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Chronic kidney disease (CKD) affects over 10% of the global population. One crucial complication of CKD is secondary hyperparathyroidism (SHPT), marked by elevated parathyroid hormone levels due to hyperphosphataemia, hypocalcaemia, and low active vitamin D from impaired renal function. SHPT increases risks of bone deformities, vascular calcification, cardiovascular events and mortality. This review examines SHPT treatment strategies in patients with CKD. First-line treatments include phosphate binders, vitamin D receptor activators and calcimimetics. When these fail, invasive options like parathyroidectomy (PTX) and thermal ablation are considered. PTX effectively reduces symptoms and improves radiological outcomes, outperforming medical treatment alone in reducing cardiovascular risk and mortality. Thermal ablation techniques, such as microwave, radiofrequency, laser or high-intensity focused ultrasound, offer less invasive alternatives with promising results. Future research should explore the molecular mechanisms of parathyroid gland hyperplasia and evaluate various treatments' impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

This real-world analysis evaluated the clinical and economic burden of non-dialysis-dependent CKD patients with and without secondary hyperparathyroidism (sHPT) in Italy. An observational retrospective study was conducted using administrative databases containing a pool of healthcare entities covering 2.45 million health-assisted individuals. Adult patients with hospitalization discharge diagnoses for CKD stages 3, 4, and 5 were included from 1 January 2012 to 31 March 2015 and stratified using the presence/absence of sHPT. Of the 5710 patients, 3119 were CKD-only (62%) and 1915 were CKD + sHPT (38%). The groups were balanced using Propensity Score Matching (PSM). Kaplan-Meier curves revealed that progression to dialysis and cumulative mortality had a higher incidence in the CKD + sHPT versus CKD-only group in CKD stage 3 patients and the overall population. The total direct healthcare costs/patient at one-year follow-up were significantly higher in CKD + sHPT versus CKD-only patients (EUR 8593 vs. EUR 5671, p < 0.001), mostly burdened by expenses for drugs (EUR 2250 vs. EUR 1537, p < 0.001), hospitalizations (EUR 4628 vs. EUR 3479, p < 0.001), and outpatient services (EUR 1715 vs. EUR 654, p < 0.001). These findings suggest that sHPT, even at an early CKD stage, results in faster progression to dialysis, increased mortality, and higher healthcare expenditures, thus indicating that timely intervention can ameliorate the management of CKD patients affected by sHPT.

Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are common and complicated clinical endocrine diseases. The parathyroid glands maintain endocrine homeostasis by secreting parathyroid hormone to regulate blood calcium levels. However, structural alterations to multiple organs and systems occur throughout the body due to hyperactivity disorder in SHPT and THPT. This not only decreases the patients' quality of life, but also affects mortality. Since current treatments for these diseases remains unclear, we aimed to develop a comprehensive review of advances in the treatment of SHPT and THPT according to the latest relevant researches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhang, Liu, Wang, Qi, Zhang and Zhang.)

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.

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Introduction: Secondary hyperparathyroidism (SHPT) represents a complication of chronic kidney disease (CKD). Vitamin D system is altered since early CKD, and vitamin D deficiency is an established trigger of SHPT. Although untreated SHPT may degenerate into tertiary hyperparathyroidism with detrimental consequences in advanced CKD, best treatments for counteracting SHPT from stage 3 CKD are still debated. Enthusiasm on prescription of vitamin D receptor activators (VDRA) in non-dialysis renal patients, has been mitigated by the risk of low bone turnover and positive calcium-phosphate balance. Nutritional vitamin D is now suggested as first-line therapy to treat SHPT with low 25(OH)D insufficiency. However, no high-grade evidence supports the best choice between ergocalciferol, cholecalciferol, and calcifediol (in its immediate or extended-release formulation). Areas covered: The review discusses available data on safety and efficacy of nutritional vitamin D, VDRA and nutritional therapy in replenishing 25(OH)D deficiency and counteracting SHPT in non-dialysis CKD patients. Expert opinion: Best treatment for low 25(OH)D and SHPT remains unknown, due to incomplete understanding of the best homeostatic, as mutable, adaptation of mineral metabolism to CKD progression. Nutritional vitamin D and nutritional therapy appear safest interventions, whenever contextualized with single-patient characteristics. VDRA should be restricted to uncontrolled SHPT by first-line therapy.

Objective: To analyze the economic burden of secondary hyperparathyroidism (sHPT) in Spain by quantifying differences in costs of pharmacological treatments and associated cardiovascular events (CVE) between renal patients with and without sHPT., Methods: We used data collected in the NEFRONA cohort study and obtained treatment and CVE costs from the BOT PLUS database and Hospital Discharge Records in the Spanish Health System (CMBD-H), respectively. We examined data from 2445 renal patients followed during 2 years for chronic kidney disease (CKD) progression and 4 years for CVE, stratifying by presence of sHPT. Patient characteristics, administered treatments and CVE were directly extracted from NEFRONA registries. Dosage for each treatment regimen was assumed based on guidelines and multiplied by official unit costs to obtain treatment costs. Costs of CVE were based on ICD-9-CM., Results: Prevalence of sHPT in the cohort was 65.6% (63.6; 67.6). Average yearly pharmacological costs for patients without sHPT were 610.33€, while costs were 1483.17€ for sHPT patients (average increase of 143.0%). Two hundred three patients registered CVE, resulting in 4-year average costs of 582.57€ for non-sHPT patients compared to 941.87€ for sHPT patients (61.7% average increase). Bivariate analyses considering presence of dialysis, hypercalcemia or hyperphosphatemia and stratified by sHPT showed higher costs for sHPT patients., Conclusions: These results show that sHPT is associated with substantially higher costs of both, pharmacological treatments and associated CVEs. Preventing the development of sHPT with early management in the course of CKD could possibly lead to better health outcomes and cost balance for health care systems., (© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

The objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT., (© 2021. The Author(s).)

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., (Copyright © 2021. Published by Elsevier Inc.)

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.

Secondary hyperparathyroidism is one of the most common complications of chronic kidney failure. If prolonged, parathyroid hormone release gains autonomy and tertiary hyperparathyroidism with parathyroid adenoma or hyperplasia can be develop. Tertiary hyperparathyroidism is associated with increased risk of mortality and morbidity; thus, treatment is recommended. Medical treatment includes phosphate binders, vitamin D analogues, and calcimimetic agents. Most cases of tertiary hyperparathyroidism can be controlled with medical treatment. When medical treatment options prove insufficient, parathyroidectomy is recommended. However, recurrence after parathyroidectomy is possible, which requires an alternative treatment. We present our percutaneous embolization experience, which has not been tried in the treatment of tertiary hyperparathyroidism in renal transplantation patients diagnosed with tertiary hyperparathyroidism., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Tertiary hyperparathyroidism associated with end-stage renal disease is characterized by progression from secondary hyperparathyroidism to an autonomous overproduction of parathyroid hormone that leads to adverse health outcomes. Rates of parathyroidectomy (PTX) have decreased with the use of calcimimetics. Optimal timing of PTX in relation to kidney transplant remains controversial. We aimed to identify the most cost-effective strategy for patients with tertiary hyperparathyroidism undergoing kidney transplant., Methods: We constructed a patient level state transition microsimulation to compare 3 management schemes: cinacalcet with kidney transplant, cinacalcet with PTX before kidney transplant, or cinacalcet with PTX after kidney transplant. Our base case was a 55-year-old on dialysis with tertiary hyperparathyroidism awaiting kidney transplant. Outcomes, including quality-adjusted life years, surgical complications, and mortality, were extracted from the literature, and costs were estimated using Medicare reimbursement data., Results: Our base case analysis demonstrated that cinacalcet with PTX before kidney transplant was dominant, with a lesser cost of $399,287 and greater quality-adjusted life years of 10.3 vs $497,813 for cinacalcet with PTX after kidney transplant (quality-adjusted life years 9.4) and $643,929 for cinacalcet with kidney transplant (quality-adjusted life years 7.4)., Conclusion: Cinacalcet alone with kidney transplant is the least cost-effective strategy. Patients with end-stage renal disease-related tertiary hyperparathyroidism should be referred for PTX, and it is most cost-effective if performed prior to kidney transplant., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (© 2020 S. Karger AG, Basel.)

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.

Secondary hyperparathyroidism is a complex pathology that develops as chronic kidney disease progresses. The retention of phosphorus and the reductions in calcium and vitamin D levels stimulate the synthesis and secretion of parathyroid hormone as well as the proliferation rate of parathyroid cells. Parathyroid growth is initially diffuse but it becomes nodular as the disease progresses, making the gland less susceptible to be inhibited. Although the mechanisms underlying the pathophysiology of secondary hyperparathyroidism are well known, new evidence has shed light on unknown aspects of the deregulation of parathyroid function. Secondary hyperparathyroidism is an important feature of chronic kidney disease-mineral and bone disorder and plays an important role in the development of bone disease and vascular calcification. Thus, part of the management of chronic kidney disease relies on maintaining acceptable levels of mineral metabolism parameters in an attempt to slow down or prevent the development of secondary hyperparathyroidism. Here, we will also review the latest evidence regarding several aspects of the clinical and surgical management of secondary hyperparathyroidism., Competing Interests: Competing interests: MR has received lecture fees from Amgen, Vifor Pharma, Kyowa Kirin, and Fresenius Medical Care. MR is member of the European Uremic Toxin (EUTox) Work Group and the Chronic Kidney Disease – Mineral Bone Disorder (CKD-MBD) Working Group. MER-O declares that she has no competing interestsNo competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2020 Rodríguez-Ortiz ME and Rodríguez M.)

CKD-MBD (chronic kidney disease - mineral and bone disorder) describes a complex syndrome of renal osteodystrophy, mineral disturbances and cardiovascular disease in patients with chronic kidney disease. The present articles intends to provide an up-to-date summary of recent clinically important developments in the field of CKD-MBD. The article touches specifically phosphate management, secondary hyperparathyroidism, vitamin D, arteriosclerosis, renal bone disease, and SGLT2-inhibitors. The summary also comments on which grade of evidence novel aspects and innovative developments in CKD-BMD are based. The author concludes that nephrologists should strive after more high-quality, large-scale randomized-controlled interventional trials in order to optimize the evidence behind CKD-MBD therapy., Competing Interests: Vortragshonorare/Forschungsförderung von: Amgen, Bayer, BMS, Pfizer, Vifor, Resverlogix, Sanifit., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

Introduction: This analysis explored laboratory mineral and bone disorder parameters and management of secondary hyperparathyroidism in patients undergoing hemodialysis in Belgium, Canada, China, France, Germany, Italy, Japan, Russia, Saudi Arabia, Spain, Sweden, the UK, and the USA., Methods: Analyses used demographic, medication, and laboratory data collected in the prospective Dialysis Outcomes and Practice Patterns Study (2012-2015). The analysis included 20,612 patients in 543 facilities. Descriptive data are presented as regional mean (standard deviation), median (interquartile range), or prevalence, weighted for facility sampling fraction. No testing of statistical hypotheses was conducted., Results: The frequency of serum intact parathyroid hormone levels > 600 pg/mL was lowest in Japan (1%) and highest in Russia (30%) and Saudi Arabia (27%). The frequency of serum phosphorus levels > 7.0 mg/dL was lowest in France (4%), the UK (6%), and Spain (6%), and highest in China (27%). The frequency of serum calcium levels > 10.0 mg/dL was highest in the UK (14%) and China (13%) versus 2% to 9% elsewhere. Dialysate calcium concentrations of 2.5 mEq/mL were common in the USA (78%) and Canada (71%); concentrations of 3.0-3.5 mEq/L were almost universal at facilities in Italy, France, and Saudi Arabia (each ≥ 99%)., Conclusions: Wide international variation in mineral and bone disorder laboratory parameters and management practices related to secondary hyperparathyroidism suggests opportunities for optimizing care.

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., (© 2020 S. Karger AG, Basel.)

Hypercalcemia due to excess parathyroid hormone (PTH) production is a common condition among patients with end-stage renal disease (ESRD), often referred to as tertiary hyperparathyroidism. There are limited effective medical treatment options currently available for such patients. Denosumab is a monoclonal antibody that inhibits osteoclast activation, thereby reducing calcium release from bones. Denosumab has been used to treat medically-refractory hypercalcemia in non-ESRD patients with hyperparathyroidism. Denosumab has also been used to treat non-PTH-mediated hypercalcemia in patients with advanced chronic kidney disease and ESRD. In this case report, we describe the use of denosumab to successfully treat a case of medically refractory hypercalcemia due to immobilization in a patient on peritoneal dialysis with severe underlying tertiary hyperparathyroidism. In spite of persistently elevated PTH, hypercalcemia quickly resolved after a single dose of denosumab. The patient subsequently developed temporary hypocalcemia requiring medical intervention. Our case report, which is the first described use of denosumab for treatment of hypercalcemia in the setting of tertiary hyperparathyroidism in a peritoneal dialysis patient, adds to the body of literature suggesting denosumab is a useful therapeutic agent in patients with ESRD. Issues with post-treatment electrolyte management and other therapeutic considerations are also discussed.

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., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Secondary hyperparathyroidism (SHPT) is a major complication of chronic kidney disease (CKD), responsible for skeletal and vascular damage with increased risk of bone fractures, cardiovascular events, and mortality. However, the optimal serum parathormone (PTH) levels for improving clinical outcomes remain uncertain. Treatment of SHPT is based on nutritional therapy, phosphate binders, vitamin D, and calcimimetics, but none of these interventions has ever been tested against placebo in randomized controlled trials. Treatment of SHPT in the elderly should consider the many peculiarities of aging in terms of physiopathology, quality of life, symptoms, subjective perception of disease, drug load, and the modifying effect of treatment on disease-related outcomes. Unfortunately, peculiarities of SHPT among elderly CKD patients are mainly unexplored. The present review aims to provide a reasonable merging of evidence regarding the management of SHPT in CKD, with more actual concepts on how to care for older patients.

The classic pathogenesis of secondary hyperparathyroidism (SHPT) began with the trade-off hypothesis based on parathyroid hormone hypersecretion brought about by renal failure resulting from a physiological response to correct metabolic disorder of calcium, phosphorus, and vitamin D. In dialysis patients with failed renal function, physiological mineral balance control by parathyroid hormone through the kidney fails and hyperparathyroidism progresses. In this process, many significant genetic findings have been established. Abnormalities of Ca-sensing receptor and vitamin D receptor are associated with the pathogenesis of SHPT, and fibroblast growth factor 23 has also been shown to be involved in the pathogenesis. Vitamin D receptor activators (VDRAs) are widely used for treatment of SHPT. However, VDRAs have calcemic and phosphatemic effects that limit their use to a subset of patients, and calcimimetics have been developed as alternative drugs for SHPT. Hyperphosphatemia also affects progression of SHPT, and control of hyperphosphatemia is, therefore, thought to be fundamental for control of SHPT. Currently, a combination of a VDRA and a calcimimetic is recognized as the optimal strategy for SHPT, and for other outcomes such as reduced cardiovascular disease and improved survival. The latest findings on the pathogenesis and treatment of SHPT are summarized in this review., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Introduction: Secondary hyperparathyroidism (SHPT) is a serious and common problem in patients undergoing maintenance hemodialysis. Minimally invasive microwave ablation (MWA) has been used to treat SHPT and shows some advantages. However, its efficacy is still undefined. The primary purpose of this study was to determine the efficacy and safety of MWA compared to total parathyroidectomy plus forearm autotransplantation., Methods: The SHPT patients who were undergoing maintenance hemodialysis (follow-up for 6 to 24 months after treatments) were divided into a MWA group (n = 33) and a parathyroidectomy group (n = 48). The efficacy (serum intact parathyroid hormone [iPTH], calcium, and phosphorus levels) and safety (hoarseness, hypocalcaemia, and persistently low iPTH) were compared between the two groups. Additionally, the study explored potential predictors of response to MWA by a logistic regression analysis., Findings: There were no significant differences in baseline characteristics between the two groups. The rates of achieving the recommended goal for iPTH were significantly higher in the MWA group than that in the parathyroidectomy group at all follow-up times: 57.58% vs. 12.50% at one-day (P < 0.001), 45.45% vs. 16.67% at 1-week (P = 0.005), 57.58% vs. 16.67% at 2-week (P < 0.001), 57.58% vs. 22.92% at 1-month (P = 0.002), and 69.70% vs. 35.42% at 3-month (P = 0.002), 76.47% vs. 28.57% at 6-month (P = 0.005), 87.50% vs. 47.37% at 12-month (P = 0.008), and 81.82% vs. 52.63% at 24-month (P = 0.015), respectively. However, there were no significant differences for phosphorus or calcium at any of the follow-up times (P > 0.05). The persistently low iPTH was more in the parathyroidectomy group (64.6%) than that in the MWA group (0%) (P < 0.001), but there was no significant difference in hoarseness or hypocalcaemia (P > 0.05). Baseline levels of iPTH (P = 0.021) and patient age (P = 0.011) were determined as predictors by univariate logistic regression analysis., Conclusion: The MWA could be an alternative to parathyroidectomy for SHPT but its eventual superiority has to be demonstrated by a proper study., (© 2019 International Society for Hemodialysis.)

Rationale: Simultaneous spontaneous bilateral quadriceps tendon rupture is a rare orthopedic injury; its initial diagnosis is misdiagnosed in up to 50% of patients with secondary hyperparathyroidism. Early diagnosis and surgical repair are important to achieve an excellent functional outcome., Patient Concerns: We report a case of simultaneous spontaneous bilateral quadriceps tendon rupture associated with secondary hyperparathyroidism., Diagnosis: Magnetic resonance imaging showed that the quadriceps tendon was completely ruptured at the osteotendinous junction. We then found bilateral quadriceps tendon rupture during the operation., Interventions: The patient underwent successful tendon repair surgery., Outcomes: The 31-year-old female patient regained full active movement of both knee joints and was able to participate in her activities of daily living., Lessons: Simultaneous spontaneous bilateral quadriceps tendon rupture in a patient with secondary hyperparathyroidism (undergoing hemodialysis) is a rare orthopedic injury that can be easily overlooked at the initial presentation. Early diagnosis and surgical repair is important to achieve an excellent functional outcome. For patients with secondary hyperparathyroidism receiving hemodialysis, strict systematic treatment of hyperparathyroidism is needed to prevent rupture or re-rupture of the quadriceps tendon.

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., (© 2019 S. Karger AG, Basel.)

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., (© 2018 Royal Australasian College of Physicians.)

Background: Since 2004, end-stage renal disease related hyperparathyroidism patients are treated mainly with cinacalcet, which ceased to be subsidized through the Australian Pharmaceutical Benefits Scheme in 2015. We aimed to investigate the impact of these changes on the treatment strategy in the Australian end-stage renal disease population., Methods: The following groups were formed according to the date of parathyroidectomy: A, before calcimimetics; B, during the era of calcimimetics; and C, after cinacalcet removal by the Australian Pharmaceutical Benefits Scheme. The primary outcome was time from start of dialysis to parathyroidectomy. Regression analysis was used to examine trends in parathyroidectomy rates., Results: Between 1998 and 2016, 195 parathyroidectomies were performed. Median time to referral was 69 (33-123), 67 (31-110) and 44 (23-102) months for groups A, B, and C, respectively (P = .55). Parathyroidectomy rates increased throughout the years (CI 0.09-1.13, R 2 =0.27, P = .02). A trend toward a dip in parathyroidectomy rates was seen during the era of cinacalcet (P = .08). Median preoperative parathyroid hormone levels increased significantly (842 [418-1,553] versus 1,040 [564-1,810] versus 1,350 [1,037-1,923] pg/mL, for groups A, B, and C, respectively [P < .01])., Conclusion: Parathyroidectomy rates seem to vary according to the availability of cinacalcet. This change in treatment strategy is accompanied with increased preoperative parathyroid hormone levels, reflecting delayed surgery and increased disease severity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Secondary hyperparathyroidism (SHP) is a frequent complication of kidney diseases. At variance with all the other forms of SHP, which are compensatory conditions, renal SHP has many pathogenetic peculiarities, which have been only in part defined. Furthermore, in the long course of chronic kidney diseases (CKD), SHP sometimes transforms into a hypercalcemic condition resembling the autonomous form of hyperparathyroidism (tertiary hyperparathyroidism; THP). The clinical consequences of SHP in CKD patients are manifold, encompassing not only bone and mineral disorders, but also other metabolic and organic changes which frequently burden these patients. Although the medical therapeutic tools have substantially increased in number and improved in their efficacy in recent decades, we have as yet no demonstration of a clear benefit regarding the major clinical outcomes. Furthermore, some of these patients, particularly when the autonomous THP develops, still require a surgical approach., (© 2019 S. Karger AG, Basel.)

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., (© 2018 S. Karger AG, Basel.)

Background: Evocalcet has been developed as a new calcimimetic agent for hemodialysis (HD) patients with secondary hyperparathyroidism (HDSHPT), eliciting fewer gastrointestinal symptoms and drug interactions. We evaluated the efficacy, safety, and optimal starting dose of evocalcet in HDSHPT., Methods: In this 3-week, Phase 2b, randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-finding study, Japanese HDSHPT with intact parathyroid hormone (iPTH) ≥240 pg/mL and serum calcium level corrected for albumin ≥8.4 mg/dL were randomized to evocalcet 0.5, 1, 2 mg/day administered orally or placebo under double-blind conditions, and cinacalcet 25 mg/day (open-label conditions)., Results: In total, 152 HDSHPT were randomized. The mean ± standard deviation (median, interquartile range) of percent changes in iPTH from baseline to end of treatment were -8.40±25.43% (-12.16, 39.60), -10.56±22.86% (-14.24, 27.85), and -20.16±34.23% (-23.83, 39.05) in the evocalcet 0.5, 1, and 2 mg/day groups and 5.44±25.85% (3.52, 35.39) and -25.86±27.76% (-29.79, 34.15) in the placebo and cinacalcet groups, respectively. The dose-response profile for each evocalcet group vs placebo showed statistically significant differences for all contrast patterns. Whole PTH, corrected calcium, ionized calcium, phosphorus, and intact fibroblast growth factor 23 decreased after treatment initiation in the evocalcet and cinacalcet groups. Adverse events were observed in 30%-50% of patients (all groups). Incidence of adverse events was similar among all groups except for decreased calcium, which occurred more frequently in the evocalcet 2 mg and cinacalcet groups., Conclusions: The dose response and safety of all administered doses of evocalcet were confirmed, as well as the efficacy of evocalcet ≥1 mg in a strictly Japanese sample of HDSHPT. Therefore, evocalcet 1 mg was considered appropriate as an initial dose for HDSHPT., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr Akizawa has received consulting fees from KHK Co., Ltd., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Fuso Pharmaceutical Industries, Ltd., Japan Tobacco Inc., Ono Pharmaceutical Co., Ltd. and NIPRO Industry, and lecture fees from KHK Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Kissei Pharmaceutical Co., Ltd., Torii Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd. Dr Fukagawa has received consulting fees from KHK Co., Ltd. and Ono Pharmaceutical Co., Ltd., and lecture fees from KHK Co., Ltd., Bayer Yakuhin, Ltd., Torii Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd., and grants from KHK Co., Ltd. and Bayer Yakuhin, Ltd. Shimazaki is employed by Kyowa Hakko Kirin Co., Ltd. The specific roles of these authors are articulated in the ‘author contributions’ section.” This does not alter our adherence to PLOS ONE policies on sharing data and materials. The evocalcet study group has no conflicts of interest to declare.

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.

Chronic kidney disease mineral bone disorder (CKD-MBD) is common in end-stage renal disease and is associated with an increased risk of cardiovascular morbidity and mortality. Mainstays of treatment include decreasing serum phosphorus level toward the normal range with dietary interventions and phosphate binders and treating increased parathyroid hormone levels with activated vitamin D and/or calcimimetics. There is significant variation in serum levels of mineral metabolism markers, intestinal absorption of phosphorus, and therapeutic response among individual patients and subgroups of patients with end-stage renal disease. This variation may be partly explained by polymorphisms in genes associated with calcium and phosphorus homeostasis such as the calcium-sensing receptor gene, the vitamin D-binding receptor gene, and genes associated with vascular calcification. In this review, we discuss how personalized medicine may be used for the management of CKD-MBD and how it ultimately may lead to improved clinical outcomes. Although genetic variants may seem attractive targets to tailor CKD-MBD therapy, complete understanding of how these polymorphisms function and their clinical utility and applicability to personalized medicine need to be determined., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Protein-energy wasting (PEW), a syndrome involving adverse changes in nutrition and body composition, is a serious problem associated with morbidity and mortality in patients with end-stage renal disease (ESRD). The pathogenesis of PEW is multifactorial, and the underlying mechanisms are not fully understood. However, recent translational work has provided compelling evidence for a causal role of parathyroid hormone (PTH) in the pathogenesis of adipose tissue browning and increased energy expenditure, a critical component of PEW in ESRD. These results provide a biological explanation for the clinical association between secondary hyperparathyroidism (SHPT) and PEW in hemodialysis patients and may serve as an additional rationale for treating SHPT. Large-scale clinical and epidemiological studies should determine the clinical significance of SHPT as a contributor to PEW and establish the optimal management of SHPT to ameliorate PEW., (© 2018 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Bone maintains extracellular calcium levels through a system called bone remodeling. Parathyroid hormone (PTH) is the major initiator of this system, which is secreted by the information through calcium sensing receptor in parathyroid cells. PTH modifies calcified bone morphology through a process of its bone action. Therefore, extremely hyperactivated parathyroid function seen in patients with chronic kidney disease has been considered to have a negative impact on the bone mechanical properties. While skeletal deformities and fragility fractures were common among dialysis patients up to the 1970s, after which methods for the treatment of hyperparathyroidism were developed, we now seldom encounter those cases with severe secondary hyperparathyroidism in Japan. In a three-dimensional morphometry of biopsied iliac bone samples obtained from dialysis patients, PTH level was inversely correlated with cortical bone thickness, however, this relationship disappeared among those with intact PTH < 1000 pg/mL. Higher PTH levels were associated with more complicated and irregular cancellous bone surface, but this change was not accompanied with decreased cancellous bone connectivity. These findings theoretically support the recent clinical study results that PTH levels no longer show a tight correlation with fracture risk in dialysis patients. Nevertheless, the use of calcium sensing receptor agonist is likely to be associated with reduced hip fracture risk in dialysis patients. Further study is needed to reveal its pharmacological mechanism on bone., (© 2018 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Anemia is a common complication of chronic kidney disease (CKD). There are various causes of renal anemia such as decreased production of erythropoietin, resistance to erythropoietin, shortened survival of red blood cells, and bone marrow fibrosis. Secondary hyperparathyroidism (SHPT) is a less recognized, but potentially significant cause of renal anemia in CKD patients. Parathyroid hormone (PTH) has been regarded as a uremic toxin that has multiple adverse effects, and its elevated levels have been associated with renal anemia in hemodialysis patients. Moreover, recent clinical studies have shown that the treatment of SHPT using either vitamin D receptor activators, calcimimetics, or parathyroidectomy leads to improvement of anemia, supporting the role of PTH in renal anemia. Emerging data have also indicated the involvement of bone-derived fibroblast growth factor 23 in renal anemia. This review summarizes recent insights into the role of PTH in renal anemia and discusses the importance of treating SHPT in improving the control of renal anemia in hemodialysis patients., (© 2018 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Severe hypocalcemia (SH) is a common and serious complication in dialysis patients with secondary hyperparathyroidism (SHPT) after parathyroidectomy (PTX). The aim is to explore the risk predictors of SH in post-PTX dialysis ESRD patients with SHPT. 129 consecutive dialysis patients with SHPT underwent PTX were retrospectively reviewed. A total of 22 clinical parameters were included in the study. SH was defined as the minimum values of serum calcium lower than 1.875 mmol/L (7.5 mg/dL) after surgery. Univariate analysis showed that pruritus, lumbar X-ray changes of renal osteodystrophy, pre- and post-operative intact parathyroid hormone (iPTH), Calcium, alkaline phosphatase, and gland mass were significantly different between SH and non-SH groups. In the multivariate logistic regression model, the pre-operative serum iPTH, calcium, and pruritus were independent risk predictors of SH. AUCs for pre-operative serum iPTH, calcium and pruritus were 0.810, 0.714 and 0.591, respectively. Patients with higher level of pre-operative serum iPTH, lower level of serum calcium and with no/mild symptoms of pruritus are at greater risk of developing SH after PTX.

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.

Rationale: Acute kidney injury (AKI) with hyperparathyroidism caused by nitrite was rare, and renal function and parathyroid hormone (PTH) decreased to normal range after therapy., Patient Concerns: Acute kidney injury was diagnosed in a 40-year-old male with hyperparathyroidism and cyanosis of his hands and both forearms., Diagnoses: The patient ate some recently pickled vegetables, and he experienced nausea, vomiting and diarrhoea without oliguria or anuria; Additionally, his hands and both forearms had a typical blue ash appearance. After admission, the laboratory findings indicated theincreasing serum creatinine (Scr) and parathyroid hormone (PTH). He was diagnosed as acute kidney injury with hyperparathyroidism caused by nitrite., Interventions: The patient stopped eating the pickled vegetables and was given rehydration, added calories and other supportive therapy without any glucocorticoids., Outcomes: According to his clinical manifestations, laboratory findings and imaging results, the patient was diagnosed with acute kidney injury with secondary hyperparathyroidism. He was given symptomatic supportive care therapy. After one week, the serum creatinine, parathyroid hormone (PTH), hypercalcemia, hyperphosphatemia, proteinuria, and urine red blood cell values decreased to normal range., Lessons: Nitrite-induced acute kidney injury with secondary hyperparathyroidism was relatively rare. After therapy, the function of the kidney and parathyroid returned to normal. This case suggests that detailed collection of medical history, physical examination and correct symptomatic treatment is very important.

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, β2 microglobulin (β2-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, β2-MG, and CysC are better than HD alone. Treatment with HD + HP every 2 weeks is recommended for maintenance HD patients., (© 2018 S. Karger AG, Basel.)