Severe Severe Secondary Hyperparathyroidism Research Articles

#1807 Use of teriparatide to prevent severe hypocalcemia after parathyroidectomy in dialysis-dependent patients: a feasibility study

Abstract Background and Aims Hungry bone syndrome is a common postoperative complication after parathyroidectomy (PTx) for severe secondary hyperparathyroidism (SHPT). We aimed to conduct a feasibility study to assess the potential impact of teriparatide on the course of postoperative hypocalcemia after PTx in dialysis-dependent patients. Method We performed a randomized controlled pilot study in 20 dialysis-dependent patients with severe SHPT undergoing total parathyroidectomy with autotransplantation of parathyroid tissue. Patients were randomized to receive either 20 mcg teriparatide (Forsteo) subcutaneously on day 1 after surgery in addition to standard postoperative care (n=11) or standard postoperative care alone (n=9). Severe postoperative hypocalcemia was defined as an ionized serum calcium level of less than 0.8 mmol/l during the first 3 days after surgery. Results Patients in the two groups did not differ in terms of pre- and postoperative laboratory data, including PTH, corrected total calcium, ionized calcium and alkaline phosphatase levels – Table 1. Severe hypocalcemia was observed in 6 patients in the teriparatide group (55%) and in 4 patients (44%) in the control group (p=0.99). The proportion of patients with symptoms of hypocalcemia was higher in patients not receiving teriparatide (67% vs 27%, p=0.17), although these differences did not reach statistical significance. All post-PTx patients received standard supplementation according to local protocol, including calcium carbonate 20 gr/day, active vitamin D 2 mcg/day per os, and intravenous calcium gluconate supplementation on demand for symptoms of hypocalcemia (e.g. numbness, tingling, or cramps). Total elemental calcium requirement after surgery (which may serve as a surrogate for the severity of hungry bone syndrome) was higher in patients receiving standard treatment alone (41 [Q1-Q3: 33; 49] grams per hospitalization vs 33 [Q1-Q3: 25; 40] grams in the teriparatide group, p=0.0375) – Fig. 1. The total length of hospital stay was 4 ± 1 days in teriparatide group and 5 ± 2 in control group, p=0.36. Conclusion In dialysis-dependent patients after PTx, we observed a trend towards an alleviation of postoperative hypocalcemia after single injection of teriparatide in addition to routine care. Further studies with larger sample sizes are needed to confirm these preliminary results.

MO816: Bone Turnover Markers as Risk Factors of Severe Hypocalcemia After Parathyroidectomy for Secondary Hyperparathyroidism

Abstract BACKGROUND AND AIMS Hungry bone syndrome is a common postoperative complication after parathyroidectomy (PTx) for severe secondary hyperparathyroidism (SHPT). We aimed to evaluate whether preoperative levels of serum alkaline phosphatase (AP) and β-crosslaps (CTX) are associated with the development of severe hypocalcemia after PTx for SHPT in dialysis-dependent patients. METHOD The retrospective study included 127 severe SHPT dialysis-dependent patients who underwent subtotal (SPTx) or total parathyroidectomy with autotransplantation of parathyroid tissue (PTx + AT) in a single high-volume centre of endocrine surgery between 2011 and 2014. Severe postoperative hypocalcemia was defined as an ionized serum calcium level <0.9 mmol/L on a day 3 after surgery. RESULTS Severe hypocalcemia was observed in 83 (65.4%) patients after PTx. Comparing to those with mild hypocalcemia, hypoCa patients were significantly younger (mean age 44.2 ± 11.3 years versus 49.7 ± 10.4 years in a non-hypoCa group; P = .0089). Patients in two groups did not differ in terms of gender (P = .198), dialysis vintage (P = .24) and type of surgery (TPTx + AT or SPTx; P = .127). Preoperative PTH level was significantly higher in hypoCa group comparing to non-hypo Ca group [134 (Q1–Q3: 103–190) pmol/L versus 93.9 (Q1–Q3: 74.6–124.3) pmol/L, respectively; P < .0001]. In univariate analysis preoperative AP level was associated with the risk of postoperative severe hypocalcemia [363.2 (Q1–Q3: 180.9–726.3) IU in hypoCa group versus 142.1 (Q1–Q3: 97.2–223.7) IU in non-hypoCa group; P < 0.0001) (Figure 1). AP level above the cut-off value of 238.5 IU/L caused a 5-fold increase risk of severe hypocalcemia. We observed a moderate negative correlation between preoperative AP level and serum ionized calcium level on the third postoperative day after PTx {ρ = –0.637 [95% confidence interval (95% CI) –0.51 to –0.74]; P < .0001}. In contrast, preoperative CTX level was not associated with postoperative severe hypocalcemia [5.34 (Q1–Q3: 4.06–6.03) µg/L in hypoCa group versus 4.6 (Q1–Q3: 3.42–5.69) µg/L in non-hypoCa group; P = .191] (Figure 2). Moreover, the correlation between preoperative AP and CTX levels was weak, even though it was statistically significant [ρ = 0.27 (95% CI 0.08–0.44); P = .006]; and we observed no statistically significant correlation between preoperative CTX and PTH levels (P = .07). The multivariate logistic regression revealed AP level as the only independent risk factor of severe hypocalcemia development after PTx [ОR 1.006 (95% CI 1.002–1.009) per each IU; P = .005]. CONCLUSION We identified serum AP level, but not CTX, as an independent risk factor of severe hypocalcemia development after surgical treatment of SHPT. The correlation between CTX and other bone turnover markers (PTH, AP) is weak in dialysis-dependent patients with severe SHPT.

POS-997 PARATHYROIDECTOMY VERSUS ORAL CINACALCET ON CARDIOVASCULAR PARAMETERS AND QUALITY OF LIFE IN DIALYSIS PATIENTS WITH SEVERE SECONDARY HYPERPARATHYROIDISM (PROCEED) - A PROSPECTIVE RANDOMIZED TRIAL

Global kidney clinical practice guidelines suggested parathyroidectomy for dialysis patients with severe secondary hyperparathyroidism (SHPT) that fail to respond to medical therapy. This study aimed to evaluate the effects of oral cinacalcet versus total parathyroidectomy with forearm autografting (PTx-FA) on left ventricular (LV) mass index, coronary arteries and heart valves calcium scores, aortic stiffness and health-related quality of life (HRQOL) measures in dialysis patients with severe SHPT refractory to vitamin D analog.

Association of plasma neutrophil gelatinase-associated lipocalin with parameters of CKD-MBD in maintenance hemodialysis patients.

Neutrophil gelatinase-associated lipocalin (NGAL) is not only a biomarker of kidney injury but also a bone-derived factor involved in metabolism. We aimed to explore relationships between plasma NGAL and chronic kidney disease-mineral bone disorder (CKD-MBD) parameters in maintenance hemodialysis (MHD) patients. First, a cross sectional observational study, including 105 MHD patients, was conducted to explore relationships between plasma NGAL levels and CKD-MBD parameters. Second, impact of parathyroidectomy and auto-transplantation (PTX + AT) on plasma NGAL was investigated in 12 MHD patients with severe secondary hyperparathyroidism (SHPT). According to Spearman correlation analysis, plasma NGAL levels were positively correlated with female (r = 0.243, P = 0.012), vintage (r = 0.290, P = 0.003), Klotho (r = 0.234, P = 0.016), calcium(Ca) (r = 0.332, P = 0.001), alkaline phosphatase (ALP) (r = 0.401, P < 0.001) and intact parathyroid hormone (iPTH) (r = 0.256, P = 0.008); while inversely correlated with albumin(Alb) (r = - 0.201, P = 0.039). After adjusting for age, sex, vintage, Alb and all parameters of CKD-MBD(Ca, P, lg(ALP), lg(iPTH), Klotho and fibroblast growth factor 23(FGF23)), lg(NGAL) were positively correlated with Ca (r = 0.481, P < 0.001), P (r = 0.336, P = 0.037), lg(ALP) (r = 0.646, P < 0.001) in Partial correlation analysis; further multiple linear regression analysis showed same positive associations between lg(NGAL) and Ca (β = 0.330, P = 0.002), P (β = 0.218, P = 0.037), lg(ALP) (β = 0.671, P < 0.001). During the 4-7days after PTX + AT, plasma NGAL decreased from 715.84 (578.73, 988.14) to 688.42 (660.00, 760.26) ng/mL (P = 0.071), Klotho increased from 496.45 (341.73, 848.30) to 1138.25 (593.87, 2009.27) pg/mL (P = 0.099). Plasma NGAL levels were positively associated with ALP in MHD patients; and downtrends were shown after PTX + AT in patients with severe SHPT. These findings suggest that NGAL is a participant in CKD-MBD under MHD condition.

A short-term non-randomized controlled study of ultrasound-guided microwave ablation and parathyroidectomy for secondary hyperparathyroidism

Background To compare the short-term clinical outcomes of ultrasound-guided microwave ablation (MWA) and parathyroidectomy (PTX) for severe secondary hyperparathyroidism(SHPT). Methods In a prospective multi-center study, we compared the outcomes of MWA and PTX for severe SHPT. The outcome measures were case rate of successful treatment, improvement of clinical symptoms, incidence of complications, and differences in treatment parameters and costs between the two groups. Results A total of 167 eligible patients were included in the study, of which 79 underwent MWA and 88 underwent PTX. There was no significant difference in rate of successful treatment between the MWA and PTX groups (χ2=2.299, p = 0.125). However, the MWA group showed significantly lower range of intact parathyroid hormone (iPTH) decrease than the PTX group (t=−2.352, p = 0.023). Postoperative clinical symptoms improved in both groups, with no significant difference between the two groups (p > 0.05). Postoperative hypocalcemia was significantly more common in the PTX group (p < 0.05). The operative time, incision and postoperative pain of the MWA group were significantly better than those of the PTX group (p < 0.05), while postoperative recurrent laryngeal nerve injury and hematoma showed no significant difference between the two groups (p > 0.05). The cost of MWA was significantly less than PTX (p = 0.000). Conclusions Both MWA and PTX are effective and safe for severe secondary hyperparathyroidism. PTX is more thorough and traumatic, while MWA is minimally invasive and postoperative iPTH is more consistent with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendation.

High ankle-brachial index predicts cardiovascular events and mortality in hemodialysis patients with severe secondary hyperparathyroidism.

Introduction:Vascular calcification related to severe secondary hyperparathyroidism (SHPT) is an important cause of cardiovascular and bone complications, leading to high morbidity and mortality in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). The present study aimed to analyze whether ankle-brachial index (ABI), a non-invasive diagnostic tool, is able to predict cardiovascular outcomes in this population.Methods:We selected 88 adult patients on HD for at least 6 months, with serum iPTH>1,000pg/mL. We collected clinical data, biochemical and hormonal parameters, and ABI (sonar-Doppler). Calcification was assessed by lateral radiography of the abdomen and by simple vascular calcification score (SVCS). This cohort was monitored prospectively between 2012 and 2019 for cardiovascular outcomes (death, myocardial infarction (MI), stroke, and calciphylaxis) to estimate the accuracy of ABI in this setting.Results:The baseline values were: iPTH: 1770±689pg/mL, P: 5.8±1.2 mg/dL, corrected Ca: 9.7±0.8mg/dL, 25(OH)vit D: 25.1±10.9ng/mL. Sixty-five percent of patients had ABI>1.3 (ranging from 0.6 to 3.2); 66% had SVCS≥3, and 45% aortic calcification (Kauppila≥8). The prospective evaluation (51.6±24.0 months), provided the following cardiovascular outcomes: 11% of deaths, 17% of nonfatal MI, one stroke, and 3% of calciphylaxis. After adjustments, patients with ABI≥1.6 had 8.9-fold higher risk of cardiovascular events (p=0.035), and ABI≥1.8 had 12.2-fold higher risk of cardiovascular mortality (p=0.019).Conclusion:The presence of vascular calcifications and arterial stiffness was highly prevalent in our population. We suggest that ABI, a simple and cost-effective diagnostic tool, could be used at an outpatient basis to predict cardiovascular events in patients with severe SHPT undergoing HD.

Clinical characteristics of 10 patients with uremic tumoral calcinosis

Objective: To analyze the clinical characteristics of patients with uremic tumoral calcinosis (UTC). Methods: A total of 10 patients with UTC were enrolled in this study, who were admitted in the Department of Nephrology, China-Japan Friendship Hospital and Beijing Chuiyangliu Hospital from March 2013 to February 2019. Results: The average age of 4 male and 6 female patients on regular hemodialysis was (39.90±8.57) years. The average dialysis duration was(5.90±2.57) years. Three patients presented as single lesion of one joint, the other 7 patients as involvement of multiple large joints. Serum calcium was elevated in 2 patients,both over 2.75 mmol/L. Serum hyperphosphatemia was seen in all patients with average level 2.22 (1.94,2.44) mmol/L. Serum intact parathyroid hormone (iPTH) was remarkably increased in 9 patients with average level 1 348.0(854.8,1 800.0) ng/L, while only 1 patient reported slight elevation (92.4 ng/L).High-sensitivity C-reactive protein increased in all 10 patients with average 35.81 (17.60,74.20) mg/L. The imaging findings before treatment suggested that a large number of irregular masses of calcification shadows deposited in the soft tissue adjacent to the joints. The outlines of calcification were clear without significant bone absorption. Nine patients with severe secondary hyperparathyroidism (SHPT) were treated with parathyroidectomy, resulting in lesions diminishing or even disappearing. A total of 32 parathyroid glands were resected, and pathological results showed that 7 parathyroids were diffuse hyperplasia, 11 as diffuse/nodular hyperplasia, the rest 14 as nodular hyperplasia. At least one hyperplastic parathyroid gland was seen in each patient. Only 1 patient received medical therapy yet no obvious improvement was observed. Conclusion: UTC is a rare complication in patients on regular hemodialysis, which is usually associated with severe SHPT. Parathyroid surgery may improve the clinical outcome.

P1428PERSISTENT HUNGRY BONE SYNDROME AND HYPOPARATHYROIDISM AFTER PARATHYROIDECTOMY FOR SECONDARY HYPERPARATHYROIDISM: ARE THERE RISK FACTORS?

Abstract Background and Aims Hungry bone syndrome (HBS) and postoperative hypoparathyroidism both are important postoperative complications after parathyroidectomy (PTx) for severe secondary hyperparathyroidism (SHPT). There is still a lack of data in the literature concerning associated risk factors of the prolonged HBS and hypoparathyroidism after PTx. We aimed to explore the risk factors for HBS and postoperative persistent hypoparathyroidism development in a long-term period after surgery. Method We performed a retrospective analysis of 55 severe SHPT patients who underwent subtotal PTx or total PTx+AT in our clinic between 2011 and 2015 with follow-up period not less than 12 months. A general cohort was divided into subgroups according to their laboratory parameters in a year after PTx. Prolonged HBS was defined as a total serum calcium concentration less than 2,1 mmol/l after 1 year from surgery. Postoperative hypoparathyroidism was defined as a iPTH value less than 10 pg/mL after one year from surgery. Results In terms of prolonged HBS persistence a general cohort of 55 patients was divided into two subgroups: a HBS group of 27 patients (49,1%) with mean age of 45,6 ± 9,02 years and a non-HBS group of 49,6 patients (50,9%) with mean age of 45,6 ± 10,8 years. Mean dialysis vintage for HBS and non-HBS groups was 107,8 ± 52,4 and 97,4± 54,5 months, respectively. The PTH level dropped significantly in both groups on the 1st day after surgery when compared with preoperative values: from 134 [92,7-186] to 5,0 [2,1–17,7] pmol/l in non-HBS group (p&amp;lt;0,001) and from 126 [101-223] to 4,1 [1,5-14,5] pmol/l in HBS group (p&amp;lt;0,001). The immediate ionized calcium levels also decreased significantly in both groups: from 1,26 [1,2-1,3] to 0,89 [0,79-1,09] in non-HBS group (p&amp;lt;0,001), and from 1,2 [1,11-1,29] to 0,88 [0,8-1,0] in HBS group (p&amp;lt;0,001). In univariate analysis the postoperative iPTH showed no significant difference between the HBS and non-HBS groups (p= 0,614) as well as ionized Ca level (p= 0,5653), difference of PTH before/after surgery (ΔPTH) (p= 0,9133), age (p= 0,2575) and dialysis vintage (p= 0,6165). Neither gender (RR 0,75 [0,44; 1,277]; p = 0.4088), nor type of surgery (RR 0,81 [0,45; 1,456]; p = 0.5815) were associated with the long-term HBS persistence. For 51 patients data of iPTH level in a 1 year after PTx were available; 21 patients (41,2 %) were included in the postoperative persistent hypoparathyroidism-positive group (hypoPT-positive), and 30 patients (58,8%) were included in the postoperative persistent hypoparathroidism-negative (hypoPT-negative) group. In both hypoPT-positive and hypoPT-negative groups postoperative iPTH levels were decreased after surgery with significant difference being compared between groups (1,0 [0,8-2,5] vs 12,6 [3,7-17,7] pmol/l, respectively; p= 0,0001). We observed a moderate positive correlation between iPTH levels on the 1st postoperative day and in a 1 year after PTx (ρ=0,548 [95% CI 0,314; 0,72]; p&amp;lt;0,0001). Type of surgery was not associated with increased risk of prolonged hypoparathyroidism (RR=1.03 [0,569; 1,866]; p=0.922). Conclusion Prolonged persistence of HBS and postoperative hypoparathyroidism are common after PTx in patients with SHPT regardless the type of surgery. Neither laboratory (postoperative iPTH, ΔPTH, ionized Ca), nor demographic (gender, age, dialysis vintage) factors were not associated with HBS persistence in a long-term period after PTx. Only serum iPTH level on the 1st day after PTx is associated with prolonged hypoparathyroidism after surgery.

Evaluation of the association of Wnt signaling with coronary artery calcification in patients on dialysis with severe secondary hyperparathyroidism

BackgroundPatients with end-stage renal disease have a higher risk of death from cardiovascular events, which can be mainly attributed to coronary artery calcification (CAC). Wnt signaling is involved in vascular development and may play a role in vascular calcification. This study aimed to evaluate CAC prevalence in patients on dialysis with severe secondary hyperparathyroidism (SHPT) and identify CAC risk factors.MethodsThe study is a retrospective analysis of the severe hyperparathyroidism registration study that prospectively recruited patients on dialysis with severe SHPT who were candidates for parathyroidectomy, from October 2013 to May 2015. CAC and bone mineral density (BMD) were measured. Demographic and clinical data including calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, Dickkopf-related protein 1 (DKK1), and sclerostin levels were analyzed. CAC scores were reported in Agatston units (AU).ResultsA total of 61 patients were included in this study. No CAC, mild CAC (<100 AU), moderate CAC (>100 AU), and severe CAC (>400 AU) were observed in 4.9%, 11.4%, 14.8%, and 68.9% of patients, respectively. DKK1 and sclerostin were not associated with CAC. In univariate analysis, CAC was significantly correlated with age, sex (male), total cholesterol, and intravenous pulse calcitriol (p<0.05). CAC was not inversely correlated with the BMD, T scores, or Z scores of the femoral neck (p>0.05). In multivariate analysis, the stepwise forward multiple linear regression revealed that CAC was associated with age, male sex and intravenous pulse calcitriol (p<0.05). Furthermore, serum sclerostin was positively correlated with the BMD of the femoral neck but negatively associated with intact parathyroid hormone (p<0.05). Serum sclerostin was significantly associated with severely low bone mass with Z-scores<-2.5 of the femoral neck, even when adjusted for serum intact parathyroid hormone, vitamin D status, dialysis pattern, sex, and DKK-1 (p<0.05).ConclusionsThe patients on dialysis with severe SHPT have a high prevalence of vascular calcification. Although the Wnt signaling pathway could play a role in hyperparathyroid bone disease, CAC may be mainly due to the treatment modality rather than the Wnt signaling pathway associated bone metabolism in patients on dialysis with severe SHPT.

SAT-066 EFFECTS OF PARATHYROIDECTOMY ON NOCTURNAL NON-DIPPING HEART RATE IN STAGE 5 CKD PATIENTS

In healthy population 24-hour heart rate (HR) displays a circadian pattern, peaking shortly after waking and falling during the night, a phenomenon known as “dipping”. Non-dipping HR is defined as nighttime HR decreased less than 10% as compared to daytime readings, which is an independent risk factor for increased cardiovascular diseases (CVD) and all-cause mortality. It is well known that patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) have high risk of CVD and mortality, however, the associations between CKD-MBD and non-dipping HR remain uncertain. Here we evaluated the features of 24-hour HR in stage 5 chronic kidney disease (CKD) and the effects of parathyroidectomy (PTX) on HR circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients. The cross-sectional study included 213 stage 5 CKD patients and 96 controls. A prospective follow-up study was conducted in 47 PTX patients. Blood examinations and 24-hour Holter monitoring were measured. HR in each hour, daytime (8:00 AM-19:59 PM) and nighttime (20:00 PM-7:59 AM) mean HR values were recorded. Night/day HR ratio was calculated as nighttime/daytime ratio of heart rate, when greater than 0.90 could be considered as non-dipping HR. Stage 5 CKD patients and healthy controls were matched for age and sex. Compared with controls, CKD patients had higher blood pressure, lower body mass index (BMI), hemoglobin, hematocrit, serum albumin and total cholesterol values. In addition, stage 5 CKD group had higher circulating adjusted calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) levels. Stage 5 CKD patients display higher 24-hour, daytime and nighttime mean HR than controls. Night/day HR ratio in controls and CKD patients were 0.81±0.080, 0.91±0.075 respectively (P＜0.0001) (Table 1). Night/day HR ratio had closely positive correlations with baseline serum Ca, iPTH and ALP, while negatively related with serum urea and albumin levels. In CKD patients, the dipping patterns of 24-hour HR were shallower in both non-PTX and PTX group, especially in severe SHPT patients(Figure 1). After PTX (median follow-up interval: 11.84±11.33 months), the non-dipping HR pattern was reversed in severe SHPT patients, and Night/day HR ratio decreased from 0.92±0.077 to 0.88±0.075 (P=0.01) (Figure 2). Twenty four hour heart rate in stage 5 CKD patients displayed non-dipping pattern, mainly due to increased nighttime HR. Severe SHPT patients have more serious non-dipping HR, which could be reversed by parathyroidectomy. Rhythm abnormalities of heart rate are suggested to be taken seriously and treated effectively in order to decrease CVD and all-cause mortality in CKD-MBD patients.

Parathyroidectomy decreases serum intact parathyroid hormone and calcium levels and prolongs overall survival in elderly hemodialysis patients with severe secondary hyperparathyroidism.

The objective of this study was to assess the effect of parathyroidectomy (PTX) treatment on prolonging overall survival (OS) as well as decreasing levels of intact parathyroid hormone (iPTH), calcium (Ca), and phosphorus (P) in elderly hemodialysis patients with severe secondary hyperparathyroidism (SHPT). A total of 304 elderly hemodialysis patients with severe SHPT were consecutively enrolled in this cohort study. According to whether PTX operations were applied, patients were classified into PTX group (N=112) and Control group (N=192) and were followed up for 3years. Mortality rate and OS were evaluated, and iPTH, Ca, and P levels were recorded. Compared to control group, increased iPTH (P<0.001), higher Ca (P=0.003), elevated AST (P=0.022), and lower Hb (P=0.049) concentrations were observed in the PTX group at baseline. The 1-year mortality (P<0.001), 2-year mortality (P<0.001), and 3-year mortality (P<0.001) was reduced in PTX group compared to Control group, and PTX was correlated with prolonged OS (P<0.001). Multivariate Cox's regression analysis further revealed that PTX treatment (P<0.001, HR=0.177) was an independent factor for better OS. Moreover, patients in PTX group had decreased iPTH (P<0.05) and Ca (P<0.05) levels compared to Control group at M1-M36, while no difference was found in serum P level between the two groups at M1-M36. Parathyroidectomy decreases iPTH and Ca levels, and it associates with favorable survival in elderly hemodialysis patients with severe SHPT.

Effects of parathyroidectomy on blood bone markers and heart rate variability in patients with stage 5 chronic kidney disease.

Decreased heart rate variability (HRV) is closely related to abnormal cardiac autonomic nervous function, especially sympathetic hyperactivity, which intensifies the risk of cardiovascular events and sudden death. HRV parameters are lower in chronic kidney disease (CKD) and parathyroidectomy (PTX) can improve these abnormalities in severe secondary hyperparathyroidism (SHPT) patients. However, few studies have evaluated correlations between circulating bone markers and HRV in CKD patients. We conducted a cross-sectional study including 134 stage 5 CKD patients with 100 controls and a prospective study of 29 PTX patients with follow-up. Circulating bone biomarkers included: (1) intact parathyroid hormone (iPTH) as bone remodeling regulator; (2) bone-specific alkaline phosphatase (BAP), representing bone formation; (3) tartrate-resistant acid phosphatase 5b (TRACP-5b), indicating bone resorption; and (4) bone-derived hormone, fibroblast growth factor 23 (FGF23). Stage 5 CKD patients had higher circulating iPTH, BAP, TRACP-5b, and FGF23 than controls and these bone markers were significantly elevated in SHPT patients. Baseline iPTH, BAP, and lnFGF23 were independently associated with HRV in CKD patients. After PTX with a follow-up (median interval: 6.7months), high blood iPTH, BAP, TRACP-5b, FGF23, and attenuated HRV were ameliorated. Furthermore, improved HRV indices were associated with reduced iPTH, BAP, TRACP-5b, and FGF23. Circulating bone markers are correlated with HRV in CKD 5 patients and PTX can improve decreased HRV, which are associated with corrected bone markers in severe SHPT patients. Thus, we propose that PTH increases sympathetic tone and both high circulating PTH levels and sympathetic hyperactivity increase bone turnover, and that the products of bone turnover influence HRV.

Effects of Parathyroidectomy on Plasma iPTH and (1-84) PTH Levels in Patients with Stage 5 Chronic Kidney Disease.

Currently, the second-generation intact parathyroid hormone (iPTH) assay is commonly used for measuring PTH levels. The iPTH assay detects both full-length (1-84)PTH and (7-84)PTH fragments, which have antagonistic effects on (1-84)PTH in bones and kidneys. The third-generation PTH assay is specific for (1-84)PTH. This study examined the features of different PTH fragments in stage 5 chronic kidney disease (CKD) and the effects of parathyroidectomy (PTX) on the above markers in severe secondary hyperparathyroidism (SHPT) patients. The cross-sectional study included 262 stage 5 CKD patients and 90 controls. A prospective follow-up study was then conducted in 34 PTX patients. Second- and third-generation assays were used to measure plasma iPTH and (1-84)PTH levels, respectively. Circulating (7-84)PTH levels were calculated by subtracting the (1-84)PTH value from the iPTH value. Different plasma PTH fragments were higher, and (1-84)PTH/iPTH was lower in CKD patients than in controls. Plasma (1-84)PTH and (7-84)PTH concentrations increased as iPTH levels increased, and (7-84)PTH increased more evidently. Plasma iPTH, (1-84)PTH and (7-84)PTH levels were 1530.5 (885.0-2111.5) pg/ml, 683.1 (431.4-1018.0) pg/ml, and 739.3 (452.6-1261.0) pg/ml, respectively, in PTX patients. Plasma iPTH, (1-84)PTH and (7-84)PTH concentrations decreased considerably, and the (1-84)PTH/iPTH ratio increased after PTX (median follow-up interval: 10.9 months). Stage 5 CKD patients had higher plasma levels of different PTH fragments, and lower (1-84)PTH/iPTH ratio. PTX could significantly reverse these abnormalities in severe SHPT patients. The iPTH assay overestimated the function of the parathyroid glands; thus, the third-generation PTH assay is likely better for the management of CKD patients.

Cholecalciferol Additively Reduces Serum Parathyroid Hormone Levels in Severe Secondary Hyperparathyroidism Treated with Calcitriol and Cinacalcet among Hemodialysis Patients.

We evaluated the improvement of intact parathyroid hormone (iPTH) levels and bone parameters by supplementing nutritional vitamin D (cholecalciferol) to combined calcimimetic (cinacalcet) and active vitamin D analog (calcitriol) among severe secondary hyperparathyroidism (SHPT) hemodialysis (HD) patients. A randomized, controlled open-label study was undertaken in 60 HD patients with serum iPTH > 1000 pg/mL or persistently high iPTH ≥ 600 pg/mL even after >3 months of calcitriol (3 μg/week). The study group received oral cholecalciferol (5000 IU/ day) and the control group received a placebo. All patients received fixed dose cinacalcet (30 mg/day, orally) and calcitriol. Calcitriol was reduced if iPTH ≤ 300 pg/mL and cinacalcet was withdrawn if serum iPTH was persistently low (iPTH ≤ 300 pg/mL) for 4 weeks after the reduction of calcitriol. A significantly lower iPTH level was noted from the 20th week in the study group compared to the placebo group, and the target iPTH ≤ 300 pg/mL was achieved at the 24th week in the study group. Most patients achieved serum 25-(OH)D3 ≥ 30 ng/mL in the study group. Nearly 40% of study patients gained >10% improvement in femoral neck (FN) bone mineral density (BMD). We conclude that cholecalciferol additively reduced serum iPTH levels, improved 25-(OH)D3 levels and improved FN BMD when used together with cinacalcet/calcitriol in severe SHPT HD patients.

Effect of Cinacalcet Combined with Calcitriol on the Clinical Outcome and Bone Metabolism in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism

Objective: To observe the clinical outcome and the effect of bone metabolism of cinacalcet combined with calcitriol in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SHPT). Methods: Thirty MHD patients with SHPT were enrolled into the study. All patients were given cinacalcet 25–75 mg and 0.5 μg calcitriol daily. Serum Ca, P, intact parathyroid hormone (iPTH), and bone metabolic markers were measured. The clinical symptoms and their changes were investigated. Results: The baseline levels of iPTH, Ca, and P were 1,787.3 ± 1,321 pg/mL, 2.54 ± 0.19 mmol/L, and 2.06 ± 0.15 mmol/L respectively. After 3 months treatment, iPTH decreased by 70%. Serum Ca and P fell to 2.39 ± 0.17 and 1.56 ± 0.50 mmol/L (p < 0.05), respectively. After 6 months, the bone-specific alkaline phosphatase, osteocalcin, and β-cross levels were decreased by 50, 37, and 49% respectively compared with corresponding values before treatment. A decline in the bone density patients was inhibited. Conclusion: Cinacalcet combined with low dose calcitriol can improve high calcium, high phosphorus, and high iPTH in MHD patients with severe SHPT and also improve bone metabolism. It can be used as a favorable choice for SHPT treatment.

The role of parathyroidectomy in the management of secondary hyperparathyroidism.

Parathyroidectomy (PTX) is often used to treat severe secondary hyperparathyroidism (SHPT) in patients receiving maintenance dialysis. However, most evidence for the proposed benefits of PTX originates from observational studies, which cannot demonstrate causality. A reconsideration of the potential role of PTX might help guide its appropriate use. Several large observational studies have suggested that PTX can reduce mortality risk. However, these studies generally suffer from bias and confounding, tempering conclusions and suggesting that the true effects of PTX may not be known. PTX has been reported to be associated with a 2% 30-day mortality, a substantial risk for what is generally an elective procedure. Additionally, biochemical control after PTX in a subset of patients may be suboptimal. The optimal surgical approach to PTX in specific clinical scenarios is also uncertain. PTX may be beneficial for certain patients with severe SHPT and clinical symptoms, but identifying patients in whom the benefits are likely to outweigh the risks is a substantial challenge. Further, great care must be taken to monitor symptoms and laboratory values in patients who undergo PTX in the immediate postoperative period and, in many cases, well beyond.

Effect of cinacalcet combined with low-dose calcitriol on clinical outcome and bone metabolism in patients with severe secondary hyperparathyroidism

To observe the clinical outcome and the effect of the combination of cinacalcet hydrochloride with low-dose calcitriol on bone metabolism in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SHPT). Methods: Thirty SHPT patients were enrolled to receive treatment of cinacalcet combined with low-dose calcitriol, with inclusion criteria as follows: maintenance on MHD>6 months; serum intact parathyroid hormone (iPTH)>600 pg/mL; parathyroid glands with more than 1 nodules by ultrasonography; traditional therapy with no effects. All patients were given cinacalcet 25-75 mg and 0.5 μg calcitriol daily. Serum Ca, P, iPTH, bone metabolic markers and bone density were measured before and after treatment. The clinical symptoms and their changes were recorded. Results: The baseline levels of iPTH, Ca and P were (1787.3±1 321.0) pg/mL, (2.54±0.19) mmol/L, and (2.06±0.15) mmol/L, respectively. After 2 weeks of treatment, serum phosphorus decreased by 20%; after 1 and 3 months of treatment, iPTH decreased by 35% and 70%. Ca and P fell to (2.39±0.17) and (1.56±0.50) mmol/L (P<0.05), respectively. The symptoms of the patients relieved. The above indicators remained stable after 12 months. Moreover, after 6 months of treatment, the alkaline phosphatase, osteocalcin and β-cross levels were decreased by 50%, 37% and 49%, respectively. The decline in patients' bone density was inhibited. No severe adverse events were observed. Conclusion: Cinacalcet hydrochloride combined with low dose calcitriol can improve high calcium, high phosphorus and high iPTH in MHD patients with severe SHPT, relieve symptoms, and improve bone metabolism. It can be used as a favorable choice for the treatment of SHPT.

Development of Severe Hyperparathyroidism Despite Short-Term Renal Replacement Therapy.

We occasionally experience cases of severe secondary hyperparathyroidism (SHPT) that require parathyroidectomy (PTX) despite undergoing short-term renal replacement therapy (RRT). Because the characteristics of such cases have never been discussed, we aimed to elucidate the pathophysiology of severe SHPT after short-term RRT by retrospectively analyzing clinical data. A total of 1013 patients with severe SHPT underwent PTX between January 2007 and April 2016 at Nagoya Daini Red Cross Hospital. Of these patients, 570 underwent RRT for ≥10years (long RRT group) and 23 for ≤1year (short RRT group). We retrospectively investigated and compared patient characteristics, preoperative data, subjective symptoms, and bone lesion incidence between the two groups. A higher proportion of subjects with congenital or hereditary diseases as primary disease for chronic kidney disease (CKD) (21.7% (5/23) vs. 6.3% (36/570); P=0.016) and longer predialysis period (21.2±14.0 vs. 10.1±9.2years; P<0.001) were observed in the short RRT group than in the long RRT group. Furthermore, lower serum calcium and phosphate levels, heavier parathyroid glands, and severe bone lesions were observed in the short RRT group than in the long RRT group. Severe SHPT after short-term RRT appeared to occur because of long-term CKD before initiating RRT. Therefore, treating mineral and bone disorders during the early CKD stage might prevent severe SHPT development before initiating RRT.

Microwave ablation: an effective treatment for mild-to-moderate secondary hyperparathyroidism in patients undergoing haemodialysis

Background: Microwave ablation (MWA) is an effective treatment for severe secondary hyperparathyroidism (SHPT), but it can also be used for mild-to-moderate secondary hyperparathyroidism (SHPT). In this randomised, controlled study, the efficacy of MWA in the treatment of mild-to-moderate hyperparathyroidism is investigated.Materials and methods: We assessed outcomes 12 months after the randomisation of 28 patients with mild-to-moderate SHPT. The subjects received either MWA plus calcitriol or calcitriol alone. The primary end-points were the rate of achieving target levels of intact parathyroid hormone (iPTH), changes in iPTH levels and the rate of patients developing severe SHPT.Results: Primary end points: the overall rates of achieving target levels of iPTH were comparable between the MWA and calcitriol alone groups (24% vs. 22%, p = 0.85). However, the rate of iPTH <150 pg/mL (lower limit of the target range) in the MWA group was higher than that in the calcitriol alone group (23% vs. 8%, p = 0.02). The mean iPTH level in the MWA group after MWA was lower than that in the calcitriol alone group (373.09 ± 322.31 vs. 552.28 ± 361.87 pg/mL, p < 0.001). There was a significant difference in the change in iPTH levels over time within the MWA group (p < 0.001) but not in the calcitriol alone group. Only one patient developed severe SHPT in the MWA group, while six patients in the calcitriol alone group developed severe SHPT (p = 0.04).Conclusions: Compared with calcitriol alone, MWA plus calcitriol decreases iPTH levels and prevents the progression of mild-to-moderate SHPT.

Spontaneous bilateral femoral neck fracture in a man with end-stage renal disease and severe secondary hyperparathyroidism

Medical treatment is the primary recommended method for in the management of severe secondary hyperparathyroidism (SHPT) in pre-dialysis individuals. This paper reports a case of end-stage renal disease (ESRD) and severe SHPT with pathologic bilateral hip fractures. A 61-year-old man, as a known case of ESRD, with radial osteoporosis and persistent SHPT ( intact PTH >2000 pg/mL) and hypercalcemia with appropriate level of phosphorus and 25(OH) D who did not respond to medical treatment referred to hospital with multiple fractures. The patient referred for subtotal parathyroidectomy. One month after parathyroidectomy, parathyroid hormone (PTH) level significantly diminished from its preoperative values. Serum calcium and phosphorus returned to normal values and muscle weakness progressively improved until the patient became able to walk again. Parathyroidectomy in patients with severe secondary hyperparathyroidism (persistent serum levels of intact PTH>800 pg/mL) is suggested, particularly when is associated with severe hypercalcemia and/or hyperphosphatemia, and progressive and debilitating hyperparathyroidism bone disease, that are refractory and resistant to medical therapy.