Severe Secondary Hyperparathyroidism Research Articles

Pretransplant Parathyroidectomy in Patients with Severe Secondary Hyperparathyroidism and Long-Term Effectiveness After Kidney Transplantation.

Kidney transplantation (KT) is the best option for patients with end-stage renal disease, but recipients still have legacy bone mineral disease from the pretransplant period, especially patients with severe secondary hyperparathyroidism (sHPT). Patients who had severe sHPT and underwent KT were analyzed retrospectively. Two groups were identified (patients with severe sHPT who had parathyroidectomy or calcimimetic before KT). Bone mineral density (BMD) was measured in the first year and last follow-up at the femoral neck, total hip, and lumbar spine using the dual-energy X-ray absorptiometry (DXA). Persistent hyperparathyroidism (perHPT) incidence was significantly higher in the calcimimetic group (75% vs. 40%, p=0.007). In patients with parathyroidectomy, BMDs were higher at femoral neck (0.818±0.114 vs. 0.744±0.134, p=0.04) and lumbar spine (1.005±0.170 vs. 0.897±0.151, p=0.01) at the first assessment. The BMD comparison between patients treated with parathyroidectomy and calcimimetic found a significant difference only in the femoral neck at second evaluation (0.835±0.118 vs. 0.758±0.129; p=0.03). In multivariate, linear regression revealed a positive association between the last BMD of the femoral neck with body mass index (CC: 0.297, 95% CI, 0.002-0.017) and parathyroidectomy (CC: 0.319, 95% CI, 0.021-0.156). Parathyroidectomy is associated with a significantly better femoral neck BMD and a lower incidence of perHPT in patients with severe sHPT.

Cost-Effectiveness and Clinical Outcomes of Secondary Hyperparathyroidism Treatments in Patients with Chronic Kidney Disease.

The study addresses the challenge of treating secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, focusing on the cost-effectiveness of surgical versus pharmacological interventions. Conducting a retrospective analysis on 152 CKD patients with SHPT at the Third People's Hospital of Chengdu, the study matched 80 patients into two groups: 40 undergoing parathyroidectomy with autotransplantation (PTX + AT) and 40 treated with calcimimetics. PTX + AT was more effective in alleviating symptoms, particularly bodily pain, and demonstrated greater cost-effectiveness over a long-term period compared to calcimimetics. This was especially significant in patients with PTH levels > 1800 pg/mL and hyperphosphatemia. Despite similar initial costs, PTX + AT led to a substantial decrease in expenses during the 2-5 years post-treatment period, PTX + AT results in an ICER of -RMB 26.71/QALY for the first post-treatment year and -RMB-111.9k/QALY for the 2-5 year period, indicating cost-effectiveness with reduced long-term costs. The study also found an increased economic burden in managing patients with hyperphosphatemia. Surgical intervention (PTX + AT) is advocated as the primary treatment strategy for severe SHPT in CKD patients, owing to its long-term economic and clinical advantages. The results underscore the need for a severity-based approach in treating SHPT.

Calcitriol Versus Calcitriol and Low Dose Cinacalcet for Treating Severe Secondary Hyperparathyroidism in Hemodialysis Patients: A Randomized Clinical Trial

Background: Secondary hyperparathyroidism is prevalent among hemodialysis patients associated with vascular and skeletal complications. Thus, treatment is required, specially before kidney transplantation. Objectives: This study aimed to compare the efficacy of calcitriol and cinacalcet versus standard-dose calcitriol in treating severe secondary hyperparathyroidism in hemodialysis patients. Methods: This randomized clinical trial was conducted on 70 hemodialysis patients with severe secondary hyperparathyroidism who were randomly allocated to two intervention groups. Group A received calcitriol 1mg PO every other night, and group B took calcitriol 1mg PO every other night and cinacalcet 30mg PO daily. The improvement of laboratory parameters was investigated 3 and 6 months after the intervention. Results: There was no significant difference between the two groups regarding age, sex, body mass index, and duration of dialysis (P > 0.05). In group A, serum levels of calcium (P < 0.001) and parathyroid hormone (PTH) (P < 0.001) were significantly reduced compared to baseline. However, phosphorus (P = 0.175) and albumin (P = 0.143) serum levels showed no significant changes. In group B, calcium (P = 0.001), PTH (P < 0.001), and serum phosphorus (P < 0.001) levels were significantly decreased after the intervention. Nevertheless, serum albumin levels showed no significant changes from baseline (P = 0.061). Changes in serum phosphorus (P < 0.001) and PTH levels (P < 0.001) were significantly different between the groups. However, changes in serum calcium (P = 0.062) and albumin levels (P = 0.773) were not significantly different (Wilcoxon signed-rank test). Conclusions: The results of this study showed that treatment with cinacalcet and calcitriol was more effective than calcitriol alone without any side effects.

Risk factors associated with the development of secondary hyperparathyroidism in dialysis patients.

Aim To determine risk factors associated with the development and severity of secondary hyperparathyroidism in dialysis patients. Methods A cross-sectional study at the Clinical Centre of the University of Tuzla (March 2022) included 104 adult patients (males 51.9%, females 48.1%) with chronic kidney diseases under dialysis treatment. Based on parathyroid hormone (PTH) values, patients were divided into two groups: study group (45/104, PTH >792pg/mL) and control group (59/104, PTH 176-792 pg/ mL). The analysis aimed to resolve whether there was a connection between the duration of dialysis, the type of therapy treatment administered, the underlying kidney disease, and the presence of comorbidities with the values of PTH, and a wide spectrum of monitored laboratory parameters. Results The most common causes of chronic renal failure were undefined kidney diseases (32.7%), followed by diabetic nephropathy (18.3%) and chronic glomerulonephritis (16.3%). In the examined biochemical parameters, a significant difference was found in mean values of alkaline phosphatase (p<0.001). The correlation was proved between the duration of dialysis (p=0.028), the values of phosphorus (p=0.031), and alkaline phosphatase (p<0.001) with absolute values of PTH. The most common present comorbidity was hypertension (78.8%), followed by cardiovascular diseases (40.4%) and diabetes (22.1%). Conclusion A number of factors contribute to the development and severity of SHPT. Modulation of therapy and better control of risk parameters can prolong and reduce the frequency of SHPT in dialysis patients, as well as the occurrence of comorbidities.

Chronic dialysis patient with severe secondary hyperparathyroidism undergoing parathyroidectomy in Indonesia: a case series

Link of Video Abstract: https://youtu.be/d196XKGsPekBackground: Parathyroidectomy is a method of treating secondary hyperparathyroidism associated with Chronic Kidney Disease (CKD), which has been largely abandoned in developed countries due to the existence of calcimimetic drugs which are reported to be effective in treating secondary hyperparathyroidism in this population. However, in developing countries like Indonesia, the availability of Calcimimetic drugs is still rare and expensive, so that parathyroidectomy can be an option. The study aimed to present four case reports of chronic HD patients with SHPT accompanied by clinical symptoms. As far as our knowledge goes, this is the first case series reported from Indonesia. Case Presentation: This research is a multicenter case series study. All patients had undergone dialysis for five years and complained of body aches. All calcium levels were within the normal range, while three patients had hyperphosphatemia and one patient had normal phosphate levels. All patients had iPTH levels &gt;1000 pg/ml in the last six months. Before the surgery, all patients had received long-term phosphate-binding drugs, including calcium-based and non-calcium-based drugs and vitamin D3 agonists. All patients underwent total parathyroidectomy with autotransplantation of parathyroid tissue in the right antebrachial regions, except for the second patient who received the transplant in the left antebrachial region due to an AV fistula in the right arm. Conclusion: In dialysis patients, especially in developing countries, approximately 10.7% of them experience SHPT with PTH levels &gt;1,000 pg/mL, and one study in Indonesia showed that around 35% of patients undergoing chronic hemodialysis had PTH levels &gt;200 pg/ml, making parathyroidectomy a highly possible option considering that medications such as cinacalcet are more expensive and not widely available.

#3724 CHANGES IN CARDIOVASCULAR CALCIFICATION AFTER PARATHYROIDECTOMY IN DIALYSIS-DEPENDENT PATIENTS

Abstract Background and Aims Vascular calcification (VC) is common in patients with end stage kidney disease on dialysis and with secondary hyperparathyroidism (SHPT). There is a lack of knowledge regarding dynamics of VC after surgical treatment of SHPT. We aimed to evaluate evolution of coronary artery calcification (CAC) and abdominal aortic calcification (AAC) after parathyroidectomy (PTx) in dialysis patients with SHPT. Method The prospective cohort study included 33 dialysis-dependent patients (mean age of 50±13 years) with severe SHPT who underwent subtotal (n = 16) or total PTx with autotransplantation of parathyroid tissue (n = 17). Cardiac computed tomography scan (quantification of coronary calcium by Agatston method) and lateral lumbar X-ray (semi-quantitative Kauppila score) were used to assess prevalence of VC before and 18 months after surgery. Levels of serum total calcium, phosphorus, parathyroid hormone (PTH), and alkaline phosphatase (AP) before and 18 months after surgery were also evaluated. Results In our cohort median dialysis vintage before surgery was 71 [Q1-Q3: 29; 136] months, total serum Ca was 2.47±0.23 mmol/l, median PTH was 139 [Q1-Q3: 90; 161] pg/ml. Prevalence of CAC before PTx was 79% (n = 26), and 61% (n = 20) of patients had AAC. Of note, 54.5% of the patients had severe coronary calcification (&amp;gt;400 AU), while only 12% were considered to have severe calcification using Kauppila score (&amp;gt;12). We observed moderate positive correlation between CAC and AAC scores (Spearman's ρ = 0.699 [95% CI: 0.48; 0.84], р&amp;lt;0.0001). Both CAC and AAC scores correlated moderately with age of the patients (ρ = 0.57 [95% CI: 0.3; 0.76], р = 0.0002, and ρ = 0.64 [95% CI: 0.39; 0.8], р&amp;lt;0.0001, respectively), AAC had weak correlation with their dialysis vintage (ρ = 0.45 [95% CI: 0.14; 0.68], р = 0.005. Median of baseline CAC was 458 [Q1-Q3: 23; 1585] AU, after 18 months - 491 [Q1-Q3: 58; 1956] AU, no statistically significant differences were observed (p = 0.91, Wilcoxon test). We did not find statistically significant differences between median of Kauppila scores before and after PTx as well: 3 [Q1-Q3: 0; 10] and 2 [Q1-Q3: 0; 10], correspondingly, p = 0.17 (Wilcoxon test) – Fig. 1. As it can be seen from Fig. 1, dynamics of both CAC and AAC values before and after PTx varied markedly across subjects. To investigate the factors that can promote VC we divided patients into 2 groups based on dynamics of САС (as the most accurate assessment method) 18 months after surgery: group 1 with CAC progression of more than 50 AU (n = 9) and group 2 with regression or progression less than 50 AU (n = 24). Patients who had progression of coronary calcification by the end of the follow-up had higher age (59±11 vs 46±12 years in 2nd group, p = 0.0128) higher serum calcium levels (2.57±0.24 vs 2.29±0.32 mmol/l in 2nd group, p = 0.0267), and higher AP levels at follow-up (69.8 [Q1-Q3: 62.8, 96.0] vs 51.7 [Q1-Q3: 41.4; 57.1] U/ml in 2nd group, p = 0.003). Univariate analysis showed no significant differences between groups comparing dialysis vintage (p = 0.53), phosphate levels (p = 0.54), PTH levels (p = 0.32). In addition, CAC progression risk was not associated with type of surgery (total vs subtotal PTx RR = 1.11 [95% CI: 0.71; 1.8], OR = 1.48 [95% CI: 0.3; 5.7], p = 0.708). Conclusion Prevalence of vascular calcification in dialysis-dependent patients with severe SHPT is high. Progression of CAC by 18 months after PTx was associated with higher age of the patients, higher follow-up levels of serum total Ca and AP.

#4993 EFFECT OF ETELCALCETIDE TREATMENT ON ERYTHROPOIESIS-STIMULATING AGENTS (ESAS) REQUIREMENT IN HEMODIALYSIS PATIENTS: A SINGLE CENTER STUDY

Abstract Background and Aims Anemia is a common consequence of advanced chronic kidney disease (CKD). There are various causes of renal anemia like decreased production of and resistance to Erythropoietin, shortened survival of red blood cells and chronic blood loss. Secondary hyperparathyroidism is a potential cause of renal anemia in CKD patients due to direct effect on Erythropoietin synthesis, red cell survival and bone marrow fibrosis [1]. There are several reports of the beneficial effect of treatment of hyperparathyroidism on hemoglobin (Hb) levels. Etelcalcetide is a novel intravenous calcimimetic used for the treatment of secondary hyperparathyroidism in hemodialysis patients. However, there are very few reports of Etelcalcetide's effect on anemia management in hemodialysis patients. We aimed to study the effect of Etelcalcitide on ESAs requirement in our hemodialysis cohort. Method This is a retrospective study in Al Wakra Hospital hemodialysis unit conducted on patients with uncontrolled secondary hyperparathyroidism who needed to be started on Etelcalcetide. Mean Hb and mean ESAs dose were calculated for a period of 6 months before and 6 months after starting Etelcalcetide, while iPTH levels were measured at the beginning and 6 months after starting Etelcalcetide. Inclusion criteria: hemodialysis patients who are on Etelcalcetide for at least 6 months. Exclusion criteria: Patients’ age &amp;lt; 18 years, hemodialysis duration &amp;lt; 12 months and patients with acute blood loss. Results Out of 94 hemodialysis patients, 26 (27.6%) were on Etelcalcetide. 2 patients were excluded, one for acute hematuria and the other for erosive gastritis. 24 patients were included (13 females and 11 males). Mean age of the patients was 58.7 years. 15 patients were on Darbepoetin, 8 on Erythropoietin and 1 patient was switched from Darbepoetin to Erythropoietin due to poor response. There was no significant difference in mean Hb levels for all the patients before and after starting Etelcalcetide (10.6 g/dl and 10.8 g/dl, respectively). Out of 24 patients, 19 had reduction while 5 had increase in ESAs dose requirement. In total, the mean reduction of ESAs dose for all the patients was 17.3%. There was a mean of 33.4% reduction in ESAs requirement for the 19 patients while a mean of 44% increase in the requirement for the 5 patients. Mean iPTH for the cohort at the time of starting Etelcalcetide and 6 months after was 1036 pg/ml and 473 pg/ml respectively. The mean reduction of iPTH for those who had decreased ESAs requirement was 58% while it was 38.8% for those who had increased ESA requirement. Conclusion This study showed that control of severe secondary hyperparathyroidism with Etelcalcetide was associated with reduction in ESAs requirement in hemodialysis patients. The more the control of hyperparathyroidism, the more the reduction of ESAs requirement. These findings were observed also in a one case report [2]. We believe that our study has one of the largest number of patients to show such an observation, however larger controlled studies are needed to confirm these preliminary findings in the improvement of anemia after treatment of hyperparathyroidism by Etelcalcetide.

Clinical Images: Increased bone metabolism in secondary hyperparathyroidism.

The patient, a 47-year-old man, was diagnosed as having severe hyperparathyroidism secondary to end-stage kidney disease (ESKD), the underlying cause being leukocytoclastic vasculitis with IgA nephritis and minimal-change glomerulonephritis, which was confirmed by kidney biopsy in 2008. The patient had been receiving hemodialysis since 2014 and had a history of multiple fractures. His treatment included azathioprine, low-dose prednisolone, calcium carbonate, vitamin D, sevelamer, cinacalcet, torasemide, carvedilol, amlodipine, moxonidine, simvastatin, low molecular weight heparin, and erythropoietin. After a sudden transitory episode of vision loss with increased C-reactive protein (18.1 mg/liter) and response to glucocorticoids, 18F–positron emission tomography/computed tomography (18F-PET/CT) evaluation was performed to rule out systemic vasculitis. Ophthalmologic examination was negative for arteritic ischemic optic neuropathy, ophthalmoparesis, loss of visual field, and diplopia. Imaging with 18F-PET/CT revealed enhanced fluorodeoxyglucose uptake in the skeleton (A and B) and thickening of cortical bone such as in the femurs (C). Bone loss as osteolytic lesions in the calvaria, increased uptake in the setting of diffuse skull thickening with loss of distinction between the inner and outer table (D), and increased uptake in mandible bones (E) could be seen. There was no evidence for vasculitis. ESKD is associated with a complex remodeling of bone, summarized as renal osteopathy (1). This might include bone resorption, periosteal reaction, brown tumors, osteoporosis, osteosclerosis, osteomalacia, and soft tissue/vascular calcifications. Imaging may reveal any number of these conditions (2, 3). In our patient, 18F-PET/CT revealed osteolytic lesions, which were considered brown tumors and interpreted as osteitis fibrosa cystica. The patient was hypocalcemic (adjusted serum calcium 1.90 mmoles/liter), with elevated alkaline phosphatase (758 IU/liter) and massively elevated parathyroid hormone levels (1,872 pmoles/liter), indicating severe secondary hyperparathyroidism. These 18F-PET/CT images reflect the widespread, strongly induced metabolic activity of bone in secondary hyperparathyroidism during ESKD. Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines.

Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.

Sagliker Syndrome – A Case Report

Aim: To present a case of Sagliker syndrome (SS), a rare syndrome caused by longterm heavy tertiary hyperparathyroidism (HPT) in end-stage renal disease (ESRD). Case report: In the year 2000, the 38-year-old man was diagnosed with ESRD. He is currently of low height, paraplegic, pigeon and barrel chested, with elongated upper extremities, deformed fingers, mandibular and maxillary asymmetric deformities with teeth malformations. Due to extremely high serum parathormone (PTH), resistant to pharmacological treatment, subtotal parathyroidectomy (PTx) was performed in 2007. However, he underwent parathyroid resurgery in 2010 for persistently high PTH of more than 2500 pg/mL (upper normal limit 69). In 2012, imaging found two suspected parathyroid glands and one of them was surgically removed. Postoperatively, the expected decrease in calcium and PTH serum concentrations did not occur. Ten years after the diagnosis of ESRD, the patient began to notice more pronounced skeletal deformities (upper, lower jaw, extremities, deformities of fingers, kyphoscoliosis) along with depressive disorder. Laboratory findings still show extremely high PTH (1994 pg/mL), low calcium, 1.89 mmol/L (normal range 2.14–2.53), and high alkaline phosphatase, 837 U/L (normal range 60–120), despite continuous pharmacological treatment. Conclusion: SS was firstly recognized by Yahya Sagliker in 2004 and it has not been described in Croatia to date. Pervasiveness and knowledge of the syndrome is still poor. The most efficient way of treating/preventing SS is early total PTx in severe secondary HPT related to ESRD. However, it can only stop progress of the disease, but cannot return skeletal deformities.

Predictive factors requiring high-dose evocalcet in hemodialysis patients with secondary hyperparathyroidism.

The dosage of evocalcet required to control serum parathyroid hormone (PTH) levels varies among secondary hyperparathyroidism (SHPT) patients. This post hoc analysis evaluated the dose-dependent efficacy of evocalcet on serum intact PTH (iPTH) levels, corrected calcium (Ca) and phosphate (P) levels, and safety, in an evaluation period (week 28 to week 30) by stratifying the previous phase 3 data with the final evocalcet dosages (low 1-2 mg [131 patients], medium 3-4 mg [90 patients], high 5-8 mg [92 patients]), and identified pre-treatment patient characteristics predicting the use of higher final evocalcet dosages via univariate and multivariate logistic regression models. At the end of the study at week 30, the median serum iPTH level was higher and the achievement ratio for the target range of Japanese Society for Dialysis Therapy (60-240 pg/mL) was lower in the final high-dose subgroup (216 pg/mL and 58%, respectively) than in the other subgroups (low: 149 pg/mL and 79%; medium: 149 pg/mL and 73%, respectively). Among the three subgroups, the mean serum corrected Ca and P levels demonstrated similar trends, and similar ratio of patients achieved the target range (corrected Ca, 8.4-10 mg/dL; P, 3.5-6.0 mg/dL) from week 28 to week 30. No dose-dependent safety concerns were identified. Younger age, prior cinacalcet use, higher serum levels of iPTH and corrected Ca, procollagen type 1 N-terminal propeptide, intact fibroblast growth factor-23, and larger maximum parathyroid gland volume were significantly associated with final high-dose evocalcet (p < 0.05 in all cases). Patients requiring final high-dose evocalcet had pre-treatment characteristics indicating severe SHPT, leading to a lower final achievement rate for the target PTH levels of Japanese Society for Dialysis Therapy. Therefore, the early initiation of evocalcet treatment for SHPT is critical. Trial registration: This trial was registered as follows: ClinicalTrials.gov: NCT02549391 and JAPIC: JapicCTI-153013.

Clinical Features and Prognosis of Severe Secondary Hyperparathyroidism: A Retrospective Study from a Single Center

PurposeSecondary hyperparathyroidism (SHPT) is one of the most common complications of chronic kidney disease and has a high rate of morbidity and mortality. Current studies on prognostic factors in SHPT are inadequate. We aimed to identify a single-center cohort of severe SHPT to elucidate relevant clinical and laboratory features and explore laboratory indicators that related to its prognosis.MethodsThe clinical data of 46 patients with SHPT, admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University in the time period ranging from January 2019 to March 2022 were analyzed retrospectively. Clinical data collected were screened univariately for influences that were associated with poor prognosis. A binary logistic regression model was constructed to analyze the independent risk factors for poor clinical prognosis, using correlated influences. The value of each indicator in predicting patient prognosis was analyzed using receiver operating characteristic curves (ROC) curves.ResultsThe causes of death among the 46 patients with severe SHPT were cardiogenic death (malignant arrhythmia, cardiac arrest) in 11 cases (47.8%), sepsis in 9 cases (39.2%), and neurogenic death (intracranial hemorrhage) in 3 cases (13.0%). Patients were divided into a good prognosis group and a poor prognosis group according to their status at the time of leaving the ICU. There was no statistically significant difference in sex, BUN, NT-pro BNP, ALP, Scr, Mg, Ca, Pi, K, CRP, Hb, and PLT between the poor prognosis group and the good prognosis groups. The age, PTH, PCT, WBC, APACHE II, and neutrophil ratio of the poor prognosis group were higher than those of the good prognosis group, and the ALB level was lower than that of the good prognosis group, with a statistically significant difference of P < 0.05. The 19 clinical indicators mentioned above were screened univariately. Among them, age, PTH, WBC, ALB, APACHE II and neutrophil ratio were significantly associated with prognosis, P < 0.05. Binary logistic regression analysis showed that age (OR = 1.076, 95% CI (1.011, 1.145)), PTH (OR = 1.004, 95% CI (1.000, 1.007)), WBC (OR = 1.295, 95% CI (1.026, 1.634)) were indicators for poor prognosis in patients with severe SHPT, and ALB (OR = 0.803, 95% CI (0.645, 0.998)) was a protective factor for poor prognosis. The ROC curve showed that the optimal cut-off point for patient age was 51 years, with a sensitivity of 86.9% and specificity of 52.2%; the optimal cut-off point for PTH was 346 pg/ml, with a sensitivity of 59.1% and specificity of 82.6%; the optimal cut-off point for WBC was 11.95 × 10^9/L, with a sensitivity of 56.52% and specificity of 91.3%; the optimal cut-off point for neutrophil ratio was 82.4%, sensitivity 82.6%, specificity 73.9%.ConclusionAge, PTH, and WBC are independent risk factors for poor prognosis of severe SHPT, and ALB is an independent protective factor for poor prognosis. Patients with severe SHPT should be assessed for risk of the poor prognosis based on age, admission PTH, WBC, ALB, and neutrophil ratio as early as possible to adjust the treatment strategy.

Effect of total parathyroidectomy in patients with secondary hyperparathyroidism: a retrospective study

PurposeTo investigate the therapeutic efficacy, feasibility, and safety of total parathyroidectomy (tPTX) in the treatment of secondary hyperparathyroidism (SHPT).MethodsThe clinical data of 34 SHPT patients admitted to the Department of Nephrology, Yuxi People’s Hospital, from January 2018 to January 2021 who had received tPTX, were retrospectively analyzed. The indications for tPTX were severe SHPT that did not respond to medical treatment and was ineligible for kidney transplantation. tPTX without autotransplantation was adopted to compare the level of symptom relief and changes in serum intact parathyroid hormone (iPTH), blood calcium, and blood phosphorus pre- and postoperatively.ResultsIn 34 patients, 142 parathyroid glands were removed, including 21 ectopic parathyroid glands (14.78%). Six patients (17.64%, 6/34) had supernumerary parathyroid glands. At 6 h postoperatively, arthralgia and bone pain were significantly reduced to almost zero in 94.12% (32/34) of patients. At 24 h postoperatively, relief of bone pain and improvement of limb movement were observed in 100% (34/34) of patients, and pruritus almost disappeared in 86.36% (19/22) of patients. There were significant differences in iPTH (χ2 = 134.93, P < 0.05), calcium (χ2 = 23.02, P < 0.05), and phosphorus (χ2 = 102.11, P < 0.05) levels preoperatively and 40 min, 24 h, 1 week, half a year, and last available (> 1 year) postoperatively.The patients were followed up for 15–47 months (median 33 months). Hypoparathyroidism was observed in three patients, who underwent neck dissection or partial thymotomy concurrently for different reasons. No intractable hypocalcemia or adynamic bone disease occurred during the follow-up period.ConclusionIn SHPT patients who were ineligible for renal transplantation, tPTX was effective, safe, and reliable, with a low recurrence rate. However, when tPTX was performed alone without autologous transplantation, bilateral neck exploration was sufficient, and central neck dissection and thymic resection were inadvisable.

ODP085 Denosumab Induced Severe Hypophosphatemia

Abstract Introduction Denosumab is a receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor used for treatment of osteoporosis and bone metastases in patients with solid tumors. Denosumab induced hypophosphatemia has been reported in less than 1% of patients, and in most cases described as mild to moderate in severity. We present a case of severe hypophosphatemia after denosumab treatment for diffuse bone metastases due to prostate cancer. Case report A 78-year-old male patient with history of diffuse bone metastases due to prostate cancer, schizophrenia on treatment and intermittent alcohol use, presented to the hospital with suicidal ideation and worsening fatigue. Patient was found to have a phosphorus levels of &amp;lt;1. 0 mg/dL (2.5-4.6 mg/dL), corrected calcium of 8.2 mg/dL (8.4-10.5 mg/dl), vitamin D 25 OH of 36.34 ng/mL (30-100 ng/mL), magnesium of 2.3 mg/dL (1.7-2.5 mg/dL), parathyroid hormone (iPTH) level of 379 pg/mL (10-65pg/mL) and serum creatinine of 1.1 mg/dL (0.5-1.2 mg/dL). Urinary studies showed 24 hour urinary phosphate 1282 mg/24h (360-1600 mg/24h), urine creatinine 1570 mg/24h (500-2150 mg/24h). There was no evidence of acidosis, chronic kidney disease, preexisting osteomalacia or vitamin D deficiency. The patient had no recent alcohol consumption and his alcohol level was undetectable. After reviewing the outside medical records it was noted that the patient had received denosumab 120 mg, 11 days prior to the hospital admission, as part of the management of bone metastases due to prostate cancer. The patient's baseline phosphorus prior to denosumab was in the low normal range. The severe hypophosphatemia and secondary hyperparathyroidism were attributed to denosumab administration. Patient was initially treated with intravenous phosphate and then transitioned to oral phosphate along with elemental calcium and calcitriol during the course of his hospitalization. Patient's phosphorus improved to 2.3 mg/dL by the time of discharge. Discussion In patients treated with denosumab, the primary concern is potential post-treatment hypocalcemia, however, our case brings attention to severe hypophosphatemia as a serious side effect to treatment with denosumab. Multiple specialties are involved in the treatment of osteoporosis and metastatic bone lesions, and each should be aware that denosumab can lead to lower serum phosphate levels due to its effects on bone resorption and reduction of proximal tubular reabsorption of the phosphate resulting in clinical symptoms of muscle weakness, bone pain, fractures and even stupor, coma and death. We therefore conclude that monitoring phosphate levels should be part of the pre- and post-treatment evaluation in patients who are candidates for treatment with denosumab, particularly high-dose denosumab. Presentation: No date and time listed

Nephrology picture: bone loss due to absence of adequate therapy for severe secondary hyperparathyroidism.

Nephrology picture: bone loss due to absence of adequate therapy for severe secondary hyperparathyroidism.

Évolution de l’incidence et des résultats à 12 mois de la parathyroïdectomie : 40 ans d’expérience dans un centre de dialyse avec deux services de chirurgie successifs

IntroductionSecondary hyperparathyroidism remains the main complication of mineral and bone metabolism in patients with chronic kidney disease. In case of resistance to medical treatment (native and active vitamin D, calcium and calcimimetics), surgical parathyroidectomy is indicated. The aim of this retrospective study is to show the evolution of the incidence and results of surgical parathyroidectomy in our center between 1980 and 2020 as patient characteristics, diagnostic and therapeutic strategies have changed. Patients and methodsWe collected data from dialysis patients who had a first surgical parathyroidectomy between 2000 and 2020 (period 2) in the same surgical department and compared them with historical data between 1980 and 1999 (period 1) operated in one other center. ResultsIn period 1, 53 surgical parathyroidectomy were performed (2.78/year, 0 to 5, 8.5/1000 patients-year) vs.56 surgical parathyroidectomy in period 2 (2.8/year, 0 to 9, 8/1000 patients-year). The patients of the 2 periods were comparable except for the higher dialysis vintage in period 1 (149±170 vs.89±94 months; P=0.02). In comparison with dialysis patients not requiring surgical parathyroidectomy during the same period, patients who had surgical parathyroidectomy were younger, had higher dialysis vintage and lower diabetes prevalence, but more frequently carriers of glomerulopathy or polycystosis. Systematically performed in period 2, cervical ultrasound identified at least one visible gland in 78.6% of cases while the scintigraphy, performed only in 66% of cases, found at least one gland in 81% of cases. Twelve months after surgery, PTH > 300 pg/mL (marker of secondary hyperparathyroidism recurrence or surgery failure) was present in 30% of patients in period 1 vs. 5.3% in period 2. Hypoparathyroidism was also more frequently observed in period 2 (35.7 vs. 18.8%). Surgical complications were also higher in period 1. ConclusionDespite therapeutic and strategic advances, severe secondary hyperparathyroidism is still as common as ever. It is favored by excessively high PTH targets, by suboptimal prevention before dialysis and poor tolerance of calcimimetics. The surgical parathyroidectomy is effective and safe in the hands of a specialized team with an ultrasound and scintigraphic preoperative assessment.

Calcific uremic arteriolopathy in a young man on intermittent hemodialysis

A 42‐year‐old man with ESKD who has been on intermittent hemodialysis for 7 years, presented with extremely painful inguinal ulcer and abdominal mass. The lesion was developed 2 weeks after repairing aneurysmal cubital AVF. At first, it was a small and painful red nodule but then its size increased and a large ulcer was developed. In addition, the physical examination revealed a palpable and painful large mass at left lower side of abdominal wall. He did not have important risk factors such as diabetes mellitus, treatment with warfarin, and use of calcium containing phosphate binders, vitamin D or calcium supplements. The patient suffered a long standing and severe secondary hyperparathyroidism. The parathyroid hormone level was too high (3100 pg/ml). In addition, serum calcium and phosphorus levels were 9.4 mg/dl and 9.8 mg/dl respectively. The SPECT-CT scan with 99 m Tc-MIBI of parathyroid glands confirmed persistence of an adenoma in right lower parathyroid gland (Figure 1, green arrow). The BMI was 32 kg/m2. He had no adherence to use of phosphate binder or calcimimetic drugs. The radiological studies showed extensive microvascular calcification in soft tissues (Figure 1, small arrow) and osteitis fibrosa cystica in long bones (Figure 1, star). The patient underwent surgical debridement of ulcer and palpable abdominal mass, wound care, intensive dialysis therapy with low calcium dialysis bath, cinacalcet, sevelamer carbonate, antibiotic and analgesic therapy. The histological sample (H&amp;E, 200X) shows Intramural calcification and obliteration of arteriole (large arrow) with extensive calcification in fat tissue (Figure 1, arrow head) which was consistent with Calcific Uremic Arteriolopathy (CUA). In addition to patient’s poor compliance to treatment of severe secondary hyperparathyroidism, the recent surgery of aneurismal AVF could also be an important trigger to development of calcific uremic arteriolopathy.

Individualising / personalizing hemodialysate composition

The effectiveness of the haemodialysis (HD) treatment directly affects the survival and quality of life of dialysis patients. In this regard, the composition of the dialysate, including the quality of the water, is very important. Normalizing the plasma electrolyte and mineral concentrations before to dialysis while reducing significant changes in the patient's intradialytic plasma concentrations is one of HD's main goals. For the purpose of avoiding intra- and interdialytic hypotension as well as pulmonary edoema, adequate sodium (Na) and water elimination is essential. The cardiovascular system and the bones may be protected by having the right amounts of calcium (Ca) and magnesium (Mg) in the dialysate. This will help to avoid extraskeletal calcifications, severe secondary hyperparathyroidism, and adynamic bone disease. A steady pH in body fluids is required for proper protein and membrane function as well as bone protection, and this is achieved by maintaining an adequate bicarbonate concentration [HCO3]. A sufficient dialysate glucose concentration prevents life-threatening hypoglycemia and severe hyperglycemia, which can cause serious cardiovascular problems and exacerbate diabetic comorbidities.

Black patients are more likely to undergo parathyroidectomy for secondary hyperparathyroidism

BackgroundPrior studies have demonstrated racial disparities in the severity of secondary hyperparathyroidism among dialysis patients. Our primary objective was to study the racial and socioeconomic differences in the timing and likelihood of parathyroidectomy in patients with secondary hyperparathyroidism. MethodsWe used the United States Renal Data System to identify 634,428 adult (age ≥18) patients who were on maintenance dialysis between 2006 and 2016 with Medicare as their primary payor. Adjusted multivariable Cox regression was performed to quantify the differences in parathyroidectomy by race. ResultsOf this cohort, 27.3% (173,267) were of Black race. Compared to 15.4% of White patients, 23.1% of Black patients lived in a neighborhood that was below a predefined poverty level (P < .001). The cumulative incidence of parathyroidectomy at 10 years after dialysis initiation was 8.8% among Black patients compared to 4.3% among White patients (P < .001). On univariable analysis, Black patients were more likely to undergo parathyroidectomy (adjusted hazard ratio = 1.83; 95% confidence interval, 1.74–1.93). This association persisted after adjusting for age, sex, cause of end-stage renal disease, body mass index, comorbidities, dialysis modality, and poverty level (adjusted hazard ratio = 1.35; 95% confidence interval, 1.27–1.43). Therefore, patient characteristics and socioeconomic status explained 26% of the association between race and likelihood of parathyroidectomy. ConclusionBlack patients with secondary hyperparathyroidism due to end-stage renal disease are more likely to undergo parathyroidectomy with shorter intervals between dialysis initiation and parathyroidectomy. This association is only partially explained by patient characteristics and socioeconomic factors.

Efficacy and Safety of Etelcalcetide in Hemodialysis Patients with Moderate to Severe Secondary Hyperparathyroidism

Background. Secondary hyperparathyroidism (SHPT) is a major risk factor for cardiovascular events and all-cause mortality in hemodialysis (HD) patients. The purpose of our study was to evaluate the effects and tolerability of etelcalcetide in HD patients with SHPT. Methods. An observational study was conducted on 16 hemodialysis patients with SHPT treated with etelcalcetide. All patients were followed up for a duration of 6 months. The primary endpoints were the reduction in mean PTH ≥ 30% and ≥40% from baseline after 6 months of etelcalcetide. All patients were divided into two groups (group A versus group B) based on baseline serum PTH level prior to etelcalcetide: above and below the median serum PTH (1300 pg/mL), respectively. Results. After 6 months, a significant decrease in PTH levels was achieved by all patients receiving etelcalcetide (p = 0.015). Both primary endpoint of reduction in PTH ≥ 40% at 6 months (p = 0.01), and the secondary endpoint of reduction in median PTH values (p = 0.0001) and median percentage reduction in PTH values (p = 0.009) were significantly achieved in group A. In contrast, a greater decline of calcium (p = 0.028) and phosphorus was reached in group B than group A. Dialysis vintage ≥ 36 months, arteriovenous fistula (AVF)-based hemodialysis, post-diluition hemodiafiltration (HDF) method, and baseline values of PTH &lt; 1300 pg/mL can positively influence the achievement of the endpoints. Furthermore, the baseline PTH &lt; 1300 pg/mL, among these variables, was the only one showing statistically significant relevance (OR 2.28, 95% CI 1.32–3.96, p = 0.015). The history of cinacalcet use negatively correlated with the possibility to reach therapeutic targets with etelcalcetide (OR 0.47, 95% CI 0.26–0.85, p = 0.031). Treatment with etelcalcetide was well tolerated and no adverse effects were observed. Conclusions. In our study, patients with low baseline PTH levels showed a better response to etelcalcetide than patients with higher PTH levels. Consequently, the possibility to reach desirable therapeutic targets could depend on SHPT severity at the time of initiation of therapy.