Vitamin D levels reverberate in monocytes modulation in hemodialysis patients.

BACKGROUND: Patients with chronic kidney disease (CKD) have a severe vitamin D deficiency and increasing epidemiological data suggesting that this deficiency may play a role in overall morbidity and mortality associated with CKD. It is known that vitamin D regulates the immune system, however, in dialysis patients this deficiency and the modulation of proinflammatory cells is unclear. Among these, monocytes arouse interest considering they constitutively express vitamin D receptors. AIM: This study aimed the evaluation of monocytic profile in CKD patients according to vitamin D levels. METHODS: Patients in hemodialysis (HD) were divided into two groups, regarding vitamin D levels: Group 1, vitamin D <26 ng/ml (n = 15) and Group 2, vitamin D ≥26 ng/ml (n = 18). Whole blood was collected aiming evaluation of (a) monocytic populations through CD14 and CD16 expression, (b) reactive oxygen species (ROS) generation, and (c) apoptosis. RESULTS: We observed that in Group 1, when compared to Group 2, there was a significant increase in intermediate monocytes (CD14++ CD16 + ; 34.7 ± 31.6 vs. 12.1 ± 6.3; p = 0.006, respectively) and decrease in classical ones (CD14 ++ CD16 - ; 45.3 ± 31.8 vs. 70.4 ± 25.1; p = 0.017, respectively). There was no difference between groups regarding nonclassical monocytes (CD14 + CD16 ++ ), as well as to apoptosis and to ROS generation. CONCLUSION: This study suggests that HD patients with lower vitamin D levels might have an intensified inflammatory outline as intermediate monocytes with an inflammatory pattern are increased in this population, when compared with patients with higher levels of vitamin D.

Review article: effects of type 2 diabetes therapies on bone metabolism.

Diabetes complications and osteoporotic fractures are two of the most important causes of morbidity and mortality in older patients, and they share many features, including genetic susceptibility, molecular mechanisms, and environmental factors. Type 2 diabetes mellitus (T2DM) compromises bone microarchitecture by inducing abnormal bone cell function and matrix structure with increased osteoblast apoptosis, diminished osteoblast differentiation, and enhanced osteoclast-mediated bone resorption. The linkage between these two chronic diseases creates a possibility that certain antidiabetic therapies may affect bone function. The treatment of T2DM has been improved in the past two decades with the development of new therapeutic drugs. Each class has a pathophysiologic target related to the regulation of the energy metabolism and insulin secretion. However, both glycemic homeostasis and bone homeostasis are under the control of common regulatory factors. This background allows the individual pharmacological targets of antidiabetic therapies to affect bone quality due to their indirect effects on bone cell differentiation and the bone remodeling process. With a greater number of diabetic patients and antidiabetic agents being launched, it is critical to highlight the consequences of this disease and its pharmacological agents on bone health and fracture risk. Currently, there is little scientific knowledge approaching the impact of most anti-diabetic treatments on bone quality and fracture risk. Thus, this review aims to explore the pros and cons of the available pharmacologic treatments for T2DM on bone mineral density and risk fractures in humans.

p-Cresyl sulfate affects the oxidative burst, phagocytosis process, and antigen presentation of monocyte-derived macrophages.

Immune system dysfunction is a common condition in chronic kidney disease (CKD). The present study investigated the effect of p-Cresyl sulfate (pCS) on human cell line U937 monocyte-derived macrophages (MDM) activity. MDM (1×106 cells/mL) were incubated with pCS (10, 25, or 50µg/mL), with or without lipopolysaccharide (LPS; 25ng/mL) and then evaluated NO production, phagocytosis and antigen-presenting molecules expression (HLA-ABC, HLA-DR, CD80 and CD86). All analyses were performed by flow cytometry. All pCS concentrations were able to increase NO production (49±12.1%, 39.8±7.75%, 43.7±11.9%, respectively) compared to untreated cells (4.35±3.34%) after 6h incubation but only the lowest concentration increased this production after 12h (82.9±8.6%, 61±7.2%, 40.8±11.7%). Combined with LPS, the same results were observed. Regarding to phagocytosis, all concentrations were able to induce bead engulfment (35.4±2.71%, 30±3.04%, 23.28±4.58%). In addition, pCS (50µg/mL) was able to increase HLA-ABC and CD80 expression, showed a slight effect on HLA-DR expression and, no difference in basal CD86 levels. pCS can induce an increased oxidative burst and phagocytosis by human macrophages while no modulation of HLA-DR or CD86 expression was induced. Together, these results suggest that pCS induces macrophage activation but interfere in antigen processing, leading to a failure in adaptive immune response in CKD.

K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients.

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

Evaluation of the role of severe hyperparathyroidism on coronary artery calcification in dialysis patients.

BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of dying from a cardiovascular event, mainly due to coronary calcification. Among the various uremic and dialysis-specific risk factors for coronary calcification are mineral metabolism disorders. The role that secondary hyperparathyroidism (SHPT) consequent to the altered calcium and phosphate metabolism plays in the pathogenesis of coronary calcification remains unclear. The aim of this study was to evaluate the prevalence of coronary artery calcification in dialysis patients with severe SHPT submitted to multislice coronary tomography (MSCT) and to identify risk factors for coronary calcification. METHODS: This study involved 23 adult dialysis patients (age >18 years) with severe SHPT who were candidates for parathyroidectomy (PTX). All were submitted to MSCT and bone densitometry during the month preceding PTX. Fasting blood samples were collected immediately before surgery. Markers of mineral metabolism, including ionized calcium, phosphorus, alkaline phosphatase, intact-parathyroid hormone (iPTH), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand, were analyzed. Dyslipidemia was assessed by determination of LDL, HDL and VLDL-cholesterol and triglyceride levels. Agatston units (AU) were used to calculate calcium scores. RESULTS: No coronary calcification was found in 30% of the patients. Moderate (calcium score > 100 AU) and severe (calcium score >400 AU) calcification was observed in 12 and 36% of the patients, respectively. In the univariate analysis, calcium volume correlated positively with VLDL-cholesterol (r = 0.44; p = 0.03) and, albeit less than significantly, with age (r = 0.35; p = 0.09), triglycerides (r = 0.39; p = 0.05) and Framingham risk index (r = 0.37; p = 0.07). We also found that OPG correlated negatively with bone mineral density at the L2-L4 lumbar vertebrae (r = -0.54; p = 0.007) and femoral neck (r = -0.43; p = 0.04). CONCLUSIONS: Although high levels of PTH should be considered a risk factor for cardiovascular death, the real role of severe SHPT on coronary calcification is to be clarified.

Evaluación estacional de la riqueza y abundancia de especies de mamíferos en la Reserva Biológica Municipal [quot ]Máirio Viana[quot], Mato Grosso, Brasil / Seasonal evaluation of mammal species richness and abundance in the [quot]Mário Viana[quot] municipal reserve, Mato Grosso, Brasil

We evaluated seasonal species presence and richness, and abundance of medium and large sized mammalian terrestrial fauna in the [quot ]Mário Viana[quot ] Municipal Biological Reserve, Nova Xavantina, Mato Grosso, Brazil. During 2001, two monthly visits were made to an established transect, 2,820 m in length. Records of 22 mammal species were obtained and individual footprint sequences quantified for seasonal calculation of species richness and relative abundance index (x footprints/km traveled). All 22 species occurred during the rainy season, but only 18 during the dry season. Pseudalopex vetulus (Lund, 1842) (hoary fox), Eira barbara (Linnaeus, 1758) (tayra), Puma concolor (Linnaeus, 1771) (cougar) and Hydrochaeris hydrochaeris (Linnaeus, 1766) (capybara) were only registered during the rainy season. The species diversity estimated using the Jackknife procedure in the dry season (19.83, CI = 2.73) was smaller than in the rainy season (25.67, CI = 3.43). Among the 18 species common in the two seasons, only four presented significantly different abundance indexes: Dasypus novemcinctus Linnaeus, 1758 (nine-banded armadillo), Euphractus sexcinctus (Linnaeus, 1758) (six-banded armadillo), Dasyprocta azarae Lichtenstein, 1823 (Azara's Agouti) and Tapirus terrestris (Linnaeus, 1758) (tapir). On the other hand, Priodontes maximus (Kerr, 1792) (giant armadillo) and Leopardus pardalis (Linnaeus, 1758) (ocelot) had identical abundance index over the two seasons. Distribution of species abundance in the sampled area followed the expected pattern for communities in equilibrium, especially in the rainy season, suggesting that the environment still maintains good characteristics for mammal conservation. The present study shows that the reserve, although only 470 ha in size, plays an important role for conservation of mastofauna of the area as a refuge in an environment full of anthropic influence (mainly cattle breeding in exotic pasture).

Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem.

Osteoporosis in hemodialysis patients is associated with high morbidity and mortality and, although extensively studied by noninvasive methods, has never been assessed through bone biopsy. The aim of this study was to use histomorphometry to evaluate osteoporosis and identify factors related to its development in hemodialysis patients. We conducted a cross-sectional study involving 98 patients (35 women and 63 men; mean age: 48.4 +/- 13 years) on hemodialysis for 36.9 +/- 24.7 months. Patients were submitted to transiliac bone biopsy with double tetracycline labeling. The bone metabolism factors ionized calcium, phosphorus, bone alkaline phosphatase, deoxypyridinoline, intact parathyroid hormone, and 25(OH) vitamin D were evaluated, as were the bone remodeling cytokines osteoprotegerin (OPG), soluble receptor-activator of NF-kappabeta ligand (sRANKL) and tumor necrosis factor-alpha (TNF)alpha. Osteoporosis was defined as trabecular bone volume (BV/TV) greater than 1 s.d. below normal (men <17.4%; women <14.7%). Forty-five patients (46%) presented osteoporosis, which was correlated with white race. We found BV/TV to correlate with age, OPG/sRANKL ratio, TNFalpha levels, and length of amenorrhea. In multiple regression analysis adjusted for sex and age, length of amenorrhea, white race, and OPG/sRANKL ratio were independent determinants of BV/TV. Histomorphometric analysis demonstrated that osteoporotic patients presented normal eroded surface and low bone formation rate (BFR/BS). Osteoporosis is prevalent in hemodialysis patients. Low BFR/BS could be involved in its development, even when bone resorption is normal. Cytokines may also play a role as may traditional risk factors such as advanced age, hypogonadism, and white race.