Intravenous calcitriol versus paricalcitol in haemodialysis patients with severe secondary hyperparathyroidism

Aim:   Secondary hyperparathyroidism (SHPT) is common among haemodialysis patients. Intensive treatment with calcitriol is often complicated by hypercalcaemia, hyperphosphataemia and elevated calcium phosphorus (Ca X PO₄) product. Paricalcitol is a vitamin D analogue developed to overcome some of the limitations of calcitriol therapy. The study objectives were to compare the response of intact parathyroid hormone (iPTH) and the incidence of hypercalcaemia, hyperphosphataemia and elevated Ca X PO₄ product in patients with severe SHPT treated with either i.v. calcitriol or i.v. paricalcitol.
Methods:   This was a single centre randomized open label study. Patients with serum intact iPTH of 50 pmol/L or more were randomized to receive either i.v. calcitriol (0.01 ug/kg) or i.v. paricalcitol (0.04 ug/kg) during every haemodialysis treatment. Serum iPTH, calcium, phosphorus and alkaline phosphatase were measured at the beginning of the study and every 3 weeks for 12 weeks.
Results:   Twenty-five patients were enrolled into the study – 12 were randomized into the calcitriol group and 13 into the paricalcitol group. There were no differences in the baseline study parameters between both groups. Serum iPTH levels were significantly reduced ( P  = 0.003) only in the paricalcitol group but not in the calcitriol group ( P  = 0.101). On the other hand, serum calcium levels were significantly increased only in the calcitriol group ( P  = 0.004 vs P  = 0.242). Serum phosphorus, alkaline phosphatase and Ca X PO₄ product were not different.
Conclusion:   Intravenous paricalcitol may be superior to i.v. calcitriol for the treatment of severe SHPT in our chronic haemodialysis population. A larger randomized controlled trial is indicated to confirm these initial findings.     

Early prediction of hypocalcemia following total thyroidectomy using combined intact parathyroid hormone and serum calcium measurement

Backgrounds

Concomitant intact parathyroid hormone (iPTH) and serum calcium measurement is deemed to be useful in predicting hypocalcemia after total thyroidectomy. This study aimed to prospectively assess the diagnostic accuracy of combined iPTH and serum calcium measurement in predicting early postoperative hypocalcemia.

Methods

From January 2010 to January 2011, 112 patients underwent total thyroidectomy in our department. A prospective study was carried out to search for factors predicting postoperative hypocalcemia. Serum calcium, phosphorus, and iPTH levels have been measured before operation and at 6, 24, and 48 h postoperatively. Hypocalcemia was defined as a serum calcium level less than 8.0 mg/dL. Sensitivity and specificity of different serum measurements have been calculated using the receiver–operator characteristics curve.

Results

Thirty-three patients (29.5 %) had transient postoperative hypocalcemia. Serum iPTH level showed the highest sensitivity and specificity in predicting hypocalcemia after 6 h (84.8 % and 93.7 %, respectively) for a criterion value ≤12.1 pg/mL. Serum calcium level showed the highest sensitivity and specificity after 24 h (93.9 and 100.0 %, respectively) for a criterion value ≤7.97 mg/dL. Combined cutoffs of 6-h iPTH and 24-h serum calcium showed sensitivity and specificity of 100.0 %.

Conclusions

The combined measurement of 6-h iPTH and 24-h serum calcium are highly predictive of early postoperative hypocalcemia. Patients with serum iPTH and calcium level?≤?criterion value are at major risk for developing hypocalcemia. These results are important in selecting patients eligible for early discharge and those patients who need calcium and vitamin D supplementation.     

Efficacy and tolerability of intravenous paricalcitol in calcitriol-resistant hemodialysis patients with secondary hyperparathyroidism: 12-month prospective study

RATIONALE/OBJECTIVES: Data are limited regarding the use of paricalcitol in calcitriol-resistant patients with secondary hyperparathyroidism (SHPT). We aimed to evaluate the effects of paricalcitol in calcitriol-resistant hemodialysis patients with SHPT. METHODS: This is a 12-month, open-label, prospective study. Forty patients with calcitriol-resistant and/or calcitriol-intolerant SHPT were included. After a washout period, all patients converted to paricalcitol with a 1:3 conversion ratio. Serum calcium and phosphorus were monitored monthly, while serum intact parathyroid hormone (iPTH) once in every 3 months. Paricalcitol dose was reduced or discontinued in case of hypercalcemia and/or hyperphosphatemia. Pre- and posttreatment electrolyte and iPTH values were compared with Student's t-test and Wilcoxon signed-rank test, respectively. MAIN FINDINGS: Forty patients completed the study. Mean initiation dose of paricalcitol was 23 ± 7 μg/week. Mean serum calcium was 8.9 ± 0.8 mg/dL at baseline and 9.4 ± 0.7 mg/dL at study end (p = 0.07). Mean monthly serum phosphorus levels stayed stable. Paricalcitol was effective in reducing iPTH levels when compared with pretreatment values (747.9 ± 497.2 pg/mL, 307.3 ± 417.1 pg/mL, respectively; p < 0.001). Thirty-two patients had to discontinue intravenous (IV) paricalcitol at some time during their treatment. Main reasons for discontinuation were as follows: hyperphosphatemia (58%), hypercalcemia (25%), and iPTH < 150 pg/mL (17%). PRINCIPLE CONCLUSIONS: Paricalcitol was found to be effective in reducing iPTH levels in calcitriol-resistant patients with SHPT despite relatively frequent drug discontinuation rates.     

Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients

Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue, in adults with SHPT has shown equal efficacy and improved survival compared to traditional treatment with calcitriol (C). We present our experience with (C) compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty-one patients (mean age 11.5±5 years) with SHPT (intact parathyroid hormone (iPTH) averaging 1,228±496 pg/ml) were studied. Seventeen received (C) followed by (P); while an additional four were treated with either (C=1) or (P=3) alone. After 26±8 weeks, average percent (%) decrease in iPTH was similar with (C) and (P) (−60.4±34% versus −65.4±28%, respectively; p=0.6). In the (P) group, the effective dose in children was greater than in adult trials based on kilogram weight. Episodes of hypercalcemia between the treatment groups were not different. However, episodes of elevated calcium × phosphorus product (Ca×P)≥70 mg²/dl² occurred more frequently in the (C) group (odds ratio=1.5; p=0.01). Paricalcitol appears to be safe and effective in pediatric patients. Data suggest that dosing should be gauged according to degree of SHPT. This should serve as impetus for future pharmacokinetic studies in pediatric dialysis patients.     

Secondary Hyperparathyroidism, Vitamin D Sufficiency, and Serum Calcium 5 Years After Gastric Bypass and Duodenal Switch

Background

The prevalence of secondary hyperparathyroidism (SHPT) is high after bariatric surgery. Vitamin D is supplied to counteract SHPT and bone disease, and we studied vitamin D associations with SHPT.

Methods

We measured serum levels of 25-OH vitamin D and parathyroid hormone (PTH) 5 years after gastric bypass and duodenal switch. One hundred twenty-five patients were included, of whom 114 (91 %) had undergone gastric bypass and 11 (9 %) had undergone duodenal switch. SHPT was defined as PTH?>?7.0 pmol/l in the absence of hypercalcemia. 25-OH vitamin D levels were divided into three categories: <50, 50–74, and ≥75 nmol/l. Serum ionized calcium, magnesium, phosphate, and creatinine were divided into tertiles.

Results

Mean age?±?SD was 44?±?9 years at 5 years follow-up. Ninety out of 125 (72 %) patients were women. SHPT was present in 45 out of 114 (40 %) gastric bypass patients and in 11 out of 11 (100 %) duodenal switch patients. The prevalence was high in all vitamin D categories studied. An inverse association between ionized calcium and PTH was found. For the gastric bypass patients, the odds ratio for SHPT in the upper two tertiles of ionized calcium was 0.35; 95 % CI, 0.15–0.79; p?=?0.011, compared with the lowest tertile. Supplements of vitamin D and calcium were not associated with a lower prevalence of SHPT at 5 years follow-up.

Conclusions

The prevalence of SHPT was high 5 years after gastric bypass and duodenal switch. SHPT was inversely associated with serum ionized calcium, but not with vitamin D. The supplementation used was insufficient to compensate for the impaired calcium absorption after surgery.     

Inhibition of parathyroid hormone: a dose equivalency study of paricalcitol and doxercalciferol

INTRODUCTION: Paricalcitol and doxercalciferol are effective in reducing parathyroid hormone PTH concentrations in patients with secondary hyperparathyroidism. The purpose of this study was to determine the relative dose of doxercalciferol (compared to paricalcitol) required to maintain equivalent PTH concentrations in dialysis patients. METHODS: Chronic hemodialysis patients treated with a stable dose of paricalcitol for at least 3 months were randomized to receive doxercalciferol at either 35, 50, or 65% of the paricalcitol dose for 6 weeks. Serum iPTH, calcium, phosphorus, and albumin were determined at baseline and monitored every 2 weeks. A linear regression analysis of percent change in iPTH values by dose group was performed to determine the conversion factor. RESULTS: 27 patients were enrolled. Initial iPTH, adjusted serum calcium, serum phosphorus, and CaxP were similar among the treatment groups. Linear regression analysis demonstrated a conversion factor of 0.57 for the dose of doxercalciferol relative to paricalcitol resulting in equivalent suppression of iPTH. Corrected serum calcium, phosphorus, CaxP product, as well as incidence of hypercalcemia, hyperphosphatemia and CaxP >50 were similar for all groups. CONCLUSION: In patients on a maintenance dose of paricalcitol, dosing doxercalciferol at 55-60% of the paricalcitol dose results in comparable inhibition of PTH.     

A comparison of dosing regimens of paricalcitol capsule for the treatment of secondary hyperparathyroidism in CKD stages 3 and 4

BACKGROUND: Intermittent dosing of calcitriol for secondary hyperparathyroidism (SHPT) has been associated with greater parathyroid hormone (PTH) reduction with fewer calcemic and phosphatemic effects than daily (QD) dosing. METHODS: Secondary analyses of three randomized, double-blind, placebo-controlled multicenter studies in stage 3 and 4 chronic kidney disease (CKD) patients with SHPT were performed to compare three times per week (TIW) with QD dosing of paricalcitol. The pharmacokinetics of TIW and QD dosing of paricalcitol capsules were assessed in a separate group of healthy subjects. RESULTS: Pharmacokinetics revealed similar steady state paricalcitol exposure between dosing regimens. In CKD patients, baseline data were similar between the TIW studies (n = 72, paricalcitol; n = 73, placebo) and QD studies (n = 35, paricalcitol; n = 40, placebo). Both dosing regimens resulted in similar efficacy (91%) for the primary end point of two consecutive > or = 30% decreases in intact PTH from baseline, but the QD regimen resulted in a greater percent reduction in intact PTH from baseline. The chances for developing increased serum calcium and phosphorus levels or Ca x P product were similar between paricalcitol and placebo groups for both treatment regimens. Furthermore, no difference in the risk for these elevations was detected between the TIW and QD regimens. CONCLUSIONS: QD dosing of paricalcitol capsules is as efficacious as TIW dosing in achieving the primary end point (2 consecutive > or = 30% reductions in PTH) in stage 3 and 4 CKD patients with SHPT. Moreover, the QD regimen had no significant effect on hypercalcemia, hyperphosphatemia or Ca x P product as compared with placebo or intermittent dosing.     

Hypoparathyroidism after Total Parathyroidectomy plus Subcutaneous Autotransplantation for Secondary Hyperparathyroidism—Any Side Effects?

Background

This retrospective, case–control study was designed to find side effects of hypoparathyroidism after total parathyroidectomy plus autotransplantation.

Methods

After successful total parathyroidectomy plus autotransplantation for symptomatic secondary hyperparathyroidism, 19 patients who had intact parathyroid hormone (iPTH) levels <10 pg/ml during the follow-up period of 1 year and 38 patients, who had levels >10 pg/ml, were enrolled as the hypoparathyroid and nonhypoparathyroid groups. Data were collected on etiology, symptoms, serum levels of calcium, phosphate, alkaline phosphatase (Alk-ptase), iPTH, and bone mineral density (BMD) at different sites. Then, 1 week, 3 months, and 1 year after surgery, serum levels of calcium, phosphate, Alk-ptase, and iPTH were measured again. Three months later, symptoms were recorded. One year after surgery, the BMD at different sites was measured again. Patients’ daily requirements of calcium carbonate and vitamin D3 were recorded at the mean follow-up of 24 months.

Results

Calcium, phosphate, and iPTH levels decreased significantly 1 week, 3 months, and 1 year after surgery, and Alk-ptase levels increased at 1 week and then decreased significantly 3 months and 1 year after surgery. Symptoms improved significantly 3 months after surgery. The BMD of different sites increased significantly at 1 year. There were no differences between the two groups regarding changes of symptoms, BMD, and calcium, phosphate, and Alk-ptase levels. Hypoparathyroid patients required significantly more calcium carbonate and vitamin D3 than nonhypoparathyroid patients did (P = 0.002).

Conclusions

Even though hypoparathyroid patients require more calcium carbonate and vitamin D3 than nonhypoparathyroid patients do, they do not have any side effects.     

A prospective randomized pilot study on intermittent post-dialysis dosing of cinacalcet

Background

Treatment of secondary hyperparathyroidism (SHPT) is important in management of patients with end-stage renal disease on hemodialysis (HD). Calcimimetic agent, cinacalcet provides an option for control of SHPT in patients who fail traditional therapy. It may not have optimal results in non-compliant patients. To enhance compliance, we evaluated effectiveness of post-dialysis dosing of cinacalcet (group AD) as compared to daily home administration (group D) in a prospective randomized trial of HD patients with refractory SHPT.

Methods

After 2-week run-in phase, patients were randomly assigned to two treatment groups. In group AD (N = 12), patients were administered cinacalcet on the day of dialysis (3 times/week) by dialysis staff, while in control group D (N = 11), cinacalcet was prescribed daily to be taken by patients at home. Intact parathyroid hormone (i-PTH), serum calcium, phosphorus, and alkaline phosphatase were followed for 16 weeks and compared to baseline in both groups. Data were analyzed using between-groups linear regression for repeated measures.

Results

No significant decline in i-PTH occurred in group AD at 16 weeks as compared to a significant drop in group D (p = 0.006). However, subgroup analysis showed effectiveness of post-dialysis dosing in patients with less severe SHPT (p = 0.04).

Conclusion

Although daily dosing overall was more effective for treatment of SHPT, dialysis dosing was effective in patients with less severe SHPT. This warrants a larger study considering the limitations of this pilot trial. In the meantime, dialysis dosing can be considered in non-compliant patients with less severe SHPT.     

帕立骨化醇治疗维持性血液透析患者继发性甲状旁腺功能亢进的疗效观察

目的观察帕立骨化醇对维持性血液透析患者继发性甲状旁腺功能亢进症的治疗效果。方法选择2018年7月至2019年7月对非选择性维生素D受体激动剂(VDRA)疗效不佳或不能耐受拟钙剂或不愿手术治疗的继发性甲状旁腺功能亢进(SHPT)的维持性血液透析患者56例,根据血液全段甲状旁腺素(iPTH)水平将所有患者分为三个组别:A组(300 pg/mL≤iPTH<600 pg/mL)、B组(600 pg/mL≤iPTH<800 pg/mL)、C组(iPTH≥800 pg/mL)。根据体重给予不同剂量的静脉帕立骨化醇注射液,分别检测患者治疗前、初始使用1个月以及达到帕立骨化醇维持剂量时,iPTH、血钙、血磷、钙磷乘积的变化情况。结果患者骨痛、瘙痒、疲乏等症状明显改善。所有患者初始治疗1个月,iPTH达标率为51.8%(29/56),达到帕立骨化醇注射液维持治疗剂量百分比为57.1%(32/56)。患者初始治疗1个月与治疗前相比,iPTH水平显著下降[(718.76±457.56)pg/mL vs.(956.68±375.61)pg/mL,P<0.001],血钙、血磷以及钙磷乘积无明显改变[(2.28±0.23)mmol/L vs.(2.23±0.27)mmol/L,(2.15±0.49)mmol/L vs.(2.29±0.48)mmol/L,(58.49±17.71)mg^2/dl2 vs.(62.90±13.93)mg^2/dl2,P>0.05]。进入维持治疗阶段的患者,维持治疗与初始治疗相比,iPTH水平仍有下降趋势,但差异无统计学意义[(424.82±221.23)pg/mL vs.(517.55±325.77)pg/mL,P>0.05],血钙、血磷以及钙磷乘积比较差异无统计学意义[(2.33±0.20)mmol/L vs.(2.31±0.24)mmol/L,(2.13±0.44)mmol/L vs.(2.00±0.42)mmol/L,(61.24±12.25)mg^2/dl2 vs.(55.76±15.66)mg^2/dl2,P>0.05]。结论帕立骨化醇对非选择性VDRA疗效不佳或不能耐受拟钙剂或不愿手术治疗的维持性血液透析患者SHPT有较好的疗效,明显缓解患者骨痛、瘙痒、疲乏等症状,显著降低iPTH水平,且不增加高钙血症的发生风险。     

Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: a randomized prospective multicentre trial.

BACKGROUND: To identify differences between the effects of calcitriol and the calcitriol analogue, maxacalcitol, on parathyroid hormone (PTH) and bone metabolisms, we conducted a randomized prospective multicentre study on patients on chronic haemodialysis. METHODS: We randomly assigned 91 patients with secondary hyperparathyroidism [intact PTH (iPTH) > or =150 pg/ml] to have either calcitriol (47 patients) or maxacalcitol (44 patients) therapy, for 12 months after a 1 month control period. Serum electrolytes, bone alkaline phosphatase (bAP), iPTH, total PTH and PTH(1-84) (whole PTH) levels were measured periodically. The first end point was a serum iPTH of <150 pg/ml, the second was the iPTH levels obtained. RESULTS: Treatment was discontinued for various reasons in nine patients in each group, but no serious side effects were observed in either group. The numbers of cases reaching the first end point were not significantly different between the two groups. Serum calcium concentration was significantly higher in the maxacalcitol than the calcitriol group during early treatment, but not at the end of treatment. Throughout the treatment period there were no significant differences between the two groups in serum iPTH, inorganic phosphate, the product of the serum calcium and inorganic phosphorus concentrations, bAP, or the ratio of whole PTH to total PTH minus whole PTH. Nor were the changes in these parameters significantly different between the two groups comparing the patients with moderate to severe hyperparathyroidism (basal iPTH > or =500 pg/ml). CONCLUSION: Calcitriol and maxacalcitol are equally effective on PTH and bone metabolism.     

Is high-dose cholecalciferol justified in children with chronic kidney disease who failed low-dose maintenance therapy?

Background

We aimed to investigate the effect of single, high-dose intramuscular cholecalciferol on vitamin D3 and intact parathyroid hormone (iPTH) levels in children with chronic kidney disease (CKD).

Methods

Between January 2012 and June 2012, we conducted a prospective, uncontrolled study at the Pediatric Nephrology Unit of King Abdulaziz University Hospital, Jeddah, to investigate the effect of single, high-dose intramuscular vitamin D3 on 25(OH)D3 and iPTH levels in vitamin D insufficient/deficient children with CKD. Serum vitamin D3, iPTH, calcium, phosphate, alkaline phosphatase (ALP), and creatinine levels were measured before intramuscular vitamin D3 (300,000 IU) administration, and these were subsequently repeated at 1 and 3 months after treatment. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA).

Results

Nineteen children fulfilled the criteria. At 3 months after treatment, vitamin D3 levels were significantly higher than at baseline (p?<?0.001) but lower than the levels at 1 month. iPTH levels decreased significantly at 3 months (p?=?0.01); however, the drop in iPTH levels was not significant at 1 month (p?=?0.447). There were no changes in calcium, phosphate, ALP, or creatinine levels after treatment.

Conclusions

Single-dose intramuscular vitamin D3 (300,000 IU) resulted in significant improvement of vitamin D3 and iPTH levels in children with CKD.     

Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients

BACKGROUND: Treatment of secondary hyperparathyroidism (SHPT) includes use of calcitriol (1,25D(3)) to suppress parathyroid hormone (PTH), but dosing of 1,25D(3) is limited by the development of hypercalcemia and a high calcium x phosphorus (Ca x P) product due to gut absorption of calcium and phosphorus as well as enhanced bone resorption. The vitamin D analog 19-Nor-1,25(OH)2-vitamin D2 (paricalcitol) and the prohormone 1alpha-OH-vitamin D2 (doxercalciferol) have been proposed as alternatives which may cause less hypercalcemia and elevated Ca x P, while still suppressing PTH. METHODS: We performed a prospective study to assess the acute bone mobilization effects of very high doses of paricalcitol and doxercalciferol. 13 hemodialysis patients received 160 mcg of paricalcitol and 120 mcg of doxercalciferol on 2 separate occasions in a research center while on a low calcium, low phosphorus diet, and sevelamer alone as a phosphorus binder. Changes in Ca, PO4, and PTH were measured over 36 h. RESULTS: Serum phosphorus rose faster, and peaked significantly higher at 36 h following doxercalciferol (2.12 +/- 0.11 mmol/l) than paricalcitol (1.85 +/- 0.07 mmol/l; p = 0.025). Ca x P product also rose more following doxercalciferol than paricalcitol, and peaked higher at 36 h (5.02 +/- 0.26 vs. 4.54 +/- 0.21 mmol/l; p = 0.061). In contrast, suppression of PTH at 36 h was comparable (63% after paricalcitol and 65% with doxercalciferol). CONCLUSION: Consistent with animal studies, paricalcitol provides profound PTH suppression, while stimulating bone resorption and/or intestinal absorption less than doxercalciferol, resulting in less elevation of serum phosphorus and Ca x P.     

Peri-aortic fat tissue and malnutrition–inflammation–atherosclerosis/calcification syndrome in end-stage renal disease patients

Purpose

Thoracic peri-aortic fat tissue (PFT) is considered as a metabolically active organ in atherosclerosis. Malnutrition, inflammation and atherosclerosis/calcification (MIAC) are the most commonly encountered risk factors of cardiovascular disease in end-stage renal disease (ESRD) patients. Calcification of the aorta was found to be an important cardiovascular risk marker predicting future events, morbidity and mortality in this population. We aimed to investigate the relationship between PFT, MIAC syndrome and thoracic aortic calcification (TAC) in ESRD patients.

Methods

Seventy-nine ESRD patients receiving hemodialysis (HD) or peritoneal dialysis (PD) and 20 control subjects were enrolled in this cross-sectional study. PFT and TAC were assessed using a 64-MDCT scanner. Patients with serum albumin <3.5 g/dL were defined as patients with malnutrition; those with serum C-reactive protein level >10 mg/L had inflammation, and those with coronary artery calcification score (CACS) >10 had atherosclerosis/calcification.

Results

TAC and PFT were significantly higher in ESRD patients compared with control subjects. There was a statistically significant relationship between PFT and TAC in ESRD patients (r = 0.458, p < 0.0001). PFT was found to be significantly increased when the MIAC components increased. PFT was positively associated with age, BMI, uric acid, hemoglobin and CAC. The multivariate analysis revealed that age and uric acid were independent predictors of increased PFT. Twenty-four (30.4 %) patients had none, 30 (37.9 %) had one component, 17 (21.5 %) had two components, and 8 (10.2 %) had all MIAC components. PFT was highest among patients having all three components (28.6 cm³) and lowest among those who do not have the MIAC syndrome (8.54 cm³). TAC was highest among patients having all three components (179.2 HU) and lowest among those who do not have the MIAC syndrome (0 HU).

Conclusions

We found a relationship between PFT and MIAC syndrome in ESRD patients.     

Total parathyroidectomy with autotransplantation for a rare disease derived from uremic secondary hyperparathyroidism,the uremic leontiasis ossea

Summary

We described six uremic leontiasis ossea (ULO) patients who underwent total parathyroidectomy with autotransplantation. ULO demonstrated more a systemic disease than a simple craniofacial deformation. The surgery seemed an effective treatment to alleviate secondary hyperparathyroidism and to improve patients’ quality of life. ULO may have a high postoperative recurrence tendency.

Introduction

ULO is a rare disease derived from uremic secondary hyperparathyroidism (SHPT). Previous studies mostly focused on the craniofacial deformations. This study aims to investigate the systemic features of the disease and the surgical outcomes.

Methods

The present study retrospectively assessed six ULO patients who underwent total parathyroidectomy (TPTX) with autotransplantation (AT). Follow-up data were recorded. The follow-up status was considered as “effectiveness” if serum intact parathyroid hormone (iPTH) levels were <150 pg/mL in the first 3 days after surgery, or as “recurrence” if serum iPTH gradually increased >300 pg/mL during follow-up in patients whose status was initially considered as “effectiveness”.

Results

Craniofacial deformations, short stature, thoracocyllosis, spine malformations, osteodynia, and muscle weakness were observed in all patients. Abnormal pulmonary functions were observed in five patients. After surgery, one patient died from respiratory failure. Surgery was effective in the remaining five patients with relieved osteodynia and stopped craniofacial deformation. A mean follow-up of 7.6 (4 to 12) months was available. Three patients suffered from recurrence of hyperparathyroidism originating from autografts.

Conclusions

Our data suggests that ULO is not only a simple disease with craniofacial malformations but is a severe systemic disease leading to increased surgical risks. TPTX with AT seems an effective treatment to relieve SHPT and to improve quality of life. ULO may have a high postoperative recurrence tendency.     

Calcitriol resistance in hemodialysis patients with secondary hyperparathyroidism

Nonselective vitamin D receptor activators (VDRA), such as calcitriol and alfacalcidol, have been successfully used in the treatment of secondary hyperparathyroidism (SHPT) in hemodialysis. Despite their beneficial effects on the control of serum PTH levels, their use has been limited by intolerance (development of hypercalcemia and hyperphosphatemia with consecutive cardiovascular toxicity). Apart from becoming intolerant, in 20–30 % of patients who use nonselective VDRA, serum PTH levels do not decrease appropriately despite increasing doses of these agents. These patients are considered calcitriol-resistant patients. Thus, calcitriol resistance and intolerance are two sides of the same coin: active vitamin D failure. Despite the clinical relevance of active vitamin D failure, definitions of resistance and intolerance are imprecise and have varied over time. More selective VDRA claim to produce less hypercalcemia and hyperphosphatemia and could help clinicians to overcome intolerance. Also, some studies have also shown that paricalcitol can be even useful in resistant patients. Significant limitations of iPTH as a reliable and useful clinical biomarker have been increasingly appreciated. There is evidence that intact PTH concentration must differ by 72 % between any two measurements before it can be considered a significant change. VDR polymorphisms could be involved in the development of SHPT in CKD patients. Interestingly, a higher incidence of the b allele of the VDR BsmI gene variant has been shown to be present in SHPT. The BsmI genotype can also affect the response of hemodialysis to IV calcitriol. A challenge for the future will be to establish biomarkers such as laboratory determinations or ultrasound findings that can help us to early identify those patients who will not respond appropriately to calcitriol or exhibit intolerable side effects .     

Cinacalcet effects on the perioperative course of patients with secondary hyperparathyroidism

Purpose

Since its registration in 2004, the calcimimetic agent cinacalcet has been established as an alternative treatment for secondary hyperparathyroidism (SHPT). Working by allosteric activation of the calcium-sensing receptor, cinacalcet can lower parathyroid hormone (PTH) and calcium (Ca) in patients with SHPT. The influence of calcimimetics on the perioperative course has been unclear so far.

Methods

We retrospectively analyzed the data of patients with primary operation for SHPT between 2004 and 2011, comparing the perioperative course of patients with and without preoperative cinacalcet treatment.

Results

Fifty-six patients had cinacalcet therapy, and 54 patients had no calcimimetic medication prior to surgery. Gender, age, hemodialysis, and medical treatment were similar in both groups. Also, PTH levels were similar preoperatively and postoperatively (preoperative, 1,249?±?676 vs. 1,196?±?601 pg/ml; postoperative, 86?±?220 vs. 62?±?91 pg/ml). Patients with cinacalcet preoperatively had significant lower Ca levels preoperatively (2.49?±?0.25 vs. 2.61?±?0.24 mmol/l) and postoperatively (1.75?±?0.37 vs. 1.86?±?0.35 mmol/l) and had a higher rate of oral Ca substitution postoperatively (93 vs. 74 %). The risk for postoperative persistent disease was slightly higher in these patients compared to those without preoperative cinacalcet therapy (5 vs. 0 %, not significant).

Conclusions

In our experience, cinacalcet did not alter the perioperative course in SHPT patients.     

Feasibility of photodynamic therapy for secondary hyperparathyroidism in chronic renal failure rats

Background

Feasibility of photodynamic therapy (PDT) for secondary hyperparathyroidism (SHPT) was examined in a rat model of SHPT.

Methods

A photosensitizer, 5-aminolevulinic acid (5-ALA), was injected intraperitoneally, and the parathyroid glands were irradiated either after surgical exposure with 385-nm light or transdermally with 630-nm light from a light-emitting diode (LED) lamp.

Results

PDT with high 5-ALA and irradiation doses caused severe hypoparathyroidism in SHPT rats within two days. Low-dose invasive PDT reduced intact parathyroid hormone (iPTH) levels in all rats from 748.9 ± 462.6 pg/mL at baseline to 138.7 ± 117.5 pg/mL at week 6, followed by a further decrease to 80.5 ± 54.0 pg/mL at week 9 in 60 % of rats or an increase to 970.0 ± 215.6 pg/mL at week 9 in 40 % of rats. Low-dose noninvasive PDT reduced iPTH levels from 1612.5 ± 607.8 pg/mL at baseline to 591.9 ± 480.1 pg/mL at week 4 in all rats. Thereafter, iPTH levels remained low in 43 % of rats and were 233.7 ± 51.6 pg/mL at week 9, whereas 57 % showed an increase, reaching 3305.9 ± 107.3 pg/mL at week 9. Control SHPT rats had iPTH levels of 2487.8 ± 350.9 and 2974.6 ± 372.1 pg/mL at week 4 and 9, respectively. The parathyroid glands of the rats with low iPTH levels were atrophied and had few parathyroid cells surrounded by fibrotic materials and no recognizable blood vessels. Those of the rats with high iPTH levels showed well-preserved gland structure, clusters of parathyroid cells, and blood vessels.

Conclusion

These results demonstrate that 5-ALA-mediated PDT for SHPT is feasible.

     

Carotid intima media thickness, oxidative stress, and inflammation in children with chronic kidney disease

Objective

We evaluated the association between inflammation and oxidative stress with carotid intima media thickness (cIMT) and elasticity increment module (E_inc) in pediatric patients with chronic kidney disease (CKD).

Methods

This analytical, cross-sectional study assessed 134 children aged 6–17 years with CKD. Anthropometric measurements and biochemistry of intact parathyroid hormone (iPTH), high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-1β, reduced glutathione (GSH), malondialdehyde, nitric oxide, and homocysteine were recorded. Bilateral carotid ultrasound (US) was taken. Patients were compared with controls for cIMT and E_inc using?≥?75  percentile (PC).

Results

Mean cIMT was 0.528?±?0.089 mm; E_inc was 0.174?±?0.121 kPa × 10³; cIMT negatively correlated with phosphorus (r ?0.19, p?=?0.028) and the calcium × phosphorus (Ca × P) product (r ?0.26, p?=?0.002), and positively with iPTH (r 0.19,p?=?0.024). After adjusting for potential confounders, hemodialysis (HD) (β?=?0.111, p?=?<0.001), automated peritoneal dialysis (APD) (β?=?0.064, p?=?0.026), and Ca x P product (β?=??0.002, p?=?0.015) predicted cIMT (R ²?=?0.296). In patients on dialysis, HD (β?=?0.068, p?=?0.010), low-density lipoprotein cholesterol (LDL-C) (β?=?0.001, p?=?0.048), and GSH (β?=??0.0001, p?=?0.041) independently predicted cIMT (R ²?=?0.204); HD, hypoalbuminemia, and high iPTH increased the risk of increased cIMT. In dialysis, E_inc was inversely associated with GSH, and in predialysis, Ca × P correlated with/predicted E_inc (β?=?0.001, p?=?0.009).

Conclusions

cIMT and E_inc strongly associate with several biochemical parameters and GSH but not with other oxidative stress or inflammation markers.     

Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism

To evaluate the response of circulating intact parathyroid hormone (iPTH) on myocardial hypertrophy in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), echocardiographic and neurohormonal assessments were performed over a 15-week period in 15 HD patients with SHPT before and after calcitriol treatment and 10 HD control patients with SHPT not receiving calcitriol therapy. We prospectively studied a group of 15 patients with significantly elevated iPTH levels (iPTH >450 pg/mL) receiving calcitriol (2 microg after dialysis twice weekly). Clinical assessment, medication status, and biochemical and hematological measurements were performed once a month. Throughout the study, calcium carbonate levels were modified to maintain serum phosphate levels at less than 6 mg/dL, but body weight, antihypertensive medication, and ultrafiltration dose remained constant. In patients treated with calcitriol, an adequate reduction of iPTH levels was found (1,112 +/- 694 v 741 +/- 644 pg/mL; P < 0.05) without changes in values of serum ionized calcium (iCa++), phosphate, or hematocrit. Blood pressure (BP), cardiac output (CO), and total peripheral resistance (TPR) did not significantly change. After 15 weeks of treatment with calcitriol, M-mode echocardiograms showed pronounced reductions in interventricular wall thickness (13.9 +/- 3.6 v 12.8 +/- 3.10 mm; P = 0.01), left ventricular posterior wall thickness (12.5 +/- 2.4 v 11.3 +/- 1.8 mm; P < 0.05), and left ventricle mass index (LVMi; 178 +/- 73 v 155 +/- 61 g/m2; P < 0.01). However, in control patients, these changes were not found after the treatment period. In addition, sequential measurements of neurohormonal mediator levels in patients receiving calcitriol showed that plasma renin (18.5 +/- 12.7 v 12.3 +/- 11.0 pg/mL; P = 0.007), angiotensin II (AT II; 79.7 +/- 48.6 v 47.2 +/- 45.7 pg/mL; P = 0.001), and atrial natriuretic peptide (ANP; 16.6 +/- 9.7 v 12.2 +/- 4.4 pg/mL; P = 0.03) levels significantly decreased, whereas antidiuretic hormone (ADH), epinephrine, and norepinephrine levels did not change significantly. The percent change in LVMi associated with calcitriol therapy had a strong correlation with the percent change in iPTH (r = 0.52; P < 0.05) and AT II (r = 0.47; P < 0.05) levels. We conclude that the partial correction of SHPT with intravenous calcitriol causes a regression in myocardial hypertrophy without biochemical or hemodynamic changes, such as heart rate, BP, and TPR. The changes in plasma levels of iPTH and, secondarily, plasma levels of neurohormones (especially AT II) after calcitriol therapy may have a key role in attenuating ventricular hypertrophy in SHPT.