Mineral Bone Metabolism Markers Research Articles

Greater urinary calcium excretion is associated with diminished bone accrual in youth with type 1 diabetes

Abstract Context The adverse skeletal effects of type 1 diabetes (T1D) include deficient bone accrual and lifelong increased fracture risk. The contributors to impaired bone accrual in people with T1D are incompletely understood. Objective To determine if urinary calcium excretion is associated with impaired bone accrual in youth with T1D and to characterize the contribution of glycemic control and markers of bone mineral metabolism to urinary calcium excretion. Design Observational study. Participants 50 participants with T1D aged 6-20 years completed a 12-month longitudinal study of bone accrual. A second cohort of 99 similarly aged participants with T1D completed cross-sectional 24-hr urine and blood collections. Main Outcome Measure Whole body less head bone mineral content (WBLH BMC) velocity Z-score and fractional excretion of calcium (FeCa). Results Participants in the bone accrual cohort had lower WBLH BMC velocity compared to a healthy reference dataset (Z-score −0.3 ± 1.0, p=0.03). FeCa was negatively associated with WBLH BMC velocity Z-score, ρ= −0.47, p=0.001. In the urinary calcium excretion cohort, intact parathyroid hormone (β= −0.4, p=0.01), beta c-telopeptide (β=0.35, p=0.007), and either hemoglobin A1c (HbA1c, β=0.08, p=0.03) or urine fractional glucose excretion (β=0.07, p=0.03) were associated with FeCa in multivariable regression models that included known determinants of urinary calcium excretion. Conclusions Urinary calcium excretion was negatively associated with bone accrual in this cohort of youth with T1D. Mechanistic studies are needed to determine if interventions to reduce urinary calcium excretion could increase bone accrual and reduce skeletal fragility in people with T1D.

Markers of Bone Mineral Metabolism in Thyroid Disorders

Abstract Background and Aim: Thyroid hormones are essential for normal skeletal development and bone metabolism. Despite various studies, the effect of thyroid hormone on bone metabolism has not been clearly understood. We studied the bone formation markers (procollagen type 1 N-propeptide [P1NP] and osteocalcin [OC]) and bone resorption markers (C-terminal cross-linking telopeptide of type 1 collagen [CTX] and tartrate-resistant acid phosphatase [TRAP]) in patients with thyroid disorders and the effect of treatment on them. Furthermore, a study correlating these markers with thyroid-stimulating hormone (TSH) levels was done. Materials and Methods: This cross-sectional study recruited 60 cases (40 – hypothyroid and 20 – hyperthyroid) and 20 controls based on inclusion and exclusion criteria. To evaluate the effect of treatment, cases were further subdivided based on the duration of treatment received into 0-month (newly diagnosed), 1–6-month, and >6-month treatment subgroups. Both the cases and control underwent a thorough history, clinical examination, and detailed investigation based on a predesigned proforma. Results: In hyperthyroidism with 0-month treatment subgroup, both formation (OC, P1NP) and resorption (CTX) markers were significantly increased compared to control (P < 0.05), which became insignificant on treatment (1–6 months) with antithyroid medication despite low TSH value. Contrarily, in hypothyroidism, a statistically significant (P < 0.05) lower mean value of markers (OC, P1NP, and CTX) was observed only in the subgroup with levothyroxine supplementation. In hyperthyroidism, both the formation (OC and P1NP) and resorption markers (CTX and TRAP) showed a strong negative (P < 0.001) correlation with TSH, the strength of correlation decreased, and became insignificant on treatment. In hypothyroidism, only P1NP and CTX showed an overall significant positive (P < 0.05) correlation with TSH. Conclusion: Hyperthyroidism has high bone turnover markers, which showed early reversibility of markers on treatment with antithyroid medication despite low TSH, whereas in hypothyroidism, significantly lower mean value of markers is seen only in the subgroup with levothyroxine supplementation, probably owing to the suppressive effect of TSH. P1NP and CTX showed high sensitivity in both hypothyroidism and hyperthyroidism. The pattern of correlation between TSH and bone metabolism markers in hyperthyroidism suggests a direct negative effect of TSH on bone turnover, whereas in hypothyroidism, it either suggests TSH showing a positive correlation at a very high level which becomes negative as the TSH value decreases or TSH is not a dominant hormone regulating bone metabolism in hypothyroidism.

#2067 Prediction of gastrointestinal bleeding hospitalization risk in hemodialysis using machine learning techniques

Abstract Background and Aims INitiativeS on advancing Patients’ outcomes In REnal disease (INSPIRE) is an academia and industry collaboration set forth to identify critical investigations needed to advance the practice of medicine in nephrology. Gastrointestinal bleeding (GIB) is one of the most common types of bleeding events in the kidney dialysis population [1]. We aimed to develop a model to predict GIB hospitalization risk in a hemodialysis (HD) patient within 180 days. We evaluated advanced machine learning algorithm (XGBoost) and compared it to traditional machine learning algorithm (logistic regression) modeling techniques. Method We used data from a kidney care network from 2017 through 2020. We included data from adult dialysis patients (age ≥18 years). GIB related hospitalization was defined based on international classification of diseases (ICD) diagnosis codes recorded as the primary, secondary, or tertiary discharge reason for hospitalization. Two distinct models were created using XGBoost and logistic regression algorithms and using the same dataset. Both models were evaluated using metrics such as area under the receiver operating curve (AUROC), accuracy, sensitivity, and specificity. Missing data was imputed using mean for quantitative data and mode for qualitative data. The dataset then was randomly divided into 60% training, 20% validation and 20% test dataset. The test data, comprising unseen patients and data was used to evaluate the performance of the model. This means that the model had never encountered the test data during its learning phase, which included training the model and then validating the model. Results The incidence of 180-day GIB hospitalization was 1.12% in the HD population (n = 5 116 with GIB hospitalization/ n = 451 653 without GIB hospitalization), and consistent in the unseen test dataset (n = 465 with GIB hospitalization/ n = 38586 without GIB hospitalization). The XGBoost model showed higher predictive performance compared to logistic regression (Table). The AUROC was 0.72 (95% confidence interval (CI) 0.69, 0.74) for the XGBoost model. In comparison, the AUROC was 0.615 (95% CI 0.60, 0.64) for the logistic regression model. Specificity was 67% versus 58% for the XGBoost model versus logistic regression model respectively. However, sensitivity for both the models was 65%. The top predictors for major GIB were consistent in both models for many factors, yet some factors showed different importance on outcome prediction (Fig. 1). Higher risk of GIB hospitalization was associated with older age, lower ferritin levels, and recent all-cause hospitalizations in both models. The XGBoost showed high importance on outcome prediction for lower hemoglobin and higher serum 25 hydroxy (25OH) vitamin D values, and the logistic regression model showed high importance for higher amounts of saline delivered during an HD treatment and lower intact parathyroid hormone (iPTH) levels. Conclusion We found advanced machine learning prediction modeling (XGBoost) appears suitable for identifying a HD patient at risk for a GIB hospitalization in the next 180 days, and outperforms traditional machine learning (logistic regression) modeling techniques. Although both models showed identical sensitivity, the XGBoost model had higher specificity. Prospective testing is needed to confirm the model's performance. The association between bone mineral metabolism markers and GIB hospitalization risk is unexpected and warrants further investigation.

Kidney function, bone-mineral metabolism markers, and calcification of coronary arteries, aorta, and cardiac valves in older adults

Background and aimsThe contribution of kidney dysfunction, especially at mild-to-moderate stages, and bone-mineral metabolism (BMM) markers to vascular calcification remains controversial or unclear. We comprehensively evaluated the association of kidney and BMM markers with coronary artery calcification (CAC) and extra-coronary calcification (ECC). MethodsIn 1931 ARIC participants (age 73–95 years) without coronary heart disease at visit 7 (2018–19), we investigated the associations of estimated glomerular filtration rate (eGFR) (with creatinine, cystatin C, and both) and five serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) with high CAC and ECC (sex-race specific ≥75th vs. <75th percentile Agatston score) or any vs. zero CAC and ECC using multivariable logistic regression. For eGFR and BMM markers, we took their weighted cumulative averages from visit 1 (1987–89) to visit 5 (2011–13). ResultsLower eGFR, regardless of equations used, was not robustly associated with high CAC or ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed robust associations with high CAC (only when modeled continuously) and ECC, independently of kidney function (e.g., odds ratio 1.94 [95%CI 1.38–2.73] for high aortic valve calcification, in the highest vs. lowest quartile). Results were generally consistent when analyzing any CAC or ECC, although cystatin C-based eGFR <60 mL/min/1.73 m2 became significantly associated with mitral valve calcification (odds ratio 1.69 [1.10–2.60]). ConclusionsAmong kidney and BMM measures tested, only serum phosphorus demonstrated robust associations with both CAC and ECC, supporting a key role of phosphorus in the pathophysiology of vascular calcification.

Preoperative hypomagnesemia as a possible predictive factor for postoperative increase of transvalvular pressure gradient in hemodialysis patients treated with transcatheter aortic valve implantation

Background Patients undergoing maintenance hemodialysis (HD) with severe aortic stenosis are at a high risk for bioprosthetic valve dysfunction after transcatheter aortic valve implantation (TAVI). Currently, preoperative factors that predict the occurrence of valve dysfunction after TAVI on HD patients remain to be elucidated. The aim of this study is to analyze the association between preoperative clinical factors and valve stenosis after TAVI on HD patients. Methods Twenty-four of HD patients who underwent TAVI at our institution between April 2012 and January 2016 were analyzed. The mean aortic transvalvular pressure gradient (MPG) and effective orifice area index (EOAi) were assessed by serial echocardiography. Associations between preoperative clinical factors and time-series changes in MPG were examined using mixed-effects linear regression model for repeated measures. Results Three patients developed severe structural valve deterioration with calcific valve stenosis requiring reoperation. A multivariate linear mixed-effects model showed that lower serum magnesium (sMg) levels were associated with the increase of MPG after TAVI (beta-coefficient = 0.019, p = 0.03). No correlation was observed with serum calcium, phosphorus, or intact parathyroid hormone. Time-series changes of MPG and EOAi had significant difference between lower and higher sMg group. All 3 of the patients who underwent reoperation showed lower preoperative sMgs. Conclusion Among bone-mineral metabolism markers, preoperative hypomagnesemia was associated with the increase of MPG after TAVI, suggesting that hypomagnesemia could predict post-TAVI valve dysfunction in HD patients. Further studies with larger sample sizes are warranted.

Abstract 10670: Kidney Function, Bone-Mineral Metabolism Markers, and Calcification of Coronary Arteries, Aorta, and Cardiac Valves in Older Adults

Background: Kidney function is a crucial determinant of bone-mineral metabolism (BMM); however, the contribution of kidney dysfunction, especially at mild to moderate stages, to vascular calcification remains controversial. Moreover, little is known about whether BMM markers are associated with coronary artery calcification (CAC) and extra-coronary calcification (ECC) beyond kidney function. Methods: In 1935 ARIC participants (age 73-95 years) with no coronary heart disease and data on CAC and ECC at visit 7 (2018-2019), we evaluated estimated glomerular filtration (eGFR) (based on creatinine, cystatin C, and both) and serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) as exposures. The exposures were modeled as weighted averages over ~15 years (visit 1 [1987-89] to visit 5 [2011-13] to allow a lag time for vascular calcification), and the outcome variables were high CAC and ECC (sex-race specific ≥75 th vs. &lt;75 th percentile Agatston score) or any CAC and ECC (Agatston score &gt;0 vs. 0) using multivariable logistic regression. Results: Low eGFR (overall range 30-149 mL/min/1.73m 2 ), regardless of equations, was not robustly associated with high CAC and ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed significant associations with high CAC and ECC, independent of kidney function ( Figure ). Considering presence of any calcification, results were generally consistent, although cystatin C-based eGFR &lt;60 mL/min/1.73m 2 was associated with mitral valve calcification (present in 47%) (odds ratio 1.70 [95% CI 1.13, 2.58]). Conclusion: Cumulative exposure to lower eGFR showed weak associations with vascular calcification in community-dwelling older adults. Among BMM markers, phosphorus was most robustly associated with CAC and ECC beyond kidney function. Our results suggest a potential key role of phosphorus in the pathophysiology of vascular calcification.

25-hydroxyvitamin D, Fibroblast Growth Factor 23, and Risk of Acute Kidney Injury Over 20 Years of Follow-Up

IntroductionLow serum 25-hydroxyvitamin D levels have been identified as a risk factor for acute kidney injury (AKI) among critically ill patients. Whether low 25-hydroxyvitamin D levels are associated with long-term incidence of hospitalization with AKI in the general population is unknown.MethodsAmong 12,380 participants (mean age, 57 years; 24% black) in the Atherosclerosis Risk in Communities (ARIC) Study who attended visit 2 (1990–1992), we explored the association of serum 25-hydroxyvitamin D with incident hospitalization with AKI. Multivariable Cox models were used to estimate hazard ratios (HRs). We also examined the association of serum fibroblast growth factor 23 (FGF23) with AKI.ResultsDuring a median follow-up of 24.3 years, 2145 participants had incident hospitalization with AKI (crude incidence rate: 8.3; 95% confidence interval [CI]: 8.0–8.7, per 1,000 person-years). In multivariable Cox models (including adjustment for kidney function), lower 25-hydroxyvitamin D and higher FGF23 levels were each significantly associated with an increased risk of AKI (HR: 1.35; 95% CI: 1.17–1.54, for lowest vs. highest quartile for 25-hydroxyvitamin D, and HR: 1.19; 95% CI: 1.05–1.36, for highest vs. lowest quartile for FGF23). The association was consistent across demographic and clinical subgroups, regardless of whether AKI was the primary diagnosis for hospitalization, and when adjusting for incident chronic kidney disease (CKD) or cardiovascular disease (CVD) as a time-varying covariate.ConclusionAmong middle- to older-age adults in the community, low 25-hydroxyvitamin D and high FGF23 levels were independently associated with an increased risk of AKI. Future studies should explore underlying mechanisms linking these bone mineral metabolism markers with kidney injury.

Serum magnesium, bone-mineral metabolism markers and their interactions with kidney function on subsequent risk of peripheral artery disease: the Atherosclerosis Risk in Communities Study.

Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium-PAD relationship is independent of or modified by kidney function. A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990-92) was studied. We investigated the association of serum magnesium and other bone-mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression. Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (<1.5 mEq/L) versus Quartile 4 (>1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40-2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 11 606). In contrast, the association was largely flat in those with eGFR <60 mL/min/1.73 m2 (n = 233) with P-for-interaction 0.03. Among bone-mineral metabolism markers, only higher iPTH showed an interaction with kidney function (P-for-interaction 0.01) and iPTH >65 pg/mL was significantly related to PAD only in those with eGFR <60 mL/min/1.73 m2. Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population.

A study of vitamin D status in Egyptian pediatric epileptic patients on monotherapy antiepileptic drugs: a hospital-based study

Introduction and aim Epilepsy is a chronic condition with an incidence of 4–10/1000 worldwide. Antiepileptic drugs (AEDs) remain the mainstay of treatment for epilepsy. AEDs in common use are carbamazepine (CBZ), phenytoin, phenobarbitone, and sodium valproate. Long-term therapy by AEDs is associated with bone disorders, affected by both duration and dose of these drugs. The effect of antiepileptic on serum vitamin D levels is controversial and uncertain, so further clinical studies to ascertain the effect of old and newer AEDs on serum levels of vitamin D level in epileptic patients are needed, thus accomplishing a suitable usage of vitamin supplementation. The aim of this study is to assess the longitudinal effect of AEDs on serum 25-hydroxyvitamin D [25(OH) D] levels and bone mineral metabolism markers among Egyptian pediatric epileptic patients on monotherapy AEDs. Participants and methods The study was carried out on 62 epileptic patients attending the Neuropediatric Outpatient Clinic, Children's Hospital Cairo University, with history of seizures (age ranges from 1 year up to 12 years), and 64 children not on AEDs as a control group. Daily dietary intake of calories, calcium, and phosphorus was characterized by dietary recall method. Patients on valproate were 37.1% of patients, whereas 32.3% were on levetiracetam and 30.6% were on CBZ. Valproate dose ranged between 10 and 40 mg/kg/day, with a mean dose of 30.4 ± 8.1 mg/kg/day, whereas levetiracetam dose ranged between 20 and 50 mg/kg/day, with a mean dose of 26 ± 8.8 mg/kg/day, and CBZ dose ranged between 15 and 40 mg/kg/day, with a mean dose of 31.8 ± 8.9 mg/kg/day. All patients on AED and control group were evaluated for vitamin D level. Serum calcium, phosphorus, Mg, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, and urea were measured for both patient and control groups. Results Marked vitamin D deficiency was detected in 31 epileptic patients (50%) (mean ± SD: 13.4 ± 7.6 ng/ml) compared with the control group (6.2%) (mean ± SD: 60.4 ± 17.9 ng/ml) (P = 0.000), whereas mild deficiency was remarkable in 19 patients with epilepsy (30.6%) compared with five (7.8%) controls. Overall, 54.8% of the severely deficient patients in vitamin D were on CBZ, whereas 41.9% were on valproate, and 3.2% were on levetiracetam, with statistical significance on comparing vitamin D level with the type of AEDs (P

Markers of Bone Mineral Metabolism and Cardiac Structure and Function in Perinatally HIV-Infected and HIV-Exposed but Uninfected Children and Adolescents.

Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth. The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites. Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected (PHEU) youth enrolled in the Adolescent Master Protocol, we evaluated associations of vitamin D [measured as 25-hydroxy-vitamin D (25-OHD)], parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function, and concentrations of NT-proBNP, a biomarker of cardiac damage. Among 485 participants (305 PHIV and 180 PHEU) with echocardiograms and bone mineralization measures, low 25-OHD (<20 ng/mL) was common among all participants (48% PHIV and 44% PHEU), but elevated PTH (>65 pg/mL) was identified more often among PHIV participants than PHEU participants (9% vs 3%, P = 0.02). After adjusting for HIV status and demographic covariates, both low 25-OHD and elevated PTH were associated with lower mean LV mass z-scores, whereas elevated PTH was associated with higher mean fractional shortening z-scores. Participants with low 25-OHD also had slightly higher mean LV end-systolic wall stress z-scores, but differences were more pronounced in PHEU participants than in PHIV participants. FGF-23 was inversely related to end-diastolic septal thickness, both overall and among PHIV participants. In this cohort of PHIV and PHEU youth, we observed associations of 25-OHD, PTH, and FGF-23 with both structural and functional cardiac parameters, supporting links between bone mineral metabolism and cardiac status.

A Cross-Sectional Study of Growth and Metabolic Bone Disease in a Pediatric Global Cohort Undergoing Chronic Hemodialysis

We sought to assess worldwide differences among pediatric patients undergoing hemodialysis. Because practices differ widely regarding nutritional resources, treatment practice, and access to renal replacement therapy, investigators from the Pediatric Investigation and Close Collaboration to examine Ongoing Life Outcomes, the pediatric subset of the MONitoring Dialysis Outcomes Cohort (PICCOLO MONDO) performed this cross-sectional study. We hypothesized that growth would be better in developed countries, possibly at the expense of bone mineral disease. In this cross-sectional study, we analyzed growth by height z score and recommended age-specific bone mineral metabolism markers from 225 patients <18 years of age maintained on hemodialysis, between the years of 2000 to 2012 from 21 countries in different regions. The patients' median age was 16 (IQR 14-17) years, and 45% were females. A height z score less than the third percentile was noted in 34% of the cohort, whereas >66% of patients reported normal heights, with patients from North America having the greatest proportion (>80%). More than 70% of the entire cohort had greater than the age-recommended levels of phosphorus, particularly in the Asia-Pacific and North America, where we also observed the greatest body mass index z score (0.99 ± 1.6) and parathyroid hormone levels (557.1 [268.4-740.5]). Below-recommended parathyroid hormone levels were noted in 26% and elevated levels in 61% of the entire sample, particularly in the Asia Pacific region. Lower-than-recommended calcium levels were noted in 36% of the entire cohort, particularly in Latin America. We found regional differences in growth- and age-adjusted bone mineral metabolism markers. Children from North America had the best growth, received the most dialysis, but also had the worst phosphate control and body mass index z scores.

CALCIDIOL IN CHILDREN WITH CHRONIC KIDNEY DISEASE STAGES 2–5

Vitamin D deficiency is characteristic for patients with chronic kidney disease (CKD). THE AIM: to study the prevalence of deficits of calcidiol in children with CKD, and to establish correlations with parathyroid hormone and other markers of bone mineral metabolism in children. PATIENTS AND METHODS. In the period from September 2015 to December 2016 we examined of calcidiol in 53 boys and 32 girls with CKD stages 2-5. The average age of the patients was 11.3+4,7 years. RESULTS. 92.5% of cases in children with CKD revealed a low level of calcidiol. Of them, 30.6% of children were in deficit of vitamin D. The incidence of vitamin D deficiency correlated with a decrease in glomerular filtration rate (r = 0.31; p&lt;0.05). We identified an inverse relationship between calcidiol levels and serum parathyroid hormone, and calcium-phosphorous product (r= -0,29, and r= -0,31; p&gt;&lt;0.05, respectively). Predictors of vitamin D deficiency may be hypoalbuminemia and hyperphosphaturia. CONCLUSION. Determination of vitamin D in children with CKD is extremely important for timely correction and prevention of the development of secondary hyperparathyroidism. Just started the correction of bone and mineral metabolism will improve the quality of life for children with CKD and prevent the development of such complications of hyperparathyroidism as bone deformation and vessels calcification. Keywords: CKD, vitamin D, parathyroid hormone, calcium x phosphorous product&gt;&lt; 0.05). We identified an inverse relationship between calcidiol levels and serum parathyroid hormone, and calcium-phosphorous product (r= -0,29, and r= -0,31; p&lt; 0.05, respectively). Predictors of vitamin D deficiency may be hypoalbuminemia and hyperphosphaturia. CONCLUSION. Determination of vitamin D in children with CKD is extremely important for timely correction and prevention of the development of secondary hyperparathyroidism. Just started the correction of bone and mineral metabolism will improve the quality of life for children with CKD and prevent the development of such complications of hyperparathyroidism as bone deformation and vessels calcification.

Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease

Background and aimsReduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. MethodsUsing data from 12,472 participants at baseline (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). ResultsDuring a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3–8.3 for eGFR <30 and 2.4–3.5 for eGFR 30–59 vs. eGFR ≥90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91–3.54] for B2M vs. 1.20 [0.91–1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11–1.94] in top quartile). ConclusionsKidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.

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

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

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

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

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

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

Metabolism, Protein Binding, and Renal Clearance of Microbiota-Derived p-Cresol in Patients with CKD.

Colonic microbial metabolism substantially contributes to uremic retention solutes in CKD. p-Cresyl sulfate is the main representative of this group of solutes, relating to adverse outcomes. Other than sulfate conjugation, p-cresol is subjected to endogenous glucuronide conjugation. Whether the balance between sulfate and glucuronide conjugation is relevant in CKD is unexplored. We prospectively followed 488 patients with CKD stages 1-5 (enrollment between November of 2005 and September of 2006; follow-up until December of 2010). Serum and urine levels of p-cresyl sulfate and p-cresyl glucuronide were measured using liquid chromatography-mass spectrometry. Total amount of microbial p-cresol was calculated by the sum of serum p-cresyl sulfate and p-cresyl glucuronide. Outcome analysis was performed for mortality and cardiovascular disease. Serum p-cresyl sulfate was a median of 193.0-fold (interquartile range, 121.1-296.6) higher than serum p-cresyl glucuronide, with a significant correlation between eGFR and proportion of serum p-cresyl sulfate to glucuronide (rho=0.23; P=0.001). There was also a significant correlation between eGFR and proportion of 24-hour urinary excretion of p-cresyl sulfate to glucuronide (rho=0.32; P<0.001). Higher serum p-cresol and lower proportion of serum p-cresyl sulfate to glucuronide were jointly and significantly associated with mortality (hazard ratio per SD higher, 1.58; 95% confidence interval, 1.10 to 2.29; P=0.01 and hazard ratio, 0.65; 95% confidence interval, 0.47 to 0.89; P<0.01, respectively) and cardiovascular disease (hazard ratio, 1.68; 95% confidence interval, 1.27 to 2.22; P<0.001 and hazard ratio, 0.55; 95% confidence interval, 0.42 to 0.72; P<0.001, respectively) after adjustment for eGFR, Framingham risk factors, mineral bone metabolism markers, C-reactive protein, and albumin. p-Cresol shows a preponderance of sulfate conjugation, although a relatively diminished sulfotransferase activity can be suggested in patients with advanced CKD. Along with total p-cresol burden, a relative shift from sulfate to glucuronide conjugation is independently associated with mortality and cardiovascular disease, warranting increased focus to the dynamic interplay between microbial and endogenous metabolism.

Abstract MP29: Kidney Function, Bone-mineral Metabolism Markers, and Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Impaired kidney function is a known risk factor for lower-extremity peripheral artery disease (PAD). Whether novel markers of kidney filtration like cystatin C and beta-2-microglobulin (B2M) differ in their associations with PAD risk compared to creatinine-based estimated glomerular filtration rate (eGFRcr) is unclear. Also, bone-mineral metabolism (BMM) disorders are commonly complicated with impaired kidney function, but it is not known whether BMM markers influenced by kidney function are associated with PAD. Hypothesis: Novel filtration markers are more strongly associated with PAD risk than eGFRcr, and BMM markers are associated with PAD risk beyond kidney function. Methods: Using data from 13215 ARIC Study participants free of clinical history of PAD at baseline (1990-1992), we applied Cox proportional hazards model to quantify the associations of biomarkers and eGFR equations incorporating these biomarkers (cystatin C, B2M, eGFRcr, and eGFR based on cystatin C and cr [eGFRcr-cys]) with PAD risk. We also evaluated whether BMM markers (fibroblast growth factor 23, parathyroid hormone, calcium and phosphorus) were associated with PAD after adjustment for eGFR. PAD was defined as hospitalizations with ICD-9 code of 440.2x and 440.3. Results: During a median follow-up of 21 years, 587 participants had at least one hospitalization with a discharge code for PAD. The novel markers cystatin C and B2M showed stronger associations with PAD compared to eGFRcr (Table). When examining BMM markers, only elevated phosphorus level was associated with PAD risk and the association remained significant after adjustment for eGFRcr-cys (Table). Conclusions: The novel filtration markers cystatin C and B2M are stronger in their association with PAD compared to eGFRcr. Moreover, higher phosphorus level was related to future PAD risk beyond kidney function. Our results suggest novel filtration markers may improve PAD risk assessment, and there is a possible role for phosphorus metabolism in the pathophysiology of PAD.

Abstract P389: Effects of Dietary Patterns on Vitamin D and Other Markers of Bone-Mineral Metabolism: Results From the Dash Trial

Background: The relationship of CVD with vitamin D levels and other markers of bone-mineral metabolism is of substantial interest. The Dietary Approaches to Stop Hypertension (DASH) diet effectively lowers blood pressure and is now recommended to promote CV health. The effects of the DASH diet on vitamin D and other markers of bone-mineral metabolism is unknown. Objective: To determine the effect of dietary patterns on blood levels of vitamin D, PTH, and ionized calcium, and urinary excretion of calcium and phosphate. Methods: Data on study outcomes were available in 334 participants from the original DASH trial. Baseline levels were obtained from blood and urine collected at the end of the run-in while on the control diet. Participants were then randomized to control diet (37% kcal total fat); fruits &amp; vegetable diet (also 37% kcal total fat); or the DASH diet (27% kcal total fat). Follow-up levels were obtained during the last week of the eight-week intervention period. Results: Mean (±SD) baseline blood levels of vitamin D, PTH , and ionized calcium were 15.1±3.7ng/ml, 46.1±18.5 ng/ml and 1.3±0.06 mmol/l, respectively. For urinary calcium and phosphate were 126.8±45.3mg/dl and 715.0±277.3 mg/dl, respectively. See table for within-diet changes. The DASH diet, net of control, reduced vitamin D by -1.29ng/ml (P= 0.005). In stratified analyses, the reduction in vitamin D appeared more prominent in blacks, but the p-value for interaction (race*diet) was non-significant (P=0.21). Otherwise, the DASH diet had no significant effect on the other markers, net of control. Compared to control, the fruit &amp; vegetable diet reduced urinary calcium and phosphorus excretion. Conclusion: The DASH diet modestly reduced vitamin D levels among all participants, with potentially larger effects in blacks. The reduction in vitamin D levels might have resulted from the lower fat content of the DASH diet. Overall, during the eight-weeks of intervention, no major harm or benefit of the DASH diet was documented on biomarkers related to bone-mineral metabolism.

PT227 Large artery stiffness and carotid intima-media thickness in relation to markers of bone mineral metabolism in postmenopausal African women: The PURE-study

PT227 Large artery stiffness and carotid intima-media thickness in relation to markers of bone mineral metabolism in postmenopausal African women: The PURE-study