Single-cell RNA sequencing reveals transdifferentiation of parathyroid chief cells into oxyphil cells in patients with uremic secondary hyperparathyroidism.

The parathyroid gland is one of the main organs that regulate calcium and phosphorus metabolism. It is mainly composed of chief cells and oxyphil cells. Oxyphil cell counts are low in the parathyroid glands of healthy adults but are dramatically increased in patients with uremia and secondary hyperparathyroidism (SHPT). Increased oxyphil cell counts are related to drug treatment resistance, but the origin of oxyphil cells and the mechanism of proliferation remain unknown. Herein, three types of parathyroid nodules (chief cell nodules, oxyphil cell nodules and mixed nodules, respectively) excised from parathyroid glands of uremic SHPT patients were used for single-cell RNA sequencing (scRNA-seq), other molecular biology studies, and transplantation into nude mice. Through scRNA-seq of parathyroid mixed nodules from three patients with uremic SHPT, we established the first transcriptomic map of the human parathyroid and found a chief-to-oxyphil cell transdifferentiation characterized by gradual mitochondrial enrichment associated with the uremic milieu. Notably, the mitochondrial enrichment and cellular proliferation of chief cell and oxyphil cell nodules decreased significantly after leaving the uremic milieu via transplantation into nude mice. Remarkably, the phenotype of oxyphil cell nodules improved significantly in the nude mice as characterized by decreased mitochondrial content and the proportion of oxyphil cells to chief cells. Thus, our study provides a comprehensive single-cell transcriptome atlas of the human parathyroid and elucidates the origin of parathyroid oxyphil cells and their underlying transdifferentiating mechanism. These findings enhance our understanding of parathyroid disease and may open new treatment perspectives for patients with chronic kidney disease.

Independent effects of secondary hyperparathyroidism and hyperphosphataemia on chronic kidney disease progression and cardiovascular events: an analysis from the NEFRONA cohort.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers. METHODS: The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE. RESULTS: The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia. CONCLUSIONS: We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients.

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. METHODS: Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. RESULTS: Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk. CONCLUSION: Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

A single-center experience of parathyroidectomy in 1500 cases for secondary hyperparathyroidism: a retrospective study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. With the deterioration of renal function, a certain proportion of CKD patients enter the uremic stage, and secondary hyperparathyroidism (SHPT) becomes a challenge. For refractory hyperparathyroidism, parathyroidectomy (PTX) plays a key role in reducing mortality and improving prognosis. Nevertheless, no consensus has been reached on the optimal surgical method. We aimed to provide evidence for the effectiveness of surgical treatment by summarizing the experience from our center. METHODS: Clinical data from 1500 patients undergoing parathyroidectomy were recorded, which included 1419 patients in a total parathyroidectomy without autotransplantation (tPTX) group, 54 patients in a total parathyroidectomy plus autotransplantation (tPTX + AT) group, and 27 patients in the other group. Perioperative basic data, intact parathyroid hormone (i-PTH) levels, serum calcium levels, serum phosphorus levels, pathological reports, coexisting thyroid diseases, short-term outcomes and complications were analyzed. Moreover, postoperative complications were compared between the tPTX and tPTX + AT groups. RESULTS: Parathyroid hormone, serum calcium and phosphorus levels decreased significantly post-surgery. Two patients died during the perioperative period. As the two most common complications, the incidences of severe hypocalcemia and hyperkalemia were 36.20% (543 cases) and 24.60% (369 cases), respectively. Pre-iPTH levels (OR = 1.001, 95% CI: 1.001-1.001, p < 0.01), serum alkaline phosphatase (ALP) levels (OR = 1.002, 95% CI: 1.001-1.002, p < 0.01) and the mass of excised parathyroid gland (OR = 3.06, 95% CI: 1.24-7.55, p = 0.02) were positively associated with postoperative severe hypocalcemia, while age and serum calcium were negatively associated with it. Pathological reports of resected parathyroid and thyroid glands indicated that 96.49% had parathyroid nodular hyperplasia, 13.45% had thyroid nodular hyperplasia, and 4.08% had thyroid papillary carcinoma. CONCLUSIONS: Parathyroidectomy is a safe and effective treatment for refractory secondary hyperparathyroidism. Severe hypocalcemia is the main complication, and coexistent thyroid diseases should never be neglected.

Decreasing Surgical Management of Secondary Hyperparathyroidism in the United States.

BACKGROUND: Secondary hyperparathyroidism (SHPT) commonly occurs in end-stage renal disease (ESRD), leading to vascular calcification and increased mortality. For SHPT refractory to medical management, parathyroidectomy improves symptoms and decreases mortality. Medical management has changed with the release of new guidelines and advent of novel medications. We investigate recent national trends in parathyroidectomy for SHPT. MATERIALS AND METHODS: We used the National/Nationwide Inpatient Sample from 2004 to 2016 to identify hospitalizations including parathyroidectomy for SHPT and calculated parathyroidectomy rates utilizing data from the United States Renal Data System. Subgroup analysis was conducted by race. Risk factors for in-hospital mortality were identified with purposeful selection and multivariable logistic regression. RESULTS: From 2004 to 2016, the rate of parathyroidectomies for SHPT per 1000 ESRD patients decreased from 6.07 (95% CI: 4.83-7.32) to 3.67 (95% CI: 3.33-4.00). Black patients underwent parathyroidectomy for SHPT at a 1.8-fold higher rate than white and Hispanic patients (5.59 versus 3.04 and 3.07). Almost all tracked comorbidities increased in prevalence. In-hospital mortality trended lower (1.5% to 0.8%, P = 0.051). Risk factors for in-hospital mortality included weight loss (OR 4.19, 95% CI: 2.00-8.78) and cardiac arrhythmia (OR 3.38, 95% CI: 1.66-6.91), while additional calendar year (OR = 0.87, 95% CI: 0.80-0.95) was protective. CONCLUSIONS: The etiology of the declining parathyroidectomy rate for SHPT is unclear; possible factors include changing guidelines emphasizing medical management, widespread availability of cinacalcet, changing practice patterns, and inadequate surgical referral.

Corneal and Conjunctival Calcification in a Dialysis Patient Reversed by Parathyroidectomy.

Mineral and bone metabolism disorders are relatively common among patients with end-stage renal disease on maintenance hemodialysis. Corneal and conjunctival calcification is the main extravascular site for calcification. Recently, this form of calcification has been linked to vascular calcification. Secondary hyperparathyroidism can lead to high levels of calcium and phosphorus and increase the risk of calcification. Here, we report a case of a 38-year-old female with severe hyperparathyroidism who underwent eye examination before and after parathyroidectomy. Anterior segment optical coherence tomography showed an improvement in the number and size of ocular calcifications 6 months after surgery. This case calls attention to the importance of eye examination in patients on dialysis and brings the possibility of recovery of calcification in a short-term follow-up.

Practice variation in the treatment of patients with renal hyperparathyroidism: a survey-based study in the Netherlands.

BACKGROUND: Renal hyperparathyroidism is a disease entity that is complex and poorly understood. Although there are guidelines regarding how to manage this patient group, evidence is scarce. Therefore, this survey-based study aims to map the physicians' attitude in terms of preference for management of renal hyperparathyroidism and the influence of patient and respondent factors. METHODS: A survey was sent to Dutch societies of nephrology, endocrinology, and surgeons with interest in endocrine surgery. The survey consisted of eight case vignettes of renal hyperparathyroidism patients who were on hemodialysis and suitable for kidney transplantation, and varied in one of three patient variables import for decision making: age (40 vs. 65 years), parathyroid hormone (40 vs. 90 pmol/L), and serum calcium level (2.25 vs. 2.8 mmol/L). For each case, respondents could choose between maintaining conservative treatment (active vitamin D metabolites), calcimimetics, or subtotal parathyroidectomy as their treatment of choice. Categorical multilevel logistic models were used to investigate the association of patient and respondent variables with treatment preference. The influence of patient variables was determined independently of each other and by means of logistic regression the probabilities of treatment choice were calculated. RESULTS: In total, 115 surveys were included in the analysis. In 6 out of 8 cases, less than two-thirds of respondents agreed on the most favoured treatment. Among patient characteristics, the main disincentive for respondents not to choose conservative therapy was an elevated serum calcium level (subtotal parathyroidectomy vs conservative OR 93.1, 95%-CI: 48.39-179.07 and calcimimetics vs conservative OR 31.2 95%-CI: 18.58-52.30). Additionally, the most significant treatment differences were found between medical specialties and the experience of the respondents, expressed as the amount of cases the physician was involved in during the past year. CONCLUSIONS: Elevated serum calcium levels were widely recognized and the prime reason for respondents to abandon conservative treatment. However, considerable disagreement in treatment preferences remained throughout the cases, demonstrating the current literature available being inconclusive in guiding physicians. Therefore, a high-quality trial comparing subtotal parathyroidectomy to medical treatment is needed to determine optimal treatment.

Etelcalcetide versus placebo for secondary hyperparathyroidism in patients receiving hemodialysis: A meta-analysis of randomized controlled trials.

AIMS: The aim of the study was to evaluate the efficacy and safety of etelcalcetide for the treatment of secondary hyperparathyroidism (SHPT) in patients receiving hemodialysis, and a meta-analysis was performed using randomized controlled trials (RCTs). MATERIALS AND METHODS: We searched studies published on PubMed, Cochrane Central Register of Controlled Trials, and Embase to collect RCTs comparing etelcalcetide with placebo for the treatment of SHPT. Unpublished studies and information were also searched in ClinicalTrials. RESULTS: Five RCTs involving 1,268 participants were eligible for inclusion in this meta-analysis. Compared with placebo, etelcalcetide contributed to more participants who achieved ≥ 30% reduction in parathyroid hormone (PTH) (relative risk (RR) 8.64; 95% CI, 6.66 to 11.19; p < 0.00001) and a PTH level of ≤ 300 pg/mL (RR 11.80; 95% CI, 8.15 to 17.08; p < 0.00001) as well as an increase in the incidence of hypocalcemia (RR 18.76; 95% CI, 4.55 to 77.26, p < 0.0001), nausea (RR 1.79; 95% CI, 1.19 to 2.70; p = 0.006), or vomiting (RR 1.82; 95% CI, 1.17 to 2.85; p = 0.008). Etelcalcetide reduced serum phosphate (mean difference (MD) -7.28; 95% CI, -8.82 to -5.74; p < 0.00001), calcium phosphorus product (MD -14.48; 95% CI, -15.07 to -13.88; p < 0.00001), and bone-specific alkaline phosphatase (MD -24.80; 95% CI, -28.91 to -20.68) levels compared with the placebo. CONCLUSION: Etelcalcetide can effectively control serum PTH and disorder of mineral metabolism but with more side effects than placebo. Further studies comparing etelcalcetide with other medication treatments for SHPT will be needed to evaluate if etelcalcetide might be a valuable choice with less pill burden for patients with SHPT receiving hemodialysis.

Effects of PTH and PTH Hypersecretion on Bone: a Clinical Perspective.

PURPOSE OF REVIEW: Hyperparathyroidism may be due to an autonomous hypersecretion of parathyroid hormone (PTH) or occurs in response to a number of physiological stimuli. A number of recent findings have provided new insights into the importance of the calcium-parathyroid-vitamin D axis to bone in normal physiology and pathological conditions. RECENT FINDINGS: PTH is known to affect bone microarchitecture with different effects on cortical and trabecular bone compartments. In trabecular bone, PTH may exert anabolic effects, whereas PTH promotes bone resorption in cortical bone. Vertebral fractures are prevalent in primary hyperparathyroidism (PHPT), and patients seem to fracture at higher values of bone mineral density (BMD) than patients with osteoporosis. This may be explained by changes in bone microarchitecture, which cannot be detected by measuring BMD. Even in mild PHPT, bone seems to benefit from parathyroidectomy. In secondary hyperparathyroidism, bone seems much more susceptible to fracture with insufficient levels of vitamin D compared with a replete vitamin status. If elevated PTH levels cannot be explained by conditions known to cause secondary hyperparathyroidism, the condition is termed normocalcemic PHPT, which also has been associated with an increased risk of fractures. Hyperparathyroidism is harmful to bone, which is why it is of importance to normalize PTH levels either by parathyroidectomy in PHPT or by counteracting conditions known to increase PTH in secondary hyperparathyroidism.

Treatment of Uremic Tumoral Calcinosis in Maintenance Hemodialysis Patients.

BACKGROUND/AIMS: Uremic tumoral calcinosis (UTC) is a rare disease with metastatic tissue calcification in maintenance hemodialysis (HD) patients. However, limited data are available on the treatment of UTC in HD patients. This article mainly discusses the diagnostic findings and efficacy of treatment on HD patients with UTC. METHODS: A retrospective analysis was conducted based on the data of 13 cases of UTC, including their clinical features, biochemical indicators, imaging findings, diagnosis, therapeutic methods, and follow-up results. Parathyroidectomy (PTX) or drug treatment was determined based on intact parathyroid hormone (iPTH) levels and clinical symptoms. RESULTS: All 13 patients were diagnosed as UTC definitely by imaging examination. The predominant areas involved were the buttocks (4 cases, 30.77%), shoulders (4 cases, 30.77%), and elbows (3 cases, 23.08%). Based on the levels of iPTH, cases were categorized into 2 different groups: PTX treatment group was associated with high levels of iPTH, while drug treatment group (lanthanum carbonate or sevelamer with sodium thiosulfate) was associated with lower iPTH levels. After PTX treatment, there was a significant decrease in serum iPTH, calcium (Ca), phosphate (P), and alkaline phosphatase levels (p < 0.05). In drug treatment group, the serum p levels were decreased significantly, along with a finding that hemoglobin levels were increased (p < 0.05). All the UTC had lessened or even disappeared after 4-6 months treatment. CONCLUSIONS: Although most UTC patients have an increased iPTH, a small number had lower iPTH levels. Based on iPTH levels and clinical symptoms, the patients were treated with PTX or drug therapy. With proper treatment, UTC disappeared without the need for surgery to remove calcinosis tissue.

Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis.

BACKGROUND: Cardiovascular mortality in patients receiving dialysis remains unacceptably high, with unexplained ancestry differences suggesting a genetic component. METHODS: We analyzed DNA samples from 37% of subjects enrolled in the EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events (EVOLVE) trial, a randomized trial conducted in patients receiving hemodialysis with secondary hyperparathyroidism, comparing cinacalcet to placebo on a background of usual care. DNA was analyzed for single-nucleotide polymorphisms (SNPs) in the genes encoding the angiotensin-converting enzyme receptor type I (AGTR1) and angiotensin-converting enzyme (ACE). Survival analyses were conducted separately in European Ancestry (EA) and African Ancestry (AfAn) due to known differences in cardiovascular events, minor alleles for the same variant and the frequency of minor alleles. Our primary determination was a meta-analysis across both races. RESULTS: Meta-analysis showed significant associations between rs5186 in AGTR1 and increased rates by 25-34% for the primary endpoint (composite of death or nonfatal myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular event), all-cause mortality, cardiovascular mortality and heart failure; all P < 0.001. Three correlated SNPs in ACE were associated with lower rates of sudden cardiac death (SCD) in EA samples. One ACE SNP, rs4318, only found in the AfAn samples, was associated with a lower rate of SCD in the AfAn samples. CONCLUSIONS: The C allele in rs5186 in AGTR1 was associated with higher rates of death and major cardiovascular events in a meta-analysis of EA and AfAn patients with end-stage kidney disease. SNPs in ACE were associated with SCD.

Successful management of tertiary hyperparathyroidism associated with hypophosphataemic rickets in an adult.

Tertiary hyperparathyroidism (THP) is a rare complication in patients with hypophosphataemic rickets (HR), usually related to long-term management with active vitamin D analogues and oral phosphate salts. If left untreated, THP may aggravate bone and renal disease. We report a case of THP, which developed during the course of HR. Preoperatively, cinacalcet administration along with gradual increase in alphacalcidol dose, led to almost normalization of serum calcium and decrease in parathyroid hormone (PTH) concentrations. The patient underwent an uneventful subtotal parathyroidectomy, resulting in PTH normalization and stabilization of eucalcaemia during 18 months of follow-up. We conclude that, except for optimal dosage of elementary phosphate and alphacalcidol, cinacalcet prior to parathyroidectomy may be an effective option in patients with HR complicated with THP.

The Importance of Adherence in the Treatment of Secondary Hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) is a frequent condition in the presence of chronic kidney disease (CKD). In CKD patients, SHPT is reported to increase both morbidity and mortality, especially cardiovascular. The difficulty in the treatment of SHPT in clinical practice is frequently encountered from a not always adequate conduct of the clinicians and a common non-compliance to the therapy of CKD patients. In this review, the greatest difficulties from clinicians and CKD-patients' point of view in the treatment of SHPT will be addressed, with particular attention to those related to dialysis features, nutritional habits, and medical therapy.

Improved Control of Secondary Hyperparathyroidism in Hemodialysis Patients Switching from Oral Cinacalcet to Intravenous Etelcalcetide, Especially in Nonadherent Patients.

BACKGROUND: Etelcalcetide is a novel second-generation calcimimetic that, because of its intravenous administration, could improve treatment adherence in secondary hyperparathyroidism (SHPT). The aim of this study was to evaluate the effectiveness of etelcalcetide compared with that of cinacalcet in controlling SHPT in patients under hemodialysis. METHODS: A prospective observational study was performed in 29 patients with SHPT under hemodialysis who switched from cinacalcet to etelcalcetide with a follow-up of 6 months. A survey was conducted of adherence to the oral calcimimetic. The primary end-point of the study was to assess whether etelcalcetide was more effective than cinacalcet in controlling SHPT. RESULTS: After the switch of treatment, none of the patients developed clinical intolerance or new adverse effects. Etelcalcetide was more effective than cinacalcet in controlling intact parathyroid hormone (iPTH), with an overall decrease in iPTH levels that was significant from the second month. Average calcium levels remained within the normal range, with a higher percentage of hypocalcemia with etelcalcetide (6.9 vs. 13.8%), which was asymptomatic in all cases. Patients who were nonadherent to cinacalcet (38%) showed a significant reduction in calcium and iPTH during follow-up with etelcalcetide. The adherent group (62%) also showed a trend to lower iPTH levels reaching statistical significance after 5 months of follow-up. The dose conversion factor for the switch from cinacalcet to etelcalcetide was etelcalcetide/session = 0.111*mg cinacalcet/day + 0.96, R2 = 0.57. CONCLUSIONS: Etelcalcetide was more effective than cinacalcet in this patient population, especially in the nonadherent subgroup, leading to better SHPT control without adverse effects.

Outcomes of cinacalcet withdrawal in Australian dialysis patients.

BACKGROUND: Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacalcet. In Australia, cinacalcet was publicly funded for dialysis patients from 2009 to 2015 when funding was withdrawn following publication of the EVOLVE study, which resulted in most patients on cinacalcet ceasing therapy. We examined the clinical and biochemical outcomes associated with this change at Australian renal centres. AIM: To assess changes to biochemical and clinical outcomes in dialysis patients following cessation of cinacalcet. METHODS: We conducted a retrospective study of dialysis patients who ceased cinacalcet after August 2015 in 11 Australian units. Clinical outcomes and changes in biochemical parameters were assessed over a 24- and 12-month period, respectively, from cessation of cinacalcet. RESULTS: A total of 228 patients was included (17.7% of all dialysis patients from the units). Patients were aged 63 ± 15 years with 182 patients on haemodialysis and 46 on peritoneal dialysis. Over 24 months following cessation of cinacalcet, we observed 26 parathyroidectomies, 3 episodes of calciphylaxis, 8 fractures and 50 deaths. Eight patients recommenced cinacalcet, meeting criteria under a special access scheme. Biochemical changes from baseline to 12 months after cessation included increased levels of serum PTH from 54 (interquartile range 27-90) pmol/L to 85 (interquartile range 41-139) pmol/L (P < 0.0001), serum calcium from 2.3 ± 0.2 mmol/L to 2.5 ± 0.1 mmol/L (P < 0.0001) and alkaline phosphatase from 123 (92-176) IU/L to 143 (102-197) IU/L (P < 0.0001). CONCLUSION: Significant increases in serum PTH, calcium and alkaline phosphatase occurred over a 12-month period following withdrawal of cinacalcet. Longer-term follow up will determine if these biochemical and therapeutic changes are associated with altered rates of parathyroidectomies and cardiovascular mortality and morbidity.

Effect of Hybrid Blood Purification Treatment on Secondary Hyperparathyroidism for Maintenance Hemodialysis Patients.

OBJECTIVE: This study aims to investigate the effects of hybrid blood purification treatment on secondary hyperparathyroidism for maintenance hemodialysis (HD) patients. METHODS: A total of 40 patients were randomly divided into 2 groups: HD combined with hemoperfusion (HD + HP) group (n = 20) and HD group (n = 20). Changes in intact parathyroid hormone (iPTH) in these 2 groups were compared before and after treatment, and iPTH levels in the HD + HP group were monitored before and after treatment. RESULTS: iPTH, ß2 microglobulin (ß2-MG), and cystatin C (CysC) levels were significantly lower in the HD + HP group than in the HD group (p < 0.05), iPTH levels were significantly higher than at the first day after treatment (p < 0.05), and iPTH level was significantly higher (p < 0.05). CONCLUSION: The clearance effects of HD + HP on iPTH, ß2-MG, and CysC are better than HD alone. Treatment with HD + HP every 2 weeks is recommended for maintenance HD patients.

Longitudinal changes in bone and mineral metabolism after cessation of cinacalcet in dialysis patients with secondary hyperparathyroidism.

BACKGROUND: The calcimimetic agent cinacalcet is effective for the management of secondary hyperparathyroidism (SHPT) in dialysis patients. Changes to reimbursement of cinacalcet in Australia provided an opportunity to assess effects of medication cessation on biochemical and clinical outcomes in dialysis patients, including changes to novel biomarkers such as calciprotein particles (CPP). CPP are nanoparticles of mineral and protein in the circulation associated with increased vascular calcification in patients with chronic kidney disease. METHODS: Dialysis patients from a single center who ceased cinacalcet between August 2015 and March 2016 were included in a prospective observational study. Bloods were taken at the time of cessation of cinacalcet and at 1, 6 and 12 months. Clinical and biochemical outcomes were compared with an age- and gender-matched cohort of cinacalcet-naïve dialysis patients. RESULTS: Sixty-two patients participated in the study. Mean age was 69.6 ± 13.2 years. Biochemical changes over 12 months following cessation of cinacalcet included an increase in serum parathyroid hormone (PTH) (42.2 [IQR 27.8-94.6] pmol/L to 114.8 [83.9-159.1] pmol/L [p < 0.001]), serum calcium (2.31 ± 0.21 mmol/L to 2.46 ± 0.14 mmol/L [p < 0.001]) and primary CPP (CPP-I) (p = 0.002). Changes in CPP were associated with an increase in PTH (p = 0.007), calcium (p = 0.002) and ferritin (p = 0.02) but a reduction in serum albumin (p = 0.001). Over the 12-month period, there were two fractures, five cardiovascular events, one episode of calciphylaxis, and one parathyroidectomy, with a mortality rate of 19% (n = 13). CONCLUSION: Uniquely we report the effects of cinacalcet withdrawal in a real world setting with demonstrated increases in PTH, serum calcium and CPP subsets, novel CKD-MBD related factors, over a 12-month period.

[Sequential parathyroidectomy under cervical plexus anesthesia for secondary hyperparathyroidism with renal function failure].

Objective: To summarize the strategy of sequential parathyroidectomy for secondary hyperparathyroidism. Methods: Between January 2009 and December 2017, 32 patients with secondary hyperparathyroidism underwent parathyroidectomy in Department of General Surgery, Peking Union Medical College Hospital. There were 11 male and 21 female patients with a mean age of 51.3 years. Eleven of them underwent bilateral neck exploration under general anesthesia, while the rest of them underwent sequential parathyroidectomy. For the patients with sequential parathyroidectomy, a unilateral neck exploration was performed in the initial operation under cervical plexus blocking anesthesia. Second operation for contralateral parathyroid lesions was performed if the serum intact parathyroid hormone (iPTH) was still higher than 1 000 ng/L or related symptoms were not relieved significantly 6 months later after initial surgery. Fisher exact test was used to compare the date between the 2 groups. Results: In the bilateral exploration group, the serum iPTH level gradually exceeded above 1 000 ng/L in 5 patients during follow-up, and reoperation were performed in 3 patients of them. In the group with sequential parathyroidectomy, the serum iPTH level after initial operation exceeded above 1 000 ng/L in 15 patients. Eleven of them underwent contralateral parathyroidectomy, which decreases the serum iPTH levels to less than 1 000 ng/L in 10 patients. Compared with the sequential parathyroidectomy group (1/11), more patients needed to be treated in the intensive care unit after operation in bilateral exploration group (6/11), although the difference was statistically insignificant (P=0.063). Conclusions: Sequential parathyroidectomy strategy is feasible for the secondary hyperparathyroidism with severe complications. Prospective controlled observation with large sample size is needed to confirm its effect.

Paricalcitol and cinacalcet have disparate actions on parathyroid oxyphil cell content in patients with chronic kidney disease.

The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.

Effect of parathyroidectomy and cinacalcet on quality of life in patients with end-stage renal disease-related hyperparathyroidism: a systematic review.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a decreased quality of life (QoL), which is attributable in part to ESRD-related hyperparathyroidism (HPT). Both cinacalcet and parathyroidectomy (PTx) are treatments for advanced HPT, but their effects on QoL are unclear. We performed a systematic review to evaluate the impact of cinacalcet and PTx on QoL. METHODS: A systematic literature search was performed using PubMed and EMBASE databases to identify relevant articles. The search was based on the following keywords: 'parathyroidectomy' or 'cinacalcet', 'secondary hyperparathyroidism' or 'renal hyperparathyroidism' combined with 'quality of life' or 'SF-36' or 'symptomatology'. Only studies reporting on QoL at baseline and during follow-up were included. QoL scores were extracted from the selected manuscripts and weighted means were calculated. Due to a lack of available data on QoL improvement in patients using cinacalcet, a meta-analysis could not be performed. RESULTS: In all, eight articles reached our inclusion criteria. Of this, five articles reported the effect of PTx on QoL. All PTx studies were observational and non-controlled. The physical component scores of the 36-item Medical Outcomes Study Short-Form Health Survey increased significantly with a weighted mean of 35.5% (P < 0.05). Mental component scores increased with 13.7% (P < 0.05). Parathyroidectomy assessment of symptom scores improved from 561 preoperatively to 302 postoperatively (-259 points; -46.2%). Visual analogue scale scores decreased significantly for skin itching (46.6%), joint pain (30.4%) and muscle weakness (28.7%) (P < 0.05). Three studies on the effect of cinacalcet on QoL were included, including one randomized controlled trial. None of these studies showed significant improvement of physical component and mental component scores. CONCLUSIONS: PTx improved QoL in patients treated for ESRD-related HPT, whereas cinacalcet did not. The difference in impact between PTx and cinacalcet on QoL has not been compared directly.