Serum Sclerostin Is Associated with Peripheral and Central Systolic Blood Pressure in Pediatric Patients with Primary Hypertension

Recent studies showed the significance of the canonical Wnt/beta-catenin pathway and its inhibitor—sclerostin, in the formation of arterial damage, cardiovascular morbidity, and mortality. The study aimed to assess serum sclerostin concentration and its relationship with blood pressure, arterial damage, and calcium-phosphate metabolism in children and adolescents with primary hypertension (PH). Serum sclerostin concentration (pmol/L) was evaluated in 60 pediatric patients with PH and 20 healthy children. In the study group, we also assessed calcium-phosphate metabolism, office peripheral and central blood pressure, 24 h ambulatory blood pressure, and parameters of arterial damage. Serum sclerostin did not differ significantly between patients with PH and the control group (36.6 ± 10.6 vs. 41.0 ± 11.9 (pmol/L), p = 0.119). In the whole study group, sclerostin concentration correlated positively with height Z-score, phosphate, and alkaline phosphatase, and negatively with age, peripheral systolic and mean blood pressure, and central systolic and mean blood pressure. In multivariate analysis, systolic blood pressure (SBP) and height expressed as Z-scores were the significant determinants of serum sclerostin in the studied children: height Z-score (β = 0.224, (95%CI, 0.017–0.430)), SBP Z-score (β = −0.216, (95%CI, −0.417 to −0.016)). In conclusion, our results suggest a significant association between sclerostin and blood pressure in the pediatric population.

Calcinosis cutis in a renal transplant patient

Calcinosis cutis is an unusual disorder characterised by calcium–phosphate deposition into cutaneous and subcutaneous tissues. There are five subtypes: dystrophic, metastatic, idiopathic, iatrogenic and calciphylaxis. Our objective was to report a patient with a history of haemodialysis-dependent end-stage renal disease (ESRD) who developed metastatic calcinosis cutis, which is usually associated with abnormalities of calcium–phosphate metabolism in renal failure. In our patient, the serum calcium and phosphate levels were normal. Additionally, we describe the diagnostic approach and the difficulties involved in the management of calcinosis cutis in patients with haemodialysis-dependent ESRD.

MO753RELATIONSHIP BETWEEN MINERAL BONE DISEASE AND ATHEROSCLEROSIS IN NON-DIABETIC PERITONEAL DIALYSIS PATIENTS

Background and Aims The term chronic kidney disease-mineral bone disorder has the role of highlighting that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease in chronic kidney disease (CKD), especially in hemodialysis. This relationship was less studied in peritoneal dialysis (PD). The aim of the present study was to evaluate the impact of metabolic bone disorder (MBD) on symptomatic atherosclerosis (stable angina SA, acute coronary syndrome ACS, ischemic stroke, peripheral artery disease PAD) in non-diabetic PD patients. We choose to exclude diabetic patients since they are already at increased risk for atherosclerosis. Method We performed a prospective study in non-diabetic population of patients in stable PD programme for at least 6 months. We analysed clinical and biological parameters of calcium-phosphate metabolism (calcemia Ca, phosphatemia P, CaxP product, intact parathormone iPTH), presence of atherosclerotic disease and we performed carotid ultrasound for measurement of intima media thickness (IMT) as a marker for subclinic atherosclerosis. Independent risk factors for atherosclerotic disease were identified by multivariate analysis through logistic regression using IBM SPSS ver. 20.0. Results 246 consecutive non-diabetic PD patients (pts) were included (128M, 118F), mean age 56.3 + 15.7 years (20-85), with a follow up of 6.5±1.1 years. 19 pts (7.7%) had calcemia (Ca)>10.2 mg/dl, no patient had a Ca<8.2 mg/dl, 127 pts (51.6%) had phosphatemia (P)>5.5 mg/dl, 45 pts (18.3%) had CaxtaP product>55 mg2/dl2, 68 pts (27.6%) had iPTH<150 pg/ml, 95 pts (38.6%) had iPTH>300 pg/ml. We found a weak positive correlation between IMT and Ca (r=0.283, p=0.005); pts with iPTH<150 pg/ml and those with iPTH>300 pg/ml had a higher risk of increased IMT compared to pts with iPTH 150-300 pg/ml (OR 4.1, p=0.009, for iPTH<150 pg/ml, respectively OR 3.4, p=0.01 for iPTH>300 pg/ml). Pts with atherosclerotic disease had significantly higher P and CaxP, without differences regarding Ca and iPTH (Table 1). An iPTH<150 pg/ml was a risk factor for SA, ACS and PAD, while iPTH>300 pg/ml was a risk factor for SA and ACS (Table 2). We perfomed multivariate analysis to identify independent risk factors for SA, ACS, stroke and PAD by entering in the analysis the factors identified in univariate analysis to be significantly associated with different manifestations of atherosclerosis. Among independent risk factors identified for atherosclerotic disease, iPTH<150 pg/ml was risk factor for SA (adjusted OR 11.5, p=0.007) and ACS (adjusted OR 221.4, p=0.01), iPTH>300 pg/ml was risk factor for ACS (adjusted OR 5.2, p=0.03), CaxP >55 mg2/dl2 was risk factor for ACS (adjusted OR 33.5, p=0.02) and ischemic stroke (adjusted OR 4.4, p=0.01). No parameters of calcium-phosphate metabolism were identified as independent risk factors for PAD. Conclusion We found significant independent correlations between different parameters which characterize MBD and presence of symptomatic atherosclerosis in non-diabetic PD pts. The most important risk factors identified were abnormally low or high iPTH level, and elevated CaxP. The most striking result was the low iPTH associated with SA and especially ACS, suggesting that an adynamic bone is incapable to buffer the serum calcium and phosphate, thus increasing the risk of vascular calcifications. Future studies may address the issue whether correction of these parameters may be associated with attenuation of atherosclerotic disease in this population.

The Impact of Electrical Stimulation of the Brain and Spinal Cord on Iron and Calcium-Phosphate Metabolism

Background: Deep-brain stimulation (DBS) electrically modulates the subcortical brain regions. Under conditions of monopolar cerebral stimulation, electrical current flows between electrode’s contacts and an implantable pulse generator, placed in the subclavicular area. Spinal cord stimulation (SCS) delivers an electrical current to the spinal cord. Epidural electrical stimulation is associated with the leakage of current, which can cause a generalized reaction. The aim of our study was to investigate whether the electrical stimulation of the cerebrum and spinal cord could have generalized effects on biochemical parameters. Materials and methods: A total of 25 patients with Parkinson’s disease (PD, n = 21) and dystonia (n = 4), who underwent DBS implantation, and 12 patients with chronic pain, who had SCS, received electrical stimulation. The blood levels of selected biochemical parameters were measured before and after overnight stimulation. Results: After DBS, the mean ± interquartile range (IQR) values for iron (off 15.6 ± 13.53 µmol/L; on: 7.65 ± 10.8 µmol/L; p < 0.001), transferrin (off: 2.42 ± 0.88 g/L; on: 1.99 ± 0.59 g/L; p < 0.001), transferrin saturation (off: 23.20 ± 14.50%; on: 10.70 ± 11.35%; p = 0.001), phosphate (off: 1.04 ± 0.2 mmol/L; on: 0.83 ± 0.2 mmol/L; p = 0.007), and total calcium (off: 2.39 ± 0.29 mmol/L; on: 2.27 ± 0.19 mmol/L; p = 0.016) were significantly reduced, whereas ferritin (off: 112.00 ± 89.00 ng/mL; on: 150.00 ± 89.00 ng/mL; p = 0.003) and C-reactive protein (off: 0.90 ± 19.39 mg/L; on: 60.35 ± 35.91 mg/L; p = 0.002) were significantly increased. Among patients with SCS, significant differences were observed for ferritin (off: 35 ± 63 ng/mL; on: 56 ± 62 ng/mL; p = 0.013), transferrin (off: 2.70 ± 0.74 g/L; on: 2.49 ± 0.69 g/L; p = 0.048), and C-reactive protein (off: 31.00 ± 36.40 mg/L; on: 36.60 ± 62.030 mg/L; p = 0.018) before and after electrical stimulation. No significant changes in the examined parameters were observed among patients after thalamotomy and pallidotomy. Conclusions: Leaking electric current delivered to the subcortical nuclei of the brain and the dorsal column of the spinal cord exposes the rest of the body to a negative charge. The generalized reaction is associated with an inflammatory response and altered iron and calcium-phosphate metabolism. Alterations in iron metabolism due to electrical stimulation may impact the course of PD. Future research should investigate the influence of electric current and electromagnetic field induced by neurostimulators on human metabolism.

Basic serum biochemical parameters in the assessment of calcium-phosphate metabolism in children

Introduction: The calcium-phosphate homeostasis is important for proper child growth and development and vitamin D plays a crucial role in this process. Aim: The aim of the study was to assess the relationship between total calcium (Ca), phosphates (Pi), parathyroid hormone (PTH) and the concentration of 25-hydroxycholecalciferol (25 (OH) D3) in children. Materials and methods: 164 serum samples were collected from children (1 day to 18 years) hospitalized in University Children’s Hospital in Krakow. Concentrations of Ca, Pi (dry chemistry-method), PTH (immunoradiometric-method) and 25(OH)D3 (HPLC) were determined. The results were analysed for all children, regardless of the age and for children under and above the age of four. Results: Analyzing all results, the mean of Ca concentration was significantly higher in the children with optimal 25(OH)D3 concentration compared to the children, who had 25(OH)D3 deficiency (p < 0.05). In samples from children ≤4 years of age, the significantly higher mean concentrations of Ca and Pi in the children with optimal 25(OH)D3 concentration compared to the children, who had suboptimal levels of 25(OH)D3 were found (p = 0.04; p = 0.002; respectively). For all results and for results from children ≤ 4 years of age, Ca and Pi concentrations were positively correlated with 25(OH)D3 concentration (p < 0.002, p < 0.01; p < 0.003, p < 0.004; respectively), there were no relationship between PTH and 25(OH)D3 concentrations. Conclusion: Comparing the results of calcium and phosphate concentration only to the appropriate reference ranges may not be sufficient to evaluate calcium-phosphate metabolism. Probably the reference values for total calcium and phosphates should be established depending on vitamin D levels, especially for young children.

Beneficial effect of successful simultaneous pancreas-kidney transplantation on plasma profile of metalloproteinases in type 1 diabetes mellitus patients

Background It is virtually unknown whether the restoring of normal glucose metabolism after successful simultaneous pancreas-kidney transplantation (SPK) improves vascular wall morphology and function in type 1 diabetic (T1D) patients. This study has been aimed to compare arterial stiffness, assessed by pulse wave velocity (PWV), carotid intima-media thickness (IMT) biomarkers of arterial wall calcification, and parameters of calcium-phosphate metabolism in T1D patients after SPK or kidney transplantation alone (KTA). Methods In 39 SPK and 39 KTA adult patients of similar age, PWV and IMT were measured at a median of 83 (62–109) months post-transplantation. Additionally, carotid plaques were visualized and semi-qualitatively classified. Circulating matrix metalloproteinases (MMPs), calcification biomarkers, and calcium-phosphate metabolism parameters were measured. Results Although PWV and IMT values were similar, the occurrence of atherosclerotic plaques (51.3 vs. 70.3%, p < 0.01), turned to be lower, especially in case of calcified lesions (35.9 vs. 64.9%, p < 0.05) in patients after SPK. There were significantly lower concentrations of MMP-1, MMP-2, MMP-3 and osteocalcin (OC) in SPK subjects. Among the analyzed biomarkers, only log MMP-1, log MMP-2 and log MMP-3 concentrations were associated with log HbA1c. In addition, both log MMP-1 and log MMP-3 were inversely related to estimated glomerular filtration rate (eGFR). Multivariate stepwise backward regression analysis revealed that MMP-1 and MMP-3 variability were explained only by log HbA1c, whereas OC variability only by eGFR. Conclusion Normal glucose metabolism achieved by simultaneously transplanted pancreas in T1D renal transplant recipients is followed by the favorable profile of circulating matrix metalloproteinases, which may reflect the vasoprotective effect of SPK.

P1304FIBROBLAST GROWTH FACTOR (FGF23) AND CARDIOVASCULAR MORTALITY IN DIALYSIS PATIENTS: A 10 YEAR PROSPECTIVE SINGLE CENTER STUDY

Background and Aims The aim of the study is to evaluate whether circulating fibroblast growth factor 23 (FGF23) predicts cardiovascular mortality in dialysis patients, independent of markers of calcium-phosphate metabolism and cardiovascular risk factors. Method A prospective observational study at Akdeniz University Medical Center including 51 peritoneal dialysis patients and 27 hemodialysis patients was undertaken from 01/2009 to 12/2019. Plasma C-terminal FGF23 concentrations in addition to other measures of mineral metabolism were performed at baseline. Patients were followed for all-cause mortality, cardiovascular mortality, non-fatal MI, non-fatal stroke, coronary revascularization, heart failure hospitalization and atrial fibrillation. Results The mean age of patients 48± 15 years. During a ten year follow up period, there were 47 deaths. The median plasma FGF23 level was 321 pg/ml (interquartile range 51-1784 pg/ml). Patients were stratified by their baseline FGF23 levels according to the tertiles. Cumulative survival analysis by tertiles of FGF23 were made with the Kaplan-Meier survival curve. Kaplan Meier analysis with log-rank did reveal a significant difference between the groups (p=0,048). Conclusion Higher FGF23 levels are associated with an increased incidence of cardiovascular mortality in dialysis patients, independent of other markers of calcium-phosphate metabolism and cardiovascular risk factors.

Factors of vascular calcification in patients with type 2 diabetes mellitus on long-term dialysis

Purpose Defining vascular calcification markers in patients on long-term hemodialysis (LTH) with type 2 diabetes mellitus (type 2 diabetes) and without type 2 diabetes. Materials and methods. The study was conducted in 82 patients with chronic kidney disease (CKD) (51 men, 31 women) on LTH, of which 25 patients (10 men, 15 women) had type 2 diabetes and 57 people (33 men, 24 women) had no diabetes. All patients underwent evaluation of calcium-phosphate metabolism, control of intact PTH (iPTH), inorganic phosphorus, and total calcium. All patients were tested for the level of fibroblast growth factor-23 (FGF-23) in blood serum using a multi-enzyme immunoassay kit, and the correlation between these parameters and the presence of vascular calcification was evaluated. Results. A correlation was found between the severity of vascular calcification and the calcium-phosphate metabolism. In the group with type 2 diabetes, there is a correlation between the level of FGF-23, iPTH, inorganic phosphorus and vascular calcification. There is also a correlation between the time on LTH and the increase in the level of FGF-23 in patients with type 2 diabetes. Conclusion. We obtained data that can indicate a more pronounced change in the vascular wall in patients with type 2 diabetes on LTH in comparison with patients without diabetes mellitus on LTH, which allows to associate high cardiovascular mortality in patients with type 2 diabetes on LTH with accelerated development of vascular calcification.