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.

The association between coronary artery calcification progression and loss of bone density in non-dialyzed CKD patients.

BACKGROUND: Coronary artery calcification (CAC) and low bone density are coexisting deleterious conditions commonly shared by chronic kidney disease (CKD) patients. In the present study, we aimed to investigate whether the progression of CAC was associated with overtime reduction in bone density in non-dialyzed CKD patients. METHODS: This is a prospective study of 24 months including 72 non-dialyzed CKD patients Stages 2 - 4 (age 57.6 ± 10.3 years, 62% male, 22% diabetics). CAC and vertebral bone density (VBD) were measured by computed tomography. RESULTS: At baseline, 46% of the patients had CAC (calcified group) and calcification was not identified in 54% of the patients (non-calcified group). The calcified group was older, predominantly male, and had lower VBD in comparison to non-calcified group. CAC progression was observed only in the calcified group (91% of the patients increased calcium score). The multiple regression analysis revealed loss of VBD as the independent determinant of CAC progression in these patients. CONCLUSIONS: CAC progression was associated with loss of VBD in non-dialyzed CKD patients.

Are prediction equations reliable for estimating resting energy expenditure in chronic kidney disease patients?

BACKGROUND: The determination of resting energy expenditure (REE) is the primary step for estimating the energy requirement of an individual. Although numerous equations have been formulated for predicting metabolic rates, there is a lack of studies addressing the reliability of those equations in chronic kidney disease (CKD). Thus, the aim of this study was to evaluate whether the main equations developed for estimating REE can be reliably applied for CKD patients. METHODS: A total of 281 CKD patients (124 non-dialysis, 99 haemodialysis and 58 peritoneal dialysis) and 81 healthy control individuals were recruited. Indirect calorimetry and blood sample collection were performed after a 12-h fasting. Two most traditionally used equations for estimating REE were chosen for comparison with the REE measured by indirect calorimetry: (i) the equation proposed by Harris and Benedict, and (ii) the equation proposed by Schofield that is currently recommended by the FAO/WHO/UNU. RESULTS: Schofield's equation exhibited higher REE [1492±220 kcal/day (mean±SD)] in relation to Harris and Benedict's equation (1431±214 kcal/day; P<0.001), and both prediction equations showed higher REE in comparison with the reference indirect calorimetry (1352±252 kcal/day; P<0.001). In patients with diabetes, inflammation or severe hyperparathyroidism, the REE estimated by the Harris and Benedict equation was equivalent to that measured by indirect calorimetry. The intraclass correlation of the REE measured by indirect calorimetry with the Schofield's equation was r=0.48 (P<0.001) and with the Harris and Benedict's equation was r=0.58 (P<0.001). According to the Bland and Altman analysis, there was a large limit of agreement between both prediction equations and the reference method. Acceptable prediction of REE (90-110% adequacy) was found in 47% of the patients by using the Harris and Benedict's equation and in only 37% by using the Schofield's equation. CONCLUSIONS: The most traditionally used prediction equations overestimated the REE of CKD patients, and the errors were minimized in the presence of comorbidities. There is a need to develop population-specific equations in order to adequately estimate the energy requirement of these patients.

Prospective evaluation of waist circumference and visceral adipose tissue in patients with chronic kidney disease.

BACKGROUND: Waist circumference (WC), a simple anthropometric measure, is associated with visceral adipose tissue (VAT) in cross-sectional studies, and thus has been used as a surrogate marker for VAT. However, associations between changes over time in WC and VAT have not been studied in chronic kidney disease (CKD) patients. METHODS: This prospective study included 87 nondialysis-dependent CKD patients (54 males, 56.2 +/- 10.4 years, BMI 27.3 +/- 5.1, GFR 35.9 +/- 14.6 ml/min/1.73 m(2)). VAT area was measured by computed tomography (CT) and WC was measured at the umbilicus level at baseline and after 12 months. RESULTS: Changes in WC correlated significantly but weakly with changes in VAT (r = 0.26, p = 0.016), likely due to a substantially smaller change in WC compared to changes in VAT. This was also reflected by a kappa coefficient of 0.26, i.e. indicative of poor agreement between WC and CT measurements in regards to quantification of changes in VAT. Likewise, the receiver operating characteristic curve analysis identified WC as poor predictor of changes in VAT (area under the curve = 0.62). CONCLUSION: Anthropometric measurement of WC is poorly correlated with changes in VAT measured by CT in nondialysis-dependent CKD patients. Therefore, caution should be taken when using WC as a surrogate marker of VAT changes in this population.

Evaluation of depressive symptoms in patients with chronic renal failure.

BACKGROUND: Although depression is the most commonly found psychiatric disorder in patients on chronic dialysis, its prevalence in earlier stages of chronic kidney disease (CKD) is not established. This study aims to investigate the prevalence of depression in patients with different stages of CKD and the factors associated with depressive affect. METHODS: A total of 155 nondialytic patients with CKD on conservative therapy and 36 patients on hemodialysis treatment were studied. Depression was rated using the Beck Depression Inventory (BDI) and the Beck Depression Inventory-Short Form (BDI-SF). Functional capacity was evaluated using the Karnofsky Performance Scale, and clinical and sociodemographic variables were also investigated. RESULTS: Using the BDI, depression was identified in 37.7% of the patients on conservative treatment and in 41.7% of those on hemodialysis (p=NS, not significant). The percentage of patients on conservative therapy with moderate or severe depression was higher when the BDI was used, compared with the BDI-SF (37.7% vs. 12.3%, p<0.001). No association was observed between depression and the stages of kidney disease. Among patients with CKD, depression was more prevalent among females (17.9%), patients of low income (54.2%), patients of social class D or E (47.4%), those living with friends or relatives (41.2%) and patients with poor functional capacity (p<0.001). CONCLUSIONS: We observed a high prevalence of depression in patients with CKD, but no significant difference was found between the stages of the disease. Depression was associated with sociodemographic characteristics and functional capacity.

Intima-media thickness is associated with inflammation and traditional cardiovascular risk factors in non-dialysis-dependent patients with chronic kidney disease.

BACKGROUND: Mortality due to cardiovascular causes is high in chronic kidney disease (CKD). Intima-media thickness (IMT) and inflammation are early atherosclerosis markers, although data are lacking about their association in the CKD non-dialysis-dependent (CKD-NDD) population. The aim of the present study was to evaluate the association between IMT, inflammation and other cardiovascular risk factors in such patients. METHODS: CKD-NDD patients (n = 122) were subjected to measurements of carotid IMT and inflammatory marker levels in a cross-sectional study. RESULTS: Mean patient age was 55.2 +/- 11.3 years (61.5% males). Median C-reactive protein (CRP) was 0.28 mg/dl (0.03-14.2). The median interleukin (IL)-6 count was 4.75 pg/ml (0.7-243), the mean adiponectin was 27.8 +/- 7.3 ng/ml and the mean IMT was 0.61 +/- 0.19 mm. Four (3.3%) patients had IMT above the normal range. IMT was higher in males (p < 0.001), patients with estimated glomerular filtration rate <60 ml/min (p = 0.030), inflammation (p = 0.005) and higher IL-6 levels (p = 0.023). IMT was correlated with age (R = 0.538; p < 0.001), waist circumference (R = 0.235; p = 0.016), CRP (R = 0.191; p = 0.035) and systolic blood pressure (R = 0.181; p = 0.048). In a multiple regression analysis, the independent determinants of IMT were age (beta = 0.512; p < 0.001) and CRP levels (beta = 0.159; p = 0.041). CONCLUSION: The present study demonstrated that although the IMT values were within the normal range, there was a clear association of IMT with age, as well as with inflammation in an asymptomatic CKD-NDD population.

Waist circumference and visceral fat in CKD: a cross-sectional study.

BACKGROUND: In the general population, waist circumference was noted to be a reliable predictor of visceral fat. In addition, increased waist circumference was strongly associated with risk factors for cardiovascular disease. In patients with chronic kidney disease (CKD), the association of waist circumference with visceral fat was never tested. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 122 patients with CKD not yet on dialysis therapy (75 men; diabetes mellitus, 30%; age, 55.3 +/- 11.3 years; body mass index, 27.1 +/- 5.2 kg/m(2); estimated glomerular filtration rate, 35.4 +/- 15.2 mL/min/1.73 m(2)) were studied. PREDICTOR: Waist circumference. OUTCOMES & MEASUREMENTS: Anthropometry, abdominal visceral fat measured by means of computed tomography, and cardiovascular disease risk factors. RESULTS: Waist circumference strongly correlated with visceral fat (r = 0.75 for men, r = 0.81 for women; P < 0.01). kappa Statistic was 0.56, indicating relatively good agreement between methods. Body mass index showed a lower correlation coefficient (r = 0.68 for men, r = 0.76 for women; P < 0.01) and poor agreement (0.36) with visceral fat in comparison to waist circumference. In men, waist circumference and visceral fat similarly correlated with high-density lipoprotein cholesterol level, triacylglycerol level, and Homeostasis Model Assessment Index (P < 0.05). In women, waist circumference correlated with age, C-reactive protein level, and Homeostasis Model Assessment Index, whereas visceral fat also correlated with low-density lipoprotein cholesterol and triacylglycerol levels (P < 0.05). LIMITATIONS: Findings are restricted to patients with CKD not yet on dialysis therapy from a single center. CONCLUSIONS: Waist circumference was strongly associated with visceral fat in patients with CKD. Associations between waist circumference and cardiovascular disease risk factors were similar to those observed for visceral fat, particularly in men. These findings suggest that waist circumference may be a simple and inexpensive tool to be used in epidemiological studies.

Hepatitis C among predialysis patients: prevalence and characteristics in a large cohort of patients.

BACKGROUND: The factors associated with hepatitis C virus (HCV) infection in predialysis patients need to be better investigated. The aims of this study were to evaluate the prevalence, risk factors, clinical, biochemical and virological characteristics of chronic HCV infection in predialysis patients. METHODS: Anti-HCV antibodies were determined in a large cohort of predialysis patients. Epidemiological and laboratorial characteristics of HCV infection were evaluated in predialysis patients and this group was matched to a control group consisting of predialysis patients without viral infection (1:3) and compared in terms of risk factors and alanine aminotransferase (ALT) levels. Logistic regression analysis was applied to identify variables independently associated with chronic HCV infection. RESULTS: A total of 1,041 patients (61% males) with a mean age of 61 +/- 15 years and mean creatinine clearance of 36 +/- 18 ml/min were included. Forty-one (3.9%) patients were anti-HCV positive and, of these, 39 (95%) presented viremia. Predialysis patients with HCV more frequently showed a history of blood transfusion before 1992 (66.7 vs. 10.3%; p < 0.001) and major surgeries (53.8 vs. 17.1%; p < 0.001), a higher proportion of undetermined etiology of kidney disease (43.6 vs. 17.1%; p = 0.001), and higher ALT levels (1.3 vs. 0.4 xULN; p < 0.001). History of blood transfusion before 1992 (p < 0.001; OR: 19), intravenous drug abuse (p = 0.002; OR: 69) and ALT levels (p < 0.001; OR: 50) were the variables that were independently associated with chronic HCV infection. The accuracy of ALT in detecting HCV infection was 92%. The most prevalent HCV genotype was 1b (48.7%) and 56.5% of patients presented high HCV viral load. CONCLUSION: Chronic HCV infection among predialysis patients is related to increased parenteral exposure. Elevated ALT levels suggest the need for HCV screening as part of the predialysis care since ALT seems to be a good marker of this infection.

Vitamin D status of chronic kidney disease patients living in a sunny country.

BACKGROUND: Vitamin D nutritional status has been poorly investigated in chronic kidney disease (CKD) patients, especially those inhabiting a subtropical area where the sunlight incidence is abundant all year. OBJECTIVE: The purpose of this study was to evaluate the status of vitamin D and to analyze the relationship of circulating 25-hydroxyvitamin D [25(OH)D] with other serum parameters of mineral metabolism in patients with CKD not yet on dialysis. DESIGN: This cross-sectional study enrolled 144 nondiabetic CKD patients not yet receiving dialysis (stages 2 to 5 of CKD). Fasting blood samples were obtained for measurements of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone, phosphorus, and calcium. RESULTS: In the entire sample, the serum concentration of 25(OH) was 34.3 +/- 18.3 ng/mL (+/-SD unless otherwise noted). A deficiency of vitamin D, i.e., 25(OH)D <15 ng/mL, was found in only one patient. Fifty-seven patients (39.6%) were considered vitamin D-insufficient (16 to 30 ng/mL). The vitamin D-insufficient group contained more females, a higher degree of proteinuria, and a lower serum concentration of 1,25(OH)(2)D. In multiple regression analysis, 25(OH)D was associated positively with 1,25(OH)(2)D, serum calcium, and proteinuria, whereas 1,25(OH)(2)D was associated only with 25(OH)D and phosphorus. The variables associated with intact parathormone were serum phosphorus and creatinine clearance, but not 1,25(OH)(2)D or 25(OH)D. CONCLUSION: Despite an elevated prevalence of vitamin D insufficiency, the serum concentration of 25(OH)D was, on average, higher than that found in patients inhabiting higher-latitude regions. This higher serum concentration may have contributed to the differences found in the relationship between vitamin D metabolites and other serum markers of mineral metabolism in our CKD patients.

Hepatitis C in chronic kidney disease: predialysis patients present more severe histological liver injury than hemodialysis patients?

BACKGROUND: The characteristics of hepatitis C virus (HCV) infection in predialysis patients are poorly understood and they could be different from hemodialysis patients. AIMS: To evaluate the demographics, laboratory and histological characteristics of chronic HCV infection in predialysis patients and to compare them with those observed in hemodialysis patients. METHODS: Thirty-nine predialysis patients with chronic HCV infection were compared to HCV-infected hemodialysis patients (ratio of 1:3) in terms of demographics, laboratory and histological characteristics. The fibrosis progression rate (FPR) was calculated as the ratio between fibrosis stage and duration of infection. RESULTS: Predialysis patients were older (57 +/- 10 vs. 45 +/- 12 years; p < 0.001), presented a higher proportion of elevated alanine aminotransferase (71.8 vs. 41.0%; p = 0.001) and aspartate aminotransferase (64.1 vs. 26.5%; p < 0.001), a higher proportion of interface hepatitis (66.7 vs. 47%; p = 0.033) and more advanced fibrosis (71.8 vs. 16.2%; p = 0.001). Among patients with estimated duration of infection, predialysis patients presented a longer duration of infection (22 vs. 6 years; p < 0.001) and no difference in FPR was observed between groups (p = 0.692). CONCLUSION: Although predialysis patients with HCV infection present more severe histological injury than hemodialysis patients, this finding probably reflects a longer duration of infection with no evidence supporting that hepatitis C presents a more aggressive course in this group.

Impact of dialyzer membrane on apoptosis and function of polymorphonuclear cells and cytokine synthesis by peripheral blood mononuclear cells in hemodialysis patients.

In an in vivo crossover trial, we compared a cellulosic with a synthetic dialyzer with respect to polymorphonuclear cells (PMN) function and apoptosis, cytokine serum levels and synthesis by peripheral blood mononuclear cells (PBMC), and complement activation. Twenty hemodialysis (HD) patients were assigned in alternate order to HD with cellulose acetate (CA) or polysulfone (PS) dialyzer. After 2 weeks, patients were crossed over to the second dialyzer and treated for another 2 weeks. Apoptosis was assessed by flow cytometry in freshly isolated PMN. Phagocytosis and production of peroxide by PMN were studied by flow cytometry in whole blood. PBMC were isolated from blood samples and incubated for 24 h with or without lipopolysaccharide (LPS). There was no impact of dialyzer biocompatibility on PMN apoptosis and function, cytokine synthesis by PBMC or on their serum levels, serum levels of C3a, and terminal complement complex (TCC). Nevertheless, after HD, serum levels of complement correlated negatively with PMN phagocytosis and peroxide production, and positively with PMN apoptosis and cytokine production by PBMC. Although the results did not show a dialyzer advantage on the immunologic parameters, complement activation may have modulated cell function and apoptosis after HD.

Variant of adynamic bone disease in hemodialysis patients: fact or fiction?

BACKGROUND: Adynamic bone disease is a type of renal osteodystrophy characterized by low bone turnover and paucity of bone cells. It was proposed that a new type of this disease featuring high osteoclastic resorption without parathyroid hormone stimulus and designated adynamic bone disease variant occurs in hemodialysis patients. The present study is designed to evaluate the frequency and characteristics of both diseases in a large series of bone biopsy specimens. METHODS: We reviewed 1,160 bone biopsy specimens from hemodialysis patients. Specimens in which adynamic bone disease was diagnosed were selected and categorized as classic or variant based on osteoclastic surface. RESULTS: In 218 bone biopsy specimens (18.8%), adynamic bone disease was identified, whereas the variant form was identified in 35 specimens (38.8%). Biopsy specimens categorized as the variant form were from patients who were younger and had greater phosphorus and parathyroid hormone levels. Histologically, the variant form presented greater osteoid volume, fibrosis volume, osteoid surface, osteoblast surface, and eroded surface. Similarly, values for all dynamic parameters were greater in the variant group. Osteoclastic surface correlated with phosphorus level, parathyroid hormone level, and osteoblast surface. Age and osteoblast surface were identified as independent determinants of the variant form. CONCLUSION: Adynamic bone disease variant seems to occur in younger hemodialysis patients with greater levels of parathyroid hormone, which acts on cell-covered bone surfaces. It probably is a transitional phase from low- to high-turnover status, rather than a true entity within the spectrum of renal osteodystrophy.

Inflammation is associated with increased energy expenditure in patients with chronic kidney disease.

BACKGROUND: Inflammation, a clinical condition observed in patients with chronic kidney disease (CKD), may be related to increased resting energy expenditure (REE). OBJECTIVES: The main objective was to investigate the relation between inflammation and REE in patients with CKD who are not undergoing dialysis. We also aimed to analyze whether a decrease in C-reactive protein (CRP) would result in a reduction in REE. DESIGN: This study enrolled 132 patients with CKD who were not undergoing dialysis, who had creatinine clearance from 5 to 65 mL.min(-1).1.73 m(-2), and who were 53.6 +/- 16 y old; 82 (62.1%) were men. Twenty-nine patients had clinical signs of infection. REE was measured by using indirect calorimetry, and inflammation was evaluated by using high-sensitivity CRP measurement. Patients were divided according to tertiles of CRP with the following intertertile ranges: first tertile, CRP < or = 0.14 mg/dL (n = 43); second tertile, CRP 0.15-0.59 mg/dL (n = 46); and third tertile, CRP > or = 0.60 mg/dL (n = 43). REE was measured before and after treatment in 10 patients who had inflammation or infection. RESULTS: After adjustment for age, sex, and lean body mass, the REE of the third (1395 kcal/d; P = 0.02) and second (1355 kcal/d; P = 0.04) tertiles was significantly higher than that of the first tertile (1286 kcal/d). In the multiple linear regression analysis (n = 132), the independent determinants of REE were lean body mass, CRP, and age (R2 = 0.55). After treatment of infection in a subgroup of 10 patients, it was observed that a significant reduction in CRP concentration was accompanied by a significant reduction of 174 +/- 165 kcal that accounted for 13% of the initial REE. CONCLUSION: This study showed that inflammation is associated with increased REE in patients with CKD.

Histologic evolution of bone disease 6 months after successful kidney transplantation.

BACKGROUND: The histologic patterns of bone disease, as well as the evolution of renal osteodystrophy after kidney transplantation (Tx), are not well defined. Information in this regard is scarce and contradictory. METHODS: Before and 6 months after Tx, analysis of biochemical, hormonal, and bone histomorphometric parameters were performed. Twenty patients (14 men and 6 women) entered the study. Median age was 36.5 (range, 20 to 55) years, and median time on dialysis was 22 (9 to 88) months. RESULTS: Bone histomorphometric diagnoses at pre-Tx were adynamic bone disease, 12; mixed bone disease, 3; mild disease, 3; and osteitis fibrosa, 2. After Tx, 11 had adynamic bone disease; 8, mild disease; and 1, osteomalacia. As a whole, dynamic parameters improved significantly in patients who had adynamic bone. Five of the 12 with this diagnosis completely recovered their bone turnover. Pre-Tx hyperparathyroidism bone features improved or resolved, but 5 of the 8 patients had low-turnover bone disease (adynamic disease, 4; osteomalacia, 1). Three of them had persistence of aluminum and/or iron deposits on bone surface, and the other 2 had hypophosphatemia and high intact parathyroid hormone levels. Overall, biochemical parameters tended toward normalization. Serum intact parathyroid hormone before Tx was correlated negatively with post-Tx trabecular thickness. CONCLUSION: Six months after Tx, bone histology remained abnormal. The high turnover bone disease improved in all cases, but in most of them low turnover bone disease emerged. Nearly half of the cases with pre-Tx adynamic bone disease recovered their bone turnover completely with some improvement observed in the majority of the remaining cases.

Pericardial fat is associated with coronary artery calcification in non-dialysis dependent chronic kidney disease patients.

Pericardial fat (PF) a component of visceral adipose tissue has been consistently related to coronary atherosclerosis in the general population. This study evaluated the association between PF and coronary artery calcification (CAC) in non-dialysis dependent chronic kidney disease (CKD) patients. This is a post-hoc cross sectional analysis of the baseline of a prospective cohort of 117 outward CKD patients without manifest coronary artery disease (age, 56.9 ± 11.0 years, 64.1% males, 95.1% hypertensives, 25.2% diabetics, 15.5% ever smokers, CKD stage 2 to 5 with estimated glomerular filtration rate 36.8 ± 18.1 ml/min). CAC scores, PF volume and abdominal visceral fat (AVF) areas were measured by computed tomography. The association of PF as a continuous variable with the presence of CAC was analyzed by multivariate logistic regression. CAC (calcium score > 0) was present in 59.2% patients. Those presenting CAC were on average 10 years older, had a higher proportion of male gender (78.7% vs. 42.9%, p < 0.001), and had higher values of waist circumference (95.9 ± 10.7 vs. 90.2 ± 13.2 cm, p = 0.02), PF volumes (224.8 ± 107.6 vs. 139.1 ± 85.0 cm3, p<0.01) and AVF areas (109.2 ± 81.5 vs. 70.2 ± 62.9 cm2, p = 0.01). In the multivariate analysis, adjusting for age, gender, diabetes, smoking and, left ventricular concentric hypertrophy, PF was significantly associated with the presence of CAC (OR: 1.88 95% CI: 1.03-3.43 per standard deviation). PF remained associated with CAC even with additional adjustments for estimated glomerular filtration rate or serum phosphorus (OR: 1.85 95% CI: 1.00-3.42, p = 0.05). PF is independently associated with CAC in non-dialysis dependent CKD patients.

Severe hypovitaminosis D in chronic kidney disease: association with blood pressure and coronary artery calcification.

Hypovitaminosis D occurs early in the course of chronic kidney disease (CKD), and its association with cardiovascular morbidity and mortality is well known. In this study, we aimed to evaluate whether the degree of hypovitaminosis D may differently affect blood pressure (BP) and coronary artery calcification (CAC) in nondialyzed CKD patients. This study included 80 CKD patients with a creatinine clearance between 15 and 60 ml/min/1.73 m(2) and serum 25 hydroxivitamin D [25(OH)D] level <30 ng/ml. Patients underwent 24-h ambulatory BP monitoring, evaluation of CAC (multi-slice computed tomography), and laboratory evaluation. Two groups, based on the degree of hypovitaminosis D, were defined according to the median 25(OH)D value. Patients with severe hypovitaminosis D [25(OH)D <17.2 ng/ml; S-group) exhibited a higher systolic BP at all time periods (24-h, nighttime, daytime) when compared to patients with mild hypovitaminosis D [25(OH)D >17.2 ng/ml; M-group]. No differences were found between the S and M-group in terms of diastolic BP and the presence of coronary calcification. In the multiple linear regression analysis, severe hypovitaminosis D was a predictor of 24-h, daytime and nighttime BP after controlling for a number of confounders. The severity of hypovitaminosis D was associated with increased BP in nondialyzed CKD patients. The degree of hypovitaminosis D was not related to CAC, which was equally elevated in both the severe and mild hypovitaminosis D groups.

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.

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.

Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy?

BACKGROUND AND OBJECTIVES: Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Patients were randomized to receive over a 6-wk period either calcium acetate (n = 19) or sevelamer hydrochloride (n = 21). RESULTS: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients. CONCLUSIONS: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes.

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.