Markers Of Mineral Metabolism Research Articles

The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.

Niacin downregulates intestinal sodium-dependent phosphate transporter 2b expression and reduces intestinal phosphate transport. Short-term studies have suggested that niacin lowers serum phosphate concentrations in patients with CKD and ESRD. However, the long-term effects of niacin on serum phosphate and other mineral markers are unknown. The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Trial was a randomized, double-blind, placebo-controlled trial testing extended release niacin in persons with prevalent cardiovascular disease. We examined the effect of randomized treatment with niacin (1500 or 2000 mg) or placebo on temporal changes in markers of mineral metabolism in 352 participants with eGFR<60 ml/min per 1.73 m2 over 3 years. Changes in each marker were compared over time between the niacin and placebo arms using linear mixed effects models. Randomization to niacin led to 0.08 mg/dl lower plasma phosphate concentrations per year of treatment compared with placebo (P<0.01) and 0.25 mg/dl lower mean phosphate 3 years after baseline (3.32 versus 3.57 mg/dl; P=0.03). In contrast, randomization to niacin was not associated with statistically significant changes in plasma intact fibroblast growth factor 23, parathyroid hormone, calcium, or vitamin D metabolites over 3 years. The use of niacin over 3 years lowered serum phosphorous concentrations but did not affect other markers of mineral metabolism in participants with CKD.

Effect of incident nocturnal home hemodialysis versus incident continuous ambulatory peritoneal dialysis on employment rate, clinical, and laboratory outcomes: A 1-year retrospective observation study.

While studies demonstrated favorable outcomes of nocturnal home hemodialysis (NHHD), direct comparison on employment rate, clinical and laboratory outcomes between the NHHD and continuous ambulatory peritoneal dialysis (CAPD) had not been previously performed. A 1-year retrospective observation study was performed in 20 incidents alternate night NHHD and 81 incident CAPD patients of Chinese ethnicity, who were sex, diabetic status, and Charlson comorbidity index matched, but not age due to our center's age limit for NHHD enrollment. The primary outcome was the difference in employment rate at 1 year. Secondary outcomes included differences in clinical parameters (weight, blood pressure, number of antihypertensive medication, dosage of phosphate binders, and erythropoietin stimulating agent) and laboratory parameters (residual renal function, mineral metabolic markers, hemoglobin). NHHD subjects were 5 years younger than CAPD patients, and they had higher employment rate (80% vs. 33.3%, P < 0.01) at 1 year, with age-adjusted odds ratio for employment was 6.10 (95% confidence interval 1.77-20.99, P = 0.04). They consumed less aluminum-based phosphate binder (0 vs. 1800 mg, P < 0.01), but showed no significant disparities in other clinical parameters. Residual renal function in both groups declined comparably, nonetheless NHHD group had lower serum phosphate (1.37 vs. 1.71 mmol/L, P = 0.01) and calcium phosphate product (3.13 vs. 4.12 mmol2 /L2 , P < 0.01), with similar hemoglobin levels. NHHD appeared to offer higher employment rate, lower dosage of aluminum-based phosphate binder and mineral metabolic markers at 1 year compared with CAPD in Hong Kong.

Fibroblast Growth Factor 23 and Anemia in the Chronic Renal Insufficiency Cohort Study.

Anemia is an early complication of CKD that is associated with increased morbidity and mortality. Prior data show associations between abnormal mineral metabolism markers and decreased erythropoiesis. However, few studies have investigated elevated fibroblast growth factor 23 as a risk factor for the development of anemia in patients with CKD. We conducted a prospective cohort study of 3869 individuals with mild to severe CKD enrolled in the Chronic Renal Insufficiency Cohort Study between 2003 and 2008 and followed through 2013. We hypothesized that elevated baseline fibroblast growth factor 23 levels are associated with prevalent anemia, decline in hemoglobin over time, and development of incident anemia, defined as serum hemoglobin level <13 g/dl in men, serum hemoglobin level <12 g/dl in women, or use of erythropoietin stimulating agents. In the 1872 of 3869 individuals who had prevalent anemia at baseline, mean age was 58 (11) years old, and mean eGFR was 39 (13) ml/min per 1.73 m2. Higher levels of fibroblast growth factor 23 were significantly associated with prevalent anemia (odds ratio per 1-SD increase in natural log-transformed fibroblast growth factor 23, 1.39; 95% confidence interval, 1.26 to 1.52), decline in hemoglobin over 4 years, and risk of incident anemia (hazard ratio per 1-SD increase in natural log-transformed fibroblast growth factor 23, 1.13; 95% confidence interval, 1.04 to 1.24; quartile 4 versus quartile 1: hazard ratio, 1.59; 95% confidence interval, 1.19 to 2.11) independent of demographic characteristics, cardiovascular disease risk factors, CKD-specific factors, and other mineral metabolism markers. The results of our prospective analyses remained unchanged after additional adjustment for time-varying eGFR. Elevated fibroblast growth factor 23 is associated with prevalent anemia, change in hemoglobin over time, and development of anemia. Future studies are needed to elucidate the mechanisms for these associations.

KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD)

Chronic kidney disease-mineral and bone disorder (CKD-MBD) encompasses laboratory and bone abnormalities and vascular calcification and has deleterious effects on clinical outcomes. KDOQI (Kidney Disease Outcomes Quality Initiative), an initiative of the National Kidney Foundation, addressed this issue with the publication of a clinical practice guideline for bone metabolism and disease in CKD in 2003, and 2 years later, a new definition and classification scheme for CKD-MBD was developed following a KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference. The initial KDIGO guideline on CKD-MBD was then published in 2009. New evidence was subsequently reviewed at the 2013 KDIGO Controversies Conference, andin 2017, KDIGO issued a clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of CKD-MBD. This commentary presents the views of the KDOQI CKD-MBD work group convened bythe National Kidney Foundation. The KDOQI work group agrees with most of the KDIGO guideline update recommendations, particularly the suggestions regarding bone mineral density testing, joint assessments of longitudinal trends in mineral metabolism markers, and dietary phosphate counseling focused on phosphate additives. However, the KDOQI work group has some concerns about the suggestions related to hypocalcemia and hypercalcemia, phosphate-binder choice, and treatment of abnormal parathyroid hormone concentrations. The overall goal of this commentary is to provide a broad discussion for the US nephrology community regarding CKD-MBD and its diagnosis, prevention, and treatment.

Testosterone deficiency in dialysis patients: Differences according to the dialysis techniques

Testosterone deficiency is a prevalent condition in male patients with chronic kidney disease. However, it is not known whether the type of renal replacement therapy has an impact on testosterone deficiency that accompanies loss of renal function. MethodsThe cross-sectional study enrolled 79 prevalent male patients on dialysis; 43 on haemodialysis (HD) and 36 on peritoneal dialysis (PD). The median age was 69 years and 31.6% were diabetics. Endogenous testosterone levels were measured by immunoluminescence assay (normal range 3–10.5ng/ml), while nutritional/inflammatory markers, bone and mineral metabolism markers, anemia, type of dialysis technique and time on dialysis were also assessed. Body composition was evaluated by bioimpedance vector analysis and bioimpedance spectroscopy. Testosterone deficiency was defined as levels below 3ng/ml. ResultsMean testosterone levels were 8.81±6.61ng/ml. Testosterone deficiency affected 39.5% of HD patients and only 5.6% of PD patients. In the univariate analysis, testosterone levels were directly correlated with type of dialysis technique (HD) (Rho Spearman 0.366; p<0.001) and time on dialysis (Rho −0.412; p=0.036) and only with the HD technique in the multivariate analysis. No other significant correlations were found. ConclusionsCirculating testosterone levels in men on dialysis were independently associated with HD technique. It can be concluded that a new factor—namely the dialysis technique—may be associated with falling testosterone levels and the associated loss of muscle mass and inflammation. Further studies are needed to establish whether the dialysis technique itself triggers testosterone elimination.

Déficit de testosterona en los pacientes en diálisis: diferencias según la técnica de diálisis

Testosterone deficiency is a prevalent condition in male patients with chronic kidney disease. However, it is not known whether the type of renal replacement therapy has an impact on testosterone deficiency that accompanies loss of renal function. MethodsThe cross-sectional study enrolled 79 prevalent male patients on dialysis; 43 on haemodialysis (HD) and 36 on peritoneal dialysis (PD). The median age was 69 years and 31.6% were diabetics. Endogenous testosterone levels were measured by immunoluminescence assay (normal range 3–10.5ng/ml), while nutritional/inflammatory markers, bone and mineral metabolism markers, anaemia, type of dialysis technique and time on dialysis were also assessed. Body composition was evaluated by bioimpedance vector analysis and bioimpedance spectroscopy. Testosterone deficiency was defined as levels below 3ng/ml. ResultsMean testosterone levels were 8.81±6.61ng/ml. Testosterone deficiency affected 39.5% of HD patients and only 5.6% of PD patients. In the univariate analysis, testosterone levels were directly correlated with type of dialysis technique (HD) (Rho Spearman 0.366; P<.001) and time on dialysis (Rho −0.412; P=.036) and only with the HD technique in the multivariate analysis. No other significant correlations were found. ConclusionsCirculating testosterone levels in men on dialysis were independently associated with HD technique. It can be concluded that a new factor —namely the dialysis technique— may be associated with falling testosterone levels and the associated loss of muscle mass and inflammation. Further studies are needed to establish whether the dialysis technique itself triggers testosterone elimination.

Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD

Vascular calcification is common among patients with chronic kidney disease (CKD),and it is associated with all-cause and cardiovascular disease mortality. Deoxycholic acid, a metabolite of circulating bile acids, is elevated in CKD and induces vascular mineralization and osteogenic differentiation in animal models. Cohort analysis of clinical trial participants. 112 patients with moderate to severe CKD (estimated glomerular filtration rate, 20-45mL/min/1.73m2) who participated in a randomized controlled study to examine the effects of phosphate binders on vascular calcification. Serum deoxycholic acid concentration. Baseline coronary artery calcification (CAC) volume score and bone mineral density (BMD) and change in CAC volume score and BMD after 9 months. Deoxycholic acid was assayed in stored baseline serum samples using liquid chromatography-tandem mass spectrometry, CAC was measured using a GE-Imitron C150 scanner, and BMD was determined using computed tomographic scans of the abdomen with calibrated phantom of known density. Higher serum deoxycholic acid concentrations were significantly correlated with greater baseline CAC volume and lower baseline BMD. After adjusting for demographics, coexisting illness, body mass index, estimated glomerular filtration rate, and concentrations of circulating markers of mineral metabolism, including serum calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor 23, a serum deoxycholic acid concentration > 58ng/mL (the median) was positively associated with baseline CAC volume (β=0.71; 95% CI, 0.26-1.16; P=0.003) and negatively associated with baseline BMD (β=-20.3; 95% CI,-1.5 to-39.1; P=0.04). Serum deoxycholic acid concentration > 58ng/mL was not significantly associated with change in CAC volume score after 9 months (β=0.06; 95% CI,-0.09 to 0.21; P=0.4). The analysis for the relationship between baseline deoxycholic acid concentrations and change in BMD after 9 months was not statistically significant, but was underpowered. The use of nonfasting serum samples is a limitation because deoxycholic acid concentrations may vary based on time of day and dietary intake. Few trial participants with complete data to evaluate the change in CAC volume score (n=75) and BMD (n=59). No data for changes in deoxycholic acid concentrations over time. Among patients with moderate to severe CKD, higher serum deoxycholic acid concentrations were independently associated with greater baseline CAC volume score and lower baseline BMD.

Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind Trial.

High circulating vitamin D levels are associated with lower cardiovascular mortality in CKD, possibly by modifying endothelial function. We examined the effect of calcitriol versus cholecalciferol supplementation on vascular endothelial function in patients with CKD. We performed a prospective, double-blind, randomized trial of 128 adult patients with eGFR=15-44 ml/min per 1.73 m2and serum 25-hydroxyvitamin D level <30 ng/ml at the University of Colorado. Participants were randomly assigned to oral cholecalciferol (2000 IU daily) or calcitriol (0.5 μg) daily for 6 months. The primary end point was change in brachial artery flow-mediated dilation. Secondary end points included changes in circulating markers of mineral metabolism and circulating and cellular markers of inflammation. One hundred and fifteen patients completed the study. The mean (SD) age and eGFR of participants were 58±12 years old and 33.0±10.2 ml/min per 1.73 m2, respectively. There were no significant differences between groups at baseline. After 6 months, neither calcitriol nor cholecalciferol treatment resulted in a significant improvement in flow-mediated dilation (mean±SD percentage flow-mediated dilation; calcitriol: baseline 4.8±3.1%, end of study 5.1±3.6%; cholecalciferol: baseline 5.2±5.2%, end of study 4.7±3.6%); 25-hydroxyvitamin D levels increased significantly in the cholecalciferol group compared with the calcitriol group (cholecalciferol: 11.0±9.5 ng/ml; calcitriol: -0.8±4.8 ng/ml; P<0.001). Parathyroid hormone levels decreased significantly in the calcitriol group compared with the cholecalciferol group (median [interquartile range]; calcitriol: -22.1 [-48.7-3.5] pg/ml; cholecalciferol: -0.3 [-22.6-16.9] pg/ml; P=0.004). Six months of therapy with calcitriol or cholecalciferol did not improve vascular endothelial function or improve inflammation in patients with CKD.

The impact of calcineurin inhibitors on neutrophil gelatinase-associated lipocalin and fibroblast growth factor 23 in long-term kidney transplant patients.

Neutrophil gelatinase-associated lipocalin (NGAL), a protein with bacteriostatic functions rapidly excreted from stimulated or damaged epithelial cells, is elevated in acute and chronic kidney disease. A calcineurin dependent signaling pathway for fibroblast growth factor 23 (FGF23) has been revealed, but the effect of calcineurin inhibitors (CNIs) on the levels of NGAL and markers of mineral metabolism in long-term kidney transplant patients has not been explored. In a cross-sectional study, 39 patients who received a first kidney transplant more than 10years ago were split into two groups based on whether (n=28) or not (n=11) they used CNIs. Only patients with well-functioning grafts defined as an estimated glomerular filtration rate ≥45mL/min per 1.73m2 were included. The median levels of NGAL, intact parathyroid hormone (iPTH), and iFGF23 were significantly higher in CNI users vs CNI nonusers, 167.0 (134.0-235.0) ng/mL vs 105.0 (91.3-117.0) ng/mL, P<.001, 13.8 (10.0-17.3)pmol/L vs 8.4 (6.4-9.9) pmol/L, P=.003, and 81.6 (56.4-116.5) pg/mL vs 61.8 (43.3-72.1) pg/mL, P=.04 respectively. The median levels of iFGF23 were higher in CNI users compared to CNI nonusers giving support to the notion of a CNI induced FGF23 resistance in the parathyroid. The net result of CNIs side effects needs to be further explored.

Changes in Markers of Mineral Metabolism After Living Kidney Donation.

BackgroundLiving kidney donors (LKDs) experience reduction in kidney function, however serum phosphate (sPi) levels are lower compared to patients with chronic kidney disease matched for reduced kidney function. Mineral metabolism adaptations that occur in LKDs have not been adequately investigated. To evaluate the effect of nephrectomy on markers of mineral metabolism in LKDs compared to healthy volunteers (HV) over 12 months.MethodsMineral parameters were evaluated in twenty-one adult LKDs and twenty HVs. Parameters included sPi, intact parathyroid hormone, fibroblast growth factor-23 (FGF23), soluble Klotho (sKl) and urinary phosphate, measured prior to donation (T0), 1 month (T1), 6 months (T6) and 12 months (T12) post-kidney donation. Statistical analyses were conducted on normalized variables and changes were assessed using 2-way analysis of variance.ResultsMean ages of LKDs and HVs were 54.1 ± 14.7 and 52.6 ± 8.0 years, respectively. There were no baseline clinical or biochemical differences between LKDs and HVs. In LKDs at T1, serum creatinine increased (from 75 ± 12 to 114 ± 22 μmol/L), FGF23 increased (52 ± 15 to 70 ± 19 pg/mL) and sKl decreased (564 [469-662] to 424 [375-523] pg/mL), all P less than 0.001. Changes were sustained at T12. After donation, LKDs consistently demonstrated lower sPi compared with T0, with the maximal sPi change at T6 (−0.19 mmol/L difference, P < 0.001). Other markers of mineral metabolism were unchanged in LKDs. There were no mineral differences in HVs over 12 months.ConclusionsProspective evaluation of mineral metabolism parameters in LKDs provides valuable insight into compensatory mechanisms after reduction in kidney function. Further reduction of sPi at T6 despite early alterations in FGF23 and sKl suggest adaptation of mineral metabolism continues long-term in LKDs.

Etelcalcetide for the treatment of secondary hyperparathyroidism

ABSTRACTIntroduction: Calcium sensing receptor is an important target for the treatment of secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is a novel peptide calcimimetic agent that has a similar mechanism of action as cinacalcet hydrochloride. Clinical trials of etelcalcetide have been performed in the US, Europe, and Japan, and these trials demonstrated the safety and efficacy of etelcalcetide in dialysis patients. Etelcalcetide has recently been approved in Europe, the US and Japan.Areas covered: We review the development, pharmacokinetics, and clinical efficacy and safety of etelcalcetide for the treatment of SHPT in hemodialysis patients. We also summarize the clinical evidence regarding cinacalcet to forecast the potential clinical benefit of etelcalcetide.Expert opinion: Etelcalcetide is an injectable calcimimetic with a longer elimination half-life than cinacalcet. The injectable formulation improves adherence and reduces pill burden, while the frequency of gastrointestinal adverse events has been comparable between cinacalcet and etelcalcetide. The longer half-life of etelcalcetide reduces the fluctuation of biochemical markers of mineral and bone metabolism, but it remains to be determined whether such a sustained effect results in improved outcomes. Further studies are needed to determine the impact of etelcalcetide on clinical outcomes, particularly in comparison with the conventional calcimimetic cinacalcet.

Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment.

To test the hypothesis that rebound of bone remodeling is responsible for clinical vertebral fractures reported in a few patients with osteoporosis after cessation of denosumab treatment. In this case-control study we compared clinical and biochemical characteristics of postmenopausal women with clinical vertebral fractures 8-16 months after the last injection of denosumab (Dmab/Fx+, n = 5) with those of treatment-naïve women with such fractures (Fx+, n = 5). In addition, 5 women who discontinued denosumab treatment but did not sustain vertebral fractures 18-20 months after the last injection were studied (Dmab/Fx-, n = 5). We measured serum microRNAs, gene expression of mRNAs of factors regulating formation and activity of osteoclasts and biochemical markers of bone and mineral metabolism. In Dmab/Fx+ and Fx+ women, blood was taken 4-8 weeks after the fracture. Compared to Fx+ women, Dmab/Fx+ women had higher serum P1NP and CTx levels, and significantly lower serum miR-503 and miR-222-2 that downregulate osteoclastogenesis and osteoclast activity, and higher RANK (13-fold) and CTSK (2.6-fold) mRNA. The respective values of Dmab/Fx- women were in the same direction as those of Dmab/Fx+ women but of a lesser magnitude. Bone fragility in women with clinical vertebral fractures after stopping denosumab therapy is pathophysiologically different from that of treatment-naïve women with osteoporosis and clinical vertebral fractures and it is associated with upregulation of markers of osteoclast formation and activity. The small number of women with this rare event studied is a limitation.

Cortical porosity not superior to conventional densitometry in identifying hemodialysis patients with fragility fracture.

Hemodialysis (HD) patients face increased fracture risk, which is further associated with elevated risk of hospitalization and mortality. High-resolution peripheral computed tomography (HR-pQCT) has advanced our understanding of bone disease in chronic kidney disease by characterizing distinct changes in both the cortical and trabecular compartments. Increased cortical porosity (Ct.Po) has been shown to be associated with fracture in patients with osteopenia or in postmenopausal diabetic women. We tested whether the degree of Ct.Po identifies hemodialysis patients with prevalent fragility fractures in comparison to bone mineral density (BMD) assessed by dual X-ray absorptiometry (DXA). We performed a post-hoc analysis of a cross-sectional study in 76 prevalent hemodialysis patients. Markers of mineral metabolism, coronary calcification score, DXA-, and HR-pQCT-data were analyzed, and Ct.Po determined at radius and tibia. Ct.Po was significantly higher in patients with fracture but association was lost after adjusting for age and gender (tibia p = 0.228, radius p = 0.5). Instead, femoral (F) BMD neck area (p = 0.03), F T-score neck area (p = 0.03), radius (R) BMD (p = 0.03), R T-score (p = 0.03), and cortical HR-pQCT indices such as cortical area (Ct.Ar) (tibia: p = 0.01; radius: p = 0.02) and cortical thickness (Ct.Th) (tibia: p = 0.03; radius: p = 0.02) correctly classified patients with fragility fractures. Area under receiver operating characteristic curves (AUC) for Ct.Po (tibia AUC: 0.711; p = 0.01; radius AUC: 0.666; p = 0.04), Ct.Ar (tibia AUC: 0.832; p<0.001; radius AUC: 0.796; p<0.001), and F neck BMD (AUC: 0.758; p = 0.002) did not differ significantly among each other. In conclusion, measuring Ct.Po is not superior to BMD determined by DXA for identification of HD patients with fragility fracture.

Kidney transplantation and hyperparathyroidism

Successful kidney transplantation eliminates endocrine and metabolic disorders that predispose to the development of hyperparathyroidism, the complication typical for the chronic kidney disease; but the process of recovery from mineral and bone disorders is slowed down. The highest incidence of post-transplant hyperparathyroidism is recorded in the first postoperative year. The risk factors for its development or persistence include the high blood levels of parathyroid hormone, calcium, phosphorus, and/or alkaline phosphatase, a prolonged dialysis therapy, severe hyperparathyroidism in the preoperative period, vitamin D deficiency, a suboptimal transplanted kidney function, and also the recipient's previous history of subtotal or incomplete parathyroidectomy. The characteristic clinical and laboratory signs of posttransplant hyperparathyroidism are bone lesions, kidney graft abnormalities, hypercalcemia, and hypophosphatemia. The diagnostic algorithm includes monitoring the markers of mineral and bone metabolism, determining the bone mineral density, and imaging of thyroid glands. Correction of post-transplant hyperparathyroidism is performed surgically or pharmacologically. The article specifies the indications to, the extent and timing of parathyroidectomy, discusses the use of native vitamin D formulations, its analogues, and calcimimetics.

OSTEOPROTEGERIN AND RANKL: A ROLE IN THE DEVELOPMENT OF CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH TERMINAL STAGE OF RENAL FAILURE RECEIVING HEMODIALYSIS

THE AIM : to clarify the possible pathogenic links between the markers of bone mineral metabolism – OPG and RANKL – with markers of cardiovascular diseases characterizing the state of the myocardium and the vascular wall of the aorta in patients undergoing renal replacement therapy. PATIENTS AND METHODS . 105 patients with C5D CKD were examined: 47 men and 58 women aged 23 to 69 years (mean age -53 ± 2.5 years). The levels of calcium, phosphorus, parathyroid hormone (PTH), osteoprotegerin morphogenetic proteins (OPG) and RANKL (ligand of the receptor activator for the treatment of Kappa B), cardiospecific protein troponin I have been determined. With the help of echocardiography «ALOKA 4000» examined the morphofunctional features of the left ventricle (LV) and aorta. The LV myocardial mass index (LVMI), peak systolic velocity in the aortic arch (Vps) were determined. RESULTS . Changes in bone mineral metabolism, including an increase in OPG and an increase in the ratio of OPG / RANKL in patients with terminal renal failure, were closely related to an increase in LVMI, a decrease in the LV ejection fraction (LVEF), and an increase in the level of troponin I. CONCLUSION . In patients with end-stage renal failure, changes in bone mineral metabolism, including a significant increase in the level of OPG and the ratio of OPG / RANKL, are revealed, which indicates a high risk of remodeling processes in the cardiovascular system (CVS), which should be taken into account when choosing cardioprotective therapy.

Bone health assessment of food allergic children on restrictive diets: a practical guide.

Food allergy in childhood is on the rise globally and is managed with avoidance diets; recent case reports of food allergic children with nutritional rickets in the literature highlight the importance of close monitoring of bone health in this population. There is no consensus as yet with regard to bone health evaluation in food allergic children; therefore, extensive literature search was performed and the existing evidence is presented, along with a relevant algorithm. Children allergic to cow's milk protein or presenting with allergy in more than three food items, as well as patients with severe allergic phenotypes or comorbidities known to affect the skeleton, seem to be at risk of metabolic bone disorders. As a practical guide, suspicious cases can be investigated with basic bone profile, whereas more severe cases (persistent bone pain and fractures) may undergo advanced bone health assessment, with bone mineral density (BMD) and metabolic bone markers' evaluation. Of note, these diagnostic steps call for further studies in the field of food allergy, as they are not performed as a routine. Evidence is accumulating with regard to vitamin D deficiency, osteopenia and imbalanced bone metabolism in those food allergic children who show poor dietary compliance or have inadequate medical supervision. Ensuring optimal bone accrual in a food allergic child is an important task for the clinician and requires close monitoring of the restrictive diet and prompt therapeutic intervention, in an effort to avoid rickets or osteopenia.

Bone mineral density and bone metabolic markers' status in children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a multisystem disorder characterized by progressive manifestations, which is inherited in an autosomal dominant manner. The majority of patients with NF1 experience a diffuse, significant reduction in bone mass over time, with osteoporosis, osteopenia in the absence of severe scoliosis, or gross bone deformities. This study aimed to determine the bone mineral density (BMD) status, evaluate bone metabolism, and to determine the relevant factors in children with NF1. The study population included 33 pediatric NF1 patients (20 males and 13 females). Bone metabolic markers, such as total calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone, and 25-OH vitamin D, the urinary calcium/creatine ratio were measured. In addition, BMD was measured at both the lumbar spine (LS) and the femoral neck in all the patients. All the patients had a low 25-OH vitamin D level, but it was significantly lower in the females than in the males (p<0.009). Overall, 18.2% of the patients had skeletal abnormalities. The lumbar Z-score was ≤2 in 21.2% of the patients, whereas the femoral neck Z-score was ≤2 in 9.1%. The urinary calcium/creatine ratio was significantly higher in the female than in the male patients (p<0.027). In all, six patients had skeletal abnormalities. It is widely known that bone mineral metabolism markers and BMD are significantly affected in NF1 patients; however, the present study did not identify any effective parameters that could be used to predict skeletal abnormalities, or diagnose early osteoporosis and osteopenia in pediatric NF1 patients.

Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort.

Heart failure is the most frequent cardiac complication of CKD. Left ventricular hypertrophy is common and develops early in CKD, but studies have not adequately evaluated the association of left ventricular mass index with heart failure incidence among men and women with CKD. We evaluated echocardiograms of 2567 participants without self-reported heart failure enrolled in the Chronic Renal Insufficiency Cohort Study. Two-dimensional echocardiograms were performed at the year 1 study visit and interpreted at a central core laboratory. Left ventricular mass index was calculated using the linear method, indexed to height2.7, and analyzed using sex-specific quartiles. The primary outcomes of incident heart failure and all-cause mortality were adjudicated over a median of 6.6 (interquartile range, 5.7-7.6) years. Among 2567 participants, 45% were women, and 54% were nonwhite race; mean (SD) age was 59±11 years old, and mean eGFR was 44±17 ml/min per 1.73 m2. During a median follow-up period of 6.6 years, 262 participants developed heart failure, and 470 participants died. Compared with participants in the first quartile of left ventricular mass index, those in the highest quartile had higher rates of incident heart failure (hazard ratio, 3.96; 95% confidence interval, 1.96 to 8.02) and mortality (hazard ratio, 1.86; 95% confidence interval, 1.22 to 2.85), even after adjustment for B-type natriuretic peptide, troponin T, mineral metabolism markers, and other cardiovascular disease risk factors. Those in the lowest quartile of ejection fraction had higher rates of incident heart failure (hazard ratio, 3.01; 95% confidence interval, 1.94 to 4.67) but similar mortality rates (hazard ratio, 1.18; 95% confidence interval, 0.89 to 1.57) compared with those in the highest quartile. Diastolic dysfunction was not significantly associated with heart failure or death. Among persons with CKD and without history of cardiovascular disease, left ventricular mass index is strongly associated with incident heart failure, even after adjustment for major cardiovascular risk factors and biomarkers.

Laboratory markers for the assessment of patients with posttraumatic coxarthrosis in preparation for hip joint arthroplasty

For the evaluation of patients with coxarthrosis (CA), who recommended for hip replacement, it is necessary to apply comprehensive approach for the study of the functional state of organs and body systems, including the use of biochemical markers of mineral, protein and lipid metabolism. Objective:to conduct a survey of patients with post-traumatic CA to de­tect metabolic disorders by means of laboratory markers and the predictability of complications after surgery. The study in­volved 35 patients (21 of men, 14 women) aged 30 to 80 years with post-traumatic CA stage IV. The control group consisted of 30 healthy people (13 men, 17 women) aged 27 to 50 years. In the serum of patients, total protein, albumin, glycoproteins, sialic acid hondroyitynsulfats, haptoglobin, glucose, total cho­lesterol, triglycerides, ALT, AST, alkaline and acid phospha­tase, HHTP, thymol, fibrinogen, interleukin IL-1, IL-4, IL-6 and circular immune complexes have been determined. Re­sults: patients with post-traumatic CA had two-fold increased levels of fibrinogen and glycoproteins in serum, sialic acid de­creased by 52,2 %, haptoglobin - by 26 % globulins - by 19.6 %, cholesterol -by 23.9 %, triglycerides -by 46.4 %, thymol test -2.2 fold, IL-1 -three-fold, IL-6 -6 ti and IL-4 -2.2 times, the activity of alkaline phosphatase -by 75.7 %, acid -25.1 % and HHTP -47.8 % compared to the control group. Conclusions: The increase in markers of acute phase in serum and activity of marker enzymes demonstrates the destructive inflammatory process in patients with a course of post-traumatic CA. The increase in cytokines and circular immune complexes is the evi­dence of increased immune reactivity due to the severity of the pathological process in joints, and it dictates necessity for care­ful monitoring after arthroplasty and pharmacological therapy to reduce the risk of complications in this category of patients.

Association of Fibroblast Growth Factor 23 With Atrial Fibrillation in Chronic Kidney Disease, From the Chronic Renal Insufficiency Cohort Study.

Levels of fibroblast growth factor 23 (FGF23) are elevated in chronic kidney disease (CKD) and strongly associated with left ventricular hypertrophy, heart failure, and death. Whether FGF23 is an independent risk factor for atrial fibrillation in CKD is unknown. To investigate the association of FGF23 with atrial fibrillation in CKD. Prospective cohort study of 3876 individuals with mild to severe CKD who enrolled in the Chronic Renal Insufficiency Cohort Study between June 19, 2003, and September 3, 2008, and were followed up through March 31, 2013. Baseline plasma FGF23 levels. Prevalent and incident atrial fibrillation. The study cohort comprised 3876 participants. Their mean (SD) age was 57.7 (11.0) years, and 44.8% (1736 of 3876) were female. Elevated FGF23 levels were independently associated with increased odds of prevalent atrial fibrillation (n = 660) after adjustment for cardiovascular and CKD-specific factors (odds ratio of highest vs lowest FGF23 quartile, 2.30; 95% CI, 1.69-3.13; P < .001 for linear trend across quartiles). During a median follow-up of 7.6 years (interquartile range, 6.3-8.6 years), 247 of the 3216 participants who were at risk developed incident atrial fibrillation (11.9 events per 1000 person-years). In fully adjusted models, elevated FGF23 was independently associated with increased risk of incident atrial fibrillation after adjustment for demographic, cardiovascular, and CKD-specific factors, and other markers of mineral metabolism (hazard ratio of highest vs lowest FGF23 quartile, 1.59; 95% CI, 1.00-2.53; P = .02 for linear trend across quartiles). The results were unchanged when further adjusted for ejection fraction, but individual adjustments for left ventricular mass index, left atrial area, and interim heart failure events partially attenuated the association of elevated FGF23 with incident atrial fibrillation. Elevated FGF23 is independently associated with prevalent and incident atrial fibrillation in patients with mild to severe CKD. The effect may be partially mediated through a diastolic dysfunction pathway that includes left ventricular hypertrophy, atrial enlargement, and heart failure events.