Bone Mineral Metabolism Parameters Research Articles

Beneficial effects of ketoanalogues on the evolution of renal function and bone mineral disorders in patients with advanced chronic kidney disease :A pilot study.

Introduction The supplementation with Ketoanalogues in patients on very low protein diets has shown an favorable effect in the evolution of renal function . The aim of the present study is to evaluate the progression of renal function in advanced CKD patients on a low protein diet (<0.8 g/kg/d) with or without additional Ketoanalogues. Methods The primary criterion is the evolution of the renal function at 6, 12 and 24 months for the two groups. The secondary criteria comprise the evolution of the body weight, mean blood pressure, 24h proteinuria, salt and protein consumption, energy consumption, hemoglobin levels, serum albumin, prealbumin, C-reactive protein, liver function tests,serum electrolyte levels and phosphate, parathormone as well as calcium levels at the same time periods. Results There was a significant nephroprotective effect of the Ketoanalogues after 12 and 24 months with no differences in the protein consumption between the two groups. Mean blood pressure, hemoglobin levels, 24-four hour proteinuria, serum electrolyte , liver function tests, salt and protein consumption, serum albumin and prealbumin did not present any significant differences. Serum bicarbonate and calcium levels were higher while serum phosphate and parathormone levels were lower in the Ketoanalogue group at all follow-up time points. During the 24 months follow-up period, 4 patients from the Ketoanalogue group and 8 patients from the control group quitted the study. Conclusion A low protein diet supplemented with Ketoanalogues exerts significant nephroprotective effects and better bone mineral metabolism parameters compared to a low protein diet only.

#2223 Glycosylated hemoglobin levels and bone phenotype in patients with end-stage kidney disease

Abstract Background and Aims Diabetes mellitus is common as both cause and comorbidity of patients with chronic kidney disease (CKD). Both diabetes and CKD are states of increased fracture risk compared to healthy controls, with multiple potential contributing mechanisms. In type 2 diabetes, hyperglycemia contributes to the accumulation of advanced glycation end-products and osteocyte dysfunction, and it may play a pathogenic role in bone fragility. In this study, we wanted to examine the association between glycemic status and bone phenotype in patients with end-stage kidney disease (ESKD). Method This is a cross-sectional cohort study of 626 patients with CKD G5-5D referred for kidney transplantation between April 2006 and December 2013. Patients with type 1 diabetes were excluded. Patients were divided into quartiles based on HbA1c. Laboratory parameters of bone mineral metabolism (including biointact parathyroid hormone (PTH), fibroblast growth factor-23 (FGF23), and sclerostin), and bone turnover markers (bone alkaline phosphatase (BALP), trimeric pro-collagen type 1 N-terminal pro-peptide (intact P1NP), and tartrate-resistant acid phosphatase 5b (TRAP5b)) were measured. Bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DEXA) (n = 537), bone histomorphometry (n = 180), and bone trabecular score (TBS) (n = 192) were available for subsets of patients. Results The median HbA1c were 4.8% in Q1, 5.1% in Q2, 5.4% in Q3, and 5.9% in Q4. Age and BMI differed across quartiles, with the highest age and BMI in Q4. Differences in bone turnover markers were found, with decreasing bone formation (BALP and intact P1NP) and decreasing bone resorption (TRAP5b) with ascending quartiles (Fig. 1). No differences across quartiles were found for FGF23, or circulating levels of sclerostin; however a weak, positive correlation between HbA1c and sclerostin was noted (rho = 0.08, p = 0.047). Overall, BMD at lumbar spine, femoral neck, and total hip increased across quartiles, the highest values in Q4 (Table 1). There were no differen in bone histomorphometry or TBS based on glycemic status. Conclusion Chronic hyperglycemia associates with suppressed bone turnover and higher BMD in patients with ESKD, even in non-diabetics. Potential mechanisms linking glucose metabolism to bone quantity and quality requires further investigation.

#129 Impact of Ramadan fasting on bone mineral metabolism in hemodialysis: a multi-center prospective study

Abstract Background and Aims Fasting is fundamental in several major religions and cultural traditions worldwide. In Islam, Ramadan fasting is characterized by daily complete eating and drinking abstinence from the dawn to sunset for an entire lunar month. Sick patients, including patients with advanced chronic kidney disease are not required to fast, however the majority of them are still choose to fast. The Impact of Ramadan fasting on bone health has not been studied prospectively. This study aims to examine the effect of Ramadan fasting on parameters of bone mineral metabolism in patients on hemodialysis. Method : This is a multi-center prospective study on 138 patients with ESKD who are maintained on intermittent hemodialysis for at least six months. Ninety-three (67%) were fasting while 45 patients (33%) did not fast. All patients' demographics, clinical and laboratory parameters were compared before and after the holy month of Ramadan. Serum biochemical parameters included serum sodium, potassium, bicarbonate, chloride, albumin, calcium, phosphorus, magnesium, intact parathyroid hormone (iPTH), FGF23, klotho, sclerostin, bone-specific alkaline phosphatase (BSAP), and tartrate-resistant alkaline phosphatase 5b (TRAP5b). Results The two groups exhibited comparable demographics and clinical parameters at baseline, except for the mean age, which was significantly lower in the fasting group (45.5 vs. 54.4 years, p-value = 0.003) and the non-smoker habit was significantly higher in the fasting group (71% vs. 56%, p-value = 0.02). There was no change in the clinical parameters by the end of Ramadan in both groups including intra-dialytic hypotension, inter-dialytic weight gain, and hypoglycemia. The basic biochemical parameters did not change significantly at the end of Ramadan in both groups, except there was an increased serum albumin level (p-value = 0.04). The BSAP levels significantly went down by the end of Ramadan in the fasting group (p-value = 0.01). The other novel serum biomarkers (FGF23, klotho, sclerostin, and TRAP5b) did not change significantly in both groups. Conclusion This multi-center prospective study demonstrates that Ramadan fasting does not significantly alter the clinical and biochemical parameters in hemodialysis patients, highlighting its safety in this population. Moreover, our findings reveal a noteworthy reduction of the higher BSAP towards normal levels in fasting patients, suggesting a potential benefit of fasting in improving high bone turnover. Further research is warranted to elucidate this phenomenon's underlying mechanisms and long-term implications, which may hold promise for managing bone health in hemodialysis patients during Ramadan fasting.

Assessment of the serum concentration of growth factors and the informativeness of ultrasonography in studying the structural conditions of the osteoarticular system in children with type III osteogenesis imperfecta

BACKGROUND:The treatment of patients with osteogenesis imperfecta requires dynamic monitoring of the structural state and metabolism of the long bones. In the available literature, practically no data are available on the use of ultrasonography to assess the skeletal system in children with osteogenesis imperfecta. Increased expression of the members of the transforming growth factor-β superfamily in the serum has been described in several congenital bone diseases; however, this has not yet been examined in children with type III osteogenesis imperfecta.
 AIM:To examine the serum concentrations of growth factors in children with type III osteogenesis imperfecta relative to healthy children and evaluate the informativeness of ultrasonography for assessing the state of the osteoarticular system in type III osteogenesis imperfecta and justify the feasibility of its use in this pathology.
 MATERIALS AND METHODS: Children aged 3–7 years with type III osteogenesis imperfecta (n= 12) were examined. In the blood serum, bone-mineral metabolism parameters were determined onaHitachi/BM 902 analyzer (Japan), and the contents of growth factors and their receptors were determined by enzyme-linked immunosorbent assay onaThermo Fisher Scientific analyzer (USA). Ultrasound examinations were performed usinganAVISUS Hitachi device (Japan). Statistical processing was carried out using the Attestat program (I.P. Gaidyshev). Quantitative data are presented as medians and quartiles (Me [Q1; Q3]) for samples with non-normal distribution. In cases with normal distribution, quantitative data are presented as M ± σ,p 0.05.
 RESULTS: In patients with osteogenesis imperfecta, the degree of bone tissue mineralization and bone turnover rates were higher and the collagen content was lower than those of their healthy peers. Fibroblast growth factor-basic underwent the greatest changes; a decrease in the content of the vascular endothelial growth factor (VEGF)-R3 receptor was accompanied by multiple increases in VEGF and VEGF-R2. Ultrasonography identified areas of deformation and multiple fractures in the area of the diaphyses and metaphyses of the femur, tibia, hip, and knee joints.
 CONCLUSIONS:Predominance was noted toward the production of growth factors responsible for the activation of osteoclastogenesis. The content of growth factors responsible for osteoclast inhibition and osteoblast activation is normal or slightly changed. Ultrasonography has demonstrated high informativeness inadetailed assessment of the osteoarticular system in patients with osteogenesis imperfecta, which allows us to recommend this noninvasive technique for wider use in this disease.

#4554 FRAX® ASSOCIATION, BONE DENSITOMETRY, BIOCHEMICAL PARAMETERS OF BONE MINERAL METABOLISM AND ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Currently, there are calculation tools that predict the risk of fractures (fx), one of which is the Fracture Risk Assessment Tool (FRAX®). Patients with advanced chronic kidney disease (CKD) have a higher risk of fx than the general population and it is an independent factor for fx. However, this tool does not consider the presence or absence of CKD, where alterations in bone mineral metabolism have important clinical consequences and their prevention should be the objective of CKD control. The aim of our study is to evaluate the FRAX® tool in patients with advanced CKD and to analyze possible relationships with parameters of bone mineral metabolism. Method Observational, descriptive, retrospective study of a series of cases of patients with advanced chronic kidney disease in our center, where demographic data, FRAX® calculation, personal history of Diabetes Mellitus, etiology of CKD, personal history of fx, measurement of bone mineral densitometry by dual energy X-ray absorptiometry (DXA), estimated glomerular filtration rate (CKD-EPI), levels of serum calcium and phosphorus, vitamin D 1. 25 levels, Parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23), use of phosphorus chelating treatment and vitamin D were collected. Descriptive results of continuous variables are expressed as mean and standard deviation or median and interquartile range (IQR) according to their distribution. For categorical data, frequency and percentage are reported. To analyze the impact of the variables on the event to be studied, a univariate and multivariate Cox regression model was used. Results 59 patients with advanced CKD with DXA performed within one year of the FRAX® analysis were analyzed. The median age was 66 years (IQR 22). 59.3% were male. 35.6% had a personal history of diabetes mellitus. The most frequent etiology of CKD was unknown etiology (18.6%), followed by vascular (16.9%). History of some type of fx:13.6% (3.6% vertebral). Estimated glomerular filtration rate CKD-EPI: 20.7 ml/min/1,73 m2 (IQR 7.5). 16.9% had osteoporosis of the femoral neck and 22% of the spine. DXA decreased in femoral neck 78% and in spine 59.3%. Low risk of major osteoporotic fracture according to FRAX® of 76.3% and 64.3% (without and with DXA) and elevated risk of major osteoporotic fracture according to FRAX® 5.1% and 8.5% (without and with DXA). Risk of hip fracture 25.4% and 30.5% (without and with DXA). These data are summarized in Figure 1 and Figure 2. In the multivariate analysis there is no relationship between bone mineral metabolism parameters and DXA. The results showed a negative correlation between glomerular filtration rate CKD-EPI and FRAX® hip (HR -1.7; 95% CI 1.46-9.6 p = 0.027) which would suggest an association between loss of renal function and loss of DXA. Patients with diabetes mellitus have a higher risk of fx (HR 3.7; 95% CI 1.46-9.6 p = 0.009). Conclusion In patients with advanced CKD, FRAX® index identifies patients at high fracture risk for whom active treatment for osteoporosis should be instituted. In patients with advanced chronic kidney disease, FRAX® underestimates those patients with decreased bone mass and elevated risk of osteoporosis. We did not find any association with biochemical parameters of bone mineral metabolism which could guide us in anticipating the treatment of osteoporosis. The loss of renal function accelerates the loss of bone mass, so we believe that the introduction of this variable is necessary in the equation, especially in this profile of patients.

#4051 FGF-23 IN CHRONIC KIDNEY DISEASE: CORRELATION WITH BONE AND CARDIOVASCULAR PARAMETERS – A PRELIMINARY STUDY

Abstract Background and Aims The FGF-23/Klotho ratio increases from early stages of chronic kidney disease (CKD) in parallel with kidney function declined. In some cases, serum FGF-23 levels increase is unbalanced, causing organ damage and increasing cardiovascular risk. The aim of our study was to evaluate the intact FGF-23 (iFGF-23) levels in a cohort of CKD patients and to establish its correlation with cardiovascular and bone mineral metabolism parameters. Method A prospective observational study in 59 adult normophosphatemic patients with CKD stage 2-4, was performed. Clinical and analytical variables (serum calcium, phosporus, intact parathyroid hormone (iPTH), iFGF-23, calcidiol and calcitriol) were evaluated. Basal transthoracic echocardiogram, bone densitometry (Lunar prodigy, GE iDXA), software trabecular bone score (TBS), iNsight clinical data analyzer and carotid Doppler ultrasound were performed. We excluded patients with background of primary hyperparathyroidism, hepatorenal polycystic disease, kidney transplant, tumoral nephrectomy, active neoplasm, tubulopathies or treatment with active vitamin D or calcimimetics. For statistical analysis, we use SPSS software (T Student, Xi2, Fisher test, ANOVA test, U-Mann Whitney test and correlations of Pearson and Spearman) Results Mean age was 62,7±10,5 years, 82,5% were men; 17,7% have CKD stage 2, 28,8% stage 3a, 42,3% stage 3b and 9,6% stage 4. The main CKD etiology was vascular (25%) and diabetes (22%). Previous cardiovascular disease was observed in 11% (ischemic heart disease 6,3%, cerebrovascular disease 3,2% and descompensated heart failure with hospitalization 1,6%). Mean iFGF-23 levels in CKD stage 2 were 80,4±38 ng/l (38-170, median 71 ng/l), in CKD stage 3a 95,5±39,7 ng/l (46-178,9 ng/l, median 85,5 ng/l), in CKD stage 3b 118,8±55,06 (35,5-285 ng/l, median 124,6 ng/l) and in stage 4 134,8±50,9 ng/l (65,25-216,5 ng/l, median 136,1 ng/l). We found correlation between iFGF-23 levels and glomerular filtration rate (Rho:-0,390, p: 0,003), as well as with CKD stages (ANOVA test, p: 0,057). We performed 48 carotid doppler ultrasound and observed mild carotid atheromatosis in 58,7%, mainly bilateral, and intima-media thickness >0,9 mm in 7,9%. In patients with atheromatosis, 38,9% showed iFGF-23 levels in second tertil and 36% in the third. We observed left ventricular hypertrophy (LVH) in 46% of patients, mostly mild degree. In bone densitometry, we found mean femoral neck T-Score of -1±1,1 and lumbar spine T-Score of -0,07±1,5, mean mineral bone density (DMO) in femoral neck of 0,89±0,25 g/cm2 and 1,17±0,20 g/cm2 in lumbar spine. Only 40% of patients had normal TBS score. We found correlation between serum iFGF-23 levels and phosphorus tubular reabsorption (r:-0,396, p: 0,002), calcidiol (Rho: 0,264, p:0,047), calcitriol (r: -0,412, p:0,002), iPTH (Rho: 0,296, p:0,025), lumbar T-Score (r: -0,320 p:0,022), lumbar DMO (r:-0,267, p:0,049) and TBS (r: -0,396, p:0,005). Conclusion We confirm an association between a glomerular filtration rate decline and an increase in serum iFGF-23 levels. The inverse correlation observed between iFGF-23 serum levels and lumbar T-Score, lumbar DMO and trabecular microarchitecture suggests a negative effect of iFGF-23 in bone mineralization.

Effect of chronic liver disease continuum upon calcium homeostasis and bone mineral metabolism: An observation from Eastern India

Background: Cirrhosis, a major and life-threatening complication of liver disease, has claimed over a million lives since 2010. It has been estimated that liver disease causes 1.03 million deaths/year globally. Chronic liver disease (CLD) affects metabolism of other organs such as the bone. The prevalence rates of hepatic osteodystrophy range from 13% to 70% in Western countries. Even higher prevalence rate between 68% and 95% has been reported from India. Reports from previous studies regarding the serum concentrations of 25(OH)D and its correlation with the progression of liver diseases have been inconsistent. Some studies have found that 25(OH)D levels decline as the liver disease progresses, whereas others found no significant difference between cirrhotic patients and non-cirrhotic patients or among the Child-Pugh groups. Vitamin D estimation is also thought to bear little predictive value to assess the progression of liver disease in etiologies such as hepatitis C. There are very few studies in the Eastern part of India to show the effect of CLD on bone mineral homeostasis. Based on this background, this study has been designed to reveal the effects of CLD and its severity on various parameters of bone mineral metabolism. Aim and Objectives: The aim of the study was to evaluate the effects of different stages of CLD on bone mineral metabolism and its homeostasis. Materials and Methods: After obtaining proper permission from the Institutional Ethics Committee, the cross-sectional study was conducted in the Department of Biochemistry in collaboration with the Department of Medicine in a tertiary care hospital in Kolkata. The study included 90 cases with established CLD and 90 age- and sex-matched controls screened from the Department of Medicine. Serum Calcium, Inorganic phosphate, 25(OH) Vitamin D, and intact parathyroid hormone (iPTH) were estimated in the Department of Biochemistry. The Child-Pugh-Tucotte score was used to grade the severity of disease. Results: It was observed that serum calcium and serum 25(OH) D levels were significantly lower in patients with CLD (P <0.0001). Serum iPTH levels were significantly higher in patients with CLD compared to controls (P < 0.0001). Conclusion: Routine serial estimation of serum calcium, inorganic phosphate, and 25(OH)D should be mandatory in patients of CLD so that adequate replacements can be initiated as a therapeutic adjunct.

MO572: Effects of Ketoanalogues on the Evolution of Bone Mineral Metabolism in Patients With Advanced Chronic Kidney Disease

Abstract BACKGROUND AND AIMS There is a mounting volume of evidence on the efficacy of ketoanalogues associated with low protein diets, concerning the nephroprotective effects in patients with advanced chronic kidney disease (CKD). The important number of capsules daily ingested associated with their important calcium content would potentially affect the bone mineral metabolism of this group of patients. The aim of this study is to investigate the effects of ketoanalogues on the evolution of the bone mineral metabolism parameters in patients with advanced CKD. METHOD This is a prospective non-randomized controlled comparative study of two groups of patients. The results are shown as mean ± ESM. The first group (intervention) (20 patients, 12/8 M/F, mean age 71.9 ± 2.9, 10 with diabetes) was treated with ketoanalogues associated with a low protein diet and the control group (17 patients, 9/8 M/F, mean age 68.2 ± 3.3, 8 with diabetes) had a conventional follow-up of CKD. We studied the evolution of the body weight, renal function (glomerular filtration rate measured by the CKD-EPI formula in mL/min/1.73 m2), 24 h proteinuria, salt and protein consumption, serum albumin, serum prealbumin, alkaline reserve, serum phosphate levels, serum parathormone levels and calcium levels corrected for serum albumin at baseline as well as 6, 12 and 24 months post-inclusion. We performed a T-test for independent groups in order to study the differences between the two groups in every time point of the study. P-values < 0.05 were considered statistically significant. RESULTS The results are shown in the Table 1. There were no differences between the two groups at baseline. There was a significant nephroprotective effect of the ketoanalogues after 12 and 24 months. Alkaline reserve and serum calcium levels were significantly higher in the intervention group after 6, 12 and 24 months. Serum phosphate and serum parathormone levels were significantly higher in the control group 6 months, 1 and 2 years after the baseline. All patients were treated with the appropriate agents for the correction of the perturbed study parameters. During the 2-year follow-up, four patients from the study group (two pre-emptive renal transplantations, one death from oncologic causes and one start of dialysis) and eight patients from the control group (three deaths and five dialysis initiations) quitted the study. CONCLUSION In conclusion, the treatment with ketoanalogues and low protein diet has a significantly positive impact on the bone mineral metabolism of the patients with advanced CKD. It is unknown whether this is due to the high calcium content of the capsules or from the fact that the renal function is better preserved in the intervention group

Advantages of the use of citrate over acetate as a stabilizer in hemodialysis fluid: A randomized ABC-treat study

Hemodialysis (HD) with bicarbonate dialysis fluid (DF) requires the presence of an acid to prevent the precipitation of calcium and magnesium carbonate. The most used acid is acetic acid, with it several complications have been described. In a previous work we described the acute changes during an HD session with a DF with citrate instead of acetate. Now we report the results in the medium term, 16 weeks. It is a prospective, multicenter, crossover and randomized study, where 56 HD patients with bicarbonate three times a week were dialysed for 16 weeks with 3 mmol/L acetate and 16 weeks with 1 mmol/L citrate. Patients older than 18 years with a previous stay on HD of more than 3 months and with a normal functioning arteriovenous fistula were included. Epidemiological data, dialysis, bioimpedance, biochemistry before and after HD, as well as hypotensive episodes, were collected monthly. After 16 weeks of citrate treatment, preHD ionic calcium and magnesium were significantly lower and PTH higher than in the acetate period. No differences were observed in the effectiveness of dialysis. Hypotensive episodes were significantly more frequent with acetate than with citrate: 311 (14.1%) vs 238 (10.8%) sessions. The lean mass index increased by 0.96 ± 2.33 kg/m2 when patients switched from LD with acetate to citrate.HD with citrate modifies several parameters of bone mineral metabolism, not only acutely as previously described, but also in the long term. The substitution of acetate for citrate improves hemodynamic stability, producing less hypotension and can improve nutritional status.

Ventajas del uso de citrato respecto al acetato como estabilizante en el líquido de hemodiálisis: estudio aleatorizado ABC-treat

Hemodialysis (HD) with bicarbonate dialysis fluid (DF) requires the presence of an acid to prevent the precipitation of calcium and magnesium carbonate. The most used acid is acetic acid, with it several complications have been described. In a previous work, we described the acute changes during an HD session with a DF with citrate instead of acetate. Now, we report the results in the medium term, 16 weeks. It is a prospective, multicenter, crossover and randomized study, where 56 HD patients with bicarbonate three times a week were dialysed for 16 weeks with 3mmol/L acetate and 16 weeks with 1mmol/L citrate. Patients older than 18 years with a previous stay on HD of more than 3 months and with a normal functioning arteriovenous fistula were included. Epidemiological data, dialysis, bioimpedance, biochemistry before and after HD, as well as hypotensive episodes, were collected monthly. After 16 weeks of citrate treatment, pre-HD ionic calcium and magnesium were significantly lower and paratiroid hormone (PTH) higher than in the acetate period. No differences were observed in the effectiveness of dialysis. Hypotensive episodes were significantly more frequent with acetate than with citrate: 311 (14.1%) vs 238 (10.8%) sessions. The lean mass index increased by 0.96±2.33kg/m2 when patients switched from DF with acetate to citrate.HD with citrate modifies several parameters of bone mineral metabolism, not only acutely as previously described, but also in the long-term. The substitution of acetate for citrate improves hemodynamic stability, producing less hypotension and can improve nutritional status.

MO473INTERACTION OF SCLEROSTIN AND OSTEOPROTHERIN IN THE DEVELOPMENT OF VASCULAR CALCIFICATIONS AT STAGE 3-5 OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims: Background and Aims: . Vascular calcification (VC) due to bone-mineral metabolism disorders is a predictor of high cardiovascular mortality in patients with late-stage chronic kidney disease (CKD) . The established bone-vascular axis in CKD, which relates to interactions between changes in the bone and vascular systems that have similar mechanisms, allows bone metabolism inhibitors to act as potential risk factors for VC. Morphogenetic protein osteoprotegerin (OPG) and glycoprotein sclerostin are opposite inhibitors of bone metabolism: OPG inhibits osteoclastogenesis, sclerostin has an inhibitory effect on osteoblastogenesis. Although both proteins are recognized as high-risk factors for remodeling the heart and large arteries in patients with CKD, the mechanisms and possibilities for correcting these changes are not fully clear. of the study was to investigate the mechanisms of the relationship between OPG and sclerostin in the development of cardiovascular complications due to calcification of the aorta and large arteries in the late stages of CKD. Method: Method The cross-sectional study included 105 patients with stage 3-5 CKD [49 men; 64.0 (23.0-76.0)years]. The glomerular filtration rate determined using the CKD-EPI equation was 38.4 (8.6–92.3) ml / min / 1.73 m2. The general clinical examination included assessment of hematopoiesis (hemoglobin, hematocrit, ferritin and transferrin), determination of total protein and albumin levels, cholesterol, electrolytes (sodium, potassium) in the blood, and indicators of nitrogen metabolism (creatinine, urea). Parameters of bone-mineral metabolism – parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase of blood serum-were evaluated. The level of morphogenetic protein OPG and glycoprotein sclerostin was determined using commercial ELISA kit from Biomedica (Austria) by enzyme immunoassay. The morphofunctional features of the aorta and large arteries were studied by duplex scanning using the Doppler effect. We determined the peak systolic velocity of blood flow in the aortic arch (Vps-peak systolic velocity) , which indirectly indicates the state of the aortic wall and its lumen. Echocardiography with Doppler imaging was performed on the "ALOKA 4000" device. The LV myocardial mass index (LVMI), LV hypertrophy variants, LV systolic and diastolic function were determined. Results Cardiovascular damage, which manifests itself in the form of various variants of left ventricular hypertrophy, aortic rigidity, arteriosclerosis and vascular calcification, and directly correlated with the severity of renal failure, was detected in 86% of the examined patients with stage 3-5 CKD. The level of OPG and sclerostin in the blood serum increased with the progression of renal failure from the 3rd to the 5th. The main associations with Vps changes were high OPG levels [OR = 2.39 95% confidence interval (95% CI) (1.34–4.86) for levels ranging from 5.98 to 9.26 pmol / L and OR = 5.54 95% CI (2.64–13.5) for levels ≥9.26 pmol / L; P <0.0001] and high sclerostin levels [OR = 2.64 95% CI (1.42–5.16) for levels ranging from 0.744 to 1.211 ng / ml and OR = 3.69 95% CI (1.76–7.31) for a level ≥1.211 ng / ml; P = 0.0001]. Thus, the logistic regression model showed that the risk of aortic calcification was significantly increased when both OPG (≥5.98 pmol / L) and sclerostin (≥0.744 ng / ml) levels were high [ uncorrected model: OR = 11.93 (4.54–25.2); P <0.0001; on the model adjusted for generally recognized cardiovascular disease risk factors: OR= 5.55 (1.43–1914); P = 0.02]. Conclusion The results suggest that bone metabolism inhibitors, OPG and sclerostin, are independently associated with aortic calcification with potential additive effects in patients with stage 3-5 CKD. The risk of vascular calcification was significantly increased when OPG and sclerostin levels were high

MO199DENOSUMAB: NOVEL APPROACH TO TREATMENT OF OSTEOPOROSIS IN RENAL DISEASE

Abstract Background and Aims Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL), an osteoclast differentiating factor. It inhibits osteoclast formation, decrease bone resorption, increase bone mineral density (BMD), and reduce the risk of fracture. There is no restriction of its use in patients with renal disease, for whom biphosphonates are considered controindicated. The aim of our study was to evaluate the effectiveness in reducing facture risk and safety of Denosumab in patients with Osteoporosis and renal disease. Method This is a prospective analysis of 17 patients with Osteoporosis (average T-score below -2.5) admitted to our Nephrology Department for CKD in the last four years. in Vasculitis, Renal Allograft Recipients. Patients with severe Hyperparatiroidism were excluded. We estimated creatinine clearance (eGFR) using Cockcroft-Gault and classified levels of kidney function using the modified National Kidney Foundation classification of CKD. All patients were adequately supplemented with calcium and vitamin D before and while taking Denosumab 60 mg every 6 months. The primary endpoint is the change in bone mineral density (BMD) at one and two years. Secondary endpoints include changes in bone mineral metabolism parameters (Ca, P, PTHi, 25-OH VitD), incidence of fractures, and renal/allograft fuction at one and two years. Results The mean age was 52.5±4 years and 8/17 (47%) were females. N.13 patients (76.5%) were renal transplant recipients (RTR) on standard triple immunosoppression including steroids (prednisone 5 mg/day), CNI and MMF, with average eGFR 65.7±12.5 ml/min. N.2 patients (11.75%) were in hemodialysis. N.2 patients (11.75%) with Anca Vasculitis on steroid therapy and average eGFR 35.6±7.2 ml/min. All patients enrolled were with a BMD T-score of greater than -4.0 and less than -2.5. Only 2 patients had a history of fractures confirmed by a radiology report. Baseline parameters: calcium 9.8±0.32 mg/dl, phosphate 3.9±0.8 mg/dl, PTHi 137±91.0 ng/L, 25-OH VitD 18.3±8.9 ng/mL. From baseline at 1 month there were an increase in PTH and a decrease in calcemia in only 2 transplant recipients (CKD II and IV), that improved with an increased dose of Vit D. There were no significant difference in baseline bone mineral metabolism parameters to year 1 and 2 in all other patients. We found no difference in eGFR and proteinuria from baseline to 1 and 2 years in RTR and ANCA vasculitis. Significant improvement in T-score was observed at 1 year and 2 years (< -1) in all patients. No one discontinued therapy for adverse events. Conclusion Denosumab may have advantages in patients with kidney dysfunction, because not excreted by the kidney and there is no need for dose adjustment. This prospective study showed a significant improvement in osteoporosis (at Dexa mean T-score ≤ -1), but particular attention should be paid to ensuring that patients are calcium and Vitamin D replete.

Influence of long-term controlled therapeutic exercises on blood pressure profile parameters, elastic properties of arterial wall, metabolic and mineral indices in females with arterial hypertension

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia Objective To study the role of therapeutic exercises (TE) in the correction of blood pressure, stiffness of the vascular wall, metabolic indices of body structure (volume, mass, area of visceral fat) and bone mineral metabolism in postmenopausal hypertensive patients. Methods. The study included 138 patients (mean age was 58.32 ± 7.61 years). All patients are divided into 3 groups. The first control group is 20 women without arterial hypertension and menopausе. The second group consisted of 58 patients with arterial hypertension (AH) and postmenopause who was not undergone complex of TE and the 3rd group - 60 women with AH and postmenopause who was undergone TE complex. Patients of all groups were examined in dynamics: at the starting point of the study and in 12 months after, ambulatory monitoring of blood pressure; sphygmography; densitometry and test for serum biochemistry parameters of blood samples, including sex hormones, vitamin D. Results. In the course of the study, blood pressure, vascular wall stiffness parameters, metabolic indices of body structure and disorder parameters of bone mineral metabolism were comparable in group 2 and 3 against the background of significantly reduced levels of sex hormones. Multidirectional correlation relationships between the studied parameters are revealed. The basic therapy in combination with therapeutic exercises led to a significant decrease in blood pressure and metabolic indices of body structure (p<.001) and to a persistent tendency of decrease the pulse wave velocity and increase of bone mineral metabolism in gr.3. Conclusion. The result of the study indicates that the exercise therapy complex used in the form of regular classes can be recommended for implementation in clinical practice with the aim of comprehensively affecting the patient’s body and developing personalized treatment tactics for postmenopausal women with hypertension.

P0894AEFFECTS OF DENOSUMAB ON BONE MINERAL DENSITY AND LOW ENERGY FRACTURES IN KIDNEY TRANSPLANT PATIENTS: SAFE AND EFFECTIVE

Abstract Background and Aims Fractures are a disabling clinical outcome after kidney transplantation (KTx), with incidence 5 to 34 times higher expected in males and females, respectively. Denosumab, a fully human monoclonal antibody that binds to RANKL with high affinity and specificity, blocking the interaction of RANKL with RANK, mimicking the endogenous effects of osteoprotegerina, increase bone mineral density; however, its effects to reduce the risk of vertebral fractures and ameliorate BMD remain undefinite in the KTx. Method Thirteen kidney recipients (aged from 50 to 79 yy, 6.2 + 5.5 (SD) yy after KTx), 6 M and 7 F (all postmenopausal) with nearly normal renal function (creat. 1.1+-0.31 mg/dl), affected by low energy vertebral fractures (21 dorsal and 1 lumbar vertebrae), evaluated by morphometric X-ray absorptiometry (Hologic DQR-4500A), were treated with denosumab (four 60-mg doses of denosumab Q6M) over 24 months. Data for vertebral heights and height ratios (P-A), covering 9 vertebral bodies were obtained, besides the data of vertebral, femural and radius BMD.The immunosuppressive regimen consisted of CNI (TAC or CsA), MMF and 8 out of 13 patients were still taking prednisone. Bone mineral metabolism parameters (whole-PTH, 25OHD3 and alcaline phosphatase) were also evaluated. Results No sides effects were observed, and all Patients concluded the study.After two years of denosumab treatment, we observed a significative reduction of vertebral T-score (from -2.12 +- 0.35 (SE) to -1.67+-0.35; p< .02), while T score of femural and radius did not show significative variation (-1.86+-0.21 versus -1.84+- 0.23 and -3.04+-0.42 versus -3.19+-0.45, respectively). The number of low energy vertebral fractures, basal versus two years control, had increased for only two dorsal vertebral fractures. However, to one of two subjects, with new dorsal vertebral fractures, was administered high dose of methylprednison for a severe kidney reject. No variations were observed in whole-PTH (89.31+-19.9 versus 68.38+-9.8 pg/ml), 25OHD3 (24.02+-2.75 versus 26.67+-2.29 ug/dl) and alcaline phosphatase (78.46+-12.73 versus 56.77+-7.14 UI). Conclusion Treatment with denosumab improve BMD at vertebral site in KTx, despite continuous steroid therapy and reduce the risk of new low energy vertebral fractures

Prevalence of Vertebral Fractures and Their Prognostic Significance in the Survival in Patients with Chronic Kidney Disease Stages 3‒5 Not on Dialysis.

Background: The prevalence of vertebral fractures (VF) and their association with clinical risk factors and outcomes are poorly documented in chronic kidney disease (CKD) cohorts. The aim of the study was to evaluate the prevalence of VF in patients with non-dialysis dependent CKD (NDD-CKD), their value in predicting mortality and its correlation with parameters of bone mineral metabolism and vascular calcification. Materials and Methods: 612 NDD 3‒5 stage CKD patients participating in the OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into two groups according to presence or absence of VF at enrollment. VF were assessed with lateral radiographs and Genant semi-quantitative method was applied. Three radiologists specialized in musculoskeletal radiology performed consensual reading of individual images obtained using a Raim DICOM Viewer and a Canon EOS 350 camera to measure with Java Image software in those who had traditional acetate X-ray. Factors related to VF were assessed by logistic regression analysis. Association between VF and death over a 3-year follow-up was assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. Results: VF were detected in 110 patients (18%). Serum phosphate levels (OR 0.719, 95% CI 0.532 to 0.972, p = 0.032), ankle-brachial index < 0.9 (OR 1.694, 95% CI 1.056‒2.717, p = 0.029) and treatment with bisphosphonates (OR 5.636, 95% CI 1.876‒16.930, p = 0.002) were independently related to the presence of VF. After a median follow-up of 35 months (IQR: 17‒37 months), 62 patients (10%) died. The causes of death were cardiovascular (n = 21, 34%) and infectious (n = 11, 18%). In the crude analysis, fractured patients group had poorer survival (log-rank test, p = 0.02). After multivariate adjustment for age, MDRD, albumin, diabetes mellitus, comorbidity, Adragao Score > 3 and serum phosphate, the presence of VF (HR 1.983, 95% CI 1.009‒3.898, p = 0.047) were an independent predictor of all-cause mortality. Conclusions: In our study 18% of patients with NDD-CKD have VF. Factors associated with VF were age, low serum phosphate levels and peripheral vascular disease. The presence of VF was an independent risk factor for mortality in stages 3‒5 NDD-CKD patients. Clinical trials are needed to confirm whether this relationship is causal and reversible with treatment for osteoporosis.

Bone mineral density, bone turnover markers, and incident fractures in de novo kidney transplant recipients

Kidney transplant recipients are at increased risk of fractures. This prospective observational study investigated whether areal bone mineral density (aBMD) as assessed by dual-energy x-ray absorptiometry can predict incident fragility fractures in de novo kidney transplant recipients and whether bone turnover markers increase diagnostic accuracy. Parameters of bone mineral metabolism including parathyroid hormone (PTH), fibroblast growth factor 23, sclerostin, calcidiol and calcitriol, and bone turnover markers were assessed in blood samples collected immediately prior to kidney transplantation in 518 adult recipients. aBMD was measured at several skeletal sites within 14 days posttransplant. Thirty patients had a history of a fragility fracture at the time of transplantation, and osteopenia or osteoporosis at the femoral neck was observed in 77%. Bone turnover markers were inversely correlated with aBMD at all skeletal sites. Low aBMD and low PTH were associated with history of fragility fracture at the time of transplantation, independent of age, gender, and comorbidity. During a median post-transplant follow-up of 5.2 years, 38 patients sustained a fragility fracture, corresponding to a fracture incidence of 14.1 per 1000 person-years. Low aBMD at the hip and lumbar spine were associated with incident fractures, independent of classical determinants, including history of fracture. PTH and bone turnover markers at the time of transplantation failed to predict incident fractures. In conclusion, aBMD is low, correlates inversely with bone turnover, and predicts incident fractures in de novo kidney transplant recipients.

A distinct bone phenotype in ADPKD patients with end-stage renal disease

Autosomal dominant polycystic kidney disease (ADPKD) is among the most common hereditary nephropathies. Low bone turnover osteopenia has been reported in mice with conditional deletion of the PKD1 and PKD2 genes in osteoblasts, and preliminary clinical data also suggest suppressed bone turnover in patients with ADPKD. The present study compared the bone phenotype between patients with end stage renal disease (ESRD) due to ADPKD and controls with ESRD due to other causes. Laboratory parameters of bone mineral metabolism (fibroblast growth factor 23 and sclerostin), bone turnover markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b) and bone mineral density (BMD, by dual energy x-ray absorptiometry, DXA) were assessed in 518 patients with ESRD, including 99 with ADPKD. Bone histomorphometry data were available in 71 patients, including 10 with ADPKD. Circulating levels of bone alkaline phosphatase were significantly lower in patients with ADPKD (17.4 vs 22.6 ng/mL), as were histomorphometric parameters of bone formation. Associations between ADPKD and parameters of bone formation persisted after adjustment for classical determinants including parathyroid hormone, age, and sex. BMD was higher in skeletal sites rich in cortical bone in patients with ADPKD compared to non-ADPKD patients (Z-score midshaft radius -0.04 vs -0.14; femoral neck -0.72 vs -1.02). Circulating sclerostin levels were significantly higher in ADPKD patients (2.20 vs 1.84ng/L). In conclusion, patients with ESRD due to ADPKD present a distinct bone and mineral phenotype, characterized by suppressed bone turnover, better preserved cortical BMD, and high sclerostin levels.

Role of fibroblast growth factor 23 in the development of cardiovascular diseases in patients with end-stage renal failure on programmed hemodialysis

To determine the nature of changes in fibroblast growth factor 23 (FGF-23) and other bone mineral metabolism parameters detectable in the blood of patients with end-stage chronic renal failure (CRF) and to analyze their links to the development of cardiovascular events in uremic intoxication. A total of 75 patients (45 men and 30 women) aged 23 to 66 years (mean age, 53±2.1 years) with Stage VD CKF were examined. The levels of parathyroid hormone (PTH), calcium, phosphorus, the morphogenetic protein FGF-23, and the cardiospecific protein troponin I were investigated. Doppler echocardiography was performed on an Aloka 4000 machine. Left ventricular (LV) mass index (LVMI), LV systolic and diastolic function, and peak systolic blood flow velocity in the aortic arch (Vps) were estimated. As LVMI became higher, there were increases in the level of PTH and that of FGF-23 that plays a significant role in the processes of bone remodeling and vascular calcification. Analysis of correlations between a change in FGF-23 concentrations depending on the morphological and functional parameters of the cardiovascular system (CVS) revealed a strong direct correlation between FGF-23 levels and LVMI (r=0.746; p<0.01), a significant inverse correlation between FGF-23 and ejection fraction (r=-0.901; p<0.05), and a direct correlation of FGF-23 and troponin I (r=0.544; p<0.05). FGF-2 increasing from moderate to very high levels indicates that there is a high risk for remodeling processes in the CVS even in the absence of baseline echocardiographic signs of myocardial hypertrophy, normal aortic pulse wave velocity, and compensation of other risk factors, such as hypertension, uremia, hyperparathyroidism, even without increasing the markers of cardiovascular events, such as hyperphosphatemia. The elevated level of FGF-23 suggests that there is a need for cardioprotective therapy, the goal of which is to correct of the level of this factor.

Bone Mineral Metabolism Parameters in Patients During Transition From CKD to ESRD

Bone Mineral Metabolism Parameters in Patients During Transition From CKD to ESRD

Predictors of persistent post transplant hyperparathyroidism (HPTx)

Post transplant persistent Hyperparathyroidism (HPTx) increases the risk for transplant complications. Purpose: to identify risk factors for HPTx in the first post transplant year. Methods: Retrospective analysis of medical records from renal transplant recipients from July/2008 to December/2010. Inclusion criteria: serum PTH ≥500 pg/ml at transplant and normal 1-year graft function (serum creatinine ≤ 2mg/dL). From a group of 224 renal transplants, 69 (30%) fulfilled the inclusion criteria, and they were divided in 2 groups, according to the serum PTH after 1 year of transplant: control, 1-year P TH&lt;150 p g/ml ( n=32) a nd P ersistent H yperparathyroidism, H PTx, 1 -year P TH ≥ 1 50 p g/ml ( n= 3 7). Data analyzed: serum calcium (Ca), phosphate (Pi), alkaline phosphatase (AP), PTH and glomerular filtration rate (GFR) at transplant, and 3, 6 and 12 months post transplant. Results: At transplant, the groups were comparable as to age, Pi and PTH. However, the length of the dialysis (78 40 vs. 50 34 months, p&lt;0.05) and Ca (8,9 0.9 vs. 8,5 0,6mg/dL, p&lt;0.05) were higher in the HPTx group. After 3 months post transplant, HPTx group maintained higher PTH levels (365.4 176.2 vs. 166.9 92.2pg/mL, p&lt;0.05), and AP (175 145 vs. 109 52UI, p&lt;0.05), than controls, despite of the comparable Ca, Pi, and GFR. From the 6th post transplant month, the HPTx group persisted with hypercalcemia (10.2 0.7 vs. 9.9 0.5mg/dL, p&lt;0.05) and low phosphate (2.6 0.5 vs. 2.9 0.7, p&lt;0.05) with higher AP and PTH levels than in controls (p&lt;0.05). At the end of the 1 post transplant year, HPTx group persisted with hypercalcemia, despite the recovery of the graft function while in the control group, the GFR recovery was associated with normalization of the bone mineral metabolism parameters. Conclusion: HPTx was associated with longer pre transplant dialysis therapy and higher Ca at transplant. Higher PTH and AP post transplant levels at the 3rd month were associated with persistent hyperparathyroidism, as well as persistent hypercalcemia and low phosphate, despite of the GFR recovery.