium score (interaction p = 0.538). CONCLUSION: The impact of EF gain on ventricular mass after KTX could not be definitely confirmed. Further prospective studies in a large sample of KTX patients should be considered to address a possible causal relationship between EF gain and cardiac hypertrophy in this population.