Episodes Of Hypocalcemia Research Articles

The Association of Calcium Derangements With 24-Hour Outcomes in the Deployed Combat Setting.

Calcium derangements remain poorly characterized in the combat trauma population. We describe the incidence of emergency department (ED) calcium derangements, associated physiologic derangements, and 24-hour mortality from the deployed combat setting. We analyzed adult casualties from 2007 to 2023 from the DoD Trauma Registry for U.S. military, U.S. contractor, and coalition casualties that had at least 1 ionized calcium value documented in the ED at a Role 2 or Role 3 military treatment facility. We constructed a series of multivariable logistic regression models to test for the association of hypocalcemia and hypercalcemia with physiological derangements, blood product consumption, and survival. Vital signs and other laboratory studies were based on the concurrent ED encounter. There were 941 casualties that met inclusion for this analysis with 26% (245) having at least 1 calcium derangement. Among those, 22% (211) had at least 1 episode of hypocalcemia and 5% (43) had at least 1 episode of hypercalcemia in the ED. The vast majority (97%, 917) received calcium at least once. Median composite injury severity scores were lower among those with no calcium derangement (8 versus 17, P < .001). Survival was higher during the total hospitalization (98% versus 93%) among those with calcium derangements but similar at 24 hours (99% versus 98%, P = .059). After adjusting for confounder, any hypocalcemic measurement was associated with an elevated international normalized ratio (odds ratio 1.94, 95% CI 1.19-3.16), acidosis (1.66, 1.17-2.37), tachycardia (2.11, 1.42-3.15), hypotension (1.92, 1.09-3.38), depressed Glasgow coma scale (3.20, 2.13-4.81), elevated shock index (2.19, 1.45-3.31), submassive transfusion (3.97, 2.60-6.05), massive transfusion (4.22, 2.66-6.70), supermassive transfusion (3.65, 2.07-6.43), and all hospital stay mortality (2.30, 1.00-5.29). Comparatively, any hypercalcemic measurement was associated with acidosis (2.96, 1.39-6.32), depressed Glasgow coma scale (4.28, 1.81-10.13), submassive transfusion (3.40, 1.37-8.43), massive transfusion (6.25, 2.63-14.83), and supermassive transfusion (13.00, 5.47-30.85). Both hypocalcemia and hypercalcemia in the ED were associated with physiological derangements and blood product use, with a greater extent observed in those with hypocalcemia compared to those with hypercalcemia. Prospective studies are underway to better explain and validate these findings.

#2793 Improvement of bone mineral density in kidney transplant recipients: it is just denosumab?

Abstract Background and Aims Post-transplant bone disease is a common complication after a kidney transplant. Several factors, including pre-existing CKD-MBD, steroid, and CNI immunosuppressive treatment, contribute to this condition and increase the risk of bone loss and fractures. Among various therapeutic strategies, Denosumab, a human monoclonal antibody against RANK-L, can decrease the risk of fracture in Kidney Transplant Recipients (KTRs). The most reported side effects are episodes of hypocalcemia, which are associated with an increase in parathyroid hormone (PTH) levels. The FDA recommends treating these episodes with calcium supplements and cholecalciferol; another alternative is the use of receptor activators (VDRa). To our knowledge, there are only a few case reports in the literature analyzing the effect of combined treatment with VDRa and Denosumab. In this observational study, we evaluated changes in laboratory data and bone density (BMD) assessed by DXA in KTRs that received Denosumab with or without VDRa supplementation. Method This retrospective study evaluated 18 kidney transplant recipients who started Denosumab therapy after transplantation. The patients were divided into two groups: those who started or increased vitamin D receptor agonist therapy within the first 6 months before the second dose of Denosumab, and those who did not. We analyzed at baseline (T0) and after 1 year from first Denosumab administration (T1) creatinine, calcium, phosphate, PTH, bone alkaline phosphatase (BALP), osteocalcin (OC), carboxy-terminal cross-linked telopeptides of type 1 collagen (CTX), and 25-OH vitamin D and BMD at vertebral lumbar spine, femoral neck and total Hip. Furthermore, we evaluated Trabecular Bone Score (TBS). We performed ANOVA and Kruskal-Wallis for continuous variables based on distribution and Fisher's test for categorical variables. To assess the correlation between variables, we used linear regression and the Pearson correlation coefficient. Additionally, we conducted logistic regression to analyze the outcomes. Results A total of 18 patients were included in the study cohort. Of these, 66.7% were females, and 33.3% were males, with an average age of 67 years (Table 1). 13 patients started or uptitrated VDRa within the first 6 months (VDRa group), while 5 did not (Control group). At baseline, the VDRa group had a lower eGFR and higher PTH compared to the Control group, although both were at the threshold of statistical significance (37.38 vs 52.20 mL/min/1.73 m², p = 0.060 and 106.77 vs 72.60 pg/mL, p = 0.069). However, they had significantly lower serum calcium levels (8.96 vs 9.90 mg/dL, p = 0.039). In terms of baseline bone structure, there were no significant differences between the two groups at any of the three sites examined. At 1 year the VDRa group had a significantly greater gain at the Total Hip (+0.08 vs −0.03 g/cm3, p = 0.048 and +10.81 vs −4.16%, p = 0.037). Additionally, the VDRa group had an increase in TBS, while the Control group had a reduction, and this absolute and percentage variation between the two was statistically significant (+0.07 vs −0.02, p = 0.034 and +6.14 vs −1.62, p = 0.043) (Table 2). In linear correlation analysis higher doses of VDRa were significantly and positively associated with Delta BMD at the Total Hip (r = 0.65, p = 0.003). However, a significant correlation was highlighted between VDRa dosage and PTH reduction (r = −0.51, p = 0.027). Finally, in univariate logistic regression analysis, the dosage of VDRA was significantly and positively associated with 5% BMD gain at the Total Hip (OR = 1.54, CI 1.08 to 1.89, p = 0.046) (Fig. 1). Conclusion After conducting our study, we found that the use of Denosumab had a positive impact on bone mineral density. In addition to that, we observed that the association with VDRa led to further improvement in BMD and better control of PTH. Despite having a small sample size, our study demonstrates that VDRa not only helps in correcting hypocalcemia but also enhances the effect of Denosumab.

Possible role for rare TRPM7 variants in patients with hypomagnesaemia with secondary hypocalcaemia.

Hypomagnesaemia with secondary hypocal-caemia (HSH) is a rare autosomal recessive disorder caused by pathogenic variants in TRPM6, encoding the channel-kinase transient receptor potential melastatin type 6. Patients have very low serum magnesium (Mg2+) levels and suffer from muscle cramps and seizures. Despite genetic testing, a subgroup of HSH patients remains without a diagnosis. In this study, two families with an HSH phenotype but negative for TRPM6 pathogenic variants were subjected to whole exome sequencing. Using a complementary combination of biochemical and functional analyses in overexpression systems and patient-derived fibroblasts, the effect of the TRPM7-identified variants on Mg2+ transport was examined. For the first time, variants in TRPM7 were identified in two families as a potential cause for hereditary HSH. Patients suffer from seizures and muscle cramps due to magnesium deficiency and episodes of hypocalcaemia. In the first family, a splice site variant caused the incorporation of intron 1 sequences into the TRPM7 messenger RNA and generated a premature stop codon. As a consequence, patient-derived fibroblasts exhibit decreased cell growth. In the second family, a heterozygous missense variant in the pore domain resulted in decreased TRPM7 channel activity. We establish TRPM7 as a prime candidate gene for autosomal dominant hypomagnesaemia and secondary hypocalcaemia. Screening of unresolved patients with hypocalcaemia and secondary hypocalcaemia may further establish TRPM7 pathogenic variants as a novel Mendelian disorder.

Differential diagnosis of convulsions in the structure of dissociative (conversion motor) disorder and chronic postoperative hypoparathyroidism: case report and literature review

Hypoparathyroidism is a rare disorder of mineral metabolism, characterized by hypocalcemia as a result of the absence or deficiency of parathyroid hormone. The severity of the condition of patients with this disease is associated with both acute episodes of hypocalcemia due to cardiac arrhythmias, laryngo- or bronchospasm, generalized seizures, and manifestations of long-term complications of the disease, such as kidney pathology. In some cases, the normalization of phosphorus-calcium metabolism due to standard treatment with active metabolites / analogues of vitamin D and calcium salts does not lead to a reduction in clinical symptoms, which requires differential diagnosis with other conditions, including such neuropsychiatric disorders as epileptic seizures and their equivalents, syncope, and psychogenic nonepileptic seizures. We present a case report of a woman with convulsions, which developed due to dissociative (conversion motor) disorder, with chronic postoperative hypoparathyroidism, receiving standard treatment and having normo- and hypercalcemia.

Bisphosphonate Use in Cardiac Transplant Patients on Dialysis: A Case Series

<h3>Introduction</h3> Decreased bone mineral density (BMD) due to glucocorticoid use is common following solid organ transplantation (SOT). Glucocorticoids increase osteoclast-mediated bone resorption while inhibiting osteoblast proliferation and differentiation. Bisphosphonates are indicated for glucocorticoid-induced osteoporosis (GIOP) prophylaxis but are not recommended with severe renal impairment. Safety of alternatives is unclear in immunosuppressed dialysis patients and may not be economical. No prior publication has described the use of bisphosphonates for GIOP in transplant patients on dialysis. <h3>Case Report</h3> We report five cases of cardiac transplant patients on hemodialysis (HD) and long-term prednisone who received up to four doses of pamidronate 30 mg intravenously (IV) in the first year post-transplant. Two of the five patients went on to have renal recovery. There were no episodes of hypocalcemia after adjusting for albumin. Three patients did not demonstrate decreased BMD at one year or more post-transplant. One patient progressed from osteopenia to osteoporosis, and another had osteopenia post-transplant but with unknown baseline. <h3>Summary</h3> Bisphosphonates are first line for preventing osteoporosis from long-term glucocorticoids; however, their role in patients with renal impairment is unclear. Reduced elimination increases risk of hypocalcemia though HD may remove some bisphosphonates. Though timing of dialysis after administration was not evaluated here, there were no episodes of hypocalcemia following thirteen total pamidronate doses. Additionally, rapid IV administration can cause acute renal failure due to accumulation in the renal tubules. Doses were given over four hours to mitigate risk, and two patients had renal recovery despite this possibility. In conclusion, low-dose pamidronate may be well tolerated by dialysis dependent SOT patients and provide a cost effective GIOP option. Additional studies are needed to determine the most effective and safe dose in this population.

Influence of deficiency or insufficiency of vitamin D on the circadian rhythm of serum calcium level

Background: mild hypocalcemia is a common laboratory finding that is not accompanied by the clinical symptoms. The most common causes of hypocalcemia are inadequate calcium intake and vitamin D deficiency. Given the high prevalence of vitamin D deficiency (insufficiency), it seems relevant to determine the daily variability of serum calcium levels before and after its supplementation.Aims: to assess the effect of 25(OH) vitamin D level on the daily profile of serum calcium and 24-hour urinary calcium levels. MATERIALS AND METHODS: the interventional, prospective, comparative study of 10 healthy volunteers (women/men - 9/1) was performed. We have analyzed the daily profiles of serum calcium and 24-hour urinary calcium levels. Summary duration of this study was 8 months and consisted two hospitalizations. Statistical analysis was done on August 2020. The descriptive statistics are represented by medians and the first and third quartiles in Me (Q1; Q3), average, maximum, and minimum values M (min; max) and by absolute and relative frequencies.Results: Me serum calcium levels (Catotaland Cacorr.) and 24-hour urinary calcium levels did not differ before and after vitamin D supplementation. However, the number of reference calcium values increased as 25 (OH) vitamin D level was reached more than 30 ng/ml from 90.8% to 100% for Catotal and from 94.2% to 97.5% for Cacorr. Episodes of hypocalcemia were registered in patients with low vitamin D levels: in 3.33% of cases according to Catotal and 5.8% for Cacorr. The frequency of hypocalcemia decreased for Catotal (to 0%) and for Cacorr. (to 2.5%) after treatment with cholecalciferol. Analysis of Catotal and Cacorr. deviations during the day showed a less variability of the calcium profile after treatment, This study also revealed circadian character of daily serum calcium profile with the presence of maximum (09:40-17:40) and minimum (23:40-07:40) values during the day.Conclusions: Our study demonstrated the improvement of daily serum calcium profile after vitamin D supplementation. We confirmed the increased number of reference calcium values, decreased variability of serum calcium levels during the day and decreased frequency of hypocalcemia.

In-House Production of Dialysis Solutions to Overcome Challenges During the Coronavirus Disease 2019 Pandemic

In-House Production of Dialysis Solutions to Overcome Challenges During the Coronavirus Disease 2019 Pandemic

The prevalence and natural history of normocalcaemic hypoparathyroidism in a United Kingdom referral population.

Normocalcaemic hypoparathyroidism (NHYPO) is characterized by low levels of parathyroid hormone (PTH) with normal levels of calcium. There is little in the current literature on this disease, with only two studies published on its prevalence, while its natural history remains relatively unknown. To identify the prevalence of NHYPO in a UK referral population and to study the natural history of the disorder. Retrospective study. Five-year follow-up. 6280 patients referred for a BMD measurement in a Metabolic Bone referral centre. Prevalence of NHYPO and variability of calcium. Based on laboratory results on the index day, 22 patients with NHYPO were identified. Four patients were excluded due to non-PTH-induced hypocalcaemia and unconfirmed data. The final prevalence was 0.29%. Only 67% had persistent normocalcaemia, and the rest had intermittent hypocalcaemia. Two of these patients also had persistently low PTH on two occasions. Most of the patients had one PTH measurement available. No patient developed permanent hypoparathyroidism. The prevalence calculated from this UK referral population is lower when compared to results from previous studies. NHYPO patients often have episodes of hypocalcaemia with some cases having no apparent reason for calcium levels below the reference range.

Behavior of Bone Mineral Metabolism in Renal Posttransplantation Patients with Severe Hyperparathyroidism

BackgroundSecondary hyperparathyroidism usually improves after renal transplantation. When it becomes persistent, it is associated with deleterious effects on the graft, bone demineralization, fractures, calcifications, and cardiovascular events. In this study we describe the development of cases of severe hyperparathyroidism occurring after renal transplantation. ObjectiveTo describe the behavior of the indicators of bone mineral metabolism in the renal transplantation patient with severe secondary hyperparathyroidism before transplantation, treated with or without parathyroidectomy. MethodsThis is a case series study conducted between 2004 and 2017 on renal transplantation patients presenting with PTH > 800 pg/mL or who required pretransplantation parathyroidectomy. ResultsWe found 36 patients with severe hyperparathyroidism, corresponding to 10.8% of transplantation recipients, with an average age of 54.5 years (±12.35). The median follow-up after transplantation was 128 months (16-159). Fourteen patients underwent parathyroidectomy before transplantation, with a median intact parathyroid hormone at the time of transplantation of 56 (3-382) pg/mL, with more episodes of hypocalcaemia and oral calcium requirement. The other patients were transplanted with a median intact parathyroid hormone of 1010 (range, 802-1919) pg/mL, reaching a median intact parathyroid hormone of 98.8 (43.8-203) at 3 years of follow-up. Only 2 patients underwent parathyroidectomy for tertiary hyperparathyroidism. ConclusionsRenal transplantation improves secondary hyperparathyroidism. Sixty-eight percent of patients presented PTH of less than 130 pg/mL after renal transplantation. Only 2 patients underwent posttransplantation parathyroidectomy.

Comparison of effectiveness and safety of high-dose native vitamin D versus active vitamin D in the treatment of hypoparathyroidism

Objective To investigate the effectiveness and safety of high-dose native vitamin D versus active vitamin D by retrospective analysis of clinical data in patients with non-surgical hypoparathyroidism (ns-HP) in our hospital. Methods ns-HP patients with stable therapeutic schedule in recent three years were included. According to the vitamin D agents used, patients were divided into three groups: active vitamin D group, native vitamin D group, and mixed vitamin D group. The effectiveness was evaluated by analysis of markers including post-treatment serum calcium, incidence of hypocalcemia, hypocalcemic symptoms and signs. The safety was evaluated in various groups by analyzing incidences of hypercalcemia and hypercalciuria, glomerular filtration rate, percentage of thiazide diuretic use, nephrocalcinosis or renal stone. Results Patients in active vitamin D group were more likely to experience episodes of hypocalcemia compared with those in native group (32.94%±21.46% vs 24.86%±10.1%, P 0.05). Conclusions Under the circumstance of regular follow-up, both high-dose native vitamin D and active vitamin D could treat ns-HP effectively and safely. Native vitamin D may be better in maintaining eucalcemia and reducing incidence of hypocalcemia compared with active vitamin D. Key words: Non-surgical hypoparathyroidism; Native vitamin D; Active vitamin D; Treatment

Dos métodos de anticoagulación en técnicas continuas de depuración extrarrenal

Introducción: Las técnicas continuas de depuración extrarrenal son la terapia de elección en pacientes críticos. Pero, no están exentas de complicaciones como la coagulación del circuito extracorpóreo. El fármaco usado tradicionalmente para la anticoagulación, es la heparina sódica. Aunque también son empleados otros métodos de anticoagulación, como el citrato. Objetivo: Evaluar la eficacia y seguridad de dos métodos de anticoagulación en pacientes tratados con terapias continuas, en unidades de cuidados intensivos del Hospital Clínic. Material y Método: Estudio observacional, retrospectivo de 54 sujetos. Se aplicaron los criterios de Insuficiencia renal aguda, descritos en el protocolo “Guía para el tratamiento sustitutivo renal en la insuficiencia renal aguda del Hospital Clínic”. Tratados mediante hemodiafiltración, combinando terapias de convección y difusión. Con fracción de filtración &lt; 25%, y dosis de efluente de 30 ml/kg/h. 27 sujetos realizaron hemodiafiltración, reposición pre-filtro y anticoagulación con heparina sódica. El resto, hemodiafiltración, reposición post-filtro y anticoagulación con citrato. Se valoraron episodios de sangrado y duración en horas de los circuitos extracorpóreos, durante 72 horas de terapia. Resultados: El citrato demostró una mayor supervivencia de filtros (95% IC, MD 65, 44.00-72.00 vs MD 36.00, 15.00-22.00, p=0,02). Los pacientes tratados con heparina presentaron más episodios de sangrado, sin diferencias estadísticamente significativas (95% IC, n=6 vs n=9, p=0.537). Hubo un episodio de hipocalcemia en el grupo citrato, corregido según protocolo. En el grupo heparina, no se presentaron casos de trombocitopenia inducida por heparina. Conclusiones: El presente estudio, demuestra una mayor eficacia en la supervivencia de los filtros en el grupo citrato. PALABRAS CLAVE: citrato; heparina; anticoagulación regional; terapia continua depuración extrarrenal; fracaso renal agudo.

Hypocalcemia Post Denosumab in Patients with Chronic Kidney Disease Stage 4-5

Background: Denosumab, a RANK-ligand inhibitor, is an effective treatment for osteoporosis in postmenopausal women and men. Unlike the bisphosphonates, it is not excreted by the kidney. Little is known, however, about its efficacy and safety in patients with severe chronic kidney disease (CKD). Methods: A retrospective study was performed in CKD 4-5D patients from a tertiary referral hospital who were treated with denosumab between 1st January 2011 and 31st March 2014. Data collected included information about the following: CKD stage, fracture history, bone mineral density, serum calcium levels pre and post denosumab treatment, episodes of hypocalcemia, relevant medications and adverse events. Results: Eight patients with CKD-5 and 6 patients with CKD-4 were identified (all female, mean age 77.1 ± 9.9). The mean pre-denosumab calcium value was 2.42 ± 0.12 mmol/l, PTH 20.2 ± 14.7 pmol/l and 25-OH vitamin D 69.1 ± 30.1 nmol/l. After denosumab treatment, 6/8 patients with CKD-5/5D, and 2/5 patients with CKD-4 developed severe hypocalcemia. Two patients developed direct adverse complications of hypocalcemia (seizure, laryngospasm, prolonged QT_c). Among the patients who developed hypocalcemia, the median time to serum calcium nadir was 21 days and the median time to correction of hypocalcemia was 71 days. Treatment of hypocalcemia required large doses of oral calcium and calcitriol, and increases in dialysate calcium concentration. Conclusions: A high rate of severe hypocalcemia was observed in patients with advanced CKD treated with denosumab. If denosumab is used in patients with severe CKD, close monitoring and aggressive replacement of calcium and calcitriol is required to avoid the development of hypocalcemia.

Tolerability of denosumab in metastatic solid tumor patients with renal insufficiency.

Denosumab is approved for the prevention of skeletal-related events (SREs) in metastatic solid tumor patients with bone metastases. Limited data regarding the safety of denosumab in patients with severe renal insufficiency suggests increased rates of hypocalcemia compared to patients with normal renal function. The purpose of this study was to assess the rates of hypocalcemia and hypophosphatemia in cancer patients with severe renal impairment. In this case series, patient demographics, primary tumor site, number of denosumab doses, and episodes of hypocalcemia and hypophosphatemia were retrospectively obtained by patient chart review. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Twenty-two metastatic solid tumor patients with severe renal insufficiency (creatinine clearance <30 mL/min) who had received denosumab at a dose of 120 mg were included. Ten of 22 patients (45 %) experienced a hypocalcemic event of any grade. Three patients (14 %) had grade 3 hypocalcemia, and no patients had grade 4 hypocalcemia. The median number of doses of denosumab prior to calcium nadir was one. Seven of 22 patients (32 %) experienced hypophosphatemia of any grade including grade 3 events in two patients (9 %). Denosumab resulted in increased rates of hypocalcemia when administered to metastatic solid tumor patients with severe renal impairment for the prevention of SREs compared to previously reported rates of hypocalcemia in the general population. However, all cases of hypocalcemia were asymptomatic and resolved prior to subsequent dosing. Due to a higher rate of hypocalcemia than reported in patients with normal renal function, patients with severe renal impairment should receive close monitoring of calcium levels while receiving denosumab.

The Effect of Vitamin D Supplementation On Calcium Excretion in Thalassemia

Abstract 1029 Purpose of study:Transfusion dependent thalassemia (TM) patients are routinely supplemented with vitamin D due to their increased risk of developing osteoporosis. Recent studies from North America have found that these patients have high rates of vitamin D “deficiency” and “insufficiency,” despite supplementation. The amount of vitamin D supplementation required to raise serum 25 hydroxy-vitamin D (25-OHD) to optimal levels is not known in these patients. Recent studies have linked 25-OHD levels to hypercalciuria and nephrolithiasis in patients with TM. The purpose of this study is to determine the effect of various doses of vitamin D supplementation on vitamin D stores and calcium excretion in TM patients. Description of project:Prospective, single-blind, placebo-controlled study of TM patients followed in the transfusion center at Weill Cornell/New York Presbyterian Hospital. Patients with 25-OHD concentrations between 15–29 ng/mL were eligible for this 3-month study. Subjects were assigned in a block type of enrollment to the “high dose” equivalent of 2,000 IU of vitamin D per day versus placebo. Results:14 subjects were enrolled, with 8 assigned to the “high dose” group and 6 assigned to the placebo group. The “high dose” group consisted of 6 females, aged 15.2–45.5 years with an average baseline 25-OHD level of 22.4 ng/mL (15–26). The “placebo” group consisted of 4 females, aged 22.5–45.7 years with an average baseline 25-OHD level of 19.8 ng/mL (16–24). After the 3 month study period, hypercalciuria developed more frequently in those treated in the “high dose” group. In the placebo group, hypercalciuria was noted in 1/6 (16.7%) spot urine calcium/creatinine tests and 0/3 (0%) 24 hour urine calcium estimations. In the “high dose” group, the corresponding number of patients based on the same methods of testing were 5/8 (62.5%) and 2/5 (40%). No episodes of hypocalcemia, hypercalcemia or nephrolithiasis occurred in either group. Conclusion:Our findings suggest that “high dose” vitamin D supplementation results in higher rates of hypercalciuria in TM patients. Further studies are necessary to determine the optimal dose of vitamin D supplementation to minimize the risk of osteoporosis while preventing nephrolithiasis in TM patients. Disclosures:No relevant conflicts of interest to declare.

Effects and Safety of Calcimimetics in End Stage Renal Disease Patients with Secondary Hyperparathyroidism: A Meta-Analysis

PurposeSecondary hyperparathyroidism (SHPT) is one of the most common abnormalities of mineral metabolism in patients with chronic kidney disease. We performed a meta-analysis to determine the effect and safety of cinacalcet in SHPT patients receiving dialysis.MethodsThe meta-analysis was performed to determine the effect and safety of cinacalcet in SHPT patients receiving dialysis by using the search terms ‘cinacalcet’ or ‘mimpara’ or ‘sensipar’ or ‘calcimimetic’ or ‘R586’ on MEDLINE and EMBASE (January 1990 to February 2012).ResultsFifteen trials were included, all of which were performed between 2000 and 2011 enrolling a total of 3387 dialysis patients. Our study showed that calcimimetic agents effectively ameliorated iPTH levels(WMD, −294.36 pg/mL; 95% CI, −322.76 to −265.95, P<0.001) in SHPT patients and reduced serum calcium (WMD, −0.81 mg/dL; 95% CI, −0.89 to −0.72, P<0.001) and phosphorus disturbances(WMD, −0.29 mg/dL; 95% CI, −0.41 to −0.17, P<0.001). The percentage of patients in whom there was a 30% decrease in serum iPTH levels by the end of the dosing was higher in cinacalcet group than that in control group(OR = 10.75, 95% CI: 6.65–17.37, P<0.001). However, no significant difference was found in all-cause mortality and all adverse events between calcimimetics and control groups(OR = 0.86, 95% CI: 0.46–1.60, P = 0.630; OR = 1.30, 95% CI: 0.78–2.18, P = 0.320, respectively). Compared with the control therapy, there was a significant increase in the episodes of hypocalcemia (OR = 2.46, 95% CI: 1.58–3.82, P<0.001), nausea (OR = 2.45, 95% CI: 1.29–4.66, P = 0.006), vomiting(OR = 2.78, 95% CI: 2.14–3.62, P<0.001), diarrhea(OR = 1.51, 95% CI: 1.04–2.20, P = 0.030) and upper respiratory tract infection (OR = 1.79, 95% CI: 1.20–2.66, P = 0.004)in calcimimetics group.ConclusionsCalcimimetic treatment effectively improved biochemical parameters of SHPT patients receiving dialysis without increasing all-cause mortality and all adverse events.

Endoscopic Thyroidectomy: The Development in a Chinese Center

Endoscopic thyroidectomy (ET) precludes the long cervical incision of the open procedure. Although endoscopy is an essential tool taught to almost every surgeon, its effective use with regard to thyroidectomy requires understanding its limitations pertaining to trauma and cancer, as well as an understanding of the advantages and disadvantages of the different endoscopic approaches. The development of an ET center in China is discussed here. Overall, 235 patients who had undergone attempted ET in Qilu Hospital of Shandong University in China from August 2001 to September 2010 were evaluated. Of the 11 men and 224 women on whom the procedure had been attempted, all but seven successfully underwent ET, 145 (63.6%) via a modified anterior chest approach, and 83 (36.4%) via a breast approach. Age ranged from 17 to 52 years, with a mean of 34.5 years. Surgery was limited, in the case of masses, to lesions smaller than 6 cm ultrasonographically. All patients were followed for at least 3 months. The 24 and 48 hours Visual Analog Scale postoperative measurements were low. Complications included four cases of cutaneous emphysema, five seromas, four episodes of anterior chest discomfort, three transient laryngeal nerve palsies, and four episodes of hypocalcemia. The seven procedures that had been converted to an open procedure comprised two patients discovered at frozen section to have poorly differentiated thyroid carcinoma, two with tumors larger than 5 cm, and three with thyroiditis. ET is readily learned, provided the surgeon is competent at both laparoscopic technique and open thyroidectomy. Procedural advantages of an endoscopic approach include superior cosmesis and decreased invasiveness.

Traitement de l’hyperparathyroïdie secondaire, résistante aux thérapeutiques conventionnelles, et de l’hyperparathyroïdie tertiaire par le cinacalcet : une stratégie efficace

The treatment of secondary hyperparathyroidism (SHPT) in dialysis patients has changed with the introduction of cinacalcet (CC), which represents a medical alternative to surgical parathyroidectomy (PTX). The aim of our study is to prospectively assess the tolerance and efficacy of CC in patients, treated in one centre using long haemodialysis, with SHPT who do not respond to conventional therapy.We prospectively observed all patients treated with CC between September 2004 and 2009. The characteristics of the patients were compared with that recorded for the patients non treated with CC. Biological factors and the efficacy of the treatment in the patients were compared before (T-0) and after (T-End) CC therapy. The haemodialysis (HD) schedule was 3 x 5 to 3 x 8 h per week. The biological criteria for CC prescription were a serum PTH level greater than 300 pg/ml, calcium level greater than 2.45 mmol/l and bone alkaline phosphatase level greater than 20 microg/l or, in cases of tertiary hyperparathyroidism (THPT), a calcium level greater than 2.55 mmol/l.Eighty-one (14.7%) among the 550 HD patients were treated with CC. As compared to the untreated population, these patients were younger and had higher body mass index (BMI) and higher protein-catabolic rate (nPCR). The treatment failed in 6.1% of the treated patients; 12.3% had severe gastrointestinal side effects and 10% underwent PTX. The treatment was successful in 81.4% patients who were prescribed a mean final CC dosage of 51+/-30 mg/day. Between T-0 and T-End (18+/-15) months), the serum PTH levels decreased by 77%, calcaemia levels decreased by 10% and phosphataemia levels decreased by 14%. Therefore, the percentage of patients with normal biological parameters increased significantly : serum PTH (150-300 pg/ml: 0 to 50%), calcaemia (2.1-2.37 mmol/l: 6 to 77%) and phosphataemia (1.15-1.78 mol/l: 58 to 84%). After 12 months, eight patients (10%) successfully weaned from CC therapy. No episodes of hypocalcaemia (<2.0 mmol/l) occurred. Treatments with alfacalcidol (68 to 40%) and sevelamer (72 to 50%) decreased, treatments with CaCO(3) remained stable (20%), those with native vitamin D increased (55 to 95%).The treatment of HD patients having SHPT and THPT with CC and vitamin D derivatives was efficacious and well tolerated in a majority of cases after the failure of conventional therapies. These treatments improved mineral metabolism significantly.

Regional Anticoagulation with Sodium Citrate in Pediatric Patients on Intermittent Hemodialysis Therapy with Bleeding Risks

Heparin‐free anticoagulation in hemodialysis (HD) is advocated for patients with clotting abnormalities and risk of bleeding.Objective: First publication on regional citrate anticoagulation (RCA) in children. RCA is free from systemic effects, guarantees excellent dialyzer life, but requires careful monitoring.Methods: We report on 3 patients treated by intermittent RCA HD (4 h each, high‐flux dialyzer F40, Fresenius): (1) 17‐year‐old boy (renal transplant failure, access via cubital Cimino fistula) after hypertensive intra‐cerebral hemorrhage (2 sessions); (2) 13‐year‐old girl (hemolytic uremic syndrome, access via jugular vein Shaldon catheter) after abdominal surgery and bleeding (8 sessions); and (3) 7‐year‐old boy (hyperoxaluria, access via PermCath® jugular vein catheter) after renal transplant biopsy (3 sessions). Sodium citrate 30% was infused into the extra corporeal circuit (blood flow 150 mL/min) before dialyzer (initial flow 30 mL/min) and calcium gluconate 10% for antidote into venous line near of catheter or fistula (initial flow 40 mL/min). Post‐dialyzer extracorporeal serum Ca++ (aim &lt; 0.3 mmol/L) and pre‐dialyzer intra‐corporeal Ca++ (aim &gt; 0.9) were measured for every 30 min. Serum Na+, K+, base excess (BE), blood flow, blood pressure, heart rate, and blood out‐flow and in‐flow pressure were also monitored.Results: For adequate RCA (mean extracorporeal serum Ca++ 0.24 ± 0.04 mmol/L), a mean citrate flow of 36.1 ± 5.9 mL/h and a mean calcium substitution rate of 40.8 ± 3.4 mL/h were needed. Intra‐corporeal Ca++ was kept at 1.10 ± 0.07 mmol/L. Extracorporeal activated clotting time (ACT) was 194 ± 41 and intra‐corporeal ACT 90 ± 12 sec. Serum Na+, K+, and BE during HD were 138 ± 2, 3.5 ± 0.3, and −0.6 ± 1.1 mmol/L, respectively. Mean arterial blood pressures of patients 1–3 were 117 ± 5, 103 ± 5, and 102 ± 6 mmHg. All patients were stable and without any bleeding during HD. The only adverse event was 1 episode of hypocalcemia (Ca++ &lt; 0.6 mmol/L) cured by stopping dialysis.Conclusions: Local anticoagulation with sodium citrate during intermittent HD can be applied safely in children and adolescents.

A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure: Rapid Communication

The control of hyperparathyroidism in patients with chronic renal failure continues to be a problem, particularly when parathyroid hormone (PTH) suppression becomes refractory to calcitriol activation of parathyroid cell 1,25-dihydroxyvitamin D receptors. To evaluate whether parathyroid cell calcium receptor activation may be useful in suppressing PTH levels, we tested the safety and effectiveness of a novel calcimimetic agent in dialysis patients with hyperparathyroidism. In a prospective, dose finding study, the calcimimetic agent, NPS R-568, was administered orally to seven patients at the start of a hemodialysis session and again 24 hours later. Plasma PTH, calcitonin and ionized calcium levels were measured over a 48 hour period and patients were observed for adverse events. Plasma PTH levels fell abruptly in all patients after a single dose of the compound, with the maximum suppression occurring within one to two hours after its administration. Following the administration of low doses (40 or 80 mg), the suppressed PTH levels rose to baseline values over 48 hours, whereas in patients who received high doses (120 or 200 mg) the mean PTH level remained 51% below baseline. Plasma calcitonin increased after the administration of both low and high doses (peak effect within 4 to 6 hr), with levels always returning to baseline by 48 hours. There were no episodes of hypocalcemia and no adverse effects were reported. We conclude that the activation of parathyroid cell calcium receptors by a novel calcimimetic compound is safe and effective in acutely suppressing PTH secretion in dialysis patients with hyperparathyroidism. Whether concomitant stimulation of calcitonin secretion will provide added beneficial effects on bone remodeling remains to be determined in long-term studies.

Efficacy and Safety of Immunoglobulin Apheresis

Extracorporeal procedures such as plasmapheresis or protein a apheresis have been applied successfully to remove autoantibodies in the treatment of severe forms of various autoimmune diseases. A newly developed immunoapheresis technique that uses columns containing polyclonal anti human immunoglobulin (Ig) antibodies was investigated in four patients with idiopathic thrombocytopenic purpura (ITP). A series of two to four treatments were performed, and the period between the two series was dependent on the actual thrombocyte count. A total of 38 treatments was carried out. During the first apheresis, IgG declined to a mean of 52.7% of the initial concentration. The IgG subclasses one through four were decreased to the same extent. The IgA was lowered to 64.4%, and IgM was lowered to 66.7%. A series of four aphereses yielded a 75-80% decline of the different Ig species. A further decrease in Ig would have been possible, but was not aimed at in this study. All Ig fractions reincreased between the two series. In two patients, a rise in thrombocytes as a response to treatment was observed. Apart from three hypotensive reactions and one episode of hypocalcemia, no further side effects occurred in 38 treatments. The authors conclude that Ig apheresis with anti human Ig antibodies is an effective and safe form of treatment. Its effect on the clinical course of autoimmune diseases merits further investigation.