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

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.

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

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.

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

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.

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

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.

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.

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.

Increased resting energy expenditure in hemodialysis patients with severe hyperparathyroidism.

Several metabolic derangements, including enhanced protein catabolism, have been suggested to be associated with increased circulating parathyroid hormone (PTH) in patients with secondary hyperparathyroidism (HPT). Such conditions, therefore, might lead to an increase in energy expenditure. The present study examined by indirect calorimetry the resting energy expenditure (REE) of 15 hemodialysis patients who have severe HPT (PTH = 1457 +/- 676 pg/ml) and were pair-matched for age and gender to 15 hemodialysis patients with mild to moderate HPT (PTH = 247 +/- 196 pg/ml). Both groups were also pair-matched for age and gender to a group of 15 healthy adult subjects (control). In six patients from the severe HPT group submitted to total parathyroidectomy, REE was determined 6 mo after the surgery. The groups were not different regarding lean body mass (LBM) measured by bioelectric impedance, serum C-reactive protein, and bicarbonate. Thyroid-stimulating hormone was within the normal range in all groups. Nonadjusted REE was significantly higher in the severe HPT group (1674 +/- 337 kcal/d) compared with patients with mild to moderate HPT (1388 +/- 229 kcal/d; P < 0.05). Both groups did not differ from the control group (1468 +/- 323 kcal/d). When adjustment of REE for LBM was performed using the multiple regression analysis, patients with mild to moderate HPT and control subjects had significantly lower REE (-231 and -262 kcal, respectively) than that of the severe HPT group. Considering all patients together, nonadjusted REE correlated directly with LBM (r = 0.61; P < 0.01). PTH correlated strongly with LBM in the severe HPT group (r = -0.82; P < 0.01). In the multiple linear regression analysis, only LBM and PTH were independent determinants of REE (n = 30; R(2) = 0.47). REE decreased significantly in the six patients who were evaluated 6 mo after parathyroidectomy (from 1617 +/- 339 to 1226 +/- 253; P = 0.02). These results demonstrate that hemodialysis patients with severe HPT have increased REE that might be reduced after parathyroidectomy.