Hyperparathyroidism In Chronic Kidney Disease Research Articles

Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.

Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD. Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness. Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.

The refractory secondary hyperparathyroidism presenting with retro-orbital brown tumor: a case report

BackgroundTertiary hyperparathyroidism describes the autonomous and excessive secretion of parathyroid hormone (PTH) by the parathyroid glands after longstanding secondary hyperparathyroidism in chronic kidney disease. Brown tumors are a sign of uncontrolled hyperparathyroidism. In this case, we have reported a refractory and destructive hyperparathyroidism storm. Also, it presented with atypical onset and unexpected adenoma location.Case presentationA 37-year-old man was diagnosed with end-stage kidney disease 22 years ago. He has been undergoing dialysis treatment since that time. Recently, he was admitted to the ophthalmology department due to the unilateral anterior bulging of the right eye and drooping of the eyelid. Magnetic resonance imaging exhibited an extraconal mass lesion located in the right orbital posterior superolateral position. Computerized tomography scans considered expansile bone lesion with peripheral calcification and originating from the sphenoid wing. The bone mass lesion was resected via craniotomy due to the compressive effect. The pathological findings were consistent with brown tumors. Plasma intact PTH level was 4557 pg/mL. The patient informed that he underwent parathyroidectomy and two leg fractures operation in a medical query. Parathyroid scintigraphy determined three distinct foci consistent with adenomas and one of them was in mediastenum. Second parathyroidectomy was recommended to the patient but the patient refused surgery. Despite his medication and dialysis regimen being revised, PTH levels were maintained at higher levels in follow-up.ConclusionsWe presented a hyperparathyroidism case that was resistant to all treatments and exhibited all the severe complications in a long-term dialysis patient. Furthermore, this case has revealed the importance and difficulty of secondary hyperparathyroidism management.

Parathyroid carcinoma case-report in a patient with multinodular goiter and chronic kidney disease: difficulties in diagnosis and treatment (observation from practice)

We would like to present a clinical case of severe primary hyperparathyroidism due to a parathyroid carcinoma of atypical location in a patient with chronic kidney disease of complex etiology and multinodular goiter. Patient S., 59 years old, was followed-up for a long time in tertiary referral hospitals for “chronic tubulointerstitial nephritis with nephrosclerosis”, secondary hyperparathyroidism due to chronic kidney disease (CKD) G3–4, osteoporosis, and a multinodular euthyroid colloid goiter. In July 2021 she was referred to the Endocrinology Research Centre in order to clarify the diagnosis because of the persistence of an extremely high level of parathyroid hormone (PTH) despite cinacalcet treatment. During examination, primary hyperparathyroidism, a left parathyroid gland lesion, multinodular goiter with subclinical thyrotoxicosis, and vitamin D deficiency were diagnosed. After the removal of the left parathyroid gland lesion (histologically confirmed parathyroid carcinoma) and a left-sided hemithyroidectomy, hypocalcemia («hungry bone syndrome») developed, but the level of parathyroid hormone remained elevated. After 3–18 months after surgery, no data for relapse of primary hyperparathyroidism was obtained. The persistent moderate increase in PTH was regarded as secondary hyperparathyroidism in CKD and hypocalcemia. Complex therapy of osteoporosis with the antiresorptive drug denosumab, vitamin D and its active metabolite, calcium preparations, and parathyroidectomy led to a significant increase in bone mineral density (BMD) and no repeated fractures 18 months after surgery.Conclusion. In patients with pre-dialysis CKD and high PTH levels, it is necessary to make a differential diagnosis between primary (PHPT) and secondary hyperparathyroidism (SHPT). Severe manifestations of primary hyperparathyroidism can be suspicious for parathyroid carcinoma.

Secondary hyperparathyroidism in chronic kidney disease: pathomechanism and current treatment possibilities.

Secondary hyperparathyroidism (SHPT) is one of the most common metabolic complications resulting from chronic kidney disease (CKD). The complexity of calcium and phosphate disorders associated with CKD is defined by the Kidney Disease Improvement Global Outcomes (KDIGO) working group as CKD-related mineral and bone disorders (CKD-MBD). The last update of the KDIGO guidelines on the conduct in CKD-MBD was published in 2017. The treatment of SHPT is based on 2 strategies: counteracting hyperphosphataemia and suppressing parathyroid hormone (PTH) secretion. Therapy should be based on optimally selected drugs, taking into account additional effects to reduce the risk of chronic complications and side effects. The creation of new drugs with a better safety profile, significant reduction of side effects, and greater efficiency in achieving target serum phosphorus and PTH values forces the gradual replacement of existing treatment with new pharmacotherapies. The aim of this study is to discuss the latest issues (in connection with the latest KDIGO guidelines) regarding the pathomechanism of secondary hyperparathyroidism and the current directions of the therapy in these disorders.

Recommended calcium intake in adults and children with chronic kidney disease-a European consensus statement.

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800-1000mg/day and not exceeding 1500mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs.

Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS-MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.

Prevalence and current approaches to the treatment of secondary hyperparathyroidism and its complications in chronic kidney disease: a literature review

There is a universal trend towards increase of patients with chronic kidney disease by 7% on average. In the Russian Federation, the annual increase is even higher, at about 10%. The average age of patients receiving renal replacement therapy is 60 years in the Tomsk region and 56 years in Russia, which is relatively lower than in European countries and the United States. With increasing age of patients receiving dialysis treatment, a progressive increase in the incidence of secondary hyperparathyroidism is recorded. Mineral and bone disorders, hyperphosphatemia, hypercalcemia all lead to premature vascular calcification, increase the risk of cardiovascular complications and death. At the same time, elderly patients are characterized by an increase in risks immediately after the start of dialysis therapy. There is a global tendency towards increase in the target level of parathyroid hormone. Parathyroidectomy is recognized as a gold standard for treatment of drug-resistant hyperparathyroidism across the world. As the development of hyperplasia in the parathyroid glands does not proceed synchronously, instead progressing at different rates and in the selective glands, methods of local influence on the altered glands have recently been developed in order to gradually control secondary hyperparathyroidism. Alternative to the total parathyroidectomy are minimally invasive non-surgical methods, attractive due to a smaller number of complications, such as bleeding and paresis of the recurrent laryngeal nerve. Examples of minimally invasive methods are local injections of preparations of the active form of vitamin D, which lead to apoptosis of parathyroid gland cells instead of their destruction, and are safer in relation to surrounding tissues. This article presents current data on the prevalence of secondary hyperparathyroidism in chronic kidney disease. An analysis of clinical trials was carried out based on articles indexed in the Scopus database, the Russian Science Citation Index, PubMed and Web of Science.

Prevalence and current approaches to the treatment of secondary hyperparathyroidism and its complications in chronic kidney disease: a literature review

There is a universal trend towards increase of patients with chronic kidney disease by 7% on average. In the Russian Federation, the annual increase is even higher, at about 10%. The average age of patients receiving renal replacement therapy is 60 years in the Tomsk region and 56 years in Russia, which is relatively lower than in European countries and the United States. With increasing age of patients receiving dialysis treatment, a progressive increase in the incidence of secondary hyperparathyroidism is recorded. Mineral and bone disorders, hyperphosphatemia, hypercalcemia all lead to premature vascular calcification, increase the risk of cardiovascular complications and death. At the same time, elderly patients are characterized by an increase in risks immediately after the start of dialysis therapy. There is a global tendency towards increase in the target level of parathyroid hormone. Parathyroidectomy is recognized as a gold standard for treatment of drug-resistant hyperparathyroidism across the world. As the development of hyperplasia in the parathyroid glands does not proceed synchronously, instead progressing at different rates and in the selective glands, methods of local influence on the altered glands have recently been developed in order to gradually control secondary hyperparathyroidism. Alternative to the total parathyroidectomy are minimally invasive non-surgical methods, attractive due to a smaller number of complications, such as bleeding and paresis of the recurrent laryngeal nerve. Examples of minimally invasive methods are local injections of preparations of the active form of vitamin D, which lead to apoptosis of parathyroid gland cells instead of their destruction, and are safer in relation to surrounding tissues. This article presents current data on the prevalence of secondary hyperparathyroidism in chronic kidney disease. An analysis of clinical trials was carried out based on articles indexed in the Scopus database, the Russian Science Citation Index, PubMed and Web of Science.

Label-Free Mass Spectrometry-Based Quantitative Proteomics to Evaluate the Effects of the Calcium-Sensing Receptor Agonist Cinacalcet on Protein Expression in Rat Brains and Livers.

BackgroundCinacalcet is a calcium-sensing receptor agonist that is clinically approved for the treatment of secondary hyperparathyroidism in chronic kidney disease and hypercalcemia in patients with parathyroid carcinoma. This study aimed to use quantitative mass spectrometry-based label-free proteomics to evaluate the effects of cinacalcet on protein expression in rat brains and livers.Material/MethodsWe randomly assigned 18 Wistar rats to 2 groups: an untreated control group (n=6) and a group treated with cinacalcet at a dose corresponding to the maximum dose used in humans (2 mg/kg/body weight, 5 days/week) divided into 7-day (n=6) and 21-day (n=6) treatment subgroups. A mass-spectrometry-based label-free quantitative proteomics approach using peptides peak area calculation was used to evaluate the changes in protein expression in examined tissues. Bioinformatics analysis of quantitative proteomics data was done using MaxQuant and Perseus environment.ResultsNo changes in protein expression were revealed in the 7-day treatment subgroup. We detected 10 upregulated and 3 downregulated proteins in the liver and 1 upregulated protein in the brain in the 21-day treatment subgroup compared to the control group. Based on Gene Ontology classification, all identified differentially expressed proteins were indicated as molecular functions involved in the enzyme regulator activity (36%), binding (31%), and catalytic activity (19%).ConclusionsThese findings indicate that long-term cinacalcet therapy can impair phase II of enzymatic detoxication and can cause disturbances in blood hemostasis, lipid metabolism, and inflammatory mediators or contribute to the acceleration of cognitive dysfunction; therefore, appropriate patient monitoring should be considered.

Vitamin D and Secondary Hyperparathyroidism in Chronic Kidney Disease: A Critical Appraisal of the Past, Present, and the Future.

The association between vitamin D deficiency and especially critical shortage of active vitamin D (1,25-dihydroxyvitamin D, calcitriol) with the development of secondary hyperparathyroidism (sHPT) is a well-known fact in patients with chronic kidney disease (CKD). The association between sHPT and important clinical outcomes, such as kidney disease progression, fractures, cardiovascular events, and mortality, has turned the prevention and the control of HPT into a core issue of patients with CKD and on dialysis. However, vitamin D therapy entails the risk of unwanted side effects, such as hypercalcemia and hyperphosphatemia. This review summarizes the developments of vitamin D therapies in CKD patients of the last decades, from calcitriol substitution to extended-release calcifediol. In view of the study situation for vitamin D insufficiency and sHPT in CKD patients, we conclude that the nephrology community has to solve three core issues: (1) What is the optimal parathyroid hormone (PTH) target level for CKD and dialysis patients? (2) What is the optimal vitamin D level to support optimal PTH titration? (3) How can sHPT treatment support reduction in the occurrence of hard renal and cardiovascular events in CKD and dialysis patients?

Bone Specific Alkaline Phosphatase and Serum Calcification Propensity Are Not Influenced by Etelcalcetide vs. Alfacalcidol Treatment, and Only Bone Specific Alkaline Phosphatase Is Correlated With Fibroblast Growth Factor 23: Sub-Analysis Results of the ETACAR-HD Study

Secondary hyperparathyroidism in chronic kidney disease poses a major risk factor for vascular calcification and high bone turnover, leading to mineralization defects. The aim was to analyze the effect of active vitamin D and calcimimetic treatment on fibroblast growth factor 23 (FGF23), serum calcification propensity (T50), a surrogate marker of calcification stress and bone specific alkaline phosphatase (BAP) in hemodialysis. This is a subanalysis of a randomized trial comparing etelcalcetide vs. alfacalcidol in 62 hemodialysis patients for 1 year. We compared the change of BAP and serum calcification propensity between the two medications and assessed the influence of FGF23 change over time. We found no significant differences in the change of BAP or serum calcification propensity (T50) levels from baseline to study end between treatment arms (difference in change of marker between treatment with etelcalcetide vs. alfacalcidol: BAP : 2.0 ng/ml [95% CI-1.5,5.4], p = 0.3; T50: –15 min [95% CI –49,19], p = 0.4). Using FGF23 change over time, we could show that BAP levels at study end were associated with FGF23 change (–0.14 [95% CI –0.21, –0.08], p < 0.001). We did not observe the same association between FGF23 change and T50 (effect of FGF23 change on T50: 3.7 [95% CI –5.1, 12], p = 0.4; R2 = 0.07 vs. R2 = 0.06). No significant difference was found in serum calcification propensity (T50) values between treatment arms. FGF23 was not associated with serum calcification propensity (T50), but was negatively correlated with BAP underlying its role in the bone metabolism.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT03182699].

Selective vitamin D receptor activator Paricalcitol and its potential benefits in hemodialysis patients with secondary hyperparathyroidism

Currently, the incidence and prevalence of chronic kidney disease (CKD) are increasing annually worldwide, and clinical data show that CKD patients commonly experience relative vitamin D insufficiency or deficiency. Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients. SHPT is an adaptive and in many cases ultimately maladaptive process that develops in response to declining kidney function, impaired phosphate excretion, failure to bioactivate vitamin D and hypocalcemia. SHPT is characterized by persistently elevated levels of parathyroid hormone (PTH) and complicated by important disturbances in mineral metabolism. Maintaining the level of vitamin D and parathyroid hormone concentrations in the target range reduce its associated complications (e.g., fractures, chronic kidney disease and cardiovascular calcification). Effective therapeutic interventions are highly desirable if the morbidity and mortality associated with uncontrolled SHPT are to be reduced. Major renal guidelines recommend use of vitamin D for secondary hyperparathyroidism in chronic kidney disease. However, because of the difficulties associated with lowering PTH while simultaneously controlling serum levels of calcium and phosphorous, traditional therapies for managing SHPT have several limitations. Selective vitamin D receptor activator paricalcitol mainly targets vitamin D receptors (VDR) in the parathyroid glands, has less effect on VDR in the intestine and other tissues, inhibits PTH strongly, triggers less hypercalcemia, and has less effect on intestinal absorption of calcium, phosphorus and bone metabolism and significantly lowers renin levels, albuminuria and blood pressure, which is supported by the results of most studies conducted over these decades. The article is devoted to the problem of treatment of patients with SHPT inpatient with renal replacement therapy with program hemodialysis.

Extended-Release Calcifediol Effectively Raises Serum Total 25-Hydroxyvitamin D Even in Overweight Nondialysis Chronic Kidney Disease Patients with Secondary Hyperparathyroidism

Introduction: Obesity increases the risk of vitamin D insufficiency, which exacerbates secondary hyperparathyroidism in chronic kidney disease. Recent studies suggest that serum total 25-hydroxyvitamin D (25OHD) levels of ≥50 ng/mL are necessary to produce significant reductions in elevated parathyroid hormone levels in nondialysis patients. Data from real-world and randomized controlled trials (RCTs) involving these patients were examined for (1) relationships between vitamin D treatments and the achieved levels of serum 25OHD and between serum 25OHD and body weight (BW)/body mass index (BMI); and (2) the impact of BW/BMI on achieving serum 25OHD levels ≥50 ng/mL with extended-release calcifediol (ERC) treatment or vitamin D supplementation (cholecalciferol or ergocalciferol). Methods: Data obtained from nondialysis patients participating in two real-world studies, one conducted in Europe (Study 1) and the other (Study 2) in the USA, and in two US RCTs (Studies 3 and 4) were analyzed for serum 25OHD outcomes after treatment with ERC, vitamin D supplements, or placebo. Results: More than 50% of subjects treated with vitamin D supplements in both real-world studies (Studies 1 and 2) failed to achieve serum 25OHD levels ≥30 ng/mL, a level widely viewed by nephrologists as the threshold of adequacy; only 7.3–7.5% of subjects achieved levels ≥50 ng/mL. Data from the European study (Study 1) showed that serum 25OHD levels had significant and nearly identical inverse relationships with BW and BMI, indicating that high BW or BMI thwarts the ability of vitamin D supplements to raise serum 25OHD. One RCT (Study 3) showed that 8 weeks of ERC treatment (60 μg/day) raised serum 25OHD levels to ≥30 and 50 ng/mL in all subjects, regardless of BW, while cholecalciferol (300,000 IU/month) raised serum 25OHD to these thresholds in 56% and 0% of subjects, respectively. The other RCT (Study 4) showed that ERC treatment (30 or 60 μg/day) successfully raised mean serum 25OHD levels to at least 50 ng/mL for subjects in all BW categories, whereas no increases were observed with placebo treatment. Conclusion: Real-world studies conducted in Europe and USA in nondialysis patients (Studies 1 and 2) showed that vitamin D supplements (cholecalciferol or ergocalciferol) were unreliable in raising serum total 25OHD to targets of 30 or 50 ng/mL. In contrast, ERC was demonstrated to be effective in one real-world study (Study 2) and two RCTs (Studies 3 and 4) conducted in US nondialysis patients in raising serum 25OHD to these targeted levels irrespective of BW.

Real-World Evaluation of Calcimimetics for the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease, in an Italian Clinical Setting.

This Italian real-world data analysis evaluated the pharmaco-utilization of calcimimetics, cinacalcet or etelcalcetide, and the economic burden of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients. From 1 January 2010 to 30 June 2020, adult patients with: (i) ≥1 prescription of etelcalcetide or cinacalcet, (ii) ≥3 hemodialysis/week, and (iii) without parathyroidectomy, were included. Based on the drug firstly prescribed, patients were allocated into etelcalcetide- and cinacalcet-treated cohorts, and the propensity score matching (PSM) methodology was applied to abate potential cohorts’ unbalances. Overall, 1752 cinacalcet- and 527 etelcalcetide-treated patients were enrolled. In cinacalcet- and etelcalcetide-treated patients, respectively, the most frequent comorbidities were hypertension (75.3% and 74.4%), diabetes mellitus (21.0% and 21.3%), and cardiovascular disease (18.1% and 13.3%, p < 0.01). In covariate-balanced cohorts, the treatment adherence and persistence rates were significantly higher in the etelcalcetide-treated (80.1% and 62.7%, respectively) vs. cinacalcet-treated cohort (62.3% and 54.7%, respectively). After PSM, the total costs for the management of cinacalcet- and etelcalcetide-treated patients, respectively, averaged EUR 23,480 and EUR 22,958, with the disease-specific drug costs (EUR 2629 vs. EUR 2355, p < 0.05) and disease-specific hospitalization costs (EUR 1241 vs. EUR 855) in cinacalcet- and etelcalcetide-treated patients. These results showed that, in etelcalcetide-treated patients, a higher treatment adherence and persistence was found, with disease-specific costs savings, especially those related to drugs and hospitalizations.

A Molecular Insight of the Role of PIN-1 Promoter Polymorphism (- 667C > T; rs2233679) in Chronic Kidney Disease Patients with Secondary Hyperparathyroidism.

Murine studies stipulate Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN-1) as a key mediator of PTH mRNA stability and is acknowledged by genome-wide-association-studies as secondary hyperparathyroidism defining trait in chronic kidney disease. Therefore, we hypothesize that molecular variants of the PIN-1 gene might affect the incidence and predisposition to secondary hyperparathyroidism in chronic renal insufficiency. A total of 281 adult participants, including 124 chronic kidney disease patients with secondary hyperparathyroidism and 157 healthy controls, were genotyped using polymerase chain reaction-restriction fragment length polymorphism method to unravel the effects of genetic risk loci (PIN-1 gene; - 667C > T; rs2233679) on the susceptibility to secondary hyperparathyroidism in chronic kidney disease. Suitable descriptive statistics was used for different variables. The genotype (x2: 8.03, 2 d. f. p = 0.0181) and allele distribution (x2: 7.27, 2 d. f. p: 0.007) of the - 667C > T variant differed significantly in cases and controls, with no deviation from Hardy-Weinberg equilibrium in either affected or control group. The observed frequencies of T allele of PIN-1 -667 C > T SNP was significantly high in CKD-SHPT group compared to control group (52.41% vs. 41.71%; p: 0.0118). TT variant of PIN-1 - 667C > T SNP was associated with increased risk for occurrence of CKD-SHPT in univariate analysis (OR: 4.6, p: 0.0032, 95% CI: 1.66-12.76). Further in multivariate analysis, both TT (OR: 3.84, p: 0.002, 95% CI: 0.79-9.26) and CT + TT (OR: 2.51, p: 0.031, 95% CI: 0.64-8.68) variants were independently associated with increased risk for CKD-SHPT, emphasizing the deleterious effect of minor T allele. Serum PTH, phosphorus levels were significantly high in CT and TT genotypes compared to CC genotype of PIN-1 -667C > T SNP (p = 0.001). PIN-1 promoter functional SNP (- 667C > T; rs2233679) appeared to be an important genetic determinant in etiopathogenesis of CKD-SHPT and genetic variants of this SNP influences the risk stratification and might serve as a predictive marker. Thus, rs2233679 can be useful for outcome predictions during diagnostic processes.

Paricalcitol versus Calcitriol + Cinacalcet for the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease in China: A Cost-Effectiveness Analysis.

Background: Chronic Kidney Disease (CKD) is a global chronic disease with increasing prevalence in recent years, particularly CKD accompanied by Secondary Hyperparathyroidism (SHPT) leads to reduced quality of life, increased mortality, a considerable economic burden for patients and society. The aim of this study was to investigate the cost-effectiveness analysis of paricalcitol vs. calcitriol + cinacalcet for CKD patients with SHPT in China in 2020.Methods: A Markov model was conducted employing data derived from published literature, clinical trials, official sources, and tertiary public hospital data in China, based on a 10-year horizon from the perspective of the healthcare system. Calcitriol + Cinacalcet was used as the reference group. CKD stage 5 (CKD-5) dialysis patients suffering from SHPT were included in the study. Effectiveness was measured in quality-adjusted life years (QALYs). The discount rate (5%) was applied to costs and effectiveness. Sensitivity analysis was performed to confirm the robustness of the findings.Results: The base case analysis demonstrated that Patients treated with paricalcitol could gain an increase in utility (0.183 QALYs) and require fewer expenditures (6925.612 yuan). One-way sensitivity analysis was performed to showed that impact factors were the price of cinacalcet, the hospitalization costs of patients with paricalcitol and calcitriol, the costs and utilities of hemodialysis and the costs of calcitriol, the costs of paricalcitol regardless of period. Probabilistic simulation analysis displayed when willingness-to-pay was ¥217113, the probability that Paricalcitol was dominant is 96.20%.Conclusion: The results showed that paricalcitol administrated to treat patients diagnosed with Secondary hyperparathyroidism in Chronic Kidney Disease, compared to calcitriol and cinacalcet, might be dominant in China.

Secondary Hyperparathyroidism in Chronic Kidney Disease: Pathophysiology and Management

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

Efficacy and safety of evocalcet in treatment of secondary hyperparathyroidism in chronic kidney disease on hemodialysis patients: A protocol for a systematic review and meta-analysis.

Background:Secondary hyperparathyroidism (SHPT) have been associated with poor health outcomes in hemodialysis patients. The cinacalcet has popularized in clinic which has efficacy but more adverse events; the novel oral calcimimetic agents evocalcet has appeared in recent years. However, it is currently unknown whether evocalcet produces more beneficial effects and fewer adverse events in patients with SHPT. The aim of this systematic review is to estimate the safety and efficacy of evocacelt.Methods:Only randomized controlled trials (RCT) will be included in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and PUBMED from July 2010 to July 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. The methodological quality including the risk of bias of the included studies will be evaluated using a modified assessment form, which is based on Cochrane assessment tool. Review Manager 5.3 software will be used for heterogeneity assessment, generating funnel-plots, data synthesis, subgroup analysis, and sensitivity analysis. We will use GRADE system to evaluate the quality of our evidence.Results:We will provide some more practical and targeted results investigating the effect and safety of evocalcet for SHPT on hemodialysis in the current meta-analysis.Conclusion:The stronger evidence about evocalcet effect and safety will be provided for clinicians and policymakers.Ethics and dissemination:Ethical approval will be unnecessary because the data being included in this systematic review come from published literature and there will be no concerns regarding privacy. Findings of this research will be disseminated in a peer-reviewed journal or conference presentations.OSF Registration number:DOI 10.17605/OSF.IO/N59RB.

Adenoma of the parathyroid gland in a young woman with chronic kidney disease: primary or tertiary hyperparathyroidism?

Clinical observation of a young woman with chronic kidney disease IV stage and hyperparathyroidism is presented. Ultrasound and99mTc-sestamibi scintigraphy of the anterior surface of the neck visualized a tumor of the left upper parathyroid gland. In a histological examination of distant education was diagnosed a solid parathyroid adenoma. The difficulty of differential diagnosis between primary and secondary/tertiary hyperparathyroidism in chronic kidney disease is discussed.

Recent advances in understanding and managing secondary hyperparathyroidism in chronic kidney disease.

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.