Publications by authors named "Aluízio Barbosa Carvalho"

42 Publications

Adynamic bone disease.

J Bras Nefrol 2021 3;43(4 Suppl 1):650-653. Epub 2021 Dec 3.

Universidade Federal de São Paulo, Department of Medicine, Nephrology Division, São Paulo, SP, Brazil.

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http://dx.doi.org/10.1590/2175-8239-JBN-2021-S108DOI Listing
December 2021

Control of hyperphosphatemia and maintenance of calcemia in CKD.

J Bras Nefrol 2021 3;43(4 Suppl 1):632-638. Epub 2021 Dec 3.

Universidade Federal de São Paulo, São Paulo, SP, Brazil.

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http://dx.doi.org/10.1590/2175-8239-JBN-2021-S105DOI Listing
December 2021

Diagnosis of bone abnormalities in CKD-MBD (Imaging and bone biopsy).

J Bras Nefrol 2021 3;43(4 Suppl 1):621-627. Epub 2021 Dec 3.

Universidade de São Paulo, Pathophysiology Laboratory (LIM-16), Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, SP, Brazil.

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http://dx.doi.org/10.1590/2175-8239-JBN-2021-S103DOI Listing
December 2021

Update of Brazilian Guidelines for Treatment and Assessment of Chronic Kidney Disease - Mineral and Bone Disorders.

J Bras Nefrol 2021 3;43(4 Suppl 1):613-614. Epub 2021 Dec 3.

Universidade Federal do Paraná, Faculty of Medicine, Department of Internal Medicine, Curitiba, PR, Brazil.

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http://dx.doi.org/10.1590/2175-8239-JBN-2021-S101DOI Listing
December 2021

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

J Bras Nefrol 2020 Jan;42(2):138-146

Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório para o Estudo do Distúrbio Mineral e Ósseo em Nefrologia, Campinas, SP, Brasil.

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.
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http://dx.doi.org/10.1590/2175-8239-JBN-2019-0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427645PMC
January 2020

Multiple extremity necrosis in fatal calciphylaxis: Case report.

J Bras Nefrol 2021 Apr-Jun;43(2):274-278

Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM), Departamento de Medicina, São Paulo, SP, Brasil.

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.
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http://dx.doi.org/10.1590/2175-8239-JBN-2020-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257280PMC
August 2021

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

J Bras Nefrol 2020 Jul-Sep;42(3):300-306

Universidade Federal de São Paulo, Departamento de Medicina, Programa de pós-graduação em Nefrologia, São Paulo, SP, Brasil.

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.
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http://dx.doi.org/10.1590/2175-8239-JBN-2019-0166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657048PMC
August 2021

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

PLoS One 2020 24;15(1):e0227870. Epub 2020 Jan 24.

Department of Internal Medicine, Division of Nephrology, Federal University of São Paulo, São Paulo, Brazil.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227870PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980492PMC
April 2020

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

J Bras Nefrol 2019 Aug 15;41(3):345-355. Epub 2019 Aug 15.

Universidade Federal de São Paulo, Disciplina de Nefrologia, São Paulo, SP, Brasil.

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.
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http://dx.doi.org/10.1590/2175-8239-jbn-2019-0009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788848PMC
August 2019

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

PLoS One 2019 23;14(7):e0219956. Epub 2019 Jul 23.

Department of Medicine, Division of Nephrology, Federal University of São Paulo, São Paulo, Brazil.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219956PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650050PMC
February 2020

There Is No Impact of Diabetes on the Endothelial Function of Chronic Kidney Disease Patients.

J Diabetes Res 2018 25;2018:7926473. Epub 2018 Nov 25.

Federal University of São Paulo, Brazil.

Background: Patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction, cardiovascular disease, and mortality. Several studies have separately analyzed endothelial function in these populations. However, data of patients with both CKD and DM are scarce. The aim of this study was to evaluate whether the presence of DM has any additional effect on the endothelial dysfunction of CKD patients.

Methods: We measured endothelial progenitor cells (EPCs), stromal-derived factor 1 alpha (SDF-1), serum and urinary nitric oxide (NO), flow-mediated dilation (FMD), and pulse wave velocity (PWV) in 37 CKD patients with DM (CKD-DM group) and in 37 without DM (CKD group).

Results: CKD-DM group had a higher prevalence of obesity ( < 0.01), previous myocardial infarction ( = 0.02), myocardial revascularization ( = 0.04), and a trend for more peripheral artery disease ( = 0.07). Additionally, CKD-DM group had higher EPC ( = 0.001) and PWV ( < 0.001) values. On the other hand, no difference in SDF-1 and serum or urinary NO and FMD was observed between the groups.

Conclusions: Endothelial dysfunction is frequent in CKD patients, and an additive effect of diabetes cannot be implicated, suggesting the predominant role of uremia in this condition.
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http://dx.doi.org/10.1155/2018/7926473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286770PMC
April 2019

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

PLoS One 2018 21;13(2):e0191009. Epub 2018 Feb 21.

Nephrology Division, Federal University of Sao Paulo, São Paulo, Brazil.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191009PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821310PMC
March 2018

The shift from high to low turnover bone disease after parathyroidectomy is associated with the progression of vascular calcification in hemodialysis patients: A 12-month follow-up study.

PLoS One 2017 6;12(4):e0174811. Epub 2017 Apr 6.

Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil.

Parathyroidectomy (PTX) may cause low levels of PTH, leading to an excessive reduction of bone turnover, which is associated with poor outcomes in dialysis patients, including vascular calcification (VC). We aimed to prospectively investigate the impact of PTX on bone remodeling and its potential consequence on the progression of VC in hemodialysis patients. In this prospective study, 19 hemodialysis patients with severe secondary hyperparathyroidism (sHPT) were evaluated. All patients underwent laboratorial tests and coronary tomography at baseline and, 6 and 12 months after PTX; bone biopsy was performed at baseline and 12-month. At baseline, all patients had increased PTH levels up to 2500 pg/mL and high turnover bone disease in their bone biopsies. Fourteen (74%) patients had VC. During the follow-up, there was a significant decrease of PTH at 6 and 12-month. At 12-month, 90% of the patients evolved to low turnover bone disease. During the period of the hungry bone syndrome (first 6 months), no change of coronary calcium score was observed. However, calcium score increased significantly thereafter (12th month). There was an association between VC progression and the severity of low turnover bone disease. In conclusion, the shift from high to low turnover bone disease after PTX occurs in parallel to VC progression, contributing to the understanding of the complex pathophysiology involving mineral metabolism and cardiovascular disease in hemodialysis patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174811PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383047PMC
September 2017

Parathyroid responsiveness during hypocalcemia after total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism.

J Bras Nefrol 2016 Jun;38(2):183-90

Universidade Federal de São Paulo, Brazil.

Introduction: Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD). Total parathyroidectomy (PTX) with parathyroid tissue autotransplantation (AT) is a treatment option in those individuals that do not respond to clinical management.

Objective: To evaluate grafted parathyroid tissue response during induced hypocalcemia among CKD patients who underwent total PTX with AT.

Methods: Eighteen patients with renal hyperparathyroidism were submitted to total PTX with parathyroid AT selected by stereomicroscopy between April and October 2008. Eleven (eight with successful kidney transplantation, 2 in peritoneal dialysis and 1 in hemodialysis) were clinically stable and eligible for testing. Hypocalcemia was induced using sodium bicarbonate infusion in 5 healthy controls and in patients 6-12 months after surgery.

Results: Among controls, hypocalcemia elicited a major rise in intact PTH (iPTH) levels 4 minutes after bicarbonate infusion. In patients, a significant decrease in ionized calcium concentration was observed [from 1.17 ± 0.12 to 1.09 ± 0.11 mean (± SE) mmol/L] in the 4th minute (p < 0.001) illustrating the nadir point. In the 10thminute, ionized calcium did not show a statistical increase compared to the 4th minute (p = 0.451). The iPTH levels ranged from 34.8 ± 18.6 to 34.1 ± 18.8 pg/mL (similar values between base line and 4thminute p = 0.087) and did not change in the 10th minute (33.3 ± 19,6 pg/ mL p = 0.693).

Conclusion: Among CKD patients tested 6-12 months after surgery, grafted parathyroid tissue revealed a blunted secretory capacity during bicarbonate induced hypocalcemia with no changes in iPTH levels.
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http://dx.doi.org/10.5935/0101-2800.20160027DOI Listing
June 2016

Effect of Statins on the Progression of Coronary Calcification in Kidney Transplant Recipients.

PLoS One 2016 21;11(4):e0151797. Epub 2016 Apr 21.

Nephrology Division, Federal University of São Paulo, São Paulo, SP, Brazil.

Background: Coronary calcification (CAC) is highly prevalent in kidney transplant recipients (KTRs) and has been associated with cardiovascular morbidity and mortality. Some studies have shown a reduction in CAC progression with statin therapy in the general and chronic kidney disease (CKD) populations.

Objectives And Methods: The aim of the present study was to evaluate the effect of statins on CAC progression in incident kidney transplant recipients. Patients were randomly assigned to the statin (n = 61, 10 mg daily) and control group (n = 59). CAC and biochemical analyses were performed at baseline and 12 months.

Results: At baseline, CAC was observed in 30% and 21% of patients in the statin and control groups, respectively (p = 0.39). The calcium score at baseline and its absolute and relative changes over 12 months of follow up were similar among the groups. In the statin group, total cholesterol (p < 0.001), low density lipoprotein cholesterol (p < 0.001) and triglycerides (p = 0.005) decreased, and the estimated glomerular function rate increased (p<0.001) significantly. CRP levels remained stable (p = 0.52) in the statin group but increased in the control group (p = 0.01). In the multivariate model, there was no difference in CAC progression between the groups (group effect p = 0.034; time-effect p = 0.23; interaction p = 0.74). Similar results were obtained when only patients with ≥ 10AU calcium score (calcified) were analyzed (group effect p = 0.051; time-effect p = 0.58; interaction p = 0.99).

Conclusion: Although statins reduce the levels of cholesterol, triglycerides, inflammation and improve graft function, the dose adopted in the current study did not delay CAC progression within 12 months of follow up.

Trial Registration: Brazilian Clinical Trials Registry RBR-32RFMB.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151797PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839705PMC
August 2016

Overweight and body fat are predictors of hypovitaminosis D in renal transplant patients.

Clin Kidney J 2015 Feb 17;8(1):49-53. Epub 2014 Nov 17.

Nephrology Division , Universidade Federal de São Paulo , São Paulo , Brazil.

Background: Hypovitaminosis D has been frequently reported after renal transplantation, but the impact of obesity and other factors in the reduction of vitamin D levels is not well established. We aimed to evaluate risk factors contributing to hypovitaminosis D among nondiabetic renal transplant recipients (RTR) with serum creatinine <2.0 mg/dL, at least 6 months after transplantation.

Methods: One hundred RTR were subjected to anthropometric evaluation and body composition assessment through bioelectrical impedance analysis; blood samples were drawn for biochemical and hormonal determinations and clinical data were retrieved from the medical records.

Results: Hypovitaminosis D was observed in 65% and overweight (body mass index, BMI >25 kg/m(2)) in 59% of cases with a significant median weight gain after transplantation of 5.1 kg. An inadequate distribution of body fat was evidenced in 50% of males and in 58% of females. Patients with either vitamin D deficiency or insufficiency presented significantly higher median values of body fat and weight gain since transplantation, as well as lower lean mass compared with patients with normal vitamin D levels (P < 0.001). Moreover, median values of waist circumference, BMI, serum leptin and parathyroid hormone levels were significantly higher in the group with vitamin D deficiency. A multivariate linear regression analysis then revealed that body fat and leptin levels, but not skin color, gender, age, glucocorticoid use, renal function, microalbuminuria and other confounding factors, were independently associated with low levels of 25 hydroxyvitamin D3 even after adjustments for seasonal variations.

Conclusion: In conclusion, the present study showed body fat and serum leptin levels to be the only independent risk factors for hypovitaminosis D among RTR.
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http://dx.doi.org/10.1093/ckj/sfu120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310423PMC
February 2015

Brazilian Registry of Bone Biopsy (REBRABO): design, data elements and methodology.

J Bras Nefrol 2014 Jul-Sep;36(3):352-9

Universidade de São Paulo.

Introduction: Mineral bone disorder (MBD) is a common condition in chronic kidney disease (CKD) patients and causes significant morbidity and mortality. Data involving prevalence of alterations in bone histological patterns, impact of different treatments and its repercussion in outcomes, such as bone fractures, hospitalization, cardiovascular disease and mortality, are scarce. Data bank registry can be a valuable tool to understand epidemiological aspects of MBD CKD. The Brazilian Registry of Bone Biopsy (REBRABO) will be a national registry, coordinating by the Brazilian Society of Nephrology - Committee of MBD-CKD.

Objective: To describe REBRABO's design, elements of data and methodology.

Methods: Will be an online national observational and multicentric data registry divided in two phases (retrospective, 1st phase) and prospective (2nd phase), including information from bone tissue histomorphometric analysis and demographics, clinical and laboratorial data from CKD-MBD patients.

Results: The REBRABO's first phase will explore data on demographics, clinical, laboratorial and bone histomorphometric analysis data from January/1986 to December/2013. The first RESULTS are expected in early 2015.

Conclusion: Studies in the field of CKD-MBD are needed, particularly those analyzing its prevalence, associations between demographic, clinical, histological parameters, and major outcomes. The REBRABO will be a unique retrospective and prospective research platform including bone biopsy data in CKD-MBD patients.
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http://dx.doi.org/10.5935/0101-2800.20140050DOI Listing
October 2016

Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients.

J Bras Nefrol 2014 Jul-Sep;36(3):289-96

Federal University of São Paulo.

Introduction: Experimental studies have suggested that indoxyl sulfate (IS), a protein-bound uremic toxin, may be involved in the development of renal osteodystrophy.

Objective: evaluate the association between IS levels and biochemical parameters related to mineral metabolism and bone histomorphometry in a cohort of pre-dialysis chronic kidney disease (CKD) patients.

Methods: This is a post-hoc analysis of an observational study evaluating the association between coronary calcification and bone biopsy findings in 49 patients (age: 52 ± 10 years; 67% male; estimated glomerular filtration rate: 36 ± 17 ml/min). Serum levels of IS were measured.

Results: Patients at CKD stages 2 and 3 presented remarkably low bone formation rate. Patients at CKD stages 4 and 5 presented significantly higher osteoid volume, osteoblast and osteoclast surface, bone fibrosis volume and bone formation rate and a lower mineralization lag time than CKD stage 2 and 3 patients. We observed a positive association between IS levels on one hand and the bone formation rate, osteoid volume, osteoblast surface and bone fibrosis volume on the other. Multivariate regression models confirmed that the associations between IS levels and osteoblast surface and bone fibrosis volume were both independent of demographic and biochemical characteristics of the study population. A similar trend was observed for the bone formation rate.

Conclusion: Our findings demonstrated that IS is positively associated with bone formation rate in pre-dialysis CKD patients.
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http://dx.doi.org/10.5935/0101-2800.20140042DOI Listing
October 2016

Autotransplant tissue selection criteria with or without stereomicroscopy in parathyroidectomy for treatment of renal hyperparathyroidism.

Braz J Otorhinolaryngol 2014 Jul-Aug;80(4):318-24. Epub 2014 Jun 11.

Department of Endocrinology and Metabology, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil.

Introduction: Several methods have been proposed to improve operative success in renal hyperparathyroidism.

Objective: To evaluate stereomicroscopy in parathyroid tissue selection for total parathyroidectomy with autotransplantation in secondary (SHPT)/tertiary (THPT) hyperparathyroidism.

Methods: 118 renal patients underwent surgery from April of 2000 to October 2009. They were divided into two groups: G1, 66 patients operated from April of 2000 to May of 2005, with tissue selection based on macroscopic observation; G2, 52 patients operated from March of 2008 to October 2009 with stereomicroscopy for tissue selection searching for the presence of adipose cells. All surgeries were performed by the same surgeon. Patients presented SHPT (dialysis treatment) or THPT (renal-grafted). Follow-up was 12-36 months. Intra-operative parathyroid hormone (PTH) was measured in 100/118 (84.7%) patients.

Results: Data are presented as means. G1 included 66 patients (38 SHPT, 24 females/14 males; 40.0 years of age; 28 THPT, 14 females/14 males; 44 years of age). G2 included 52 patients (29 SHPT, 11 females/18 males; 50.7 years of age; 23 THPT, 13 females/10 males, 44.4 years of age). SHPT patients from G2 presented preoperative serum calcium higher than those of SHPT patients in G1 (p<0.05), suggesting a more severe disease. Definitive hypoparathyroidism was found in seven of 118 patients (5.9%). Graft-dependent recurrence occurred in four patients, two in each group. All occurred in dialysis patients.

Conclusion: Stereomicroscopy in SHPT/THPT surgical treatment may be a useful tool to standardize parathyroid tissue selection.
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http://dx.doi.org/10.1016/j.bjorl.2014.05.012DOI Listing
January 2015

Expression of fibroblast growth factor 23, vitamin D receptor, and sclerostin in bone tissue from hypercalciuric stone formers.

Clin J Am Soc Nephrol 2014 Jul 24;9(7):1263-70. Epub 2014 Apr 24.

Nephrology Division, Federal University of São Paulo, São Paulo, Brazil; and

Background And Objectives: Increased bone resorption, low bone formation, and abnormal mineralization have been described in stone formers with idiopathic hypercalciuria. It has been previously shown that the receptor activator of NF-κB ligand mediates bone resorption in idiopathic hypercalciuria (IH). The present study aimed to determine the expression of fibroblast growth factor 23 (FGF-23), vitamin D receptor (VDR), and sclerostin in bone tissue from IH stone formers.

Design, Setting, Participants, & Measurements: Immunohistochemical analysis was performed in undecalcified bone samples previously obtained for histomorphometry from 30 transiliac bone biopsies of idiopathic hypercalciuria stone-forming patients between 1992 and 2002 and 33 healthy individuals (controls). Serum parameters were obtained from their medical records.

Results: Histomorphometry disclosed 21 IH patients with high and 9 IH patients with normal bone resorption. Importantly, eroded surfaces (ES/BS) from IH patients but not controls were significantly correlated with VDR immunostaining in osteoblasts (r=0.51; P=0.004), sclerostin immunostaining in osteocytes (r=0.41; P=0.02), and serum 1,25-dihydroxyvitamin D (r=0.55; P<0.01). Of note, both VDR and sclerostin immunostaining were significantly correlated with serum 1,25-dihydroxyvitamin D in IH patients (r=0.52; P=0.01 and r=0.53; P=0.02, respectively), although VDR and sclerostin expression did not differ between IH and controls. IH patients with high bone resorption exhibited a significantly stronger sclerostin immunostaining than IH patients with normal bone resorption. FGF-23 expression in osteocytes from IH patients did not differ from controls and was not correlated with any histomorphometric parameter.

Conclusions: These findings suggest the contribution of VDR and sclerostin, as well as 1,25-dihydroxyvitamin D, to increase bone resorption in idiopathic hypercalciuria but do not implicate FGF-23 in the bone alterations seen in these patients.
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http://dx.doi.org/10.2215/CJN.10030913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078962PMC
July 2014

Intraoperative PTH cutoff definition to predict successful parathyroidectomy in secondary and tertiary hyperparathyroidism.

Braz J Otorhinolaryngol 2013 Aug;79(4):494-9

Paulista School of Medicine, Federal University of São Paulo, SP, Brazil.

Unlabelled: In order to improve success rates in surgery of renal hyperparathyroidism, we evaluated intraoperative PTH (IOPTH) measurement utility.

Method: 86 patients underwent total parathyroidectomy with intramuscular presternal autotransplantation from 04/2000 to 10/2009 and were followed for 26.5 months on average (prospective cohort). Patients were divided in secondary (SHPT) and tertiary hyperparathyroidism (THPT). SHPT group was composed by patients under dialysis treatment, THPT group included renal grafted ones. IOPTH (Elecsys-PTH-Immunoassay/Roche) was measured at anesthesia induction (IOPTH-0') and 20 minutes (IOPTH-20') after parathyroidectomy.

Results: 80.2% (69/86) presented with 80% decrease or more in the IOPTH-20' and all were cured. In 11/86 patients (12.7%), a lower IOPTH-20' drop (70-79%) was observed, and 2 of them (18.1%) failed to cure. 6/86 (6.9%) patients presented IO-PTH-20' decrease of less than 70%: two were cured, in three a supernumerary/ectopic parathyroid was found and removed, and in one of these six patients, surgery was finished after 4-gland excision and the patient failure to cure.

Conclusion: IOPTH-20' decrease of 80% or more compared to IOPTH-0' predicts cure in all renal patients throughout follow-up. A decay of less than 70% points to missed or hyperfunctioning supernumerary gland and is predictive of surgical failure in 66.6%. A marginal IOPTH drop of 70-79% leaves the decision whether or not surgery should be continued up to the experienced surgeon.
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http://dx.doi.org/10.5935/1808-8694.20130088DOI Listing
August 2013

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

Clin Oral Implants Res 2014 Oct 8;25(10):1182-8. Epub 2013 Jul 8.

Pos-Graduate Program, Division of Plastic Surgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

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.
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http://dx.doi.org/10.1111/clr.12229DOI Listing
October 2014

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

J Bone Miner Metab 2013 Sep 21;31(5):551-5. Epub 2013 Mar 21.

Nephrology Division, Federal University of São Paulo, Rua Borges Lagoa, 960, São Paulo, SP, 04038-002, Brazil,

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 (β = 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.
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http://dx.doi.org/10.1007/s00774-013-0442-0DOI Listing
September 2013

Secondary hyperparathyroidism status in Brazil: Brazilian census of parathyroidectomy.

J Bras Nefrol 2011 Dec;33(4):457-62

Comitê de Distúrbio Mineral e Ósseo na Doença Renal Crônica, Sociedade Brasileira de Nefrologia, São Paulo, SP, Brasil.

Introduction: Secondary hyperparathyroidism (SHP) is a common and serious complication of chronic kidney disease (CKD), with a negative impact on morbidity and mortality. Despite advances in the clinical management of SHP, treatment failure still occurs in a significant number of patients. In such cases, parathyroidectomy (PTx) is indicated.

Objective: To have an overview of the prevalence of severe SHP and of its surgical treatment in hemodialysis (HD) patients in Brazil.

Methods: This was an observational and descriptive study. Data were obtained from questionnaires posted to 660 dialysis units (DU).

Results: Results are expressed in absolute values and percentages, or means and standard deviation, as appropriate. 226 (34%) DU answered the questionnaire, providing data about 32,264 HD patients. The prevalence rate of severe SHP (PTH > 1,000 pg/mL) was 10.7 % (n = 3,463). 68 hospitals countrywide perform PTX. Around 40% of them are university centers. 49 (21.7%) DU reported not to have a specialized medical center to refer their patients with severe SHP. 74 (33%) DU reported that the time interval between surgery indication and its performance was over 6 months. The main recognized obstacles to surgery performance were: difficulty to perform the preoperative exams, lack of head and neck surgeons and the long waiting time.

Conclusions: Although severe SHP is highly prevalent in Brazil, a significant number of patients do not have access to PTx. Better public health policies and liaison between nephrologists and head and neck surgeons are urgently required to change this reality.
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December 2011

[Management of hyperphosphatemia in CKD].

J Bras Nefrol 2011 Apr-Jun;33(2):191-6

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December 2011
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