Mineral Bone Disorder Research Articles

Relationship between anemia and biochemical parameters of mineral bone disorders in chronic kidney disease stages 3-5 pre-dialysis patients

Background: Anemia and mineral bone disorders (MBD) accompany chronic kidney disease (CKD) and worsen as CKD progresses. Different biochemical parameters of CKD-MBD have been associated with anemia of CKD but are less well evaluated in low resource settings. In this study, we evaluated the role CKD-MBD disorders as a cause of anemia in CKD non-dialysis patients.
 Methods: This cross-sectional study recruited 115 patients with CKD who attended outpatient department (OPD) of Nephrology in BIRDEM General Hospital between January and June 2019. Patients, who were on iron, erythropoietin, calcium or vitamin D therapy in any form within the preceding 3 months and patients with known parathyroid disorders, metabolic bone diseases or anemia with definite etiology were excluded. Each patient’s demographic, clinical and biochemical parameters were recorded. Associations between anemia and serum levels of calcium (corrected), phosphate, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D] and alkaline phosphatase were evaluated.
 Results: Total patients were 115 including 71 (61.7%) females. Mean age was 57.8 years. Most patients were in CKD stage 4 (43, 37.4%) and 5 (45, 39.1%). Mean duration of diabetes and hypertension were 12.7 and 7.2 years respectively. Mean serum creatinine (mg/dL), hemoglobin (gm/dL), calcium (mg/dL), albumin (gm/L), phosphate (mg/dL), alkaline phosphatase (U/L), PTH (pg/mL) and 25(OH)D (ng/mL) were 3.1, 10.5, 8.7, 37.9, 4.0, 119.1, 211.1 and 15.1 respectively. Hemoglobin in CKD stages 3-5 pre-dialysis patients had positive correlation with calcium and 25(OH)D and negative correlation with phosphate, alkaline phosphatase and PTH. Among these parameters of CKD-MBD, correlation with alkaline phosphatase was significant (r=-0.352, p=0.001)
 Conclusion: Anemia in CKD patients is multifactorial and this study concludes that CKD-MBD is yet another entity contributing to anemia in such pre-dialysis patients.
 Birdem Med J 2020; 10(3): 187-191

Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients

Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19–2.14, 1.60 per mg/dL; 1.14–2.23 and 0.82 per 10 pg/mL; 0.68–0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis.

Impact of physical activity and exercise on bone health in patients with chronic kidney disease: a systematic review of observational and experimental studies

BackgroundChronic Kidney Disease (CKD) patients frequently develop life-impairing bone mineral disorders. Despite the reported impact of exercise on bone health, systematic reviews of the evidence are lacking. This review examines the association of both physical activity (PA) and the effects of different exercise interventions with bone outcomes in CKD.MethodsEnglish-language publications in EBSCO, Web of Science and Scopus were searched up to May 2019, from which observational and experimental studies examining the relation between PA and the effect of regular exercise on bone-imaging or -outcomes in CKD stage 3–5 adults were included. All data were extracted and recorded using a spreadsheet by two review authors. The evidence quality was rated using the Cochrane risk of bias tool and a modified Newcastle-Ottawa scale.ResultsSix observational (4 cross-sectional, 2 longitudinal) and seven experimental (2 aerobic-, 5 resistance-exercise trials) studies were included, with an overall sample size of 367 and 215 patients, respectively. Judged risk of bias was low and unclear in most observational and experimental studies, respectively. PA was positively associated with bone mineral density at lumbar spine, femoral neck and total body, but not with bone biomarkers. Resistance exercise seems to improve bone mass at femoral neck and proximal femur, with improved bone formation and inhibited bone resorption observed, despite the inconsistency of results amongst different studies.ConclusionsThere is partial evidence supporting (i) a positive relation of PA and bone outcomes, and (ii) positive effects of resistance exercise on bone health in CKD. Prospective population studies and long-term RCT trials exploring different exercise modalities measuring bone-related parameters as endpoint are currently lacking.

THE CORRELATION BETWEEN BONE MINERAL DISORDERS AND SOME CLINICAL AND SUBCLINICAL FACTORS IN THE PATIENTS WITH DIALYSIS CHRONIC KIDNEY DISEASE

Objectives: To investigate the correlation between the concentration in blood of bone minerals: Phosphorus, calcium, PTH, vitamin D, β2 microglobulin, aluminium with some clinical and subclinical factors in patients with dialysis chronic kidney patients. Materials and Methods: Descriptive cross-sectional study, include 163 patients with dialysis chronic kidney disease, from January 2017 to December 2018 at the Department of Haemodyalysis, District 2 Hospital, Ho Chi Minh City. Results: Serum phosphorus is negatively correlated with age r = - 0.342; positively correlated with albumin: r = 0.156, urea: r = 0.328, creatinine: r = 0.175, calcium x phosphorus index: r = 0.809,PTH: 0.273. Corrected serum calcium is negatively correlated with albumin: r = - 0.917, Hb: r = - 0.369, urea: r = - 0.178, creatinine: r = - 0.188, calcium x phosphorus index: r = 0.492. Plasma PTH positively correlated with dialysis time: r = 0.336, β2 microglobulin: r = 0.247; negatively correlated with Aluminum: r = - 0.161. Serum vitamin D negatively correlated with age: r = - 0.166, β2microglobulin: r = - 0.231. Serum aluminium positively correlated with diastolic blood pressure: r = 0.207 and systolic: r = 0.209. Serum β2 microglobulin positively correlated with dialysis time: r = 0.233, urea: r = 0.168; negatively correlated with Aluminum: r = - 0.224. Conclusion: Some bone mineral in dialysis patients are correlated with age, dialysis time, blood pressure, albumin, urea, creatinine. There is also a intercorrelation between bone minerals. Therefore, it is necessary to screen for bone mineral disorders and correlations as recommended by KDOQI, KDIGO. Key words: End-stage chronic kidney disease, dialysis, correlation, bone mineral disorders

THE CORRELATION BETWEEN BONE DENSITY AND SOME CLINICAL AND SUBCLINICAL FACTORS IN THE PATIENTS WITH DIALYSIS CHRONIC KIDNEY DISEASE

Objectives: To investigate the correlation between bone density and osteoporosis with some clinical and subclinical factors in patients with dialysis chronic kidney patients. Materials and Methods: Descriptive cross-sectional study, include 163 patients with dialysis chronic kidney disease, from January 2017 to December 2018 at the Department of Haemodyalysis, District 2 Hospital, Ho Chi Minh City. Results: Bone density was negatively correlated with age at the lumbar spine (LS) (r = - 0.225), total hip (total H) (r = - 0.288), femoral neck (FN) (r = - 0.352); with urea at the total H (r = - 0.206), FN (r = - 0.194); with PTH at LS (r = - 0.266), total H (r = - 0.219), FN (r = - 0.168); with β2 Microglobulin at the LS (r = - 0.269). Bone density was positively correlated with glomerular filtration rate at the LS (r = 0.200), FN (r = 0.179); with vitamin D at the LS (r = 0.218) and total H (r = 0.179). Multivariate regression analysis of the risk of decreased bone density at the FN has 2 factors: age (OR = 1.117), PTH (OR = 1.001); at the LS, there are 3 factors: gender (OR = 4.572), PTH (OR=4.078), age (OR = 1.045); at the total H, there are 2 factors: PTH (OR = 3.683), age (OR = 1.117). Osteoporosis in all 3 positions was related to sex (p &lt; 0.05) and age group (p &lt; 0.01). Osteoporosis was associated with PTH, Phosphorus, Aluminum disorders at the FN (p &lt; 0.05), with PTH at the LS (p &lt; 0.05), with PTH, calcium at the total H (p &lt; 0.05). Multivariate regression analysis of the risk of osteoporosis has 3 factors: age (OR = 4.058), PTH (OR = 2.967), female (OR = 2.841). Conclusion: Bone density, osteoporosis is correlated, associated with common factors and factors associated with bone mineral disorders in patients with dialysis chronic kidney disease (CKD - MBD). Key words: End-stage chronic kidney disease, dialysis, bone density

Mineralização vascular associada a distúrbio mineral ósseo em paciente com doença renal crônica - relato de caso

A doença renal crônica (DRC) é uma afecção comum na rotina clínica de animais de companhia e sua presença está associada há alterações polissistêmicas, como distúrbios minerais ósseos relacionados a ação de toxinas urêmicas como o paratormônio (PTH). O desequilíbrio da homeostasia causada pelo excesso do PTH pode cursar com repercussões clínicas como osteodistrofia fibrosa, calcificações teciduais e progressão da doença renal. Objetiva-se com o presente trabalho, descrever o caso de um paciente canino de quatro anos de idade, portador de DRC associada a distúrbio mineral ósseo com repercussões como osteodistrofia fibrosa e alterações cardiovasculares como hipertensão arterial sistêmica, hipertrofia concêntrica do ventrículo esquerdo e calcificações vasculares.

Correlation between Serum Magnesium and Parathyroid Hormone in Hemodialysis Patients.

Background: It is considerable that chronic kidney disease–mineral bone disorder (CKD-MBD) is a vital issue in chronic kidney disease patients. Parathyroid hormone (PTH) is a fundamental factor in the pathogenesis of this disorder in dialysis patients. It is believed that plasma magnesium (Mg2+) has an essential role in the regulation of PTH secretion in a manner which is slightly similar to calcium. Objectives: Illustrates the relationship between serum magnesium and serum parathyroid hormone in hemodialysis patients. Patients and Methods: A cross-sectional study had been carried out in the Hemodialysis Unit, Zagazig University Hospitals, Faculty of medicine, Zagazig University from the period between December 2018 and May 2019. The study included (77) participants diagnosed with end stage renal disease on regular hemodialysis. Results: There is no statistically significant correlation between serum magnesium and serum parathyroid hormone. Conclusion: Our findings suggest that factors other than serum Mg may be more important in the regulation of PTH secretion and action. Our findings require further investigations with larger and multicentric studies.

Complications of metabolic acidosis and alkalinizing therapy in chronic kidney disease patients: a clinician-directed organ-specific primer.

Chronic kidney disease is prevalent, affecting more than one in ten adults. In this population, metabolic acidosis is considered a key underlying pathophysiological feature, tying together bone mineral disorders, sarcopenia, insulin resistance, vascular calcification, pro-inflammatory and pro-thrombotic states. This review aims to address the paucity of literature on alkalinizing agents, a promising treatment option that has known adverse effects.

Risk factors and renal outcomes of low bone mineral density in patients with non-dialysis chronic kidney disease.

Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD. We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ - 1.0), osteopenia (- 1.0 > T score > - 2.5), and osteoporosis (T score ≤ - 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score < - 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD). Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12years; male 61%). Over a median follow-up of 4.3years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49-0.77)) and spot urine Na/K ratio (1.07 (1.00-1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92-1.41) for osteopenia; 1.43 (1.01-2.04) for osteoporosis, P for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to T score discordance classification. Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.

Genetic variants of mineral metabolism in health and disease.

Disturbances in mineral metabolism are common among individuals with chronic kidney disease and have consistently been associated with cardiovascular and bone disease. The current review aims to describe the current knowledge of the genetic aspects of mineral metabolism disturbances and to suggest directions for future studies to uncover the cause and pathogenesis of chronic kidney disease - mineral bone disorder. The most severe disorders of mineral metabolism are caused by highly penetrant, rare, single-gene disruptive mutations. More recently, genome-wide association studies (GWAS) have made an important contribution to our understanding of the genetic determinants of circulating levels of 25-hydroxyvitamin D, calcium, phosphorus, fibroblast growth factor-23, parathyroid hormone, fetuin-A and osteoprotegerin. Although the majority of these genes are known members of mineral homeostasis pathways, GWAS with larger sample sizes have enabled the discovery of many genes not known to be involved in the regulation of mineral metabolism. GWAS have enabled remarkable developments in our ability to discover the genetic basis of mineral metabolism disturbances. Although we are far from using these findings to inform clinical practice, we are gaining understanding of novel biological mechanisms and providing insight into ethnic variation in these traits.

Meeting Treatment Goals in Patients on Extramural Dialysis in Health Social Security in Mexico

Introduction: For the majority of renal replacement therapy history, the main treatment option for patients with end-stage renal disease (ESRD) in Mexico has been peritoneal dialysis. However, the use of hemodialysis is overwhelmingly increasing, driving public health care institutions to subrogate this service. Even when the actual hiring model for subrogation is accurate, there is a lack of quality control points in the hemodialysis prescription, poor adherence to clinical practice guidelines, and a few or no record of outcomes in hemodialysis patients of these subrogated services. The objective of this work is to fill this information gap to allow for uniform and safe hemodialysis for patients of Mexico. Material and Methods: An observational and cross-sectional study was performed, including all patients receiving chronic hemodialysis treatment in subrogated units of Mexican Social Security Institute (IMSS) in the northern region of Mexico City. Clinical and biochemical data as well as hemodialysis dose by Kt/V and urea reduction rate were collected and evaluated. To determine distribution, mean or median and SD or interquartile range were used; for nominal variables, the difference in proportions was estimated using the χ² test; proportions were analyzed for biochemical values using the statistical package SPSS version 25. Results: In our study, >60% (485) of the patients were anemic with an average hemoglobin of 9.39 mg/dL (SD ± 1.83); serum calcium was found below 8.4 mg/dL in 51.3% (383) of patients, and only in 45.8% (342) was at an optimal level of this parameter. Only 33.5% of patients have arteriovenous fistula for dialysis access. The hemodialysis dose was optimal in >75% of patients. Conclusions: It is necessary to enhance and monitor treatment of comorbidities in patients with ESRD in subrogated hemodialysis units in México. We observed adequate prescription of hemodialysis in a majority of patients, achieving quality control points for removal of nitrogen products. Yet, there is a lack of quality control of comorbidities; therefore, we should aim to optimize treatment for mineral-bone disorder, anemia, and nutritional status.

SO069CIRCADIAN RHYTHMS OF THE BONE-MINERAL AXIS IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Chronic kidney diseases disrupt normal bone-mineral axis endocrine functions causing the onset of mineral bone disorders (MBDs). The general and hemodialysis (HD) populations have been found to exhibit diurnal rhythms in phosphate (PO4), calcium (Ca), and parathyroid hormone (PTH) regulation (Trivedi et al. J Nephrol. 2015), but reference values for fluctuations have not been established in HD patients and do not consider PO4 binder use. We profiled the diurnal rhythms of MBD labs overall and stratified by PO4 binder use in a large nationally representative HD population in the United States. Method We used prevalent in-center HD patient (vintage &amp;gt;90 days) data on adults (age ≥18 years) treated at a dialysis organization in 2018. Mean annual pre-HD blood PO4, corrected Ca, and intact PTH levels were computed in 2-hour periods through 24 hours for the population and stratified by binder use. HD initiation time was a varying exposure, allowing patients to switch time groups if blood draws occurred in multiple time periods. Mean MBD lab levels with 95% confidence limits were plotted using nonparametric smoothing spline models to fit data and calculate trajectories throughout the day. Results The population of adult HD patients (n=156,873) was: mean age 62.8±14.3 years, 57.1% male, 58.2% white race, 41.9% with diabetes, 19.6% with congestive heart failure, and HD vintage 1510±1289 days. Mean pre-dialysis albumin=3.8±0.4 g/dL, PO4=5.4±1.5 mg/dL, corrected Ca=9.1±0.6 mg/dL, PTH=468±333 pg/dL for the population. Mean PO4, corrected Ca and PTH levels varied remarkably by 0.9 mg/dL, 0.2 mg/dL, and 186 pg/dL throughout the day. For PO4 and PTH, nadir levels occurred from 0900 to 1100 hours (5.3±1.6 mg/dL and 473±340 pg/dL), followed by a rise to a mid-day peak from 1700 to 1900 hours (5.8±1.8 mg/dL and 562±401 pg/dL), and the highest levels had a peak time from 2300 to 0100 hours (6.2±2.1 mg/dL and 659±389 pg/dL) (Figure 1A &amp; C). Corrected Ca showed relatively inverse fluctuations to PO4 and PTH, with peak levels from 1100 to 1300 hours (9.2±0.7 mg/dL) and nadir levels from 1900 to 2100 hours (9.0±0.7 mg/dL) (Figure 1B). Similar fluctuations and levels were observed for PO4 and PTH among patients using any phosphate binder type (90.7%), however, patients not using a phosphate binder exhibited absolute values that were persistently lower at every timepoint (Figure 1D &amp; F). Corrected Ca levels were similar by any binder use (Figure 1E). Conclusion Our results suggest PO4, Ca, and PTH levels have a diurnal variation of 0.9 mg/dL, 0.2 mg/dL, and 186 pg/dL in hemodialysis patients. PO4 and PTH exhibit a nadir in the morning, a mid-day peak and a larger nocturnal peak. Ca exhibits relatively inverse diurnal fluctuations with PO4 and PTH. Patients using any binder exhibit similar fluctuations and levels of PO4 and PTH; while patients not requiring a binder have similar fluctuations, yet persistently lower levels of PO4 and PTH. Given PO4 binder and calcimimetic therapies are commonly used for treatment of MBDs based on pre-dialysis blood levels, these findings provide insights for further research and pose the question if algorithms are warranted to compute daily time-adjusted levels for MBD laboratories.

P0889TO WHAT EXTENT CAN WE ACHIEVE MINERAL BONE METABOLISM TREATMENT TARGETS AS SUGGESTED BY UPDATED 2017 KDIGO GUIDELINES IN PATIENTS WITH PREDIALYSIS CHRONIC KIDNEY DISEASE

Abstract Background and Aims The mineral bone disorder is an essential problem in chronic kidney disease (CKD). It is an independent modifiable risk factor for renal damage progression and CKD related mortality. Therefore, it is important to treat chronic kidney disease mineral bone disorder (CKD-MBD) according to international guidelines. Data on the management of mineral bone disorders in predialysis patients is scarce. We aimed to investigate the proportion of CKD-MBD patients reaching targets suggested by the updated 2017 KDIGO guidelines. Method We performed a multicenter cross-sectional study. We recruited consecutive adult (&amp;gt;18 years of age) CKD 3-5 patients who were on regular nephrology outpatient clinic follow up. Patients who have GFR loss over 30% in the last six months, patients with malignancy, and decreased life expectancy due to severe comorbid disease and patients on renal replacement therapy were excluded. Data were collected in two-time points: one during the recruitment (second data point) and one, three to six months prior to the current visit (first data point). Persistent laboratory abnormalities were defined by out of normal range values in both time points. Therapeutic inertia was calculated for hyperphosphatemia. It was defined as a lack of using phosphate binders despite hyperphosphatemia. Results We examined a total of 213 patients for 3 different nephrology outpatient clinics. Of these patients, 49.5 % were male, with a mean age of 64,9 ± 12,0 years. 51.7 % of the patients were diabetic, 78 % were hypertensive, and 20.1 % had a history of coronary artery disease. Laboratory values related to MBD are shown in Table 1. KDIGO guideline targets were not reached in 14.8%, 18.4%, 59.0%, 71.0% patients regarding Ca, P, PTH, and vitamin D in the first visit. The targets were not reached in 15.0%, 19,2%, 61,2%, 81% patients regarding Ca, P, PTH, and vitamin D in the second visit. Persistence of out of target values were observed in 5.8%, 9.9%, 49.2% and 65.4% of the patients for Ca,P, PTH and Vitamin D respectively. The prevalence of therapeutic inertia for hyperphosphatemia was 34,4 % in the second visit Conclusion Regarding KDIGO guidelines, MBD is not optimally managed in predialysis CKD patients. Clinicians should have an active attitude regarding the correction of MBD even at the earlier stages of CKD.

P0871THE IMPACT OF ENDOGENOUS PTH/PTH1R/ATF4 AXIS ON TRABECULAR AND CORTICAL BONE REMODELING AND BONE GROWTH OF YOUNG RATS WITH EXPERIMENTAL CHRONIC KIDNEY DISEASES

Abstract Background and Aims Chronic kidney disease - mineral bone disorder (CKD–MBD) is one of the major clinical complications in patients with chronic kidney disease (CKD). Bone remodeling has been suggested to play a fundamental role in the maintenance of skeletal integrity via a balance between the bone formation/resorption process. The parathyroid hormone (PTH) is a key hormone controlling bone metabolism. PTH is known to affect bone with a net catabolic and anabolic effect but the mechanisms responsible for these differing effects are poorly understood. Previously, we demonstrated the distinct effect of mild degree of CKD on trabecular and cortical bone strength in rapidly growing rats (Pawlak et al. PlosOne, 2016). The aim of the present study was to evaluate the effect of endogenous PTH, its receptor PTH1R and activating transcription factor 4 (ATF4) – the major regulators of the anabolic PTH response in osteoblasts on bone remodeling and growth of young rats with experimental CKD. Method Four-week old Wistar male rats were divided into 2 groups: with CKD induced by surgical 5/6 subtotal nephrectomy, and sham-operated (CON). After one (CON-1; CKD-1) and three months (CON-3; CKD-3) of the surgery the femurs were collected and their lengths were measured. The activity of alkaline phosphatase (ALP), a bone formation marker, and tartrate-resistant acid phosphatase (TRACP5b) reflecting bone resorption were determined in homogenates from trabecular and cortical left femurs. The expression of PTH1R and ATF4 gene was determined by QRT-PCR in right femurs. Serum PTH was analyzed using ELISA kit. Computations were performed using Statistica ver.10 computer software. Results Serum PTH was increased in CKD-3 compared to CKD-1, moreover the slight increase in PTH levels was noted in CKD-3 compared to appropriate controls (both p&amp;lt;0.05). The activity of ALP and TRACP5b in trabecular bone tissue were significantly lower in CKD-3 compared to CKD-1 rats (p&amp;lt;0.01 and p&amp;lt;0.05; respectively). There was a strong positive correlation between ALP and TRACP5b in this bone region (R =0.624, p =0.002), whereas both ALP and TRACP5b were inversely related to serum PTH (R = -0.534, p =0.012 and R = -0.636, p =0.002; respectively). The activity of TRACP5b in cortical bone tissue was significantly higher in CKD-3 compared to CKD-1 group (p&amp;lt;0.05), and it was positively associated with PTH levels (R =0.597, p =0.004). There was no difference in ALP activity between the studied groups, and ALP was not associated with TRACP5b in this bone region. The expression of ATF4 and PTH1R genes was significantly increased in the CKD-3 group compared with the appropriate control (p&amp;lt;0.01 and p&amp;lt;0.05; respectively) and with the CKD-1 group (p&amp;lt;0.05 and p&amp;lt;0.01; respectively). The expression of ATF4 was inversely correlated with ALP and TRACP5b in trabecular bone (R = -0.534, and R = -0.528, both p&amp;lt;0.05), whereas it was positively related to TRACP5b in cortical bone region (R =0.418, p&amp;lt;0.05). The femoral length was significantly increased during 3-month of CKD development (p&amp;lt;0.000), and it was positively associated with PTH levels (R =0.571, p =0.007), cortical TRACP5b activity (R =0.609, p =0.002) and tended to be related with ATF4 gene expression (R =0.409, p =0.065). In contrast, the femoral length was inversely related to ALP activity in trabecular bone tissue (R= -0.656, p =0.0007). Conclusion The endogenous PTH, through PTH1R/ATF4 axis, inhibited trabecular bone remodeling. In contrary, PTH/PTH1R/ATF4 system intensified bone resorption in cortical bone region. This opposite effect of PTH on bone remodeling was associated with the intensification of growth process in the long bones of young rats with CKD.

P0817SMOKING WAS ASSOCIATED WITH LOWER SERUM LEVEL OF SOLUBLE ALPHA KLOTHO IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE:RESULTS FROM THE KOREAN COHORT STUDY FOR OUTCOMES IN PATIENTS WITH CHRONIC KIDNEY DISEASE (KNOW-CKD)

Abstract Background and Aims Soluble αklotho (sklotho) in systemic circulation, which is mainly derived from renal tubule, has been reported to play important roles in mineral bone disorders, cardiovascular complications and renal progression in CKD. Although decreased renal parenchymal mass is thought to be a main cause of decreased serum level of sklotho in CKD, various factors causing renal tubular injury such as hypoxia, oxidative stress, proinflammatory cytokines and uremic toxins are also known to decrease the renal tubular expression of αklotho. Because smoking contributes to hypoxia and oxidative damage, we hypothesized that smoking might be related to decreased sklotho in patients with non-dialysis CKD. Method To test this hypothesis, we analysed data of 2,101 subjects with non-dialysis CKD from a currently on-going Korean multi-centers prospective cohort study of CKD (KNOW-CKD, NCT01630486 at www.clinicaltrials.gov) in whom serum klotho was measured using an enzyme-linked immunosorbent assay kit (Immuno-Biological Laboratories Co, Gunma, Japan). The intra-assay and inter-assay coefficients of variations were 0.57-1.78% and 3.01-6.12% respectively. Results Mean age was 53.6±12.2 years and 1282 (61.0%) were men. The number of current, former and never smokers were 338 (16.1%), 642 (30.6%), and 1118 (53.2%) respectively. The median pack-year was 20.0 (interquartile range: 10.0-35.0). Mean eGFR by CKD-EPICr equation was 53.0±30.7 ml/min/1.73m2 and mean UACR was 903.9±1423.8 mg/g. Median serum sklotho was 536.0 (IQR: 419.5 – 667.0) pg/ml. In multivariable linear regression with backward stepwise adjustment by all significant factors for sklotho in univariate linear regression, smoking pack-year was independent variable for sklotho. (β= -0.786, p=0.032 95% CI for β: -1.504 to -0.069). Age and serum uric acid were also negatively associated with sklotho, while eGFR, serum alkaline phosphatase, and serum hemoglobin were positively associated with sklotho in the same analysis. Median sklotho of never, former, and current smokers were 551.0 (IQR:430 – 689.3) pg/ml, 509.5 (IQR: 407.8 – 645.3) pg/ml, and 521. (IQR: 397.8 – 645.0) pg/ml respectively. Linear mixed model adjusted by sex, age, eGFR, hemoglobin, alkaline phosphatase, and uric acid demonstrated that sklotho in never smokers was significantly higher than former (p=0.004) and current smokers (p=0.001). But there was no difference in sklotho between former and current smokers. Conclusion Smoking was associated with lower serum sklotho in non-dialysis CKD. But no difference in sklotho between former and current smoker casted doubt on causal relationship between smoking and serum sklotho

P1107CENTRALIZED CONTROL OF HEMODIALYSIS PROCEDURES AND CORRECTION OF CKD COMPLICATIONS WITH BI TOOLS

Abstract Background and Aims Life expectancy of patients with terminal stage of chronic kidney disease depends on the quality of dialysis therapy and timely and adequate correction of dialysis complications. The goal of this work is to improve the treatment quality for dialysis patients in a setting of multi-facility hospital by employing of Business intelligence (BI) tools for centralized control of diagnostic and treatment process. Method We have created a system for centralized control of patients’ condition, using Microsoft Power BI platform. This system allows to analyze the process of hemodialysis procedure as well as treatment of hypertension, anemia and mineral bone disorder. The system generates various reports that may include parameters of a specific patient, single clinic, or multi-facility hospital for the period from arbitrary date to the day, previous to the report generation date. The effect of system usage was assessed on 288 patients from 30 hemodialysis facilities of “Nefrosovet” private organization, for the period of 6 month. Results Before deployment of the system, target value of Kt/V (1.4) was reached or exceeded in 49% of hemodialysis procedures, median duration of hemodialysis procedure was 227±18 minutes (mean total duration per week - 683 minutes). As the result of usage of centralized control and prescription correction system, target values of Kt/V was reached or exceeded in 65% of hemodialysis procedures, median duration of hemodialysis procedure increased to 238±11 minutes (mean total duration per week - 714 minutes). Before the start of the study, hypotensive episodes were registered in 34% of hemodialysis procedures, and hypertensive episodes were registered in 22% of hemodialysis procedures. As the result of centralized control of hemodialysis procedures, number of procedures with hypotensive episodes reduced to 28%, and number of procedures with hypertensive episodes reduced to 17%. Number of patients with blood hemoglobin value in target range of 100-120 g/l, increased from 1617 patients (56%) to 2051 patients (71%). Number of patients with blood ferritin value in target range of values, increased from 1013 patients (35%) to 1386 patients (48%). Number of patients with TSAT value in target range of values, increased from 873 patients (30%) to 1097 patients (38%). We have also noticed an increase in number of patients with target values of calcium and phosphorus metabolism parameters: calcium corrected for albumin – from 1992 (69%) to 2165 (75%) patients, phosphorus – from 693 (24%) to 982 (34%) patients, intact parathyroid hormone (iPTH) – from 635 (22%) to 837 (29%) patients. Conclusion The usage of BI based centralized patients’ condition control system allows to improve adequacy of dialysis therapy and quality of CKD complications correction in dialysis patients.

P1412CARDIO PULMONARY AND CKD-MBD INTERACTIONS IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Emerging evidence suggests that pulmonary hypertension (PHT) is closely associated with cardiac, pulmonary, and mineral bone diseases in hemodialysis patients. Previous results indicated that extra osseous calcifications might be a risk factor for PHT although results in human studies about this association have been conflicting. Multiple factors including abnormal calcium phosphate levels, uremia and inflammation are known to be important in vascular calcification development. In hemodialysis patients’ vascular calcifications may be evaluated by different techniques. The utilization of plain X-ray for screening vascular calcifications has been suggested by KDOQI and KDIGO .In this study, we examined the association between PHT, peripheral vascular calcification by plain X-Ray score, and echocardiographic parameters in hemodialysis patients. Method Chronic (&amp;gt; 6 months) hemodialysis patients (150) on a three times per week dialysis schedule were studied. Two-dimensional trans thoracic echocardiography was performed before dialysis. Global systolic function was evaluated by left ventricular ejection fraction (LVEF). Systolic pulmonary arterial pressure (SPAP) was recorded. Pulmonary hypertension was defined as, pulmonary artery pressure (PAP) greater than 35 mm Hg based on European Society of Cardiology Guideline. Vascular calcification score is evaluated in plain X-ray of pelvis and hands. Each film is divided into four sections. Any vascular calcification either in an irregular or linear pattern is considered. The presence of vascular calcifications in each section is rated as 1 and its absence as 0. Final score is the sum of all sections and ranges from 0 to 8.Demographic data and lab results including Calcium (Ca), Phosphorous (P), Ca X P product, 25OH-vitD and iPTH were collected for all enrolled patients. The effects of different peripheral vascular calcification scores in plain X-Ray, structural heart abnormalities in echocardiography and Ca-P-iPTH- vit D axis disorders on the development of pulmonary hypertension were evaluated to elucidate cardio, pulmonary and CKD-MBD interactions. Results Hemodialysis patients had a high prevalence of PHT (30%), which warrants special attention to this important complication in hemodialysis population. Severe peripheral VCs (VCs &amp;gt;3) were independent risk factor for PHT. In addition to the old age, duration of hemodialysis, and mitral valve disease, the presence of higher Ca- P product was another independent predictor of PHT in chronic hemodialysis patients. Conclusion Prevalence of PHT in dialysis patients seems to be high, and is closely associated with peripheral VC, mineral bone disorders and structural heart abnormalities suggesting further a strong cardio pulmonary renal interaction.

P1424IMPACT OF DIRECTLY OBSERVED TREATMENT OF ONE ALFACALCIDOL ON MINERAL BONE DISORDER PROFILE IN DIALYSIS PATIENTS-A SINGLE UNIT PILOT STUDY

Abstract Impact of directly observed treatment of one-alfacalcidol on mineral bone disorder profile in dialysis patients- A single unit pilot study Background and Aims Secondary hyperparathyroidism (SHPT) is a common mineral bone disorder observed in patients with end-stage renal disease. Management of SHPT can be challenging mainly due to poor medication compliance. Directly observed treatment (DOT) has shown to improve management outcomes in other conditions like tuberculosis. We conducted a pilot study to investigate the impact of DOT with one alfacalcidol for SHPT in our cohort of dialysis patients. Method This prospective observational study was conducted on 21 end stage renal disease patients on dialysis from a single centre who were commenced on one alfacalcidol on dialysis days under direct observation .All patients had not shown any improvement in PTH despite increase in one alfacalcidol either admitted to or were suspected to have medication non-adherence. Serum bone mineral profile including parathormone (PTH), corrected calcium, phosphate and alkaline phosphatase were recorded before and after initiation of DOT. Treatment outcome was measured by comparing the mean change in the biochemical profile prior DOT initiation and at the lowest PTH value achieved on DOT. Data was analysed by paired t test using SPSS software. Results The mean age of our sample at the time of commencing DOT therapy was 52 years. Our sample had a predominance of males (67%) and Asian ethnicity (62%). 71% had a history of hypertension and 43% were diabetic. DOT one alfacalcidol therapy produced a significant reduction in the mean PTH value (pre-DOT- 92.2 vs post DOT-36.1 pmol/L, p&amp;lt;0.001). There was a significant rise in the corresponding mean corrected calcium levels (pre-DOT- 2.22 vs post-DOT-2.45 mmol/L, p=0.001) (table–1). Over a mean follow up of 8 months, a significant reduction in the one alfacalcidol dose requirement was observed in 52.38% of our cohort. Conclusion DOT one alfacalcidol therapy produced a significant improvement in the mineral bone profile in our cohort of dialysis patients. DOT approach can help to improve the outcomes in dialysis patients with poor compliance.

P1430BETA C-TERMINAL TELOPEPTIDE OF TYPE I COLLAGEN: CORRELATIONS WITH MINERAL METABOLISM PARAMETERS AND CARDIAC VALVULAR CALCIFICATIONS IN A COHORT OF HEAMODIALYSIS PATIENTS

Abstract Background and Aims Beta-carboxyterminal telopeptide of type I collagen (beta-CTx) is considered a marker of bone resorption in patients affected by osteoporosis. Nevertheless, its role in mineral bone disorder (MBD) of CKD patients is not clear. The aim of this study was to explore in a group of haemodialysis patients (HDp): 1) The levels of beta-CTx; 2) The correlation between beta-CTx levels and other mineral metabolism (MM) parameters; 3) The association between beta-CTx and CKD-MBD specific therapy 4) The relation between beta-CTx and cardiac valvular calcifications (VC). Method We studied a group of 21 HDp (F/M 9/12, age 68[54-78] years) randomly selected from the HDp actually followed-up in our Department. Dialysis vintage was 52[23-80] months. All HDp were on a three-weekly hemodialysis schedule, with a prescribed dialysate calcium of 1.5 mmol/l. Before the first dialysis session of the week, after the long interdialytic interval, the levels of beta-CTx, total and ionized calcium (tCa and iCa), Phosphorus (P), Magnesium (Mg), intact PTH (iPTH), total and bone isoform of alkaline phosphatase (tALP and bALP), 25-hydroxyvitamin D (25OHVD), 1,25-dihydroxyvitamin D (1,25OH2VD), and other general biochemical parameters were measured (Figure 1). At the same time, data concerning MM therapies were recorded. In all the studied patients, the presence of VC was searched in the the most recent echocardiographic study. Results Beta-CTx levels showed a significant positive correlation with tALP (r 0.92, p &amp;lt;0.0001), bALP (r 0.89, p &amp;lt;0.0001) and iPTH (r 0.87, p&amp;lt;0.0001) and a negative correlation with tCa (r – 0.43, p=0.05) and iCa (r – 0.52, p=0.01). No significant correlation was found with the other MM and general biochemical parameters and with the general features of the studied cohort. 18 patients (85.7%) were taking P binders (72.2% Ca-based and 27.8% Ca-free). In 20 patients (95.2%) vitamin D therapy, either in the natural, active or both natural and active form (35%, 15% and 50%, respectively) was prescribed. 6 patients (28.6%) were in therapy with Cinacalcet. No difference was found in beta-CTx levels according to the presence and the type of each of the above mentioned therapies. Conclusion Taking into account the limitations of this preliminary small size observational study, our data showed that beta-CTx levels are high in HDp. Beta-CTx correlates with iPTH, tALP and bALP. The negative correlation with tCa and iCa probably might be influenced by the negative correlation between iPTH and serum Calcium. Beta-CTx levels are not associated with CKD-MBD specific therapy or with cardiac valvular calcifications. Further prospective and randomized studies, including a higher number of HDp and possibly bone histology are needed to elucidate the possible role of beta-CTx as a marker of bone disease in HDp.

P0892PROFILE OF FIBROBLAST GROWTH FACTOR 23 IN CHRONIC KIDNEY DISEASE IN INDIAN POPULATION

Abstract Background Chronic kidney disease (CKD) is a complex disease. Recent discovery that fibroblast growth factor 23 (FGF23) play a major role in development of CKD related bone mineral disorder (BMD) indicated a paradigm shift in our understanding of CKD–BMD. Recent research indicates that higher levels of FGF23 are associated with rapid progression of CKD and higher mortality in CKD patients. It is found that FGF23 level in blood is elevated significantly early in the course of CKD, even before a rise in parathyroid hormone (PTH) level which could contribute directly to tissue injury in heart, blood vessels and kidneys, apart from just being a marker of adverse outcome, and this needs further research. The dietary habits, especially phosphate intake is likely to be different in Indian CKD population compared to western CKD population. Aims and objectives Method This is an observational study on 75 consecutive patients visiting Apollo hospital nephrology OPD in Chennai, India from June 2015 to Nov 2015. FGF23 level were determined simultaneously with serum creatinine, albumin, Vitamin D level, serum calcium, phosphate and serum PTH level done on enrolment. Serum samples when not immediately processed, were stored at -20oC. Results The age of the patient population varied from 19 to 80 years, mean 53.33 yrs with a SD of 15.49. 57(76%) were males and 18(24%) females. In our study, 46.7%patients belonged to CKD stage 4 while CKD stage 3 and 5 had 25.3% and 28% among the study population respectively. The mean FGF23 level in study population was 154.82pg/ml (Normal range 11-48.6 pg/ml). Though the FGF23 values in stage 5 CKD were higher than those in stage 3 and 4 CKD, the difference was not statistically significant (p=0.74). In our study, 63 patients (84%) had high FGF23 level and 56(74.7%) patients were already on phosphate binding drugs and PTH suppressing drugs like vit D or cinacalcet for at least 2 months. 48(85.7%) patients of those on medications and 15 (79%) of those not on medications had high FGF23 level (P value -0.48, Yates P value-0.739). In our study, PTH had an inverse correlation with eGFR and the association was statistically significant (P value 0.001). Serum Phosphorus level had an inverse correlation with eGFR and the association was statistically significant (P value 0.0001). Correlation of FGF23 values with eGFR was negative which was expected as the FGF23 levels increased with decreasing eGFR, but the association was not statistically significant. Similar results were obtained when FGF23 values were studied for association with serum calcium levels where the P value was 0.359 which was not statistically significant. Similarly, vit D levels had a negative association with P value of 0.077 and PTH levels had a positive association with P value of 0.987 (No statistical significance). Similarly, FGF23 levels and phosphate levels had a positive association without statistical significance(p= 0.224). Conclusion In conclusion, our data indicate that the rise of serum FGF23 levels in progressive Indian CKD patients is a common finding in CKD stage 3 and beyond.