Survival in hemodialysis in Brazil according to the source of payment for the treatment: Public Healthcare System (SUS) versus private insurance / Sobrevida na hemodiálise no Brasil de acordo com a fonte pagadora do tratamento: Sistema Único de Saúde versus convênio privado

ABSTRACT Introduction: Brazil has the largest public and universal healthcare system in the world, but little is known about the outcomes of patients on hemodialysis (HD) in the country according to the source of funding for the treatment. Objective: To compare the profile and survival of patients under HD treatment funded by the Public Healthcare System (SUS) to those with private insurance. Methods: Retrospective analysis of adults undergoing HD between 2012 and 2017 in 21 dialysis centers in Brazil that provided both by the SUS and private health insurance. Participants, regardless of the paying source, received similar dialysis treatment. Data were censored after 60 months of follow-up or at the end of 2019. Results: 4,945 patients were included, 59.7% of which were financed by the SUS. Patients financed by SUS, compared to those with private insurance, were younger (58 vs. 60 years; p < 0.0001) and with a lower prevalence of diabetes (35.8% vs. 40.9%; p < 0.0001). The 60-month survival rates in these groups were 51.1% and 52.1%, respectively (p = 0.85). In the analysis of the subdistribution proportional hazard ratio by the Fine-Gray model, including adjustment for concurrent outcomes, a significant increase in the risk ratio for death was found (1.22 [95% confidence interval 1.04 to 1.43]) in patients with treatment funded by the SUS. Conclusions: Patients on HD with treatment funded by the SUS have a higher adjusted risk of death when compared to those with private insurance, despite similar dialysis treatment. Factors not directly related to dialysis therapy could explain this difference.

Resumo Introdução: O Brasil possui o maior sistema público e universal de saúde do mundo, mas pouco se sabe sobre os desfechos dos pacientes em hemodiálise (HD) no país de acordo com a fonte de financiamento do tratamento. Objetivo: Comparar o perfil e a sobrevida dos pacientes que têm o tratamento de HD custeado pelo Sistema Único de Saúde (SUS) com aqueles com convênio privado. Métodos: Análise retrospectiva dos adultos incidentes em HD entre 2012 e 2017 em 21 centros de diálise no Brasil que atendiam tanto pelo SUS quanto por convênios privados. Os participantes, independentemente da fonte pagadora, receberam tratamento dialítico semelhante. Os dados foram censurados com 60 meses de acompanhamento ou ao final de 2019. Resultados: Foram incluídos 4945 pacientes, sendo 59,7% financiados pelo SUS. Os pacientes financiados pelo SUS, em comparação aos que tinham convênio privado, eram mais jovens (58 vs 60 anos; p < 0,0001) e com menor prevalência de diabetes (35,8% vs 40,9%; p < 0,0001). As taxas de sobrevida, em 60 meses nesses grupos foram de 51,1% e 52,1%, respectivamente (p = 0,85). Na análise da razão de risco proporcional de subdistribuição pelo modelo de Fine-Gray, incluindo ajuste para desfechos concorrentes, foi encontrado um aumento significativo na razão de risco para morte (1,22 [intervalo de confiança de 95% 1,04 a 1,43]) nos pacientes com tratamento custeado pelo SUS. Conclusões: Pacientes em HD com tratamento custeado pelo SUS têm um risco ajustado de morte mais elevado do que aqueles com convênio privado, apesar do tratamento dialítico semelhante. Fatores não relacionados diretamente à terapia dialítica poderiam justificar esta diferença.

Bone mass measurement by DXA should be interpreted with caution in the CKD population with vascular calcification.

BACKGROUND: KDIGO guidelines suggest the use of dual-energy X-ray absorptiometry (DXA) to assess bone mineral density (BMD) in patients with CKD 3a-5D. Previous studies have demonstrated an association between trabecular bone mass loss and coronary artery calcification (CAC) progression. This study aimed to prospectively investigate the relationship between BMD changes, quantified by DXA, and CAC progression in the non-dialyzed CKD population. METHODS: In this post hoc study, BMD by DXA was measured at the lumbar spine and total hip at baseline and 12-months. Patients were categorized according to BMD changes into 3 different groups: LOSS, UNCHANGED and GAIN. CAC quantification was obtained by multislice computed tomography at baseline and 12-months. RESULTS: 87 patients (55.6 ± 10.7 years, 62% males, 30% diabetic, eGFR = 39.2 ± 18.1 mL/min/1.73m2) were enrolled. CAC was found in 41 (47%) of the patients at baseline and CAC progression in 25 (64%) of them. Considering the lumbar spine and total hip BMD changes together, 24%, 48%, and 25% of the patients were in the LOSS, UNCHANGED and GAIN groups, respectively. Compared to the UNCHANGED or LOSS groups, the GAIN group had an increase in calcium score (p = 0.04) and a higher proportion of patients with CAC progression (p = 0.01). In the logistic regression analysis, CAC progression was 4.5 times more likely to be in the GAIN group. CONCLUSIONS: The association between the increase in BMD values and the progression of vascular calcification was the result of two concomitant processes overlapping, leading to a misinterpretation of DXA results. Thus, the use of DXA for the evaluation of bone mass, especially at the lumbar spine, must be applied with restraint and its results very carefully interpreted in CKD patients.

Cortical bone density by quantitative computed tomography mirrors disorders of bone structure in bone biopsy of non-dialysis CKD patients.

Bone biopsy is still the gold standard tool to evaluate either trabecular or cortical bone, though the quantitative computed tomography of the vertebrae (QCT), a non-invasive technique, could be useful to evaluate bone structure in patients with chronic kidney disease (CKD). Cortical bone microstructure derangements have been associated with poor outcomes in the general population. An association between trabecular bone density, assessed by QCT, and bone volume and microarchitecture by histomorphometry, has been previously documented. This relationship has not yet been fully evaluated in cortical bone in the CKD scenario. The aim of this study was to evaluate the relationship among vertebrae density measured by QCT, structural histomorphometric parameters of cortical bone and biochemical and hormonal data in 50 CKD stage 2-5ND patients. This was a post hoc analysis of a cross-sectional study where cortical porosity and cortical thickness were analyzed in undecalcified bone samples from the iliac crest. The cortical bone density was obtained by QCT from the thoracic vertebrae. The patients were 52 ± 10 years, 68% men, 30% diabetes and the estimated glomerular filtration rate 34 ± 16 mL/min/1.73 m2. Cortical porosity was 4.6% (3.6; 6.6) and cortical thickness was 578.4 ± 151.8 µm, while cortical bone density was 149.2 ± 58.3 HU. Cortical density correlated with cortical thickness (p = 0.001) but not with cortical porosity (p = 0.30). Higher porosity was associated with older age (p = 0.02), higher levels of PTH (p = 0.04) and lower renal function (p = 0.03), while smaller thickness was associated with higher levels of PTH (p = 0.02). Lower density was associated with older age (p = 0.02) and higher levels of PTH (p = 0.01). In conclusion, cortical bone density measured by QCT was able to mirror the cortical thickness of bone biopsy in pre-dialysis CKD patients. In addition, PTH action on cortical bone can be already seen in this population.

The pitfall of treating low bone turnover: Effects on cortical porosity.

Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46±13years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)] and correlated with PTH (p=0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p=0.015) and the delta of PTH (p=0.03); it was also higher among non-white patients than in white patients (p=0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r(2)=0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.

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.

A hipoalbuminemia parece estar associada a uma maior taxa de hospitalização nos pacientes em hemodiálise / Hypoalbuminemia seems to be associated with a higher rate of hospitalization in hemodialysis patients

Resumo Introdução: Anemia, inflamação e hipoalbuminemia são complicações frequentemente observadas em pacientes submetidos à hemodiálise crônica. Existem poucos dados nacionais que avaliam a associação dessas condições à morbidade e mortalidade especialmente considerando a região nordeste do país onde a ocorrência de anemia e desnutrição é elevada. Objetivo: O objetivo desse estudo foi avaliar o impacto da presença da anemia, inflamação e hipoalbuminemia sobre os desfechos clínicos (óbito e hospitalização) de pacientes sob hemodiálise. Método: Trata-se de um estudo de coorte prospectivo observacional com pacientes pre avaliados 221 pacientes adultos, considerando-se os valores de hemoglobina, proteína C reativa (PCR), albumina sérica no início do estudo. A ocorrência de hospitalização e óbito foi computada em um seguimento aproximado de 13 meses. Resultados: A ocorrência de hospitalização e óbito não diferiu entre os grupos com e sem anemia (Hb ≤ 10g/dL) ou inflamação (PCR ≥ 0,5mg/dL). Houve um maior número de hospitalização entre os pacientes com hipoalbuminemia. A albumina não apresentou correlação com os níveis séricos de PCR. Observou-se um menor tempo livre de hospitalização entre os pacientes com hipoalbuminemia (p = 0,008), houve uma tendência de menor tempo livre de hospitalização entre os pacientes com PCR aumentado (p = 0,08), e a anemia não se relacionou com o tempo livre de hospitalização. Não houve diferença na sobrevida em relação à presença de anemia, inflamação e hipoalbuminemia. A análise de regressão de Cox apontou a hipoalbuminemia como fator independente relacionado à hospitalização, mesmo após ajustes para idade, presença de diabetes, PCR e hemoglobina. Conclusão: A hipoalbuminemia, e não anemia ou inflamação, mostrou-se um marcador independente de hospitalização em pacientes submetidos à hemodiálise.

Abstract Introduction: Anemia, inflammation and hypoalbuminemia are frequent disorders among patients underwent hemodialysis. There are few national data, particularly from Northeast region where anemia and malnourished were common findings, analyzing the association between these conditions and clinical outcomes. Objective: The aim of this study was to evaluate the impact of the presence of anemia, inflammation and hypoalbuminemia on clinical outcomes (death and hospitalization) of hemodialysis patients. Methods: In this prospective observational study 221 adult patients were evaluated, considering the presence of anemia (hemoglobin ≤ 10 g/dL), inflammation (C-reactive protein (CRP) ≥ 0,5 mg/dL) and hypoalbuminemia (albumin < 3,8 g/ dL) at baseline. Clinical outcomes were recorded over 13 months. Results: The occurrence of hospitalization and death did not differ between the groups with and without anemia or inflammation. Patients with hypoalbuminemia had more hospitalizations, and the presence of hypoalbuminemia was associated with shorter hospitalization event-free time (p = 0.008). There was a trend of shorter hospitalization event-free time among patients with increased PCR (p = 0.08). There was no correlation between albumin and CRP levels. The presence of anemia, inflammation and hypoalbuminemia were not associated with lower survival. Adjusting for confounders, hypoalbuminemia was a predictor of hospitalization in hemodialyzed patients. Conclusion: The presence of hypoalbuminemia, but not anemia or inflammation, was able to predict hospitalization in hemodialysis patients.

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.

Effect of rosuvastatin and sevelamer on the progression of coronary artery calcification in chronic kidney disease: a pilot study.

INTRODUCTION: Coronary artery calcification (CAC) is highly prevalent among chronic kidney disease (CKD) patients and its strong association with mortality has been recognized early in the course of CKD. The aim of the present study was to test the effect of rosuvastatin and sevelamer hydrochloride on the progression of CAC in nondialyzed CKD patients. METHODS: An open-label, randomized and controlled pilot study was conducted including 117 CKD patients (62% men, 56.9 ± 11.2 years, eGFR 36 ± 16.5 ml/min). Patients were randomly assigned to rosuvastatin (n = 38; 10 mg/day), to sevelamer hydrochloride (n = 38; 2,400 mg/day) and to control (n = 41) groups. CAC (by multislice computed tomography) and biochemical analyses were performed at baseline and after 24 months. RESULTS: At baseline, CAC was observed in 55%, 58% and 61% of patients in the rosuvastatin, sevelamer hydrochloride and control groups, respectively (p = 0.87). Calcium score at baseline as well as its absolute and relative changes during 24 months were similar among the groups. Low density lipoprotein cholesterol (LDL-c) was higher and decreased significantly in the rosuvastatin group (p < 0.01). The analysis adjusting for LDL-c showed that the drug regimens were not associated with the progression of CAC (drug effect p = 0.85; time-effect p < 0.001; interaction p = 0.76). CONCLUSIONS: Treatment with rosuvastatin and sevelamer hydrochloride may not delay the progression of CAC in non-dialysis dependent CKD patients.

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

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

Is coronary artery calcification associated with vertebral bone density in nondialyzed chronic kidney disease patients?

BACKGROUND AND OBJECTIVES: Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventy-two nondialyzed CKD patients (age 52 ± 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 ± 18.2 ml/min per 1.73 m(2)) were studied. VBD and CAC were quantified by computed tomography. RESULTS: CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score ≥ 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 ± 52 Hounsfield units) correlated inversely with age (r = -0.41, P < 0.001) and calcium score (r = -0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC. CONCLUSIONS: Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD.

Ventricular arrhythmia in incident kidney transplant recipients: prevalence and associated factors.

Cardiovascular mortality in kidney transplant recipients has shown to be substantially elevated particularly in the first year of transplantation. Complex ventricular arrhythmia (VA) has been pointed as one of the etiologies of sudden death. The aim of this study was to evaluate the prevalence of VA and to investigate the factors associated with their occurrence in incident kidney transplant recipients. A total of 100 incident kidney transplant recipients were included in the study (39.7 ± 10.1 years, 55% male, 43.6 ± 10.1 days of transplantation, 66% living donors). All the patients underwent 24 h electrocardiogram, echocardiogram and multi-slice computed tomography. Thirty percent of the patients had VA. Left ventricular hypertrophy was observed in 57% of the patients while heart failure was found in 5%. Coronary artery calcification (CAC) was observed in 26 patients, from which 31% had severe calcification. The group of patients with VA was predominantly male, had been on dialysis therapy for a longer time and had more coronary calcification. In the multiple logistic regression analysis, male gender and CAC score were independently associated with the presence of VA. In conclusion, kidney transplant recipients exhibited a high prevalence of VA and the factors associated with its occurrence were the male gender and the presence of CAC.

Coronary calcification is associated with lower bone formation rate in CKD patients not yet in dialysis treatment.

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4-2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone-formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p = .009; odd ratio (OR) = 0.15; 95% confidence interval (CI) 0.036-0.619]. This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone-formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients.

Impact of cardiovascular calcification in nondialyzed patients after 24 months of follow-up.

BACKGROUND AND OBJECTIVES: Coronary artery calcification (CAC) is highly prevalent among patients with chronic kidney disease (CKD), and it has been described as a strong predictor of mortality in the dialysis population. Because there is a lack of information regarding cardiovascular calcification and clinical outcomes in the earlier stages of the disease, we aimed to evaluate the impact of CAC on cardiovascular events, hospitalization, and mortality in nondialyzed patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a prospective study including 117 nondialyzed patients with CKD (age, 57 +/- 11.2 years; 61% male; 23% diabetics; creatinine clearance, 36.6 +/- 17.8 ml/min per 1.73 m(2)). CAC was quantified by multislice computed tomography. The occurrence of cardiovascular events, hospitalization, and death was recorded over 24 months. RESULTS: CAC >10 Agatston units (AU) was observed in 48% of the patients [334 (108 to 858.5) AU; median (interquartiles)], and calcification score >or=400 AU was found in 21% [873 (436-2500) AU]. During the follow-up, the occurrence of 15 cardiovascular events, 19 hospitalizations, and 4 deaths was registered. The presence of CAC >10 AU was associated with shorter hospitalization event-free time and lower survival. CAC >or=400 AU was additionally associated with shorter cardiovascular event-free time. Adjusting for age and diabetes, CAC >or=400 AU was independently associated with the occurrence of hospitalization and cardiovascular events. CONCLUSIONS: Cardiovascular events, hospitalization, and mortality were associated with the presence of CAC in nondialyzed patients with CKD. Severe CAC was a predictor of cardiovascular events and hospitalization in these patients.

Serum ferritin level remains a reliable marker of bone marrow iron stores evaluated by histomorphometry in hemodialysis patients.

BACKGROUND AND OBJECTIVES: As well as being a marker of body iron stores, serum ferritin (sFerritin) has also been shown to be a marker of inflammation in hemodialysis (HD) patients. The aim of this study was to analyze whether sFerritin is a reliable marker of the iron stores present in bone marrow of HD patients. DESIGN: Histomorphometric analysis of stored transiliac bone biopsies was used to assess iron stores by determining the number of iron-stained cells per square millimeter of bone marrow. RESULTS: In 96 patients, the laboratory parameters were hemoglobin = 11.3 +/- 1.6 g/dl, hematocrit = 34.3 +/- 5%, sFerritin = 609 +/- 305 ng/ml, transferrin saturation = 32.7 +/- 22.5%, and C-reactive protein (CRP) = 0.9 +/- 1.4 mg/dl. sFerritin correlated significantly with CRP, bone marrow iron, and time on HD treatment (P = 0.006, 0.001, and 0.048, respectively). The independent determinants of sFerritin were CRP (beta-coef = 0.26; 95% CI = 24.6 to 132.3) and bone marrow iron (beta-coef = 0.32; 95% CI = 0.54 to 2.09). Bone marrow iron was higher in patients with sFerritin >500 ng/ml than in those with sFerritin < or =500 ng/ml. In the group of patients with sFerritin < or =500 ng/ml, the independent determinant of sFerritin was bone marrow iron (beta-coef = 0.48, 95% CI = 0.48 to 1.78), but in the group of patients with sFerritin >500 ng/ml, no independent determinant of sFerritin was found. CONCLUSIONS: sFerritin adequately reflects iron stores in bone marrow of HD patients.

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.

The progression and impact of vascular calcification in peritoneal dialysis patients.

BACKGROUND: Progression of coronary artery calcification (CAC) has been described in hemodialysis patients, and severe CAC has been associated with the occurrence of cardiovascular events in this population. Little information is available regarding peritoneal patients. AIM: To prospectively evaluate peritoneal dialysis patients in order to identify the variables associated with the rate of CAC progression, as well as to determine the impact that baseline CAC has on clinical outcomes over a 1-year follow-up period. METHODS: Using multislice coronary tomography, calcium scores were estimated at baseline and after 12 months in 49 peritoneal dialysis patients. Patients with and without CAC progression were compared with respect to clinical characteristics and biochemical variables, including lipid profile, parameters of mineral metabolism, and markers of inflammation. Cardiovascular events, hospitalizations, and all-cause mortality were recorded. RESULTS: At baseline, 29 patients (59%) presented CAC and a median calcium score of 234.7 (range 10.3-2351) Agatston units. Progression of CAC was observed in 13 patients (43%) who, in comparison with those presenting no CAC progression, were older, presented higher baseline calcium scores, and had higher mean glucose levels, lower mean high density lipoprotein cholesterol levels, and more months using low calcium peritoneal solution. We also observed a trend toward more often presenting with a history of hypertension, exhibiting more hyperphosphatemic and hyperglycemic events, and having lower albumin levels. In multiple logistic regression, only baseline calcium score was independently associated with progression of CAC. A shorter cardiovascular event-free time and a trend toward lower survival rates were observed in the group with CAC. Hospitalization event-free time did not differ between the groups. CONCLUSION: Determining CAC provides important prognostic data in peritoneal dialysis patients. Baseline calcium score and disturbances in glucose, mineral, and lipid metabolism were indicative of higher risk of CAC progression in this population.

The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among end-stage renal disease patients. There is evidence that coronary calcification is a marker of atherosclerotic vascular disease and is predictive of cardiovascular events, especially in patients on renal replacement therapy. It has recently been suggested that CHD begins in the pre-dialysis period. However, data regarding coronary calcification in this population is scarce. This study was aimed at evaluating such coronary calcification and identifying related factors. METHODS: A total of 96 chronic kidney disease out-patients who were not on dialysis were included. Patients presenting neoplastic, infectious or inflammatory diseases were excluded. Demographic characteristics, clinical profiles, laboratory test results and multislice computed tomography scans were evaluated. RESULTS: The median age was 55 years (range 20-69 years), 67% were men and the median creatinine clearance was 37 ml/min/1.73 m(2). Coronary calcification, defined as a coronary artery calcification score (CACS) >0 Agatston units (AU), was seen in 61 patients (median 89.1 AU, range 0.37-2299.3 AU). On average, these patients were older, more often had diabetes, higher body mass indices and higher Framingham risk indices, as well as presenting higher proteinuria, intact parathyroid hormone (iPTH), blood glucose and triglyceride levels compared with those without calcification. Multiple logistic regression analysis, adjusted for age and diabetes, identified iPTH and triglyceride levels as independent determinants of calcification. Severe calcification (CACS >400 AU) was seen in 22 patients, who were also older and more frequently had a history of cardiovascular disease (CVD), as well as having higher levels of phosphorus, blood glucose and soluble Fas (sFas). Multiple logistic regression analysis, adjusted for age and diabetes, identified phosphorus and sFas levels as independent determinants of severe coronary calcification. CONCLUSION: Coronary calcification is highly prevalent in pre-dialysis patients and correlates with traditional and non-traditional risk factors for CVD.