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.

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.

Coronary calcification in hemodialysis patients: the contribution of traditional and uremia-related risk factors.

BACKGROUND: Coronary artery calcification is a common feature of atherosclerosis, occurring in 90% of angiographically significant lesions. There is recent evidence that coronary artery calcification is frequent in hemodialysis patients and it has been suggested that this increased incidence may be associated to uremia-related factors. The development and progression of coronary artery calcification is similar to osteogenesis. The aim of this study was to evaluate the relationship between coronary artery calcification, uremia-related factors, and bone histomorphometry in hemodialysis patients. METHODS: A total of 101 hemodialysis patients were assessed for biochemical markers of inflammation, oxidative stress, and bone metabolism. Subsequently, they were submitted to multislice coronary tomography (MSCT) and transiliac bone biopsy. RESULTS: The median calcium score was 116.2 (range 0 to 5547). Fifty-two percent of the patients showed moderate and severe coronary artery calcification, 20% had calcium scores greater than 1000. In univariate analysis, age (r= 0.57, P < 0.000001), osteoprotegerin (OPG) (r= 0.44, P= 0.00002), and body mass index (BMI) (r= 0.24, P= 0.01) correlated positively with calcium score. Bone trabecular volume and trabecular thickness correlated negatively with calcium score (r=-0.24, P= 0.02; r=-0.22, P= 0.03). There was a correlation of borderline significance between calcium score and C-reactive protein (CRP) (r= 0.18, P= 0.062). The multiple linear regression analysis identified OPG as the only variable independently associated with coronary artery calcification. CONCLUSION: Coronary artery calcification is highly prevalent in the hemodialysis population and is associated with older age, higher BMI, inflammation and reduced trabecular bone volume. Higher OPG is independently associated with coronary artery calcification and may represent an incomplete self-defensive response to the progression of atherosclerosis in hemodialysis patients.

Avaliação da histologia óssea e cardiovascular em ratos urêmicos paratireoidectomizados submetidos à dieta rica e pobre em fósforo associado à infusão de paratôrmonio / Adverse effects of hyperphosphatemia on myocardial hypertrophy, renal function and bone in rats with renal failure

A hiperfosfatemia (HP) contribui para a patogênese da doença cardiovascular e da osteodistrofia renal. Avaliamos o efeito da HP na histologia cardiovascular, na função renal e no tecido ósseo em uremia experimental. Ratos Wistar foram submetidos a PTx e Nx com reposição contínua de paratormônio ou eram sham operados. Apenas o conteúdo de fósforo era diferente nas dietas. O peso do coração corrigido para o peso do animal e a creatinina foram maior no grupo PTx+Nx+HP que nos demais grupos. A histologia não evidenciou calcificação vascular ou fibrose. / Hyperphosphatemia (HP) contributes to cardiovascular disease and renal osteodystrophy. We evaluated the effect of HP on cardiovascular system, renal function and bone in experimental uremia. Wistar rats were submitted to PTx and Nx with rat parathormone replacement, or were sham-operated. Only phosphorus content differentiated diets. Heart weight normalized to body weight and creatinine levels were higher in PTx+Nx+HP rats than in any other group. We detected no cardiovascular calcification or fibrosis...

Incidência de infecçäo hospitalar em um hospital universitário / Incidence of hospital infection in a university hospital

Utilizando-se das informaçöes contidas nos prontuários médicos dos pacientes que se encontravam internados no Hospital Professor Edgard Santos da Universidade Federal da Bahia, no período de 16/05/85 a 13/06/85, descreveram-se entre outros indicadores a incidência da infecçäo hospitalar total e específica por enfermaria de ocorrência e pelo tempo de permanência. A taxa encontrada foi de 5,13 por 1000 pacientes-dia, sendo que as enfermarias de Oftalmologia, Pediatria e Doenças Infecciosas e Parasitárias foram as que apresentaram maior risco. As infecçöes do aparelho respiratório e aparelho urinário apresentaram-se com maior freqüência. Verificou-se também que o risco do paciente apresentar infecçäo hospitalar aumentou na medida em que também aumentava o seu tempo médio de permanência no hospital, exceto para aqueles que ficaram internados por mais de 30 dias