Mineral Bone Disorder Research Articles

Inflammation induces osteoclast differentiation from peripheral mononuclear cells in chronic kidney disease patients: crosstalk between the immune and bone systems.

Inflammation and immune system alterations contribute to bone damage in many pathologies by inducing the differentiation of osteoclasts (OCs), the bone resorbing cells. This link is largely unexplored in chronic kidney disease (CKD) and haemodialysis (HD) patients, in which reduced renal function is accompanied by an increased inflammatory state and skeletal abnormality. We used ex vivo culture experiments to investigate the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) of CKD and HD patients, focusing on immune cell subsets and inflammatory cytokines such as LIGHT and receptor activator of nuclear factor κB ligand (RANKL). We observed spontaneous osteoclastogenesis with a significant increase in OC formation and bone resorbing activity in late-stage CKD and HD patients when compared with early-stage CKD patients and healthy donors, likely due to an increased expression of RANKL and LIGHT (homologous to Lymphotoxins exhibiting Inducible expression and competing with herpes simplex virus Glycoprotein D for herpes virus entry mediator [HVEM], a receptor expressed by T lymphocytes) in PBMCs. Specific inhibition of these cytokines in PBMCs isolated from CKD stages 3b-5 and HD patients induced the reduction of OC formation in vitro. The phenotypic characterization of peripheral blood cells revealed a significant increase of OC precursors (CD14+CD11b+CD51/61+) and CD14+CD16+ monocytes in advanced CKD and HD patients compared with the control group. Our results suggest that circulating inflammatory monocytes from advanced CKD or HD patients trans differentiate into OCs in vitro and play a relevant role in mineral bone disorders and that LIGHT and RANKL represent new potential therapeutic targets in these settings.

Challenging look at therapeutic trend of chronic kidney disease–mineral bone disorder in children

Challenging look at therapeutic trend of chronic kidney disease–mineral bone disorder in children

Aldosterone antagonist therapy and its relationship with inflammation, fibrosis, thrombosis, mineral-bone disorder and cardiovascular complications in peritoneal dialysis (PD) patients

BackgroundHigh aldosterone level may contribute to pathogenesis of hypertension, vessels damage and cardiovascular system deterioration in chronic kidney disease patients. Besides its classical action via mineralocorticoid receptor, aldosterone is also involved in cell growth, inflammation, oxidative stress, endothelial dysfunction and exerts fibroproliferative effects. The aim of the study was to assess whether aldosterone antagonist treatment may influence serum level of inflammatory, fibrosis, thrombosis and mineral-bone metabolism markers in peritoneal dialysis (PD) patients and blood pressure, aortic stiffness, echocardiographic indices after 12 months of treatment.MethodsTwenty-two patients on PD were assigned to spironolactone treatment in dose of 50 mg daily during 12 months. Fifteen PD patients were assigned to control group. Echocardiographic indices, PVW, SBP, DBP (mean values from ABPM) and biochemical parameters such as: aldosterone, osteopontin, IL-6, selectin-P, TGF-β, PTH, MMP-2 were performed at the beginning and after 12 months in spironolactone and control group.ResultsThere were no statistically significant differences in echocardiographic indices, PWV, BP (ABPM readings) and biochemical markers: MMP-2, serum aldosterone, TGF-β, IL-6, selectin-P, PTH level after 12 months of spironolactone treatment. There was statistically significant rise in osteopontin level after 12 months of spironolactone treatment. Episodes of life-threatening hyperkalemia were not reported.ConclusionsAldosterone antagonists use in PD patients seems to be safe. Longer duration or higher dosage of spironolactone seems to be more effective in improving cardiovascular system status in PD patients. Further studies are required to determine relationship between mineralocorticoid receptor blockade and mineral-bone disturbances in PD patients.

Biochemical markers of mineral bone disorder in South African patients on maintenance haemodialysis

Despite the high mortality and morbidity associated with abnormalities in mineral and bone metabolism in haemodialysis patients, there is limited data on the pattern of mineral bone disorder in African CKD population. Therefore, the purpose of this study was to describe the pattern of mineral bone disease by evaluating biochemical parameters in patients on maintenance haemodialysis (MHD). We evaluated the serum/plasma intact parathyroid hormone (iPTH), corrected calcium, phosphate, total alkaline phosphatase (TALP) and 25 -OH vitamin D levels of two hundred and seven patients undergoing MHD at two dialysis centers in Johannesburg. The MHD patients (133 men, 74 women) had a mean age of 54.5±15.6 years with a median dialysis vintage of 24 months (IQR, 12-48) and a mean kt/V of 1.45±0.28. The prevalence of hyperparathyroidism (iPTH >150 pg/ml), hyperphosphataemia, hypocalcaemia and 25-OH vitamin D deficiency (<30 ng/ml) was 73.4%, 57.0%, 20.3% and 80.7 % respectively. The combination of markers of bone turnover (iPTH >150pg/ml and TALP> 112 U/L) suggestive of high turnover bone disease, was present in 47.3 % of the study population. In multiple-logistic regression analysis, the odds ratio for developing hyperparathyroidism with hypocalcaemia and hyperphosphataemia were 5.32 (95% CI 1.10 - 25.9, P = 0.03) and 3.06(95 % CI 1.15 - 8.10, P=0.02) respectively. Ninety eight (47.3%) of the MHD patients had iPTH within the recommended kidney disease improving global outcome (KDIGO) guidelines. Secondary hyperparathyroidism and 25-OH vitamin D deficiency were common in our haemodialysis patients. Hypocalcaemia and hyperphosphataemia were strong predictors for developing secondary hyperparathyroidism.

Profile of chronic kidney disease related-mineral bone disorders in newly diagnosed advanced predialysis diabetic kidney disease patients: A hospital based cross-sectional study

AimChronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD population. There are limited data on the pattern of these disturbances in diabetic CKD patients. Therefore, a study was conducted to find out the profile of mineral bone disorders in T2DM patients with pre-dialysis CKD. MethodsIn this cross-sectional design, diabetic patients with newly-diagnosed stage 4 and 5 CKD were evaluated. Serum levels of calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D and total alkaline phosphatase (ALP) were measured in all patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). ResultsA total of 72 eligible patients participated (44 males, 28 females; age 54.2±11.7). Patients with CKD Stage 5 had a lower level of corrected serum calcium and significantly higher level of inorganic phosphorus, total ALP and iPTH as compared to stage 4 patients. Overall, 38.5% were hypocalcemic, 31.43% were hyperphosphatemic. 24.2% of CKD subjects were vitamin D deficient (<10ng/ml) and 41.4% having vitamin D insufficiency (10–20ng/ml). In stage 4, hyperparathyroidism (iPTH>110pg/ml) was detected in nearly 43% of patients. In stage 5, only 32% patients was found to have hyperparathyroidism (iPTH>300pg/ml).There was a good correlation between iPTH and total ALP (r=0.5, p=0.0001) in this cohort. 25 (OH) vitamin D was inversely correlated with ALP (r=−0.39, P=0.001) and showed negative correlation with urine ACR (r=−0.37, P=0.002). As a group, the osteoporotic CKD subjects exhibited higher iPTH (220.1±153.8 vs. 119±108pg/ml, p<0.05) as compared to those who were osteopenic or had normal bone density. There was significant correlation between BMD and iPTH (adjusted r=−0.436; P=0.001). In the multivariate regression model, we found intact PTH to predict BMD even after adjustment of all the confounders. ConclusionThe current study showed that adynamic bone disease is prevalent even in pre-dialysis CKD population. High bone turnover disease may not be the most prevalent type in diabetic CKD. However, it could contribute to the development of osteoporosis in CKD subjects. Serum total ALP can serve as a biochemical marker to identify pattern of bone turnover where intact PTH is not available.

Prevalence of mineral bone disorders among hemodialysis patients in Menoufia Governorate, Egypt

Objective The aim of this study was to determine the prevalence of mineral bone disorders (MBDs) among hemodialysis (HD) patients in Menoufia Governorate. Background As kidney function declines, there is progressive deterioration in mineral homeostasis manifesting as disruption of serum and tissue concentrations of phosphorus and calcium (Ca), as well as changes in circulating levels of hormones such as parathyroid hormone (PTH). These mineral and endocrine functions are critically important in the regulation of both bone modeling and bone remodeling. Chronic kidney disease-MBD describes a broad clinical syndrome that develops as a systemic disorder of mineral and bone metabolism because of chronic kidney disease. Patients and methods This study was carried out on 100 patients with end-stage renal disease on regular HD in Menoufia Governorate. After obtaining informed consent, the included patients underwent the following examination: complete blood count, blood sugar level, lipid profile, blood urea level, serum creatinine level, albumin level, uric acid level, Ca level, phosphate level, alkaline phosphatase level, and PTH level. Results Hyperparathyroid bone disease was prevalent in 55% of the studied patients and low bone turnover in 30% of the studied patients, and both of the two groups showed highly significant association with serum Ca and phosphate levels. Suggestive MBD-related symptoms were prevalent in both high bone turnover and low bone turnover (60 and 70%, respectively). Hypocalcemia and hyperphosphatemia were observed in 64 and 74% of the studied patients, respectively. Conclusion The prevalence of MBD among the studied HD patients was 85% depending on abnormal PTH levels (55% of patients with high PTH level and 30% with low PTH levels). Most of patients with high PTH level (high bone turnover) had low serum Ca with high serum phosphorus levels (83.6 and 81.8%, respectively), whereas most of patients with low PTH levels (low bone turnover) had normal serum Ca with high serum phosphorus levels (60 and 63.3% respectively).

Newly Developed Rat Model of Chronic Kidney Disease-Mineral Bone Disorder.

Aim: Chronic kidney disease–mineral bone disorder (CKD–MBD) is associated with all-cause and cardiovascular morbidity and mortality in patients with CKD. Thus, elucidating its pathophysiological mechanisms is essential for improving the prognosis. We evaluated characteristics of CKD–MBD in a newly developed CKD rat model.Methods: We used male Sprague–Dawley (SD) rats and spontaneously diabetic Torii (SDT) rats, which are used as models for nonobese type 2 diabetes. CKD was induced by 5/6 nephrectomy (Nx). At 10 weeks, the rats were classified into six groups and administered with a vehicle or a low- or high-dose paricalcitol thrice a week. At 20 weeks, the rats were sacrificed; blood and urinary biochemical analyses and histological analysis of the aorta were performed.Results: At 20 weeks, hemoglobin A1c (HbA1c) levels, blood pressure, and renal function were not significantly different among the six groups. Serum calcium and phosphate levels tended to be higher in SDT-Nx rats than in SD-Nx rats. The urinary excretion of calcium and phosphate was significantly greater in SDT-Nx rats than in SD-Nx rats. After administering paricalcitol, serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels were significantly higher in SDT-Nx rats than in SD-Nx rats. The degree of aortic calcification was significantly more severe and the aortic calcium content was significantly greater in SDT-Nx rats than in SD-Nx rats.Conclusions: We suggest that our new CKD rat model using SDT rats represents a useful CKD–MBD model, and this model was greatly influenced by paricalcitol administration. Further studies are needed to clarify the detailed mechanisms underlying this model.

Declining Rates of Hip Fracture in End-Stage Renal Disease: Analysis From the 2003-2011 Nationwide Inpatient Sample.

The incidence of hip fracture in patients with end-stage renal disease (ESRD) is considerably higher than that in the general age- and sex-matched population. Although medical therapy for chronic kidney disease mineral bone disorder (CKD-MBD) has changed considerably over the last decade, rates of hip fracture in the entire ESRD population have not been well-characterized. Herein, we evaluated temporal trends in rates of hip fracture, in-hospital mortality, and costs of associated hospital stay in ESRD. We identified hospitalizations for hip fracture from 2003 to 2011 using the Nationwide Inpatient Sample, a representative national database inclusive of all ages and payers. We incorporated data from the United States Renal Data System and the US Census to calculate population-specific rates. Between 2003 and 2011, we identified 47,510 hip fractures in the ESRD population. The overall rate of hip fracture was 10.04/1000 person-years. The rate was 3.73/1000 person-years in patients aged less than 65 years, and 20.97/1000 person-years in patients aged 65 or older. Age- and sex-standardized rates decreased by 12.6% from 2003 (10.23/1000 person-years; 95% confidence interval [CI], 7.99/1000 to 12.47/1000) to 2011 (8.94/1000 person-years; 95% CI, 7.12/1000 to 10.75/1000). Hip fracture rates over time were virtually identical in patients aged less than 65 years; however, rates decreased by 15.3% among patients aged 65 years or older; rates declined more rapidly in older women compared with older men (p for interaction = 0.047). In-hospital mortality rate after hip fracture operation declined by 26.7% from 2003 (8.6%; 95% CI, 6.8 to 10.4) to 2011 (6.3%; 95% CI, 4.9 to 7.7). In ESRD, age- and sex-standardized hip fracture rates and associated in-hospital mortality have declined substantially over the last decade. © 2017 American Society for Bone and Mineral Research.

Identification of differentially expressed miRNAs associated with chronic kidney disease-mineral bone disorder.

The purpose of this study is to characterize a meta-signature of differentially expressed mRNA in chronic kidney disease (CKD) to predict putative microRNA (miRNA) in CKD-mineral bone disorder (CKD-MBD) and confirm the changes in these genes and miRNA expression under uremic conditions by using a cell culture system. PubMed searches using MeSH terms and keywords related to CKD, uremia, and mRNA arrays were conducted. Through a computational analysis, a meta-signature that characterizes the significant intersection of differentially expressed mRNA and expected miRNAs associated with CKD-MBD was determined. Additionally, changes in gene and miRNA expressions under uremic conditions were confirmed with human Saos-2 osteoblast-like cells. A statistically significant mRNA meta-signature of upregulated and downregulated mRNA levels was identified. Furthermore, miRNA expression profiles were inferred, and computational analyses were performed with the imputed microRNA regulation based on weighted ranked expression and putative microRNA targets (IMRE) method to identify miRNAs associated with CKD occurrence. TLR4 and miR-146b levels were significantly associated with CKD-MBD. TLR4 levels were significantly downregulated, whereas primiR- 146b and miR-146b were upregulated in the presence of uremic toxins in human Saos-2 osteoblast-like cells. Differentially expressed miRNAs associated with CKD-MBD were identified through a computational analysis, and changes in gene and miRNA expressions were confirmed with an in vitro cell culture system.

Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation.

Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR). In 80 KTR patients (31F/49M, 54.7±10.3 years) we studied the relationships of serum Sclerostin with eGFR, Calcium, Phosphate, Alkaline Phosphatase (AP), intact Parathyroid hormone (iPTH), soluble alpha-Klotho (sKlotho), intact Fibroblast Growth Factor 23 (iFGF23), 25-hydroxyvitamin D(25D) and 1,25-dihydroxyvitamin D (1,25D). Thirty healthy subjects (35.0±12.4 years, eGFR 109.1±14.1 ml /min/1,73m2) served as control for Sclerostin, iFGF23 and sKlotho. With a median eGFR of 46.3 mL/min/1.73m2 (IQR, 36.2–58.3) our KTR had median Sclerostin levels of 23.7 pmol/L (IQR: 20.8–32.8), not different from controls (26.6 pmol/L, IQR: 22.0–32.2; p = n.s). Sclerostin correlated negatively with AP (r = -.251; p = 0.023) and positively with iFGF23 (r = .227; p = 0.017) and 25D (r = .214; p = 0.025). Age-adjusted multiple regression analysis identified AP and 1,25D as negative and 25D and sKlotho as positive best predictors of Sclerostin. No correlation was evident with eGFR. The negative correlation with AP confirms the direct anti-anabolic role of Sclerostin. The associations either negative or positive with iFGF23, sKlotho, and vitamin D metabolites suggest also a modulatory role in mineral homeostasis. In particular, the associations with iFGF23 (positive) and 1,25D (negative) underline the relevant inhibitory action of Sclerostin on vitamin D activation. In conclusion, Sclerostin levels in KTR are normal and influenced more by bone turnover than by eGFR. Its involvement with other hormones of mineral homeostasis (FGF23/Klotho and Vitamin D) is part of the sophisticated cross-talk between bone and the kidney.

Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function.

The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality. The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m2) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011. A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance (Pinteraction=0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance (i.e., <1.5 ml/min per 1.73 m2), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance (i.e., ≥1.5 ml/min per 1.73 m2; Pinteraction<0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk (Ptrend<0.001 for both) irrespective of residual renal urea clearance strata (Pinteraction=0.34 and Pinteraction=0.53, respectively). Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population.

Assessment of bone turnover markers to predict mineral and bone disorder in men with pre-dialysis non-diabetic chronic kidney disease

BackgroundChronic kidney disease (CKD) is commonly associated with disturbances in mineral metabolism and bone disease. Bone biopsy is the gold standard in diagnosing mineral bone disorder. Hence the search for non-invasive assessment of bone health gains importance. We undertook to assess the bone health in men with stage 4 and 5 chronic kidney Disease. MethodsWe recruited 32 male subjects with Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25-hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline phosphatase were assayed. Bone mineral density (BMD) was estimated using dual-energy X-ray absorptiometry. ResultsCKD is associated with significantly higher levels of bone-specific alkaline phosphatase and intact parathyroid hormone and lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to controls. In the multivariate linear regression model, bone-specific alkaline phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator Characteristic analysis for prediction of reduced BMD in CKD showed both intact parathyroid hormone and bone-specific alkaline phosphatase have significant predicting power. ConclusionThe combination of bone-specific alkaline phosphatase and intact parathyroid hormone has more significant predicting power and is a more reliable index for non-invasive assessment of bone health in men with chronic kidney disease, than either marker when used alone.

Prevalence and factors promoting the occurrence of vitamin D deficiency in the elderly

Vitamin D deficiency affects a large part of the population of elderly people, especially women, who live in moderate climate countries due to a reduced amount of vitamin D in the diet (small sea fish consumption) and reduced content of 7-dehydrocholesterol, which causes decreased skin synthesis. The lowest seasonal concentration of 25(OH)D3 is usually observed during winter and spring. Sun exposure influences 25(OH)D3 concentration more strongly in men than in women. Sociodemographic factors that increase the risk of vitamin D deficiency in the elderly include poor environmental conditions, low economic status, lower educational level, drug exposure (smoking), reduced physical activity, overall poor health and obesity, which causes reduced skin exposure to sunlight. The use of medications or supplements that contain vitamin D and staying in a nursing home that employ such supplementation are factors that prevent deficiency. Significant prevalence of diseases of the gastrointestinal tract may contribute to cholecalciferol and ergocalciferol malabsorption or impair their liver transformation. In addition, the high incidence of chronic kidney disease in old age reduces processing hydroxylation of vitamin D and the formation of active metabolites. Vitamin D deficiency can not only cause bone mineralization disorders, but also increase incidence of cardiovascular diseases, cancers, type 2 diabetes and depression. The aim of this study was to summarize current knowledge about the risk factors of vitamin D deficiency development in the elderly population.

A Comparative Study of Intravenous Injection Form and Oral Jelly Form of Alendronate Sodium Hydrate for Bone Mineral Disorder after Gastrectomy

Background/Aims: Osteoporosis is found to have high prevalence after gastrectomy and therefore, it is important to prevent this condition by means of effective medication, such as alendronate sodium hydrate. Methods: A total number of 48 gastric cancer patients diagnosed with osteoporosis after R0 gastrectomy was registered in this study between December 2013 and August 2014. Twenty-three patients received intravenous (i.v.) alendronate sodium hydrate and 25 patients received the drug in an oral jelly form. Serological and urinary examinations related to bone metabolism and bone mineral density (BMD) were performed periodically and the results obtained from the 2 groups were compared. Results: BMD increased, serum levels of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b, and the urine level of urine N-terminal telopeptide decreased with time in both groups. However, the serum Ca level did not change. Two-way analysis of variance revealed no significant differences in these factors between the 2 groups. Conclusion: It is essential to prevent both forms of osteoporosis by using alendronate sodium hydrate after gastrectomy for gastric cancer. A prospective, randomized, controlled trial in many patients following long duration should be conducted to clarify the benefits of i.v. alendronate sodium hydrate.

Low-trauma fractures without osteoporosis.

In clinical practice, areal bone mineral density (aBMD) is usually measured using dual-energy X-ray absorptiometry (DXA) to assess bone status in patients with or without osteoporotic fracture. As BMD has a Gaussian distribution, it is difficult to define a cutoff for osteoporosis diagnosis. Based on epidemiological considerations, WHO defined a DXA-based osteoporosis diagnosis with a T-score <-2.5. However, the majority of individuals who have low-trauma fractures do not have osteoporosis with DXA (i.e., T-score <-2.5), and some of them have no decreased BMD at all. Some medical conditions (spondyloarthropathies, chronic kidney disease and mineral bone disorder, diabetes, obesity) or drugs (glucocorticoids, aromatase inhibitors) are more prone to cause fractures with subnormal BMD. In the situation of fragility fractures with subnormal or normal BMD, clinicians face a difficulty as almost all the pharmacologic treatments have proved their efficacy in patients with low BMD. However, some data are available in post hoc analyses in patients with T score >-2. Overall, in patients with a previous fragility fracture (especially vertebra or hip), treatments appear to be effective. Thus, the authors recommend treating some patients with a major fragility fracture even if areal BMD T score is above -2.5.

Mineral metabolism and cardiovascular disease in CKD.

The mineral bone disorder of CKD, called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), has a major role in the etiology and progression of cardiovascular disease in CKD patients. Since the main emphasis in CKD-MBD is on three categories (bone abnormalities, laboratory abnormalities, and vascular calcifications), we have routinely accepted ectopic cardiovascular calcifications as a central risk factor in the pathophysiology of CKD-MBD for cardiac events. However, recent compelling evidence suggests that some CKD-MBD-specific factors other than vascular calcification might contribute to the onset of cardiovascular disease. Most notable is fibroblast growth factor-23 (FGF23), which is thought to be independently associated with cardiac remodeling. Slow progression of cardiac disorders, such as vascular calcification and cardiac remodeling, characterizes cardiac disease due to CKD-MBD. In contrast, fatal arrhythmia may be induced when QT prolongation occurs with CKD-MBD treatment, such as with lower Ca dialysate or the use of calcimimetics. Sudden onset of fatal cardiac events, such as heart failure and sudden cardiac death, due to fatal arrhythmia would be another distinctive phenomenon of CKD-MBD. This may be defined as CKD-MBD-specific cardiac complex syndrome.

Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease.

Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis. There are many uremia-associated factors that contribute to bone fragility, including severe secondary hyperparathyroidism, skeletal resistance to parathyroid hormone, and bone mineralization disorders. Uremia also aggravates bone volume loss, disarranges microarchitecture, and increases the deterioration of material properties of bone through abnormal bone cells or excess oxidative stress. In this review, we outline the prevalence of fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and discuss possible factors that exacerbate the mechanical properties of bone.

Advanced glycation end-products (AGEs) accumulation in skin: relations with chronic kidney disease-mineral and bone disorder.

Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients. Twenty prevalent HD patients (HD group) and healthy subjects (Control group, n = 24), performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH), transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.

Long-Term Progression of Coronary Artery Calcification Is Independent of Classical Risk Factors, C-Reactive Protein, and Parathyroid Hormone in Renal Transplant Patients

Aims: Compared to the general population, mortality is significantly increased in renal transplant recipients. In the general population, coronary artery calcification (CAC) and its evolution over time are associated with cardiovascular and all-cause mortality, and the study of this biomarker could provide useful information for describing the long-term progression of coronary heart disease in renal transplant recipients. Methods: We followed up a cohort of 113 renal transplant patients by performing three multi-detector computed tomography studies over 83.6 ± 6.8 months. Data analysis was performed by logistic regression analysis and by mixed linear modelling. Results: Progression was observed in 34.5% of patients. Baseline CAC and time-to-transplantation were the sole variables that predicted CAC evolution over time. Neither classical nor nontraditional risk factors, biomarkers of renal function (GFR) and kidney damage (albuminuria) or biomarkers of bone mineral disorder (BMD), such as serum phosphorus, calcium, and PTH, were associated with the long-term progression of coronary calcification. Serum triglycerides predicted CAC progression only in logistic regression analysis, while in addition to baseline CAC, time to transplantation was the sole variable predicting CAC progression when the data were analyzed by mixed linear modelling. These data suggested that, in addition to the background calcification burden, other unmeasured factors play major roles in promoting the evolution of coronary calcification in the transplant population. Conclusion: CAC progression continued over the long-term follow-up of renal transplant patients. This phenomenon was unaccounted for by classical and nontraditional risk factors, as well as by biomarkers of renal dysfunction and renal damage.

Clinical Epidemiology of Mineral Bone Disorder Markers in Prevalent Hemodialysis Patients in the Xinjiang Uyghur Autonomous Region in China.

We investigated the clinical epidemiology of mineral bone disorder markers in prevalent hemodialysis (HD) patients in Xinjiang, the largest province in China. Data were obtained from 59 hospitals. A total of 3725 patients tracked from January 1 to December 31, 2014, were enrolled. Serum calcium (Ca) levels, phosphorus (P) levels, and intact parathyroid hormone (iPTH) levels were analyzed. Serum Ca levels were lower compared to the International Dialysis Outcomes and Practice Patterns Study (DOPPS4) and the Chinese DOPPS. The hypercalcemia rate was similar to DOPPS4 and lower than in the Chinese DOPPS. Serum P levels were higher than in DOPPS4 and lower than those in the Chinese DOPPS. Hyperphosphatemia rates were higher than DOPPS4 and lower than Chinese DOPPS. Serum iPTH levels were higher than in DOPPS4 and the Chinese DOPPS. We demonstrated higher serum P and iPTH levels in Xinjiang HD patients than in the DOPPS4 and Chinese DOPPS. In contrast, serum Ca levels were lower than the other two studies. High hypocalcemia and hyperphosphatemia rates may suggest that HD services in Xinjiang are inadequate. A multidiscipline chronic kidney disease (CKD) care program needs to be established to improve chronic kidney disease-mineral and bone disorder (CKD-MBD) target achievement in Xinjiang.