CaxP Product Research Articles

#521 Increasing levels of aortic peak wave velocity along with prolonged higher CaxP product is associated with mortality in peritoneal dialysis

Abstract Background and Aims Valvular calcification is concordant with vascular calcification and develops faster in end-stage renal disease patients than in the average population. There are contradictory reports about the pathophysiology and the predictive value of valvular calcification regarding mortality in this patient population. Aortic peak wave velocity (Vmax) measurement is a non-invasive and reliable marker for the diagnosis of valve calcification. Our study analyzes cardiovascular risk prediction effect of increasing levels of Vmax at different time points in peritoneal dialysis (PD) patients. Method We conducted a retrospective, single-center study of incident PD patients under follow-up between January 1992 and January 2023 in our clinic. Demographics, laboratory, and echocardiographic findings were obtained from medical records. Patients without a baseline echocardiography were excluded. ΔVmax is defined as the last Vmax minus baseline Vmax levels. The patients were divided into two subgroups: Vmax-stable and Vmax-increased. Results The baseline demographics, laboratory, and clinical characteristics, including daily elemental calcium and calcitriol usage, were similar between Vmax-stable and Vmax-increased groups. Baseline calcium (Ca), phosphate (P), and annual CaXP levels were significantly higher in Vmax-increased group [p = 0.01, p = 0.02, and (F(1,27) = 10.415, p = 0.003), respectively]. Cardiovascular mortality was 9.8% in Vmax-stable group and 26.8% in Vmax-increased group (p = 0.02). Conclusion During a follow-up of 20 years, increasing Vmax values were associated with higher CaxP levels in PD patients. Increased Vmax levels, along with higher CaxP levels, are associated with cardiovascular mortality. Even without clinical manifestations, Vmax follow-up is a non-invasive, easily accessible method and might identify the high-risk group regarding cardiovascular mortality in the PD population.

THE EFFECT OF PARICALCITOL AND CALCITRIOL WITH OR WITHOUT CALCIMIMETICS ON PULSE WAVE VELOCITY AND SERUM LEVELS FOR PARATHYROID HORMONE, CALCIUM AND PHOSPHORUS IN MAINTENANCE HEMODIALYSIS PATIENTS.

Different vitamin D analogs might have advantages over calcitriol. To evaluate the effects of paricalcitol vs. calcitriol based vitamin D receptor activators on calcium-phosphate metabolism and pulse wave velocity in hemodialysis patients. Observational, cross-sectional and 1 year follow-up study. 181 hemodialysis patients were enrolled in this study as divided in to 5 groups based on vitamin D therapy. Baseline and 12th month data on blood biochemistry, pulse wave velocity and cumulative dose of treatments were compared in each study group as well as in overall paricalcitol vs. calcitriol-based treatment groups. From baseline to 12th month, significant improvement in pulse wave velocity and parathyroid hormone was shown in paricalcitol-based treatment group without a significant change in calcium, phosphate, alkaline phosphatase. A significant increase in pulse wave velocity, serum phosphate levels, calcium x phosphate product and serum alkaline phosphatase levels were noted in calcitriol-based treatment group with no significant change in serum calcium and parathyroid hormone levels. Our findings revealed superiority of paricalcitol than calcitriol based vitamin D receptor activator therapy in terms of serum phosphate levels, CaxP product, dose requirement for vitamin D and the control of pulse wave velocity.

Biochemical and Hematological Parameters in a Group of Chronic Kidney Disease Patients in Albania

Chronic kidney disease is a serious, life threating health problem. It is also known as chronic kidney failure, as it is a process of irreversible loss of nephrons, which at the end stage leads to kidney failure. There are many different reasons that lead to kidney failure, such as: hypertension, diabetes, polycystic kidney disease, glomerulonephritis, parathyroid glands dysfunction, etc. The aim of this study was to evaluate the biochemical and hematological profile in a group of chronic kidney patients in Albania. A group of 247 chronic kidney disease patients is included in this study (170 adult males and 77 adult females). A group of biochemical parameters, such as urea, CRP, albuminemia, HbA1C, creatinine, ALT, AST, calcium, phosphate, CaxP product, sodium, potassium and hematological parameters, such as hemoglobin, red blood cells, white blood cells and PTH, where measured and compared to the findings from the control group. Results were analyzed statistically using SPSS 20 program for windows. From data analysis, we found a reduced count of red blood cells and hemoglobin, statistically significant change, compared to the control group (p0.05). High levels of PTH, serum urea, creatinine and hyperphosphatemia, accompanied by hypocalcemia, were found statistically significant compared to the control group (p0.05). From our observations, hypertension, diabetes and kidney stones were the main causes leading to chronic kidney disease. Evaluation of these parameters, results to be significant in the differentiation and management of the health state of these patients.

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

Abstract 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.

Risk factors associated with valvular calcification in patients with chronic kidney disease. Analysis of NEFRONA study

IntroductionPatients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. Material and methodsPart of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. ResultsWe included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. ConclusionsA significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

Factores de riesgo asociados a la calcificación valvular en pacientes con enfermedad renal crónica. Análisis del Estudio Nefrona

IntroductionPatients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. Material and methodsPart of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. ResultsWe included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33ml/min with significant decrease to 30.9ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. ConclusionsA significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

SAT-LB72 Design of the PaTH Forward Phase 2 Trial of TransCon PTH, a Long-Acting PTH, in Patients With Hypoparathyroidism

Background:Hypoparathyroidism (HP) is caused by a deficiency in parathyroid hormone (PTH), which leads to hypocalcemia and hyperphosphatemia. Standard of care (SoC), i.e. large doses of calcium (Ca) and active vitamin D, worsens hypercalciuria and increases the serum Ca (sCa) x serum phosphate (sP) product. Studies have shown that continuous subcutaneous infusion of PTH(1-34) normalizes sCa, sP, serum magnesium, urine Ca (uCa) and bone turnover better than SoC or once- or twice-daily injections of PTH in HP patients. TransCon PTH, an investigational long-acting prodrug of PTH (1-34) transiently bound to an inert carrier via a linker, is under development as a potential once-daily replacement therapy for HP. Under physiological conditions, linker auto-cleavage occurs, releasing active PTH at a controlled rate with ~60 hour half-life. Phase 1 trial results demonstrated that once-daily TransCon PTH provided a flat, infusion like profile within the normal range of PTH 24 hours per day, increasing sCa while controlling uCa and decreasing sP, with no evidence of bone anabolic activity.Phase 2 Design:PaTH Forward is a global phase 2 trial evaluating the safety, tolerability, and efficacy of TransCon PTH in adult subjects with HP. Patients with HP treated with SoC were randomized at sites worldwide to daily TransCon PTH 15, 18 or 21 µg PTH(1-34) or daily blinded placebo via pen-injector for 4 weeks. The primary composite endpoint requires 1) normal albumin-adjusted sCa, and 2) normal Fractional Excretion of Ca (or ≥50% decrease from baseline), and 3) not taking active D, and 4) taking ≤1000 mg/d of Ca. After four weeks, all subjects enter an open-label extension period with the opportunity to receive TransCon PTH individually optimized to doses of 6 to 30 µg daily to evaluate long-term safety and efficacy. Other endpoints include the impact of treatment on patient experience, CaxP product, bone turnover markers, and bone mass by DXA and TBS to confirm the lack of anabolic effect.Preliminary Results:Approximately 55 subjects are expected to be randomized and dosed. Preliminary diary data on the initial 8 subjects completing 4 weeks of follow-up in the extension trial shows that all have discontinued SoC. Additional information will be presented at ENDO 2020. The Phase 2 trial is designed to inform the starting dose for a global pivotal phase 3 trial and evaluate TransCon PTH as a “true” PTH replacement therapy.

Impact of hepatitis virus infection on arterial calcification among incident hemodialysis patients

BackgroundThe impact of hepatitis virus infection on arterial calcification (AC) was not studied. ObjectiveTo study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection. Cases and methods172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin. Results86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group.In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P<0.001 in all).HBV group had significantly lower serum P, CaxP and PTH in comparison to SN group (4.6±0.66 vs. 5.45±0.77mg/dL, 36.4±7.2 vs. 44.1±8.69, and 348±65.4 vs. 405.9±83.2pg/mL, P<0.001, <0.001, and 0.035 respectively). On the other hand, HCV group did not show any significant difference in any of the studied parameters compared to SN group. ConclusionHCV positive patients are more prone to develop AC that is more extensive. HBV positive patients were less likely to have arterial medial calcification, probably related to lower serum phosphorus, CaxP product and PTH. HCV infection should be added as risk factor for AC among CKD patients. Further studies are needed to confirm these findings.

Impact of hepatitis virus infection on arterial calcification among incident hemodialysis patients

BackgroundThe impact of hepatitis virus infection on arterial calcification (AC) was not studied. ObjectiveTo study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection. Cases and methods172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin. Results86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group.In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P<0.001 in all).HBV group had significantly lower serum P, CaxP and PTH in comparison to SN group (4.6±0.66 vs. 5.45±0.77mg/dL, 36.4±7.2 vs. 44.1±8.69, and 348±65.4 vs. 405.9±83.2pg/mL, P<0.001, <0.001, and 0.035 respectively). On the other hand, HCV group did not show any significant difference in any of the studied parameters compared to SN group. ConclusionHCV positive patients are more prone to develop AC that is more extensive. HBV positive patients were less likely to have arterial medial calcification, probably related to lower serum phosphorus, CaxP product and PTH. HCV infection should be added as risk factor for AC among CKD patients. Further studies are needed to confirm these findings.

Refractory secondary hyperparathyroidism in waiting list for parathyroidectomy: who we should operate first in a quaternary hospital in Brazil regarding survival

Background: Few centers in Brazil perform parathyroidectomy (PTX) for recalcitrant secondary hyperparathyroidism (SHPT) generating a long queue. There is little data regarding prioritize criteria besides chronological order and survival.Objectives: To determine the difference of clinical and laboratory factors between PTX patients and those who remained in the line despite the need for surgery and their survival.Methods: A retrospective cohort study was conducted in a quaternary hospital in Brazil, where 43 patients with PTX indication due to severe SHPT were followed from 2009 to 2016. While 31 patients underwent PTX, 12 remained in the queue. Data on clinical and laboratory factors were collected for comparison and Kaplan–Meier and Cox regression survival analysis were used.Results: PTX group was younger (40.9 vs. 49.3 years, p = .03), had higher PTH levels (2578 vs. 1937 pg/ml, p = .01) and higher CaxP product (62 vs. 47.5, p = .02). There were no percentage differences between groups of fractures, calciphylaxis and other complications due to SHPT. Patients who were not operated had a worst overall survival (5 y 62.2% vs. 96.7%, p = .04) with a HR for death of 8.08 (p = .07, PTX as a TVC). Other variables associated with decreased survival included a history of previous myocardial infarction (HR: 10.4, p = .01) and age per additional year (HR: 1.09, p = .02).Conclusions: Patients with severe SHPT are at increased risk of death while waiting for PTX. Clinical events like fracture were not used to prioritize patients beyond consecutive order. Therefore, optimizing priority criteria for PTX may result in improved survival in this population.

OP035: Vitamin D Status and Mortality in Patients with Stable Angina

of follow-up (PWV2). Samples for FGF-23 and 25(OH)D3 were determined cross-sectionally. Patients were divided into two groups cccording to 25(OH)D3 levels: Insufficiency (group 1, 25(OH)D3 30 ng/mL). Results: Patients in Group 1 (n: 91) had significantly higher annual mean values of phosphorus, CaxP product and FGF-23 compared to Group 2 (n: 26) (p < 0.018, 0.044 and 0.046, respectively). Administered elementary calcium dose was significantly higher in Group 1 than in Group 2 (p < 0.014). Patients in Group 1 had higher PWV1 and PWV2 measurements compared to Group 2 (p < 0.018 and 0.011). Serum levels of 25(OH)D3 were negatively correlated with mean phosphorus (p = 0.039) and mean administered elemantary calcium dose (P= 0.017). On multivariate analysis, levels of 25(OH)D3 were independently associated with the adjusted dose of elementary calcium (P< 0.002). Conclusion: Low level of 25(OH)D3 is not only a primary risk factor for cardiovascular health but might occur as a result of high phosphorus level or high cumulative calcium intake. While targeting to control renal osteodistrophy and achieving a higher 25(OH)D3 and lower FGF 23 for better outcome, better phosphorus control and minimum calcium supplementation should be the priority in the plan.

The Importance Calcium Phosphorus Product in Renal Insufficiency

High serum phosphorus (P) levels in chronic renal failure (CRF) lead to parathyroid hormone (PTH) resistance of skeletal system. Serum calcitriol level increases and calcium (Ca) reabsorbtion from intestine decreases. Because of these abnormalities calcifications occur in soft tissues and perivascular tissues. Cardiovascular complications occur and high CaxP product levels seen in laboratory results. Our aim was to find out the critical level of CaxP product in different treatment groups of patients with CRF. CRF patients who did not require dialysis before (preD, N=36), chronic renal disease patients on peritoneal dialysis (PD, N=36), chronic renal disease patients receiving hemodialysis treatment (HD, N=35), renal transplant patients (Tx, N=36), and healthy individuals (N=30) evaluated for the study. Total of 173 patients (77 male, 96 female) included to the study. Patients body mass indexes calculated. Blood levels of PTH, Ca, P and cystatin C (CysC) levels were measured (Siemens Healthcare Diagnostics, USA). Kolmogorov-Smirnov test is used to check the normality of data among groups. One Way Analysis of Variance is used for normally distributed groups. For non-normally distributed data, Kruskal Wallis Analysis of Variance is used for comparison of groups. Associations between categorical variables are assessed using the cross-tables and Chi-squared tests. The Receiver operating characteristics (ROC) analysis is used to measure the performance of biochemical parameters in detecting kidney dysfunction. Greater than 1mg/dL CysC levels accepted as renal dysfunction. The cut-off value for CaxP product was obtained as 37.535. Area under the ROC curve was 0.678 (p=0.002), the sensitivity and specificity were 0.573 and 0.800, respectively. Median value of all groups for CaxP was found as 37.730; very near the cut-off value (37.535). There was a significant difference in CysC levels between the two groups of dialysis according to cut-off value of 37.535. (p<0.05) In our study according to ROC analysis results, CaxP product critical value for all the patients which grouped according to treatment modalities is 37,535. In serum Ca and P parameters show high measurement performance and CaxP value is easy to access. The critical value that we found in our study groups should be confirmed for detection of renal failure and cardiovascular complications in future research.

Cardiac valve calcification in predialysis chronic kidney disease patients: Prevalence and risk factors

Valvular calcification is a common finding in patients with end-stage chronic kidney disease (CKD) and associated with increased all-cause and cardiovascular mortality. The aim of the study was to determine the prevalence and risk factors associated with cardiac valve calcification in patients with stage IV and V CKD, not yet on dialysis. The study enrolled 61 CKD patients (34 M, mean age 62.6±13.6 years) and 22 ageand sex-matched healthy controls. All participants underwent a clinical assessment, laboratory analyses, echocardiography and carotid artery ultrasound. Calcification of the aortic and mitral valve was more frequently in patients with CKD stages IV-V than the healthy controls (47.5% : 9.1%, p=0.001). CKD patients were divided according to the presence of valvular calcification in 2 groups: group A with calcification (n=29) and group B without calcification (n=32). Patients from group A were significantly older (p<0.01), had lower creatinine clearance (p<0.01), and higher levels of P (p <0.05), CaxP product (p<0.05) and PTH (p<0.05) compared to patients from group B. Echocardiography showed a higher prevalence of left ventricular hypertrophy (LVH, p<0.01) in group A compared with group B. In patients of group A, carotid intima-media thickness (IMT) was higher (p<0.001) and calcified plaques were more frequent (p=0.005) than those in group B. Valvular calcification is highly prevalent in the predialysis period of CKD and is associated with disorders of mineral metabolism, left ventricular hypertrophy and vascular calcification.

Analysis of the calcium-phosphorus metabolism and function of the parathyroid glands in patients with type 1 diabetes mellitus

Objective. To analyze the calcium-phosphorus metabolism in patients with diabetes mellitus (DM) type 1 depending on the functional state of the kidneys. Materials and Methods. The study involved 235 patients with type 1 diabetic (males). One hundred and thirty-four patients entered the group without diabetic nephropathy (DN) and 101 patients entered the group with DN. To study the phosphorous-calcium metabolism in patients with type 1 diabetes there were studied the following parameters in blood plasma: the level of intact parathyroid hormone (PTH), total calcium (Ca), ionized calcium (Ca2+), serum phosphorus (P), as well as calculated CaxP product. Results. In patients with type 1 diabetes in the progression of DN the increase of P was observed from stage 4 CKD and reduction of Ca ? from CKD stage 5. The increase of the level of PTH was observed from the stage of CKD 3, although isolated cases of secondary hyperparathyroidism were registered in patients with stage CKD 2. At the same time in a large group of the patients with type 1 diabetes there was observed level of PTH below the target values of the stages CKD 3, 4, 5. The deterioration of glycemic control in patients with type 1 diabetes is associated with decreased level of PTH. In patients with type 1 diabetes without DN and with DN there was observed inverse relationship between the level of glycated hemoglobin (HbA. 1c). Conclusion. In patients with type 1 diabetes the progression of DN leads to various disorders of phosphorus-calcium metabolism: reduction of Ca, higher level of P, alter the function of the parathyroid glands (secondary hyperparathyroidism and reduction of PTH below the target value). Deterioration of glycemic control in patients with type 1 diabetes is associated with a reduction of PTH.

Efficacité du cinacalcet en pratique clinique chez les patients dialysés présentant une hyperparathyroïdie secondaire : observatoire ECHO – Expérience française

In chronic kidney disease patients with secondary hyperparathyroidism (SHPT), the recommended K/DOQI™ target serum levels of parathyroid hormone (PTH), calcium (Ca) and phosphorus (P) are difficult to reach and maintain stable. We present the results of the French cohort from the European study ECHO which investigated the use and effectiveness of cinacalcet in real-world clinical practice. MethodsAn observational study of the SHPT management in dialysis patients, partially retrospective (from 6 months prior to cinacalcet initiation) and partially prospective (up to 12 months of cinacalcet treatment). ResultsFour hundred and eighty-five French patients were enrolled from 44 centres. Cinacalcet was given in combination with active vitamin D treatment (39%) and phosphate binders (87%). After 12 months, the proportion of patients reaching recommended K/DOQI™ target levels had increased from 2.5% to 28.8% for PTH, from 46.8% to 50.1% for Ca, from 40.0% to 49.9% for P and 54.8% to 77.7% for the CaxP product. The proportions of patients using active vitamin D and sevelamer decreased by 6% and 20% respectively. Adverse events were reported in 37 (7.6%) patients, mainly nausea (2.1%), vomiting (2.1%) and dyspepsia (1.2%). ConclusionsThe results of this study are consistent with data from controlled and randomized studies showing that cinacalcet increases the proportion of patients achieving the K/DOQI™ targets for PTH, Ca, P and CaxP in real-world clinical practice.

Relationship between Fetuin-A and Systemic Lupus Erythematosus as a Predictor Marker for Atherosclerosis

Problem statement: Associations between serum levels of fetuin-A, C3 complement, calcium × phosphate product and calcification risk index and lipid profile in SLE patients were established. However, the mechanism of accelerated atherosclerosis accompanied with SLE remains elusive. We therefore turned to investigate the association between Fetuin-A, disease activity and accelerated atherosclerosis in patients with SLE. Approach: Serum blood samples were taken from 100 female SLE patients. All Patient samples were analyzed by ELISA for determination of Fetuin-A level. Calcium, Phosphate, C3 compelement, Lipid profile, Creatinine and urea were measured also in SLE patients compared with healthy control volunteers. Results: We found that Serum fetuin-A had been positively associated with carotid arterial stiffness, independent of known atherogenic factors in healthy subjects. Furthermore, Fetuin-A was correlated negatively with IMT, SLEDAI, CRI, CaxP product, Triglycerdies, VLDL and LDL. While it was correlated positively with C3 complement. Conclusion: Fetuin-A deficiency accompanied with increasing levels of calcium and phosphate gave an evidence that there was a key role of fetuin-A as a strong inhibitor of Cardio Vascular Calcification (CVC) by formation of a complex called (calciprotein) with calcium and phosphate in blood stream. So, Identification of biologic markers of disease activity associated with atherosclerosis may help to optimize therapy for this important manifestation of systemic autoimmune disease.

Relationship of Fibroblast Growth Factor 23 with Left Ventricle Mass Index and Coronary Calcificaton in Chronic Renal Disease

Background: to evaluate the relationship between FGF23 and changes in biochemical parameters, left ventricle mass index, coronary, aortic and, valve calcifications. Methods: Totally 185 patients with chronic renal disease were included in this prospective, cross-sectional study. The patients were stratified according to GFR levels (mL/min/1.73m²) into 5 groups: ≥60, 45-59, 30-44, 15-29 and <15 (group 1-5 respectively).Biochemical parameters, serum FGF23 levels were measured. Echocardiographic assessments and Coronary artery calcification (CAC) with multidetector computerized tomography (MDCT) were done, left ventricle muscle mass (LVMI) was measured all patients. Results: Left ventricular hypertrophy (LVH), aortic and valve calcification were detected in 27.8%, 25.3% and 12% of patients respectively. CAC was detected in 18 patients. LVMI and FGF23 levels were found to increase proportionally with the severity of renal failure. A significant positive correlation between FGF-23 level and serum phosphate, log_PTH, and CaxP product was found. While a correlation between FGF-23 and valve calcification was detected, no correlation could be detected with LVMI, LVH, coronary and aortic calcification. Conclusion: In CKD, circulating FGF-23 and LVMI levels gradually increase with declining renal function such that by the time patients reach end-stage renal disease. Correlation between log_FGF23and valve calcification was significant, whereas no statistically significant relationship was found between log_FGF23and LVMI, LVH, aortic and coronary artery calcifications.

Sevelamer carbonate experience in Indian end stage renal disease patients

This open label, multicentric, comparative clinical trial was done to compare the efficacy and tolerability of two sevelamer formulations, sevelamer carbonate, and sevelamer hydrochloride, in the treatment of hyperphosphatemia in Indian end stage renal disease (ESRD) patients. A total of 97 ESRD patients on hemodialysis, were enrolled. Patients were randomized to receive either sevelamer carbonate or sevelamer hydrochloride. All patients were evaluated every week for 6 weeks for efficacy and safety variables. Total 88 patients completed the study. After 6 weeks of therapy, there were similar reductions (P<0.0001) in mean serum phosphorus and the CaxP product both the groups. The responder rates for test and reference groups were 75%, 68.18% respectively (P=0.3474). The adverse events reported were nausea, abdominal pain/discomfort, heartburn, constipation, diarrhea, increased prothrombin time, and severe arthritis. No serious adverse events were reported. There was no significant difference between the groups for adverse events and the laboratory parameters. From the results of this multicentric, comparative, randomized clinical study on sevelamer carbonate we can recommend that sevelamer carbonate may be used as a phosphate binder in Indian chronic kidney disease patients.

Metastatic pulmonary calcification.

A 49-year-old man undergoing maintenance hemodialysis three times weekly for the past 14 years due to presumed hypertensive nephrosclerosis was submitted to a chest x-ray during evaluation of flu-like symptoms that resolved 3 days later. The chest x-ray disclosed interstitial infiltrates and bilateral apical opacities (Figure 1). There was no history of chronic cough, exertional dyspnea and exposition to tobacco or occupational aerosols. His current medications included only sevelamer 4 pills/day (800 mg/pill) and amlodipine 10 mg/day. He had been previously submitted to several courses of calcitriol to control hyperparathyroidism with no effect. Laboratory evaluation revealed hemoglobin 10.4 g/dL, white blood cell count 4120/mm3 (normal differential count), platelet count 192 × 103 cells/μL, ferritin 1639 ng/mL, transferrin iron saturation 28.7%, serum iron 4.1 μg/dL, parathyroid hormone 4700 ng/L (normal range 16–65 ng/L) serum phosphorus 8.1 mg/dL (2.61 mmol/L), serum calcium 11.0 mg/dL (2.74 mmol/L). An axial computed tomographic (CT) scan of the chest showed multiple bilateral centrilobular calcified nodules mainly in the upper lobes, suggestive of calcium deposition (Figure 2). Pulmonary function test demonstrated mild restriction disorder. Bronchoalveolar wash was negative for mycobacterial and fungal infections. There was also evidence of vascular calcification in hands and legs demonstrated by radiographies. Parathyroid scintigraphy disclosed marked uptake in the upper projection of right and left thyroid lobes. The patient was started on daily dialysis, phosphate-binding optimization and was referred to parathyroid surgery. Fig. 1. Lung radiography disclosing interstitial infiltrates and bilateral apical opacities. Fig. 2. Axial CT scan demonstrating multiple bilateral centrilobular calcified nodules, mainly in the upper lobes. Pathological pulmonary calcifications can be broadly divided into metastatic calcifications and dystrophic calcifications [1]. Metastatic pulmonary calcifications occur in normal lung tissue, mainly due to alterations in calcium and phosphorus metabolism and alkali environment [2]. This patient presented severe hyperparathyroidism secondary to renal disease and a CaxP product of 89.1 mg2/dL2. No alkalosis period was detected, even after a dialysis session. Metastatic pulmonary calcification diagnosis is based on CT findings and clinical features, unless there is clinical suspicion of other processes (mycobacterial or fungal infections). Therapy is limited to ensuring adequate dialysis, correcting calcium–phosphorus product and hyperparathyroidism; moreover, discontinuing vitamin D analogs may help [3].

Uremic Tumoral Calcinosis in Patients on Peritoneal Dialysis: Clinical, Radiologic, and Laboratory Features

Uremic tumoral calcinosis (UTC) has been analyzed in uremic patients on hemodialysis, but little is known about UTC in peritoneal dialysis (PD). In this study, we aimed to characterize UTC in uremic patients on PD. We retrospectively reviewed uremic patients on PD who developed UTC over a 9-year period. Clinical, radiologic, and laboratory features; treatments; and outcomes in those patients were assessed. One of the patients (case 7) is described as a case example. The study enrolled 7 patients with a mean age of 41 years. Mean time from PD to UTC was 45.3 months. All patients were anuric but adequately dialyzed. Cardinal symptoms were local tenderness and limited range of joint motion. Lesions were mostly multifocal (n=6) and predominantly involved shoulders, hands, feet, hips, and wrists. Metatarsophalangeal joint UTC was misdiagnosed as tophaceous gout in 2 patients. Main laboratory findings were hyperphosphatemia (7.9 ± 0.8 mg/dL), high Ca×P product [>65 mg(2)/dL(2) (range: 81.1 ± 11.5 mg(2)/dL(2))], secondary hyperparathyroidism (SHPT) with various levels of intact parathyroid hormone (iPTH: 592.2 ± 315.2 pg/mL; <250 pg/mL in 2 patients). Medical treatments for UTC included P restriction, non-Ca-based phosphate binders, and adequate dialysis with low-Ca dialysate, but all treatments were ineffective. Parathyroidectomy (n=3) can partially ameliorate UTC, but only 1 patient (case 7), who had extremely high iPTH (1085 pg/mL), manifested hungry bone syndrome (HBS) and had remarkable resolution of UTC. By contrast, in patients who underwent renal transplantation (n=3), UTC completely resolved by about 1 year after surgery. Uremic tumoral calcinosis develops in anuric PD patients with uncontrolled hyperphosphatemia; it is usually multifocal, occurring around the weight-bearing joints or overused smaller joints. Aggressive medical therapy alone is ineffective, and parathyroidectomy appears to be unsatisfactory except in the presence of severe SHPT with postoperative HBS.