RNA-Seq-based transcriptomics analysis during the photodynamic therapy of primary cells in secondary hyperparathyroidism.

BACKGROUND: The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. RESULTS: In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM-receptor interaction, focal adhesion and protein digestion and absorption. Protein-protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. CONCLUSIONS: The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT.

A basidomycetous hydroxynaphthalene-prenylating enzyme exhibits promiscuity toward prenyl donors.

The fungal prenyltransferase ShPT from Stereum hirsutum was believed to prenylate 4-hydroxybenzyl alcohol and thereby be involved in the vibralactone biosynthesis. In this study, we demonstrate that hydroxynaphthalenes instead of benzyl alcohol or aldehyde were accepted by ShPT for regular C-prenylation in the presence of both dimethylallyl and geranyl diphosphate. Although the natural substrate of ShPT remains unknown, our results provide one additional prenyltransferase from basidiomycetes, which are less studied, in comparison to those from other sources. Furthermore, this study expands the chemical toolbox for regioselective production of prenylated naphthalene derivatives. KEY POINTS: •Basidiomycetous prenyltransferase •Biochemical characterization •A DMATS prenyltransferase prenylating hydroxynaphthalene derivatives.

Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease-Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients.

RATIONALE & OBJECTIVE: Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April 2017. STUDY DESIGN: New-user design within prospective cohort. SETTING & PARTICIPANTS: 2,596 new users of etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS). PREDICTORS: Baseline PTH, prior cinacalcet use, initial etelcalcetide dose. OUTCOME: Trajectories of etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after etelcalcetide initiation. ANALYTICAL APPROACH: Cumulative incidence methods for etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses. RESULTS: By August 2019, etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH ≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium < 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after etelcalcetide initiation. LIMITATIONS: Data are unavailable for provider dosing protocols, dose holds, or reasons for discontinuation. CONCLUSIONS: In the 12 months after etelcalcetide initiation, patients had large and sustained reductions in PTH levels. These results support the utility of etelcalcetide as an effective therapy to achieve the KDIGO-recommended guidelines for CKD-MBD markers in HD patients.

The rate, cost and outcomes of parathyroidectomy in the united states dialysis population from 2016-2018.

BACKGROUND: In end-stage kidney disease, patients may undergo parathyroidectomy if secondary hyperparathyroidism cannot be managed medically. This study was designed to estimate the parathyroidectomy rate in the United States (US) and to quantify changes in costs and other outcomes after parathyroidectomy. METHODS: This was a retrospective observational cohort study using US Renal Data System data for 2015-2018. Parathyroidectomy rates were estimated for adult hemodialysis and peritoneal dialysis patients alive at the beginning of 2016, 2017, and 2018 who were followed for a year or until parathyroidectomy, death, or transplant. Incremental differences in economic and clinical outcomes were compared before and after parathyroidectomy in adult hemodialysis and peritoneal dialysis patients who received a parathyroidectomy in 2016 and 2017. RESULTS: The rate of parathyroidectomy per 1,000 person-years decreased from 6.5 (95% CI 6.2-6.8) in 2016 to 5.3 (95% CI 5.0-5.6) in 2018. The incremental increase in 12-month cost after versus before parathyroidectomy was $25,314 (95% CI $23,777-$27,078). By the second month after parathyroidectomy, 58% of patients had a corrected calcium level < 8.5 mg/dL. In the year after parathyroidectomy (versus before), hospitalizations increased by 1.4 per person-year (95% CI 1.3-1.5), hospital days increased by 12.1 per person-year (95% CI 11.2-13.0), dialysis visits decreased by 5.2 per person-year (95% CI 4.4-5.9), and office visits declined by 1.3 per person-year (95% CI 1.0-1.5). The incremental rate per 1,000 person years for hematoma/bleed was 224.4 (95% CI 152.5-303.1), for vocal cord paralysis was 124.6 (95% CI 59.1-232.1), and for seroma was 27.4 (95% CI 0.4-59.0). CONCLUSIONS: Parathyroidectomy was a relatively uncommon event in the hemodialysis and peritoneal dialysis populations. The incremental cost of parathyroidectomy was mostly attributable to the cost of the parathyroidectomy hospitalization. Hypocalcemia occurred in over half of patients, and calcium and phosphate levels were reduced. Clinicians, payers, and patients should understand the potential clinical and economic outcomes when considering parathyroidectomy.

Modulation of cardiometabolic risk and CardioRenal syndrome by oral vitamin D3 supplementation in Black and White Southern Sahara residents with chronic kidney disease Stage 3: focus on racial and ethnic disparities.

OBJECTIVES: Several studies have shown that cholecalciferol supplementation (25OHD-S) in chronic kidney disease (CKD) improves kidney injury by reducing fibrosis-related vascular calcification and declining apoptosis-linked nephron damage. METHODS: The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeks versus in 2000 IU/d/24 weeks in CKD Stage 3 with serum 25OHD level < 20 ng/mL. The study was undertaken on 156 black subjects and 150 white subjects Southern Sahara (SS). All biomarkers of cardiometabolic (CMet) and cardiorenal (CRenal) syndrome, Renin-angiotensin-aldosterone system (RAAS) profile, secondary hyperparathyroidism (SHPT), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin T (cTnT) and atherogenicity risk were assessed by biochemical methods. Estimate glomerular filtration rate (eGFR) by chronic CKD-EPI equation formula. Total serum vitamin D by liquid chromatography-tandem mass spectrometry (MS). RESULTS: Vitamin D deficiency alters in the same manner CMet, CRenal, and others biomarkers in both groups SS; however, these disorders are more acute in blacks compared to whites SS. Oral 25OHD-S a highlighted improvement of eGFR drop, SHPT decrease, decline proteinuria, and cardiac failure risk (NT-proBNP and cTnT) attenuation. Concomitantly, 25OHD-S normalizes Renin, Aldosterone, and Angiotensin System (RAAS) activity. Nevertheless, homocysteine and Lp (a) do not modulate by 25OHD-S. CONCLUSIONS: The oral vitamin D3 supplementation, according the dose, and the treatment duration does not like in black-skinned people versus to white-skinned inhabitants, while the 02 groups are native to the same Saharan environment. It emerge that a high intermittent dose through an extensive supplementation (60,000 IU/36 weeks) was more effective in black subjects. At opposite, a lower dose during a short period supplementation is sufficient (2000 IU/24 weeks) in white subjects.

Long-Term Effect of Microwave Ablation on Patients Undergoing Hemodialysis for Moderate Secondary Hyperparathyroidism: A Retrospective Cohort Study.

OBJECTIVES: A previous 12-month study confirmed that microwave ablation (MWA) was effective for moderate secondary hyperparathyroidism (SHPT). A further analysis was performed in this study to evaluate the efficacy of MWA for moderate SHPT over an observational follow-up period of up to 60 months. METHODS: This was a retrospective cohort study of patients involved in a previous randomized controlled trial. Patients were divided into an MWA group (those who underwent MWA followed by drug therapy according to the patient's clinical situation) and a control group (those who received drug therapy only). The primary outcome was the composite endpoint. During the efficacy assessment phase, the two groups were compared in terms of the proportion of patients with intact parathyroid hormone (iPTH) levels <300 pg/ml and the differences in iPTH levels. RESULTS: Twenty-seven patients were included in this study: 13 in the MWA group and 14 in the control group. The median (interquartile range) follow-up periods of the MWA and control groups were 58 (54-60) and 58 (49-60) months, respectively. The proportion of patients with iPTH levels <300 pg/ml in the MWA group was slightly higher than that in the control group (6/13 [46.2%] versus 2/14 [14.3%], respectively; p = .08). Furthermore, iPTH levels in the MWA group were lower than in the control group during the efficacy assessment phase (411 ± 299 pg/ml versus 516 ± 369 pg/ml, respectively; p <.01). CONCLUSIONS: MWA helped to contain the necessary iPTH levels in patients undergoing hemodialysis for moderate SHPT in a 60-month timeframe.

Osteoblastic differentiation of bone marrow mesenchymal stem cells in uremic rats.

Severe secondary hyperparathyroidism (SHPT) represents a high turnover bone disease, osteitis fibrosa, but the pathogenesis of osteitis fibrosa remains to be fully elucidated. We examined the characteristics of the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts in uremic rats. We bred 5/6 nephrectomized (Nx) rats with a high phosphorus (P) diet to induce SHPT (Nx + HP), or Nx (Nx + ND) and normal rats (Nc + ND) fed a standard diet (ND). After 8 weeks, BMSCs were isolated from the femur and serum were analyzed. BMSCs underwent flow cytometric examination for the expression patterns of cell surface markers (CD90+, CD29+, CD45-, and CD31-). Serum creatinine (Cre) levels were significantly elevated in the Nx + NP rats compared with the Nc + NP rats. Cre levels in the Nx + HP rats were levels to those in the Nx + ND rats. Serum P and PTH levels were significantly elevated in the Nx + HP rats compared with the Nx + ND rats. Bone morphometrical analysis showed increases in both osteoid volume and eroded surfaces in the Nx + HP but not in the Nx + ND rats. The populations of harvested BMSCs were similar between all three groups. Alp, Runx2, Pth1r and Cyclin D1 mRNA expression in the BMSCs from the Nx + ND rats were significantly suppressed compared with those isolated from the Nc + ND groups. Alizarin red staining tended to be similar to the expression of these mRNA. These results suggest that the BMSCs differentiation into osteoblasts was disturbed in the uremic rats.

Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis.

BACKGROUND: Secondary hyperparathyroidism (sHPT), a complication of chronic kidney disease (CKD) characterized by persistently elevated parathyroid hormone (PTH), alterations in calcium-phosphorus homeostasis, and vitamin D metabolism, affects 50% of children receiving dialysis. A significant proportion of these children develop CKD-mineral and bone disorder (CKD-MBD), associated with an increased risk of fractures and vascular calcification. The standard of care for sHPT in children includes vitamin D sterols, calcium supplementation, and phosphate binders. Several agents are approved for sHPT treatment in adults undergoing dialysis, including vitamin D analogs and calcimimetics, with limited information on their safety and efficacy in children. The calcimimetic cinacalcet is approved for use in adults with sHPT on dialysis, but is not approved for pediatric use outside Europe. METHODS: This review provides dosing, safety, and efficacy information from Amgen-sponsored cinacalcet pediatric trials and data from non-Amgen sponsored clinical studies. RESULTS: The Amgen cinacalcet pediatric clinical development program consisted of two Phase 3 randomized studies, one Phase 3 single arm extension study, one open-label Phase 2 study, and two open-label Phase 1 studies. Effects of cinacalcet on PTH varied across studies. Overall, 7.4 to 57.1% of subjects who received cinacalcet in an Amgen clinical trial attained PTH levels within recommended target ranges and 22.2 to 70.6% observed a ≥ 30% reduction in PTH. In addition, significant reductions in PTH were demonstrated in all non-Amgen-supported studies. CONCLUSIONS: To help inform the pediatric nephrology community, this manuscript contains the most comprehensive review of cinacalcet usage in pediatric CKD patients to date.

The Role of Vitamin D in CKD Stages 3 to 4: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Deficiency of 25-hydroxyvitamin D (25[OH]D) is common in patients with chronic kidney disease stages 3 and 4 and is associated with poor outcomes. However, the evaluation and management of vitamin D deficiency in nephrology remains controversial. This article reports on the proceedings from a "controversies conference" on vitamin D in chronic kidney disease that was sponsored by the National Kidney Foundation. The report outlines the deliberations of the 3 work groups that participated in the conference. Until newer measurement methods are widely used, the panel agreed that clinicians should classify 25(OH)D "adequacy" as concentrations > 20ng/mL without evidence of counter-regulatory hormone activity (ie, elevated parathyroid hormone). The panel also agreed that 25(OH)D concentrations < 15ng/mL should be treated irrespective of parathyroid hormone level. Patients with 25(OH)D concentrations between 15 and 20ng/mL may not require treatment if there is no evidence of counter-regulatory hormone activity. The panel agreed that nutritional vitamin D (cholecalciferol, ergocalciferol, or calcifediol) should be supplemented before giving activated vitamin D compounds. The compounds need further study evaluating important outcomes that observational studies have linked to low 25(OH)D levels, such as progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality. We urge further research funding in this field.

Comparative efficacy and safety of paricalcitol versus vitamin D receptor activators for dialysis patients with secondary hyperparathyroidism: a meta-analysis of randomized controlled trials.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a severe complication for dialysis patients. Vitamin D receptor activators (VDRAs) are used to treat SHPT, but the comparative efficacy and safety between paricalcitol and other vitamin D receptor activators for management of SHPT in dialysis patients has been unproven. METHODS: We searched PubMed, Embase, and the Cochrane Library for the time period through June 2017 to identify randomized controlled trials that evaluated paricalcitol compared with other VDRAs for treatment of SHPT. The primary outcome was the percentage of patients with target reduction of intact parathyroid hormone (iPTH) from baseline. Secondary outcomes included incidences of hypercalcemia and hyperphosphatemia. The random-effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Eight studies (N = 759) were eligible for final inclusion. Compared with other VDRAs, no significant differences were found in the percentage of patients with target reduction of intact parathyroid hormone (iPTH) from baseline for paricalcitol treatment of SHPT in dialysis patients (RR, 1.01; 95% CI, 0. 87-1.18; p = 0.85). There were no differences in the incidence of hypercalcemia (RR, 0.95; 95% CI, 0.74-1.21; p = 0. 65) and hyperphosphatemia (RR, 0.94; 95% CI, 0.77-1.16; p = 0.58). CONCLUSIONS: The presently available evidence is insufficient to draw a conclusion regarding whether paricalcitol therapy has a comparative efficacy and safety over other VDRAs for treating dialysis patients with SHPT. Large-sample, well-conducted, high-quality RCTs with patient-level outcomes (i.e., mortality) are urgently needed.

Long-Term Therapy Outcomes When Treating Chronic Kidney Disease Patients with Paricalcitol in German and Austrian Clinical Practice (TOP Study).

Paricalcitol is approved for prevention and therapy of secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), with only short-term data in clinical routine settings. A 12-month observational study was conducted in Germany and Austria (90 centers, 761 patients) from 2008 to 2013. Laboratory values, demographical, and clinical data were documented in 629 dialysis patients and 119 predialysis patients. In predialysis patients, median intact parathormone (iPTH) was 180.0 pg/mL (n = 105) at the start of the study, 115.7 pg/mL (n = 105) at last documentation, and 151.8 pg/mL (n = 50) at month 12, with 32.4% of the last documented iPTH values in the KDOQI (Kidney Disease Outcomes Quality Initiative) target range. In dialysis patients, median iPTH was 425.5 pg/mL (n = 569) at study start, 262.3 pg/mL (n = 569) at last documentation, and 266.1 pg/mL (n = 318) at month 12, with 36.5% of dialysis patients in the KDOQI target range. Intravenous paricalcitol showed more homogenous iPTH control than oral treatment. Combined analysis of all dialysis patients indicated comparable and stable mean serum calcium and phosphate levels throughout the study. Clinical symptoms, such as itching, bone pain, and fatigue, were improved compared with study entry. The spectrum and frequency of adverse events mirrored the known pattern for patients on dialysis. Paricalcitol is efficacious and has a consistent safety profile in sHPT over 12 months.

Comparative Effectiveness of MRI, 4D-CT and Ultrasonography in Patients with Secondary Hyperparathyroidism.

Objective: Accurate preoperative localization of abnormal parathyroid glands is crucial for successful surgical management of secondary hyperparathyroidism (SHPT). This study was conducted to compare the effectiveness of preoperative MRI, 4D-CT, and ultrasonography (US) in localizing parathyroid lesions in patients with SHPT. Methods: We performed a retrospective review of prospectively collected data from a tertiary-care hospital and identified 52 patients who received preoperative MRI and/or 4D-CT and/or US and/or 99mTc-MIBI and subsequently underwent surgery for SHPT between May 2013 and March 2020. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each imaging modality to accurately detect enlarged parathyroid glands were determined using histopathology as the criterion standard with confirmation using the postoperative biochemical response. Results: A total of 198 lesions were identified intraoperatively among the 52 patients included in this investigation. MRI outperformed 4D-CT and US in terms of sensitivity (P < 0.01), specificity (P = 0.455), PPV (P = 0.753), and NPV (P = 0.185). The sensitivity and specificity for MRI, 4D-CT, and US were 90.91%, 88.95%, and 66.23% and 58.33%, 63.64%, and 50.00%, respectively. The PPV of combined MRI and 4D-CT (96.52%) was the highest among the combined 2 modalities. The smallest diameter of the parathyroid gland precisely localized by MRI was 8×3 mm, 5×5 mm by 4D-CT, and 5×3 mm by US. Conclusion: MRI has superior diagnostic performance compared with other modalities as a first-line imaging study for patients undergoing renal hyperparathyroidism, especially for ectopic or small parathyroid lesions. We suggest performing US first for diagnosis and then MRI to make a precise localization, and MRI proved to be very helpful in achieving a high success rate in the surgical treatment of renal hyperparathyroidism in our own experience.

Predictors of hyperkalemia after total parathyroidectomy in patients with drug-refractory secondary hyperparathyroidism.

Background: The purpose of this retrospective study was to explore the primary possible risk factors for the development of postoperative hyperkalemia after total parathyroidectomy with autotransplantation (TPTX + AT) in patients with drug-refractory secondary hyperparathyroidism (SHPT). Methods: The clinical data of 149 patients receiving maintenance dialysis for drug-refractory SHPT, who underwent TPTX + AT, were reviewed and analyzed. Demographic data, dialysis status, and laboratory test indices were collected from enrolled patients. According to the postoperative serum potassium level >5.3 mmol/L or not, they were divided into hyperkalemia group and non-hyperkalemia group. The differences in general clinical data and laboratory indicators between the two groups were compared; logistic regression analysis was performed to analyze the risk factors affecting the development of postoperative hyperkalemia in patients; receiver operating characteristic (ROC) subject workup curves were analyzed for the threshold values of postoperative hyperkalemia. Results: Of the 149 participants, 25 (16.78%) developed postoperative hyperkalemia after TPTX + AT. Univariate analysis suggested that dialysis duration, SHPT duration, dialysis modality, and preoperative alkaline phosphatase, blood potassium, and blood calcium levels were independently associated with the development of hyperkalemia after TPTX + AT. Univariate logistic analysis suggested that dialysis duration [odds ratio (OR) 1.18, 95% confidence interval (CI): 1.03, 1.35, P=0.014], preoperative blood potassium (OR 4.95, 95% CI: 2.05, 11.96, P<0.001), and preoperative blood calcium (OR 16.17, 95% CI: 1.36, 191.58, P=0.027) were 3 factors that predicted hyperkalemia after TPTX + AT. According to ROC curve analysis, the optimal cutoff point for dialysis duration was 8.5 years, the optimal cutoff level for preoperative blood potassium was 4.57 mmol/L, and the optimal cutoff level for preoperative blood calcium was 2.31 mmol/L. Of these 3 factors, preoperative blood potassium had a more balanced sensitivity, specificity, and optimal diagnostic efficacy. Conclusions: Patients with drug-refractory SHPT are prone to hyperkalemia after TPTX + AT. Duration of dialysis and preoperative blood potassium and blood calcium levels can help predict the development of postoperative hyperkalemia.

Prevalence and associated factors of secondary hyperparathyroidism after Roux-en-Y gastric bypass: A meta-analysis.

This study aimed to investigate the prevalence and factors associated with secondary hyperparathyroidism (SHPT) after Roux-en-Y gastric bypass (RYGB). We searched PubMed, EMBASE, and CENTRAL for relevant studies using search terms gastric bypass, RYGB and hyperparathyroidism. Thirty-four cohort studies with 4331 patients were incorporated into the final meta-analysis. Overall estimates of the prevalence of SHPT following RYGB were 39%. Subgroup analyses indicated the pooled prevalences of SHPT were 25%, 42%, 48%, and 54% for ≤1 year, >1 and ≤5 years, >5 and ≤10 years, and >10 years, respectively, after RYGB. Meta-regression showed that SHPT occurred was positively related to follow-up durations (p = 0.001). Additionally, SHPT prevalence was higher in studies in which calcium and vitamin D supplementation were considered inadequate than in those which were adequate (p = 0.002). SHPT is highly prevalent in individuals with obesity after RYGB. It seems to progress with time after surgery. Routine calcium and vitamin D supplementation post-RYGB together with targeted treatment of vitamin D deficiency, reasonable adjustment of the doses of supplementation with regular follow-up, and improved patient compliance, as well as long-term screening, are necessary to prevent the development of SHPT.

Effectiveness and Safety of Ultrasound-Guided Local Paricalcitol Injection in Treating Secondary Hyperparathyroidism in ESRD: A Retrospective Study.

PURPOSE: To compare the safety and efficacy of percutaneous paricalcitol injection with intravenously administered paricalcitol in treating parathyroid hyperplasia in patients with secondary hyperparathyroidism (SHPT). METHODS: This study was approved by the Ethics Committee of our institution. We retrospectively collected data on patients who received percutaneous paricalcitol injection (24 patients) and intravenously administered paricalcitol (22 patients) based on their intact parathyroid hormone (iPTH) level. Serum iPTH, calcium, phosphorus, and the volume of the parathyroid gland were measured at several indicated time points after treatment, and adverse events associated with the two treatments were evaluated. RESULTS: After 6 months of follow-up, we found that patients from the percutaneous injection group had significantly decreased levels of iPTH (from 1887.81 ± 726.81 pg/mL to 631.06 ± 393.06 pg/mL), phosphate (from 1.94 ± 0.36 mmol/L to 1.71 ± 0.34 mmol/L), and volume of the parathyroid gland (from 0.87 ± 0.50 cm3 to 0.60 ± 0.36 cm3), with relief from ostealgia within 48-72 h. In the intravenously administered group, the levels of iPTH decreased from 686.87 ± 260.44 pg/mL to 388.47 ± 167.36 pg/mL; while there was no significant change in phosphate levels, the volume of the parathyroid gland and ostealgia relief were observed at the end of follow-up. The serum calcium level did not significantly change, and no severe complications were observed in both groups. In vitro fluorescence-activated single cell sorting (FACS) analysis indicated that paricalcitol induced parathyroid cell apoptosis in a dose-dependent manner. CONCLUSIONS: Percutaneous paricalcitol injection is a selective treatment for SHPT in ESRD.

Efficacy and safety of intravenous paricalcitol treatment in Chinese hemodialysis patients: a real-world database analysis.

BACKGROUND: The aim of this retrospective observational study based on real-world data was to evaluate the efficacy and safety profile of paricalcitol in Chinese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT) in routine clinical practice. METHODS: From the Better Life for Future database, a total of 668 Chinese hemodialysis patients from 104 dialysis centers between January 2015 and May 2019 were included in the analysis set. Intact parathyroid hormone (iPTH), total serum calcium (Ca), phosphate (P), dosage of intravenous (IV) paricalcitol (Zemplar®) were analyzed and discussed via retrospective analysis of the database during the treatment. RESULTS: Patients were divided into five groups according to the duration of follow-up. Median iPTH levels decreased from 1,183 pg/mL at baseline to 676 pg/mL at the final visit, or 30.88% (P<0.0001). A total of 56.14% of patients had a ≥30% decrease and 29.34% of patients had a ≥50% decrease in iPTH level. Serum Ca levels shown significantly increased in the group of Month 12-24 (P=0.0479). Serum phosphate levels remained stable in all follow-up groups. The average dose of paricalcitol was 20±9 µg/week. The total dose of paricalcitol and baseline iPTH were negatively correlated with the decrease in iPTH levels. CONCLUSIONS: This is the first national retrospective real-world observational study since intravenous paricalcitol is available in China since 2014. This study demonstrates the use of paricalcitol as an effective and well-tolerated treatment for the control of PTH during its use in routine practice.

A Systematic Review and Meta-analysis of Efficacy and Safety of Calcimimetic Agents in the Treatment of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease.

BACKGROUND: Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, but there is no detailed description of the advantages and disadvantages of calcimimetics agents of SHPT in CKD patients. We tried to pool the published data to verify the effectiveness of calcimimetics agents and to compare the advantages and disadvantages of cinacalcet compared with control in the treatment of SHPT in CKD patients. METHODS: We included eligible studies of published papers from January 1st, 2000 to December 31st, 2020 in Medline, Pubmed and Web of science databases, and the data were extracted for this meta-analysis. RESULTS: Twenty-seven studies were eligible, and all the included studies were randomized controlled trials (RCT) including patients treated with long-term dialysis. The results indicated that calcimimetic agents can reduce the parathyroid hormone (PTH, pg/ml) level (WMD = -178.22, 95% CI: -238.57, -117.86, P < 0.00001), calcium (Ca, mg/dl) level (WMD = -0.71, 95% CI: -0.86, -0.55, P < 0.00001), phosphorus (P, mg/dl) level (WMD = -0.32, 95% CI: -0.55, -0.08, P = 0.008), calcium-phosphorus product level (WMD = -7.73, 95% CI: -9.64, -5.82, P < 0.00001). Calcimimetic agents increased the bone alkaline phosphatase (BSAP, ng/ml) levels and rate of achieving target PTH, and reduced osteocalcin levels and the rate of parathyroidectomy. Calcimimetic agents increased the total adverse events' rate, the rate of hypocalcemia and gastrointestinal side effects (nausea, vomiting, abdominal pain and diarrhea), but there was no significant difference in serious adverse events between the calcimimetic agent group and control group. CONCLUSION: Calcimimetic agents can reduce the PTH level, Ca level, P level, calcium-phosphorus product level and do not increase serious adverse events.

Ultrasound-Guided Radiofrequency Ablation: A New Attempt to the Treatment of Refractory Hyperparathyroidism Secondary to Chronic Kidney Disease.

INTRODUCTION: To evaluate clinical application value of radiofrequency ablation (RFA) in refractory hyperparathyroidism secondary to chronic kidney disease (CKD) by comparing the safety and effectiveness of RFA with parathyroidectomy with autotransplantation (PTX + AT). METHODS: A retrospective study was conducted on 80 patients with CKD with refractory hyperparathyroidism who underwent RFA or PTX + AT between January 2018 and February 2021. Serum parathyroid hormone (PTH), calcium, and phosphorus levels, complications, clinical symptoms, visual analogue scale (VAS) scores, hospital stay duration, and postoperative recurrence rate were compared between the 2 groups. RESULTS: Serum PTH, phosphorous, and calcium levels and the VAS scores improved significantly after RFA and PTX + AT (P < 0.05). Significant differences were observed between the 2 groups in postoperative (day 1 and week 1) levels of serum PTH and postoperative day 1 of serum calcium and phosphorus levels (P < 0.05), with more pronounced reduction after PTX + AT. Although the incidence of recurrent laryngeal nerve (RLN) injury was slightly higher in the RFA group compared with the PTX + AT group (26.67% vs. 16.67%; P > 0.05), RFA markedly decreased the risk of severe hypocalcemia (SH) (20% vs. 46.67%; P < 0.05) and shortened hospital stay (7.53 ± 2.67 days vs. 12.13 ± 3.86 days; P < 0.05). The 6-month recurrence rate was 23.3% (7 of 30) in the RFA group and 30% (9 of 30) in the PTX + AT group (P > 0.05). CONCLUSION: RFA can treat refractory secondary hyperparathyroidism (SHPT) with similar clinical efficacy as surgery and achieve faster recovery and a lower incidence of postoperative SH.

Uremic leontiasis ossea: distinctive imaging features allow differentiation from other clinical causes of leontiasis ossea.

Skeletal changes are a common complication in patients with chronic kidney disease and traditionally labelled as renal osteodystrophy. Uremic leontiasis ossea is a rare and severe form of renal osteodystrophy with characteristic overgrowth of the craniofacial bones. Imaging, in particular computed tomography, is valuable for the diagnosis and management of such rare condition. Uremic leontiasis ossea has distinctive imaging features with significant overgrowth of the jaw and characteristic internal serpiginous tunneling. The recognition of its radiological appearance and abrupt management are essential to avoid its devastating esthetic and functional impairments.

Application of nanocarbon negative imaging technology in surgery for secondary hyperparathyroidism.

BACKGROUND: Our objective is to evaluate the application values and effects of nanocarbon negative imaging technology in surgery for patients with the fifth stage of chronic kidney disease complicated with secondary hyperparathyroidism (SHPT). METHODS: Eighty-nine patients with SHPT in the fifth stage of chronic kidney disease admitted to the Department of Thyroid and Breast Surgery at the Affiliated Hospital of Nantong University between January 2018 and August 2020 were selected. All patients underwent total parathyroidectomy (tPTX) and were randomly divided into a group receiving nanocarbon (observation group; group A) and a control group (group B). Patients were followed up for 6 months after surgery and several observation indexes were compared and analyzed. RESULTS: Compared with the control group, the parathyroid glands in the observation group treated with nanocarbon were more clearly exposed, and better performances were seen in the operation time, blood loss, and recovery rate of bone pain (P<0.05). The postoperative follow-up blood intact parathyroid hormone level (iPTH) and recurrence rate control were also improved in the observation group and the differences were statistically significant (P<0.05). CONCLUSIONS: In the fifth stage of chronic kidney disease with SHPT, the application of nanocarbon negative imaging technology can significantly reduce the recurrence rate of hyperparathyroidism, improve the surgical effect, and improve the long-term quality of life and survival rate of patients.