Management Of Secondary Hyperparathyroidism Research Articles

Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism.

Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.

Bariatric surgery and secondary hyperparathyroidism; a mini-review

Bariatric surgery is a type of weight loss surgery that is commonly used to treat obesity. However, this surgery can also affect the body’s calcium and PTH metabolism, leading to the development of secondary hyperparathyroidism (SHPT). Several factors contribute to the development of SHPT after bariatric surgery. Malabsorption of calcium due to reduced intestinal surface area, decreased intake of calcium-rich foods, and altered vitamin D metabolism play a significant role. The loss of weight-bearing adipose tissue can also disrupt the balance between bone formation and resorption, leading to increased bone turnover and calcium release from the skeleton. The management of SHPT after bariatric surgery involves a multidisciplinary approach. Calcium and vitamin D supplementation is essential to correct deficiency and maintain bone health. However, achieving optimal calcium and vitamin D levels can be challenging due to malabsorption issues and the need for higher supplementation doses. In some cases, pharmacological interventions such as calcimimetics or PTH analogs may be required to control PTH levels. However, these medications should be used cautiously due to limited data on their safety and efficacy in the bariatric surgery population. Prevention of SHPT is an important aspect of managing patients undergoing bariatric surgery. Nutritional counseling and regular monitoring of calcium, vitamin D, and PTH levels can help identify and address deficiencies early on. Additionally, using procedures that preserve the duodenum and proximal jejunum, such as duodenal switch or biliopancreatic diversion with duodenal switch, may reduce the risk of developing SHPT.

Comparative Effectiveness of Alternative Treatment Approaches to Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: An Observational Trial Emulation

Optimal approaches to treat secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis (HD) have yet to be established in randomized controlled trials (RCTs). Two observational clinical trial emulations. Both emulations included adults receiving in-center HD from a national dialysis organization. The patients who had SHPT in the period between 2009 and 2014, were insured for≥180 days by Medicare as primary payer, and did not have contraindications or poor health status limiting theoretical trial participation. The parathyroid hormone (PTH) Target Trial emulation included patients with new-onset SHPT (first PTH 300-600pg/mL), with 2 arms defined as up-titration of either vitamin D sterols or cinacalcet within 30 days (lower target) or no up-titration (higher target). The Agent Trial emulation included patients with a PTH≥300 pg/mL while on≥6μg weekly of vitamin D sterol (paricalcitol equivalent dose) and no prior history of cinacalcet. The 2 arms were defined by the first dose or agent change within 30 days (vitamin D-favoring [vitamin-D was up-titrated] vs cinacalcet-favoring [cinacalcet was added] vs nondefined [neither applies]). Multiple trials per patient were allowed in trial2. The primary outcome was all-cause death over 24 months; secondary outcomes included cardiovascular (CV) hospitalization or the composite of CV hospitalization or death. Pooled logistic regression. There were 1,152 patients in the PTH Target Trial (635 lower target and 517 higher target). There were 2,726 unique patients with 6,727 patient trials in the Agent Trial (6,268 vitamin D-favoring trials and 459 cinacalcet-favoring trials). The lower PTH target approach was associated with reduced adjusted hazard of death (HR, 0.71 [95% CI, 0.52-0.93]), CV hospitalization (HR, 0.78 [95% CI, 0.63-0.98]), and their composite (HR, 0.74 [95% CI, 0.61-0.89]). The cinacalcet-favoring approach demonstrated lower adjusted hazard of death compared to the vitamin D-favoring approach (HR, 0.79 [95% CI, 0.62-0.99]), but not of CV hospitalization or the composite outcome. Potential for residual confounding; low use of cinacalcet with low power. SHPT management that is focused on lower PTH targets may lower mortality and CV disease in patients receiving HD. These findings should be confirmed in a pragmatic randomized trial. Optimal approaches to treat secondary hyperparathyroidism (SHPT) have not been established in randomized controlled trials. Data from a national dialysis organization was used to identify patients with SHPT in whom escalated treatment may be indicated. The approach to treatment was defined based on observed upward titration of SHPT-controlling medications: earlier titration (lower target) versus delayed titration (higher target); and the choice of medication (cinacalcet vs vitamin D sterols). In the first trial emulation, we estimated a 29% lower rate of death and 26% lower rate of cardiovascular disease or death for patients managed with a lower versus higher target approach. Cinacalcet versus vitamin D-favoring approaches were not consistently associated with outcomes in the second trial emulation. This observational study suggests the need for additional clinical trials of SHPT treatment intensity.

Paricalcitol and Extended Release Calcifediol for Treatment of Secondary Hyperparathyroidism in Non-Dialysis Chronic Kidney Disease: Results From a Network Meta-Analysis.

Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia. The objective of this analysis was to compare the efficacy and adverse effects of extended release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on biomarkers PTH, calcium and Phosphate in patients with non-dialysis CKD (ND CKD). A systematic literature research (SLR) was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting. Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on two overlapping networks, due to non-reporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared to ERC (0.2 mg/dl increase, 95% CI: -0.37 to -0.05 mg/dl). No differences in effects on phosphate were observed. This NMA showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well tolerated treatment option for the management of SHPT in patients with ND CKD.

Erythropoietin-Resistant Therapy in Routine Hemodialysis Patients: A Case Report

Background: Anemia in chronic kidney disease can be caused by erythropoietin deficiency. Erythropoietin stimulating agent (ESA) is the treatment of choice for anemia in patients with chronic kidney disease. Some patients for some reason fail to reach target hemoglobin levels despite maximal ESA doses. Case illustration: We reported a 58-year-old man suffering from CKD with recurrent anemia despite the maximum dose of ESA. The investigations showed secondary hyperparathyroidism due to complications of chronic kidney disorders. Discussion: Our patient's resistance to erythropoietin therapy was caused by inadequate dialysis and secondary hyperparathyroidism. The management is focused on the adequacy of hemodialysis and the management of secondary hyperparathyroidism with nutrition and medication. Keywords: anemia, kidney failure, hemodialysis, hyperparathyroidism.

Evaluation of Cholecalciferol Efficacy in the Management of Secondary Hyperparathyroidism in Hemodialysis Patients

The deficiency of vitamin D is public among hemodialysis (HD) patients and is a key factor in the development of secondary hyperparathyroidism (SHPT). Secondary hyperparathyroidism is currently accomplished by lowering circulating phosphate levels with parathyroid hormone (PTH), vitamin D analogs, and oral binders. The current study aim was to assess the efficacy of cholecalciferol in the management of secondary hyperparathyroidism in hemodialysis patients with concomitant vitamin D deficiency/insufficiency. A total of 53 patients were taken with25 male and 28 female patients. After treating patients with cholecalciferol, serum PTH levels improved significantly, with mean pre-treatment levels of 486.99±191.10, which had decreased to a mean post-treatment level of 301.66±201.08. Serum Vitamin D levels also improved significantly, with mean pre-treatment levels of 10.86±4.98, which increased to a mean post-treatment level of 29.98±17.24. Patients treated with cholecalciferol had no significant change in phosphorous and calcium levels. Keywords: Parathyroid Hormone; Cholecalciferol; Vitamin D; Secondary Hyperparathyroidism; hemodialysis; Pakistan

Treatment of secondary hyperparathyroidism in non-dialysis CKD: an appraisal 2022s.

The situation of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients not on dialysis (ND-CKD) is probably best characterised by the Kidney Disease: Improving Global Outcomes Chronic Kidney Disease-Mineral and Bone Disorder Update 2017 guideline 4.2.1 stating that the optimal parathyroid hormone levels are not known in these stages. Furthermore, new caution became recommended with regard to the routine use of active vitamin D analogues in early CKD stages and moderate SHPT phenotypes, due to their potential risks for hypercalcaemia and hyperphosphataemia aggravation. Nevertheless, there is still a substantial clinical need to prevent the development of parathyroid gland autonomy, with its associated consequences of bone and vascular damage, including fracture risks and cardiovascular events. Therefore we now attempt to review the current guideline-based and clinical practice management of SHPT in ND-CKD, including their strengths and weaknesses, favouring individualised approaches respecting calcium and phosphate homeostasis. We further comment on extended-release calcifediol (ERC) as a new differential therapeutic option now also available in Europe and on a potentially novel understanding of a required vitamin D saturation in more advanced CKD stages. There is no doubt, however, that knowledge gaps will remain unless powerful randomised controlled trials with hard and meaningful endpoints are performed.

Comparison between Paricalcitol versus cinacalcet therapy in the management of secondary hyperparathyroidism among prevalent hemodialysis patients

Abstract Background Secondary hyperparathyroidism (SHPT) is one of the components of chronic kidney disease–mineral bone disorder (CKD-MBD) with significant contribution to the morbidity and mortality among prevalent hemodialysis (HD) patients. Objectives Multicentric experience study to compare the effectiveness of Intravenous (IV) paricalcitol versus oral cinacalcet and oral cinacalcet plus oral alfacalcidol as treatment regimens of secondary hyperparathyroidism (SHPT) among chronic haemodialysis (HD) patients. Methods Retrospective observational cohort study, 1year time horizon, 130 prevalent HD patients with SHPT were recruited from three main HD centres in Aljouf region in Saudi Arabia. Patients were divided into 3 groups: Group I (50) HD patients were treated by intravenous paricalcitol, group II (50) HD patients who received oral cinacalcet plus oral alfacalcidol, Group III (30) HD patients were on oral cinacalcet. Serum Intact parathyroid hormone, Calcium, Phosphorus and alkaline Phosphatase tests were assessed every 3 months. Results 130 (61 (47%) females, (53%) 69 males) HD patients, mean age 56.30 ± 19.1 years, mean HD duration 4.86±4.15 year. The mean of PTH is significantly reduced in all studied groups (P &amp;lt; 0.001). Mean Δchanges in iPTH concentration in group I, II, III was (-242.11±148.75,225.54±153.91,-254.83±275.17)(P &amp;gt; 0.05) respectively with statistical non-significant differences. Increase of CaxPo4 with paricalcitol group as mean ΔChange in (CaxPO4) was in the group I, II, III(15.39±9.46,1.97±11.74,-2.89 ±9.37) respectively (P &amp;lt; 0.001). Significant increase in serum phosphorus from the baseline in patients in group II. Conclusions Intravenous Paricalcitol based regimen assumed to be equally effective in suppressing SHPT in prevalent hemodialysis patients when compared to the combination of oral Cinacalcet with oral alfacalcidol or treatment with oral cinacalcet alone, with less incidence of hyperphosphatemia with paricalcitol or cinacalcet in comparison to alfacalcidol regimen.

Personalized Prediction of Short- and Long-Term PTH Changes in Maintenance Hemodialysis Patients.

Background: Personalized management of secondary hyperparathyroidism is a critical part of hemodialysis patient care. We used a mathematical model of parathyroid gland (PTG) biology to predict (1) short-term peridialytic intact PTH (iPTH) changes in response to diffusive calcium (Ca) fluxes and (2) to predict long-term iPTH levels.Methods: We dialyzed 26 maintenance hemodialysis patients on a single occasion with a dialysate Ca concentration of 1.75 mmol/l to attain a positive dialysate-to-blood ionized Ca (iCa) gradient and thus diffusive Ca loading. Intradialytic iCa kinetics, peridialytic iPTH change, and dialysate-sided iCa mass balance (iCaMB) were assessed. Patient-specific PTG model parameters were estimated using clinical, medication, and laboratory data. We then used the personalized PTG model to predict peridialytic and long-term (6-months) iPTH levels.Results: At dialysis start, the median dialysate-to-blood iCa gradient was 0.3 mmol/l (IQR 0.11). The intradialytic iCa gain was 488 mg (IQR 268). Median iPTH decrease was 75% (IQR 15) from pre-dialysis 277 to post-dialysis 51 pg/ml. Neither iCa gradient nor iCaMB were significantly associated with peridialytic iPTH changes. The personalized PTG model accurately predicted both short-term, treatment-level peridialytic iPTH changes (r = 0.984, p < 0.001, n = 26) and patient-level 6-months iPTH levels (r = 0.848, p < 0.001, n = 13).Conclusions: This is the first report showing that both short-term and long-term iPTH dynamics can be predicted using a personalized mathematical model of PTG biology. Prospective studies are warranted to explore further model applications, such as patient-level prediction of iPTH response to PTH-lowering treatment.

Secondary Hyperparathyroidism in Chronic Kidney Disease: Pathophysiology and Management

Serum calcium concentration is the main determinant of parathyroid hormone (PTH) release. Defect in the activation of vitamin D in the kidneys due to chronic kidney disease (CKD) leads to hypocalcemia and hyperphosphatemia, resulting in a compensatory increase in parathyroid gland cellularity and parathyroid hormone production and causing secondary hyperparathyroidism (SHP). Correction and maintenance of normal serum calcium and phosphate are essential to preventing SHP, hungry bone disease, cardiovascular events, and anemia development. Understanding the pathophysiology of PTH and possible therapeutic agents can reduce the development and associated complications of SHP in patients with CKD. Medical interventions to control serum calcium, phosphate, and PTH such as vitamin D analogs, calcium receptor blockers, and parathyroidectomy are needed in some CKD patients. In this review, we discuss the pathophysiology, clinical presentation, and management of SHP in CKD patients.

Comparison between paricalcitol versus cinacalcet therapy in the management of secondary hyperparathyroidism among prevalent hemodialysis patients

Introduction: Secondary hyperparathyroidism (SHPT) is one of the components of chronic kidney disease–mineral bone disorder (CKD-MBD) with significant contribution to the morbidity and mortality among prevalent hemodialysis (HD) patients. Objectives: This multi-centric experience study aims to compare the effectiveness of intravenous (IV) paricalcitol versus oral cinacalcet and oral cinacalcet plus oral alfacalcidol as treatment regimens of SHPT among chronic HD patients. Patients and Methods: This is a retrospective observational cohort study, in which 130 prevalent HD patients with SHPT was recruited from three main HD centres of Aljouf region in Saudi Arabia. Patients were divided into three groups; group I (50) HD patients were treated by IV paricalcitol, group II (50) HD patients who received oral cinacalcet plus oral alfacalcidol, group III (30) HD patients were on oral cinacalcet. Serum intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (Po4) and alkaline phosphatase (ALP) tests were assessed at 0, 3, 6, and 9 months. Results: A total of 130 (61 (47%) females, (53%) 69 males) HD patients with mean age 56.30 ± 19.1 years, and with mean HD duration of 4.86±4.15 years were enrolled in the study. The mean of iPTH is significantly reduced in all studied groups (P&lt;0.001). Mean Δchanges in iPTH concentration in groups I, II, III were -242.11±148.75, -225.54±153.91 and -254.83±275.17 respectively; P&gt;0.05) with statistical non-significant differences. Increase of Ca×Po4 with paricalcitol group as mean ΔChange in (Ca×PO4) was in the groups I, II, III (15.39±9.46, 1.97±11.74, -2.89±9.37) respectively (P&lt;0.001). Our study showed a significant increase in serum phosphorus from the baseline in patients of group II. Conclusion: IV paricalcitol based regimen assumed to be equally effective in suppressing SHPT in HD patients when compared to the combination of oral cinacalcet with oral alfacalcidol or treatment with oral cinacalcet alone.

MO571PRACTICE PATTERNS ON THE MANAGEMENT OF SECONDARY HYPERPARATHYROIDISM IN THE UNITED STATES: RESULTS FROM A MODIFIED DELPHI PANEL

Abstract Background and Aims The 2017 Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) guidelines inform clinical practice for the management of secondary hyperparathyroidism (SHPT) internationally; however, many recommendations lacked high or moderate clinical evidence as defined by KDIGO. An expert panel was convened to establish clinical consensus for the current management of SHPT in the United States (US). Method The panel comprised 10 US healthcare providers (HCPs; [6 nephrologists, 1 surgeon, 1 nurse practitioner, 1 pharmacist, 1 dietician]) and 1 patient. HCP panelists participated in a modified Delphi process over 3 phases, addressing 126 questions based on a review of the literature and published guidelines. The threshold for consensus was 66%. In phases 1 and 2, panelists anonymously completed electronic surveys considering a ‘typical’ patient with SHPT unless otherwise specified. In phase 1, panelists answered 126 questions based on their own knowledge and experiences. In phase 2, panelists were reminded of their answers to closed-ended questions that did not achieve consensus in phase 1 and were asked if they would change their responses in light of the most common response. For open-ended questions, they were asked if they agreed with summary statements that captured the most common answers. Phase 3 was an unblinded virtual meeting where panelists reviewed the consensus reached in phases 1 and 2, and through active discussion, resolved those questions that had not reached consensus. The patient completed a separate electronic survey, which complemented key points in the HCP survey, and provided perspective during the virtual meeting. Results All 11 panelists completed the entire modified Delphi process. Sixty-three out of 126 (50%) and 116/126 (92.1%) questions reached consensus or addressed practice-specific information not requiring consensus by the end of phase 1 and 2, respectively; all questions reached consensus by the end of phase 3, including modification of 2 questions and the addition of 1 question. The panel unanimously agreed that SHPT treatment is often started too late and suggested additional markers for early identification of patients requiring treatment are needed. Serum levels of calcium, phosphate, and parathyroid hormone (PTH) should be monitored starting at CKD stage G3a at intervals of every 6 months, 3–6 months for CKD G3b, and at least every 3 months at CKD G4 and above. Thresholds for interventions could not be defined in absolute terms for all patients due to patient-and practice-specific factors. However, in patients on dialysis, serum levels of phosphate &amp;gt; 5.5 mg/dL (1.8 mmol/L) and calcium &amp;gt; 9.5 mg/dL (2.4 mmol/L), warrant increased monitoring and consideration of therapeutic interventions. Serum intact PTH &amp;gt; 300 pg/mL (32 pmol/L) typically indicates a need for SHPT treatment, with a consensus preferred target of 150–300 pg/mL (16–32 pmol/L); patients on dialysis were considered out of PTH target at ≥ 8 times the upper limit of normal (&amp;gt; 520 pg/mL [55 pmol/L] intact PTH). HCPs were concerned about vascular calcification in all patients with CKD 3a–G5D. The panel reached consensus on the use of several SHPT interventions, including a consensus preference for the intravenous calcimimetic etelcalcetide over the oral calcimimetic cinacalcet in appropriate in-center dialysis patients requiring PTH-lowering therapy; cinacalcet was agreed to be first-line therapy in appropriate patients on home dialysis (Table 1). Factors such as formularies and dialysis center protocols were recognized to influence therapeutic choices. Conclusion Ten US HCPs reached consensus on many aspects of SHPT management, further defining therapeutic strategies and highlighting the need to be proactive. While the panel expressed evidenced-based preferences for certain therapies, factors such as cost and dialysis center protocols may affect decision making.

MO792CONTEMPORARY MINERAL AND BONE DISORDER MARKERS AND TREATMENT AMONG HEMODIALYSIS PATIENTS IN THE EUROPEAN DIALYSIS OUTCOMES AND PRACTICE PATTERNS STUDY (DOPPS)*

Abstract Background and Aims Chronic kidney disease mineral and bone disorder (CKD-MBD) is characterized by abnormalities in serum calcium, phosphorus, and parathyroid hormone (PTH) and associated with morbidity and mortality. Previous publications from the Dialysis Outcomes and Practice Patterns Study (DOPPS) have demonstrated country differences in the prevalence and treatment of CKD-MBD among hemodialysis patients in participating European countries. We aim to compare the distribution of CKD-MBD related labs and treatments across countries in a contemporary population of European hemodialysis patients. Method DOPPS is an international prospective cohort study of hemodialysis patients ≥18 years of age. Patients are enrolled randomly from a representative sample of dialysis facilities within each nation at the start of each study phase. The current analysis includes n=1,701 patients from 91 facilities in the initial prevalent cross section of Europe DOPPS phase 7 (2019-present; Belgium, Germany, Italy, Spain, Sweden, UK). Results from Belgium should be considered preliminary as initial questionnaire completion is ongoing. Results The % of patients with a high PTH (&amp;gt;600 pg/mL) ranged from 6% in Italy to 24% in the UK, with 12-17% having high PTH in all other countries. Mean serum total calcium ranged from 8.7 in Germany to 9.1 mg/dL in the UK (Table). Mean serum phosphorus varied from 4.5 in Belgium to 5.3 mg/dL in Germany. Dialysate calcium of 2.5 mEq/L was predominant in Germany, Sweden, and the UK while 3.0 mEq/L was the most common prescription in Belgium, Italy, and Spain. Calcimimetic prescription ranged from 13% in the UK to 32% in Spain. Etelcalcetide prescription ranged from 1% in the UK to 12% in Spain and 14% in Italy. Active vitamin D prescription ranged from 27% in Belgium to 75% in Sweden. Nearly all vitamin D prescriptions were administered intravenously in Spain versus about half in Italy; in all other countries, the route of active vitamin D administration was primarily oral. Patient age and dialysis vintage varied by country, potentially contributing to some of the observed country differences in MBD marker levels and treatment practices. Conclusion CKD-MBD related abnormalities in PTH, serum phosphorus and calcium remain common in European dialysis patients, with prevalence varying considerably by country. Substantial international variation in CKD-MBD treatments was also observed in prescription of vitamin D and calcimimetics. Uptake of the relatively new calcimimetic, etelcalcetide, varied considerably by country. A detailed understanding of the effect of treatment variation on CKD-MBD marker levels and patient outcomes is needed to provide important insights for the European HD community in optimizing management of secondary hyperparathyroidism.

MO524CALCIMIMETIC ADHERENCE AND PREFERENCE IN THE MANAGEMENT OF SECONDARY HYPERPARATHYROIDISM IN EUROPE: A PILOT STUDY

Abstract Background and Aims Oral cinacalcet (CIN) and IV-administered etelcalcetide (ETEL) are calcimimetics available for the management of secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. This pilot study assessed patient adherence to calcimimetic therapy and calcimimetic preference of nephrologists and nurses based on adapted questionnaires. Method A cross-sectional survey was conducted with HD patients currently using a calcimimetic, and nephrologists and dialysis nurses who prescribed/administered calcimimetic in 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden and the United Kingdom). Patient questionnaires were adapted from the Medication Adherence Report Scale (MARS), the Beliefs about Medicines Questionnaire (BMQ-specific Necessity and Concern), and Treatment Intrusiveness Scale (TIS) to understand patterns of adherence and perceptions of medications; questions about gastrointestinal (GI) symptoms were included. Questionnaires for nephrologists and nurses were adapted from the Treatment Rating Scale (TRS), Health Professional Preference Scale (HPPS), and Prescribing Comparator Scale (PCS) to understand calcimimetic preference. Questionnaires were translated and administered in the local language. Results Sixty HD patients (33 CIN and 27 ETEL), 16 nephrologists and 18 dialysis nurses participated in the survey. ETEL patients were younger than CIN patients (mean age: 57 vs. 59 yrs). ETEL patients also had a lower pill burden (mean no. of pills: 6 vs. 11) and had numerically fewer hospitalizations in the last 6 months (mean no. of days: 1.5 vs 3.9) than CIN patients. Self-reported adherence to CIN was high (mean MARS: 4.7±0.7). ETEL and CIN patients did not perceive medications (excluding dialysis, diet and dietary restrictions) as interfering with their life (mean TIS: 1.5±0.5 vs. 1.6±1.6) and neither calcimimetic group had a specific belief in medicines in terms of necessity (mean BMQ CIN: 2.4±0.6 and ETEL: 2.3±0.4) or concerns about potential side-effects (mean BMQ CIN: 3.1±0.6 and ETEL: 3.5±0.7). ETEL patients were less likely than CIN patients to experience GI symptoms in the prior month: nausea (11% vs. 49%), vomiting (11% vs. 24%), and diarrhea (15% vs. 33%). Overall, the adapted patient questionnaires showed good internal consistency for MARS (Cronbach’s α=0.99) and BMQ-Necessity and BMQ-Concerns scales (CIN: α=0.74 and ETEL: α=0.81) but lower consistency for TIS (α=0.3 for both CIN and ETEL). Nephrologists and nurses had been practicing for a mean of 17 yrs. Nephrologists and nurses viewed ETEL to have more efficacy, lower risk of side effects, lower risk of non-adherence, lower burden for patients compared to CIN according to the TRS. According to HPPS, the top 3 treatment attributes for ETEL preference vs. CIN among nephrologists were encouraging patient adherence (93%; n=14/15), minimizing patient burden (87%; n=13/15) and having fewer side effects (80%; 12/15). Similar for nurses, encouraging patient adherence (88%; n=15/17) and minimizing patient burden (94%; n=16/17) were top attributes for ETEL preference as well as improving patient quality of life (82%; 14/17). Based on PCS, the majority of nephrologists agreed that compared to CIN, ETEL will ensure high adherence (100%), achieve better PTH control (93%; 14/15), reduce treatment burden for patients (87%; 13/15), improve patient’s quality of life (80%; 12/15), and improve effectiveness without increasing side-effects (80%; 12/15); they also agreed that ETEL created more work for nursing staff (80%; 12/15). Two thirds of nephrologists (n=10/15) agreed that ETEL would be more efficacious than CIN. Conclusion In this pilot study, CIN patients self-reported high adherence and both calcimimetic groups did not perceive medications to be concerning or intrusive. Nephrologists and nurses showed preference for ETEL than CIN. The questionnaires were validated and will be administered in a large study.

Maxillary Brown Tumor as a Rare Complication of Hyperparathyroidism

Secondary hyperparathyroidism is a common complication of end stage renal disease (ESRD). The inherent impaired phosphorus and calcium metabolism result in altered bone metabolism, which rarely may manifest as osteitis fibrosa cystica with approximately 2% presenting as brown tumors. Brown tumors are areas of excessive bone resorption replaced by giant cells and fibrovascular tissue. Maxillofacial brown tumors are rare and result in increased patient morbidity due to associated nasal bleeding, diffuse pain and focal deformities. Nonetheless, these tumors are treatable and may regress following reduced parathyroid hormone (PTH) levels. Case of a 64-years-old Hispanic male with history of ESRD on hemodialysis for more than 20 years, secondary hyperparathyroidism with fragility fractures of femur status post parathyroidectomy on years 1999 and 2010, coronary artery disease and hypertension, who was consulted to our service for evaluation of a bleeding nasal septum mass suspected of a brown tumor. The patient presented to the emergency room with a massive spontaneous nasal bleeding which was subsequently controlled and evaluated by imaging. Maxillofacial CT scan without contrast showed an expansile soft tissue mass at the right maxillary sinus measuring 3.4 x 3.5 x 3.7 cm with innumerable, similar lesions distributed throughout the cranial, cervical and visualized portions of the shoulder girdle bones. Biochemical evaluation was remarkable for PTH levels 1,229 pg/ml (nl, 18.5 – 88.0 pg/ml), corrected serum calcium 9.0 mg/dl (nl, 8.3 – 10.6 mg/dl), alkaline phosphate levels 391 U/L (nl, 46 – 116 U/L), serum phosphoros 5.5 mg/dl (nl, 2.5 – 4.5 mg/dl), calciferol levels 32.2 ng/ml (nl, 30 – 100 ng/ml) and an estimated glomerular filtration rate at 21 ml/min/1.73 m2 (nl, > 60 ml/min/1.73 m2). An excisional tissue biopsy showed osteoclastic-like multinucleated cells consistent with a brown tumor. These findings are consistent with secondary hyperparathyroidism complicated with osteitis fibrosa cystica. Following histologic diagnosis, a 99mTc-Sestamibi parathyroid scan showed two focal lesions of increased radiotracer uptake in the lower poles of the thyroid confirming parathyroid hyperplasia. Patient’s medical therapy was optimized by increasing cinacalcet dose and adding calcitriol, while continuing Sevelamer. Serum calcium, PTH, and phosphorous levels were closely monitored. Finally, patient was referred for parathyroidectomy. Patients with ESRD are at high risk of developing secondary hyperparathyroidism. Even with prior parathyroidectomy, these patients can develop disease recurrence. Early recognition and management of secondary hyperparathyroidism is crucial to decrease disease complications such as Brown tumors.

Old and New Drugs for the Management of Bone Disorders in CKD.

Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease (CKD), especially those undergoing dialysis. Renal osteodystrophy, which describes an alteration of bone morphology, is an important component of this systemic disorder and may explain the elevated risk of fracture which adversely affects morbidity and mortality. The most common form of renal osteodystrophy is high-turnover bone disease (osteitis fibrosa), which is induced by secondary hyperparathyroidism (SHPT). During the past decade, there has been considerable advances in the management of SHPT, with the introduction of the calcimimetic agents, the optimized use of nutritional and active vitamin D, and the accumulated experience with surgical parathyroidectomy. Studies supported that these advances could translate into improvement of renal bone disease and fracture prevention, as well as decreasing the risk of cardiovascular events and mortality. In this review, we summarize the available clinical evidence on the effect of old and new drugs on bone disorders in patients with CKD.

Management of Secondary Hyperparathyroidism Among Patients Who Transition from Daily At-Home to Three-Times-Weekly Oral Cinacalcet Given In-Center

Management of Secondary Hyperparathyroidism Among Patients Who Transition from Daily At-Home to Three-Times-Weekly Oral Cinacalcet Given In-Center

Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52\xa0weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan

BackgroundEtelcalcetide is a second-generation calcimimetic for the management of secondary hyperparathyroidism (SHPT) in patients on dialysis. We performed a post-marketing surveillance (PMS) to obtain information on the safety and efficacy of etelcalcetide in clinical practice in Japan.MethodsThis PMS enrolled SHPT patients who started initial treatment with etelcalcetide between April 1, 2017 and February 28, 2018 in Japan. Safety [adverse drug reactions (ADRs)] and efficacy [serum intact parathyroid hormone (iPTH), corrected calcium (cCa), phosphorous (P), and alkaline phosphatase (ALP)] were recorded for up to 52 weeks or until treatment discontinuation. Treatment decisions were at the physician’s discretion.ResultsOf 1226 patients enrolled across 282 centers, safety and efficacy data were available for 1195 and 1192, respectively, while 933 continued treatment to Week 52. The starting dose was 5 mg in 82.0% of patients. There were 218 ADRs in 169 patients (14.1%). Metabolism and nutrition disorders (8.8%), adverse laboratory test results (1.8%), and gastrointestinal disorders (1.6%) were the most frequent classes of ADRs. Hypocalcemia-related ADRs occurred in 104 patients (8.7%). The percentage of patients with iPTH levels within the target range (60–240 pg/mL) steadily increased from 19.5% at Week 0 to 64.1% at Week 52 or last dose. cCa, P, and ALP levels remained well controlled.ConclusionThis was the first real-world, large-scale, long-term observational PMS of etelcalcetide in Japan. We did not observe any new safety concerns. Etelcalcetide was associated with clinically relevant improvements in serum iPTH and maintenance of serum cCa, P, and ALP levels.

Development of evocalcet for unmet needs among calcimimetic agents

ABSTRACT Introduction The calcium-sensing receptor is an important treatment target for secondary hyperparathyroidism (SHPT) in patients undergoing dialysis. In addition to vitamin D receptor activator, cinacalcet has recently been widely used for SHPT management, and the significant suppression of parathyroid hormone (PTH) with better control of serum calcium and phosphorus has been reported. However, low adherence and insufficient dose escalation mainly due to frequent gastrointestinal adverse events, still remain as major issues. To overcome these unmet needs, we have developed a new oral calcimimetic agent evocalcet, which has recently been approved by the Pharmaceutical Affairs Act in Japan. Areas covered PubMed was searched from inception until April 2020 with the word evocalcet to summarize the development of this new calcimimetic agent, its pharmacokinetics, and the results of clinical trials, along with an overview of the differences among calcimimetic agents. This review also includes the management of SHPT with a focus on calcimimetics. Expert opinion Evocalcet evoked fewer gastrointestinal-related adverse events while suppressing PTH at a lower dose than cinacalcet. These data suggest evocalcet may contribute to better adherence and sufficient dose escalation in patients with SHPT. Whether or not evocalcet improves clinical outcomes remains to be elucidated.

P1416EFFECT OF SWITCH FROM CINACALCET TO ETECALCETIDE IN HEMODIALYSIS PATIENTS WITH A POOR CONTROL OF SECONDARY HYPERPARATHYROIDISM

Abstract Background and Aims Patients on hemodialysis (HD) show a high incidence of secondary hyperparathyroidism (SHPT). An inadequate control of this condition increases morbidity and mortality, most of the times due to lack of adherence to the treatment. There is currently an available intravenous calciomimetic drug that could be an alternative to improve the prognosis and management of SHPT. Objectives To analyze the switch from cinacalcet to etelcalcetide in patients with a poor control of SHPT. Method: A descriptive observational study was carried out with patients on HD with iPTH levels over 400 pg/mL who had previously been treated with cinacalcet for at least 6 months and then with etelcalcetide for a year. The analysis assessed their basal characteristics, the evolution of their analytical parameters (calcium/phosphorus/iPTH) and their comorbidity, and a questionnaire was completed to observe their adherence to treatment. Results The study included 34 patients; average age 65±15 years (58% men); hemodialysis time 84±69 months. The main comorbidities were: 97% hypertension; 44% diabetes; and 47% heart disease. The average basal dose of cinacalcet was 62±26 mg/session, and the average dose of etelcalcetide was 2.8±2.6 mg/session. Over the 12 months of treatment with etelcalcetide a better control of iPTH was observed (from 681±279 to 291±190, p=0.004), with a decrease of iPTH by &amp;gt;50% in 79% of the patients. There were no significant changes in the levels of albumin, calcium or magnesium, but a significant decrease was observed in the levels of phosphorus, Ca x P product and alkaline phosphatase. 44% of the patients showed hypocalcemia after 6 months of treatment, which was asymptomatic in all cases and was corrected with an increase in the oral administration of calcium (44%) or with a change of dialysate [Ca] concentration (50%). None of the patients reported clinical intolerance with etelcalcetide. Table 1: Conclusion