Oral versus intramuscular cholecalciferol replacement in hemodialysis patients with vitamin D deficiency

Introduction: Low 25-hydroxyvitamin D (25(OH)D) level in hemodialysis (HD) patients is associated with high bone turnover, secondary hyperparathyroidism, and decreased bone mineral density (BMD). Objective: To investigate the efficacy of equivalent doses of pulse oral cholecalciferol versus intramuscular (IM) cholecalciferol in correcting serum 25(OH)D levels in HD patients with vitamin D deficiency. Patients and Methods: In a prospective randomized open-label clinical trial, 80 HD patients with 25(OH)D level <20 ng/mL and serum intact parathyroid hormone (iPTH) level >100 pg/mL were enrolled in the study. Patients were divided into two groups. Group I: 40 HD patients received oral cholecalciferol 25 000 IU weekly for 12 weeks. Group II: 40 HD patients received a single dose of IM cholecalciferol 300 000 IU. Patients were maintained on their regular medications as alfacalcidol or phosphate binders. Serum calcium, phosphorus, 25(OH)D, alkaline phosphatase and iPTH were monitored at 0, 6th, and 12th week of intervention. Results: Significant increase in serum 25(OH)D level in group II patients who received IM (intramuscular) cholecalciferol, with delta mean a change of vitamin D level was 2.92 ±7.29 ng/mL over three months in comparison to the insignificant change in oral cholecalciferol group. Additionally there was a significant increase in the mean of serum calcium in comparison to oral cholecalciferol group, while we found a statistically significant decrease in alkaline phosphatase level in both groups too (P<0.05). The mean of iPTH levels was reduced significantly with IM cholecalciferol dose (1064.00 ± 787.60 to 609.9 ± 551.41 pg/mL; P<0.05). Conclusion: Intramuscular cholecalciferol dose is more effective at increasing 25(OH) D levels in dialysis patients than oral supplementation, achieves more increase in serum calcium and reduce iPTH levels. However, the longer duration of treatment is required to achieve recommended levels of vitamin D and suppress high iPTH levels.

MO793COMPARATIVE STUDY BETWEEN THE IMPACT OF ETELCALCETIDE AND CINACALCET ON LEVELS OF IPTH, FGF-23, KLOTHO PROTEIN, SCLEROSTIN, CA AND P IN DIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM. RESULTS FROM A PROSPECTIVE RANDOMIZED TRIAL

Background and Aims The treatment of secondary hyperparathyroidism is one of the main tasks in the correction of mineral and bone disorders (MBD) in patients with chronic kidney disease (CKD). However, the results of therapy for secondary hyperparathyroidism are still unsatisfactory. In our prospective randomized controlled trial were evaluated the effect and safety of 26 weeks of treatment with etelcalcetide (intravenous route of administration) compare with cinacalcet (oral administration) on CKD-MBD parameters in patients on program hemodialysis with secondary hyperparathyroidism. Method The study group included 50 stable patients receiving hemodialysis with secondary hyperparathyroidism (PTH &gt; 300 pg/ml) and corrected Ca level greater than 2.2 mmol/L, who were randomized in a 1: 1 ratio for treatment with etelcalcetide (n = 25) or cinacalcet (n = 25) for 26 weeks. All patients were monthly evaluated the levels of P, Ca, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP); the levels of FGF 23, Klotho protein and sclerostin were assessed once in 3 months. The dose of both drugs was adjusted according to the serum iPTH level. The nature, frequency, and severity of treatment-emergent adverse events were assessed. Results Therapy with cinacalcet and etelcalcetide led to a significant decrease in the level of iPTH in the blood serum from 613.1 ± 235.1 to 302.2 ± 205.1pg/ml (p&lt; 0.01) and from 671.2 ± 272.3 to 358,6 ± 292.5 pg/ml (p &lt;0.01), by 49.2% and 53.4%, respectively. A significant decrease in the levels of corrected Ca was noted in both groups: in the etelcalcetide group from 2.20 ± 0.12 to 2.06 ± 0.18 mmol/L (p &lt;0.05), in the cinacalcet group from 2.25 ± 0.12 to 2.04 ± 0.21 mmol/l (p &lt;0.05). There was no significant change in the P levels. The alkaline phosphatase level significantly decreased in the cinacalcet group from 178.7 ± 116.8 to 78.9 ± 34.1 U/L, p &lt;0.05) and in the etelcalcetide group from 170,3 ± 115.7 to 87.1 ± 30.8 U/L, p &lt;0.05. There was a significant increase in Klotho protein levels by the end of the study from 17.9 ± 5.0 to 57.1 ± 39.3 (p &lt;0.05) and from 17.6 ± 3.7 to 91.6 ± 56.2 pg/ml (p &lt;0.05), respectively, in the cinacalcet and etelcalcetide group. Changes in FGF-23 and sclerostin by 6 months reached statistically significant changes only in the etelcalcetide group, a decrease from the FGF-23 level from 42.7 ± 22.2 to 23.0 ± 12.3 pg/ml and an increase in the level of sclerostin from 1, 59 ± 0.31 to 2.20 ± 0.33 ng/ml (p &lt;0.05). During the study, 2 patients in the cinacalcet group dropped out due to dyspeptic symptoms and 1 patient in the etelcalcetide group dropped out due to hypocalcemia. Conclusion Etelcalcetide and cinacalcet are effective PTH-lowering drugs with a comparable safety profile. Treatment with etelcalcetide, in contrast to cinacalcet, was associated with significant increases in sclerostin and decreases in FGF-23, which may have beneficial effects on outcomes and requires further study.

MO587PREVALENCE OF MINERAL AND BONE DISORDERS MAKERS AMONG RECIPIENTS OF KIDNEY TRANSPLANT: SINGLE-CENTER EXPERIENCE

Background and Aims Mineral and bone disorders (MBD) are common after successful kidney transplantation in patients with chronic kidney disease (CKD). We aimed to evaluate the prevalence of biochemical abnormalities among recipients of kidney transplant. Method We performed a cross-sectional study of 236 patients underwent successful kidney transplantation in our clinic between 2007 and 2019. Median age was 49 [Q1-Q3: 39; 58] years, mean estimated glomerular filtration rate (eGFR) was 51,1±21,8 ml/min/1,73 m2. Most of the patients received hemo- or peritoneal dialysis treatment, pre-emptive transplantation was performed in 6% cases. For those previously received dialysis, median duration of any type of dialysis was 21 [Q1-Q3: 11; 36] months. Median time after transplantation reached 42 [Q1-Q3: 19; 75] months. We evaluated serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P) and alkaline phosphatase (AP) levels. Target ranges were defined according to National guidelines on CKD-MBD as follows: 2,1 - 2,5 mmol/l for total Ca, 0,87 – 1,49 mmol/l for P; normal AP level is defined considering a gender (53-128 Е/l for men, 42-98 Е/l for women). Target iPTH level for optimal and slightly decreased transplant function (corresponding chronic kidney diasease (CKD) stage 3T) was defined as 35-70 pg/ml, for eGFR corresponding CKD 4T – as 70-110 pg/ml, for CKD 5T – as 70-150 pg/ml. Results In our cohort normal iPTH level was observed only in 13% cases, whereas 84% of the patients had hyperparathyroidism. iPTH inversely correlated with eGFR (ρ= -0,454 [95%CI: -0,55; -0,34], р&lt;0,0001 – fig.1) and its level differed significantly between groups with different CKD stage (р&lt;0,0001, Kruskall-Wallis test) – fig.2. However, fraction of patients with target iPTH did not differ in recipient groups with normal and decreased eGFR (p=0,118). Hypercalcaemia was observed in 29% cases; there was a weak correlation of serum total Ca level with iPTH (ρ= 0,282 [95%CI: 0,15; 0,4], р&lt;0,0001) and AP (ρ=0,181 [95%CI: 0,05; 0,31], р=0,006) – fig.3. Hypophosphatemia was seen much more frequently during the first year after transplantation than in long-term period (30,3% vs 6,4% respectively, р=0,0002). Serum P level varied significantly in groups with different eGFR (p&lt;0,0001, Kruskall-Wallis test), increasing in parallel with declining of transplant function – fig.4. The percentage of patients within a target range of AP amounted to 54%, above the target range – 40,7%. In total, only 6,8% of our cohort had all laboratory parameters within the target range. Conclusion We observed a high prevalence of biochemical abnormalities in kidney transplant patients confirming that transplantation itself does not cure mineral and bone disorders in CKD patients.

MO806SAFETY OF INTRAVENOUS PARICALCITOL TREATMENT IN CHINESE HEMODIALYSIS PATIENTS: A REAL-WORLD DATABASE ANALYSIS

Background and Aims The aim of this analysis based on the real-world database was to observe the effect of paricalcitol on the safety profile in Chinese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT) under routine clinical practice. Method From the Better Life for Future database, a total of 668 Chinese hemodialysis patients from 104 dialysis centers between January 2015 and May 2019 were included in the analysis set. Intact parathyroid hormone (iPTH), total serum calcium (Ca), phosphate (P), dosage of intravenous (IV) paricalcitol (Zemplar®) were analyzed and discussed via retrospective analysis of the database during the treatment. Results Patients were divided into five groups according to the duration of follow-up. Median iPTH levels decreased from 1183 pg/ml at baseline to 676 pg/ml at the final visit, or 30.88% (p &lt; 0.0001). Serum Ca levels shown significantly increased just in the group of Month 12–24 (P=0.0479) (Table 2). The incidence of hypercalcemia for three consecutive blood draws was significantly lower than the incidence of hypercalcemia for at least once or two draws in all groups (Table 3). Subgroup analyses of patients with hyperphosphatemia showed a rapid phosphate reduction, within the first few weeks, along with the reduction in the iPTH level (Figure 1). Conclusion This is the first national retrospective real-world observational study since intravenous paricalcitol is available in China since 2014. This study adds valuable information to real-world data investigating the use of paricalcitol in Chinese HD patients and demonstrated the use of paricalcitol as an effective and well-tolerated treatment for the control of PTH during its use in routine practice. The occurrence of hypercalcemia is mostly transient, followed by continuous treatment, the blood calcium level tends to be stabilized, and the blood phosphorus level will be improved with the control of PTH.

Can Surgeons Use Parathyroid Hormone Levels as Predictive Value in Parathyroid Adenomas?

Aim: Previous studies using different methods for PTH measurement have found a mild to moderate correlation between iPTH and gland weight. The aim of this study was to describe the relationship between parathyroid hormone and parathyroid adenoma volume, in patients with parathyroid adenomas as predictive value. Material and Methods: The multicenteric study was prepared by retrospectively collecting data from 244 patients with parathyroid adenoma who underwent parathyroidectomy and followed up between 2010 and 2020. Results: Two hundred forty and four (female/male = 203/41) patients with a mean age of 51.41 [min-max: 17 to 88] years. The mean iPTH concentrations preoperatively were 584.27 ng/L [min-max: 18.9 to 5011ng/L]. The mean diameter of adenoma of patients was 2,865 mm3 [min-max: 0.119 to 42.3 mm3]. After parathyroidectomy, PTH values were reevaluated and found as 47.2 ng/L [min-max: 0.2 to 903 ng/L]. In the patients with large parathyroid adenoma volume, preoperative PTH hormone values were statistically significantly higher (p=0.001). Conclusion: Our current study found a positive association between baseline iPTH levels and adenoma weight. These results suggest that serum iPTH level may be useful in predicting parathyroid adenoma volume.

The association of secondary hyperparathyroidism and myocardial damages in hemodialysis end-stage renal disease patients: assessed by cardiovascular magnetic resonance native T1 mapping

Background Secondary hyperparathyroidism is a common complication of end-stage renal disease (ESRD), which may be associated with cardiovascular diseases. Thus, this study aimed to explore myocardial damage using non-contrast cardiovascular magnetic resonance (CMR) in ESRD patients undergoing hemodialysis and further investigate its relationship with parathyroid hormone (PTH) toxicity. Methods Seventy-two adult ESRD patients receiving regular hemodialysis and 30 healthy subjects underwent CMR examination. Continuous CMR cine sections from the mitral valve level to the left ventricular (LV) apex in the short-axis plane, cine series of vertical two-chamber long-axis plane, and horizontal four-chamber plane were acquired. Native T1 mapping was obtained using modified Look-Locker inversion recovery (MOLLI) sequences. Native T1 values and myocardial strain were analyzed. Immunoreactive parathyroid hormone (iPTH) was obtained from all enrolled patients. Results Forty (55.6%) hemodialysis ESRD patients were found to have increased iPTH levels. LV ejection fraction (LVEF) of both ESRD patients with targeted and increased iPTH levels was decreased compared with healthy subjects (55.9 ± 12.0% vs. 65.0 ± 4.5%; 51.7 ± 12.8 vs. 65.0 ± 4.5%, both P < 0.05). The mean peak radial strain (PRS), peak circumferential strain (PCS), and peak longitudinal strain (PLS) were lowest in ESRD patients with increased iPTH; however, no significant difference was observed among these three groups. Segmentally, from base to apex, the native T1 of ESRD patients with increased iPTH levels tended to be higher than those with targeted iPTH and healthy subjects (all P < 0.05). In ESRD patients with targeted iPTH, both native T1 of basal and middle segments were significantly higher than normal subjects (basal, 1304 ± 41 ms vs. 1238 ± 36 ms, P = 0.001; middle, 1300 ± 43 ms vs. 1242 ± 50 ms, P < 0.001). Comparing global native T1 values in the three groups, ESRD patients with targeted and increased iPTH level showed increased native T1 (1305 ± 41 ms vs. 1251 ± 49 ms, P = 0.001; 1334 ± 40 ms vs. 1251 ± 49 ms, P < 0.001, respectively). Native T1 values of the basal segment and global native T1 were moderately associated with iPTH (r = 0.4, P < 0.001; r = 0.5, P < 0.001). Multiple linear regression analysis showed that global native T1 values (beta = 1.0, P = 0.01) were independently associated with iPTH. Conclusions Elevated iPTH level was associated with and was an independent risk factor for myocardial damage in ESRD patients undergoing maintenance hemodialysis. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) ChiCTR-DND-17012976, 13/12/2017, retrospectively registered.

Association between Parathyroid Hormone and Anemia: A Cross-Sectional Observational Study of maintenance Hemodialysis Patients of a Tertiary Care Center

Objective The objective of this study was to assess the relationship between intact parathyroid hormone levels (iPTH) and hemoglobin (Hb) levels in patients with end-stage renal disease (ESRD) who were on hemodialysis. Material and methods An observational, cross-sectional study was conducted in the Department of Nephrology at Jinnah Postgraduate Medical Centre in Karachi, Pakistan. Patients were enrolled in this study after consent and institutional review board approval. Serum samples were collected for Hb level, iPTH level, vitamin D, urea and creatinine, ferritin, and transferrin saturation. Results Ninety four patients were inducted into this study; men comprised 66.0% of the patients, and Diabetes mellitus was the commonest etiology of ESRD. Most of the patients were on dialysis for more than 5 years on twice per week hemodialysis. Mean Hemoglobin was 9.29g/dl, iPTH 576.59ng/dl and Vitamin D 25.47ng/ml. Significant inverse correlation was found between anemia and i-PTH levels. Conclusion Hyperparathyroidism is one of the major contributor anemia among maintenance hemodialysis patients.

A Pediatric Parathyroid Carcinoma: An Unusual Clinical Presentation and Mini-review

Introduction: Primary hyperparathyroidism (PHPT) is a rare condition in the pediatric population. Parathyroid carcinoma (PC) is a very uncommon cause of PHPT, accounting for < 1% of pediatric PHPT cases. It is challenging to distinguish between parathyroid adenoma (PA), the most common cause of PHPT, and PC. In this report, we described a young female who presented with a history of progressive limping and was finally diagnosed with PC. Case Presentation: A 15-year-old girl presented with progressive limping and bone pain for 8 years. She was referred by an orthopedic surgeon because of elevated intact parathyroid hormone (iPTH) for further evaluation. Physical examination revealed a large, firm, and non-tender neck mass, left hip tenderness, and limited range of motion. The initial biochemistry tests showed a borderline high calcium level of 10.8 mg/dl, an elevated iPTH level of 2876 pg/mL, and a decreased phosphorus level of 2.4 mg/dL. The 99mTechnetium (Tc) sestamibi scan displayed early intense activity in the right thyroid lobe persisting in the three-hour repeat scan, compatible with a parathyroid lesion. The patient underwent right-sided neck exploration and parathyroidectomy. Intraoperative and pathology findings confirmed the diagnosis of PC. Immunohistochemistry (IHC) staining revealed creatine kinase (CK) and CD31 in endothelial cells of the tumor. Ki67 staining was also positive in 2% - 3% of tumor cells. The whole exome sequencing (WES) study was negative for cell division cycle 73 (CDC73) and multiple endocrine neoplasia 1 (MEN1) genes. Conclusions: PC should be considered as a differential diagnosis of PHPT in the pediatric population, even in the presence of mild hypercalcemia.

Clinical phenotypes of primary hyperparathyroidism in hospitalized patients who underwent parathyroidectomy

Objective. The aim of our study was to investigate the distribution of the PHPT clinical manifestations and biochemical features in patients who underwent parathyroidectomy. Materials and methods. Medical records of 449 patients from three Medical Centers (Saint-Petersburg, Russia), hospitalized during a period from 2011 to 2018, were reviewed. History and anthropometric data, laboratory results (iPTH, total and iCa, phosphorus, ALP, 24-h urinary calcium, 25(OH)D) and imaging data (ultrasonography, scintigraphy, CT/MRI scan, DXA) were analyzed. Results. Three hundred ninety-four patients were included in the final analysis. Median age was 60 years with 94.2 % being women. Symptomatic disease was evident in 222 (56.4%) patients, asymptomatic in 172 (43.6%). Skeletal involvement was more common for women, while frequency of other manifestations did not differ in both genders. There was no difference between symptomatic and asymptomatic patients in age. Serum iPTH level was higher in symptomatic patients (202.9 and 181.0 pg/ml, p=0.022). Serum 25(OH)D level was estimated in few patients and negatively correlated with PTH (r= -0.294, p=0.005), iCa (r= -0.268, p=0.010) and total Ca (r= -0.284, p=0.014) levels. Manifestations of CVD were observed in 67.7% of cases and affected equally both symptomatic and asymptomatic patients (70.7% and 63.4%, p=0.076). Both age and BMI were higher in patients with CVD, whether or not they were symptomatic (62 and 53 years, p<0.0001; 30.4 vs 26.0 kg/m2, p<0.0001, respectively). Conclusions. This experience illustrates that symptomatic phenotype is still the most common form of PHPT.

Effect of switching from cinacalcet to etelcalcetide on secondary hyperparathyroidism in patients undergoing hemodialysis: an ESCORT trial

Background Etelcalcetide is the first intravenously administered calcimimetic agent used to manage secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. We evaluated the safety and efficacy of replacing cinacalcet with etelcalcetide in HD patients. Methods One hundred and thirty-three patients HD on cinacalcet were screened, and 93 patients with serum-intact parathyroid hormone (iPTH) level of ≥ 60 pg/mL and serum albumin-corrected calcium (cCa) level of ≥ 8.4 mg/dL were enrolled. The patients were divided into three groups based on the dose of cinacalcet (i.e., 25, 50, and ≥ 75 mg) and switched to etelcalcetide. Etelcalcetide was administered three times per week for 24 weeks. The primary and secondary endpoints were etelcalcetide conversion dose and etelcalcetide effectiveness for iPTH levels (target range: 60–240 pg/mL), respectively. Results Of the 68 patients whose iPTH level was within the management target at screening, 60 patients maintained the target level at the end of the study. Among patients whose iPTH level exceeded 240 pg/mL at screening, it decreased from 401 ± 246 pg/mL to 220 ± 209 pg/mL (p < 0.001) at the end of the study. Among 22 patients with the iPTH level of ≥ 240 pg/mL, 17 achieved the target level. The mean dose of cinacalcet was 41.4 ± 22.2 mg/day and that of etelcalcetide at the end of the study was 6.4 ± 3.7 mg/session in all patients. In 45 patients whose iPTH level was within the management target throughout the study and active vitamin D agent and calcium-based phosphate binder doses were constant, the mean dose of cinacalcet was 45.0 ± 22.4 mg/day and that of etelcalcetide at the end of the study was 6.1 ± 3.1 mg/session. The spKt/V might affect the ratio of etelcalcetide per session to oral cinacalcet per day (45 patients, p = 0.087; 90 patients, p < 0.05) in the generalized linear model. Etelcalcetide-induced severe adverse events were not observed. Conclusions This study reports the conversion dose of etelcalcetide and demonstrates its safety and efficacy in HD patients with SHPT previously treated with cinacalcet. Trial registration UMIN, UMIN000027637; Registered on June 5, 2017.