Impacts of parathyroidectomy on calcium and phosphorus metabolism disorder, arterial calcification and arterial stiffness in haemodialysis patients.

BACKGROUND: Secondary hyperparathyroidism (SHPT) and calcium and phosphorus metabolism disorder are important complications in haemodialysis patients. Parathyroidectomy (PTX) may prevent or delay the progress of vascular calcification in haemodialysis patients. OBJECTIVE: To investigate the impacts of PTX on calcium and phosphorus metabolism, arterial calcification and arterial stiffness in haemodialysis patients with SHPT. METHODS: Twenty-one SHPT-haemodialysis patients were selected for PTX. The preoperative and postoperative 1-year scores of coronary artery calcification were measured via multislice spiral CT, along with the brachial-ankle pulse wave velocity (baPWV), and preoperative and postoperative 1-year indexes such as calcium, phosphorus, calcium-phosphorus product concentration and parathyroid hormone (PTH) level were compared. RESULTS: Compared with the preoperative score, the postoperative 1-year coronary artery calcification score was significantly reduced; the mean baPWVs of the bilateral limbs were reduced; and the levels of serum calcium, phosphorus, calcium-phosphorus product concentration and PTH were all reduced; all differences were statistically significant (P < 0.05). CONCLUSIONS: PTX can be used to correct calcium and phosphorus metabolism disorder, reduce arterial calcification, and improve arterial stiffness.

Effects of zoledronate on the radiation-induced collagen breakdown: a prospective randomized clinical trial

Background: A negative side effect of therapeutic irradiation is the radiation-induced bone loss which can lead, in long term, to pathological fractures. Until today, the detailed mechanism is unknown. If osteoclasts would mainly contribute to the pathological bone loss, bisphosphonates could potentially counteract the osteolytic process and possibly help to prevent long-term complications. The aim of this study was to evaluate the effect of zoledronic acid on the early radiation-induced degradation of bone collagen fibrils by monitoring the urinary excretion of hydroxylysylpyridinoline and lysylpyridinoline under radiotherapy. Patients and methods: A total of 40 patients with skeletal metastases were assigned for a local radiotherapy and bisphosphonate treatment. The patients were prospectively randomized into two treatment groups: group A (n = 20) received the first zoledronate administration after and group B (n = 20) prior to the radiotherapy. Urine samples were collected from each patient on the first day, in the middle, and on the last day of the radiation therapy. Measurement of the bone metabolites hydroxylysylpyridinoline and lysylpyridinoline was performed by high-performance liquid chromatography. Statistical analysis was performed using the Mann–Whitney U test. Results: The hydroxylysylpyridinoline and lysylpyridinoline excretion decreased significantly in the combined bisphosphonate and radiotherapy group (p = 0.02, p = 0.08). No significant change of the hydroxylysylpyridinoline and lysylpyridinoline excretion was determined in the patients that received solely irradiation. Conclusion The results indicate the ability of zoledronate to prevent the early radiation-induced bone collagen degradation suggesting that the radiation-induced bone loss is mainly caused by osteoclastic bone resorption rather than by a direct radiation-induced damage (AU)

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Cinacalcet in patients with chronic kidney disease: a cumulative meta-analysis of randomized controlled trials.

BACKGROUND: Calcimimetic agents lower serum parathyroid hormone levels in people with chronic kidney disease (CKD), but treatment effects on patient-relevant outcomes are uncertain. We conducted a systematic review and meta-analysis to summarize the benefits and harms of calcimimetic therapy in adults with CKD and used cumulative meta-analysis to identify how evidence for calcimimetic treatment has developed in this clinical setting. METHODS AND FINDINGS: Cochrane and Embase databases (through February 7, 2013) were electronically searched to identify randomized trials evaluating effects of calcimimetic therapy on mortality and adverse events in adults with CKD. Two independent reviewers identified trials, extracted data, and assessed risk of bias. Eighteen trials comprising 7,446 participants compared cinacalcet plus conventional therapy with placebo or no treatment plus conventional therapy in adults with CKD. In moderate- to high-quality evidence (based on Grading of Recommendations Assessment, Development, and Evaluation criteria) in adults with CKD stage 5D (dialysis), cinacalcet had little or no effect on all-cause mortality (relative risk, 0.97 [95% confidence interval, 0.89-1.05]), had imprecise effect on cardiovascular mortality (0.67 [0.16-2.87]), and prevented parathyroidectomy (0.49 [0.40-0.59]) and hypercalcemia (0.23 [0.05-0.97]), but increased hypocalcemia (6.98 [5.10-9.53]), nausea (2.02 [1.45-2.81]), and vomiting (1.97 [1.73-2.24]). Data for clinical outcomes were sparse in adults with CKD stages 3-5. On average, treating 1,000 people with CKD stage 5D for 1 y had no effect on survival and prevented about three patients from experiencing parathyroidectomy, whilst 60 experienced hypocalcemia and 150 experienced nausea. Analyses were limited by insufficient data in CKD stages 3-5 and kidney transplant recipients. CONCLUSIONS: Cinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D, but does not appear to improve all-cause or cardiovascular mortality. Additional trials in CKD stage 5D are unlikely to change our confidence in the treatment effects of cinacalcet in this population.

Confusion on the complexity of calcium balance.

Calcium balance is an overall assessment of the net calcium taken in minus the net calcium taken out. It can only be assessed when patients are in steady state and requires complicated isotope methods that can simultaneously assess intestinal absorption and endogenous secretion, urinary and stool excretion, bone calcium uptake and removal, and dialysate calcium removal. By virtue of the need for steady state, formal balance studies cannot be accurately carried out in patients on dialysis. However, many of the components of calcium balance have been assessed. Importantly, because 99% of calcium is in bone, studies must accurately assess both the rapidly exchangeable calcium from the bone surface and the net bone calcium balance that results from the difference in bone formation minus resorption. While it is tempting to adjust the dialysate calcium concentration to correct the net positive calcium balance that is likely present in patients who receive calcium-based phosphate binders, the reality is that the highly variable, yet important, role of bone cannot be easily assessed at the bedside. Thus, it is best to prevent the calcium overload in the first place by avoiding high-dose calcium-based phosphate binders and optimizing bone remodeling.

[The French clinician's guide to the Kidney disease: Improving global outcomes (KDIGO) for chronic kidney disease-mineral and bone disorders (CKD-MBD)]. / L'essentiel des nouvelles recommandations des kidney disease: improving global outcomes (KDIGO) pour les désordres du métabolisme minéral et osseux à l'usage du clinicien francophone.

The new recommendations of "Kidney disease: improving global outcomes" for the definition and classification of chronic kidney disease and mineral and bone disorders were released in August 2009. We report the most important of these recommendations and a brief comment from a clinician's point of view. The main points to be noted with regard to the new recommendations are as follows: serum calcium should be in the normal range; phosphorus concentration should be lowered toward the normal range and serum parathyroid hormone (PTH) levels should be two to nine times the upper limit of the normal range; bone remodelling can be assessed using alkaline phosphatase; the use of calcium-phosphorus (Ca x P) product as an index is not recommended anymore; at any stage of CKD, vitamin D deficiency and insufficiency must be corrected; vascular calcification should be detected in a simple way using lateral abdominal radiography and echocardiography; a bone biopsy should be performed before therapy with bisphosphonates; the prescription of dialysate calcium should be individualized within the range of 1.25-1.5 mmol/l; the phosphate binder (calcium- or non-calcium-based) and the other treatments for secondary hyperparathyroidism should be individualized based on a global strategy. A majority of these recommendations are not based on evidence and their feasibility and relevance need to be assessed.

Calcium balance in dialysis is best managed by adjusting dialysate calcium guided by kinetic modeling of the interrelationship between calcium intake, dose of vitamin D analogues and the dialysate calcium concentration.

Calcium mass balance (Ca(MB)) is determined by the difference between Ca absorbed between dialyses (Ca(Abs)) and the Ca removed during dialysis (J(d)Ca(2+)). A mathematical model to quantify (1) Ca(Abs) as a function of Ca intake (Ca(INT)) and the doses of vitamin D analogues, and (2) J(d)Ca(2+) as a function of Ca(2+) dialysance, the mean plasma Ca(2+) ((M)C(pi)Ca(2+)) minus dialysate Ca(2+) (C(di)Ca(2+)), ultrafiltration rate (Q(f)) and treatment time is developed in this paper. The model revealed a basic design flaw in clinical studies of Ca-based as opposed to non-Ca-based binders in that C(di)Ca(2+) must be reduced with the Ca-based binders in order to avoid a positive Ca(MB) relative to the non-Ca-based binders. The model was also used to analyze Ca(MB) in 320 Renal Research Institute hemodialysis patients and showed that all patients irrespective of type of binder were in positive Ca(MB) between dialyses (mean +/- SD 160 +/- 67 mg/day) with current doses of vitamin D analogues prescribed. Calculation of the optimal C(di)Ca(2+) for the 320 Renal Research Institute patients revealed that in virtually all instances, the C(di)Ca(2+) required for neutral Ca(MB), where Ca removal during dialysis was equal to Ca accumulation between dialyses, was less than 2.50 mEq/l and averaged about 2.00 mEq/l. This sharply contradicts the recent KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease - Mineral and Bone Disorder, that suggests a C(di)Ca(2+) of 2.5-3.0 mEq/l. Review of the KDIGO work group discussions shows that this discrepancy stems from the unwarranted work group assumption that intradialytic Ca(MB) is zero. We strongly believe that this guideline for dialysate Ca(2+) is inappropriate and should be modified to more realistically reflect the needs of dialysis patients.

[Prevalence and quality of control of calcium and phosphorus metabolism disorders among Lithuanian hemodialysis patients in 2004 and 2005]. / Kalcio ir fosforo apykaitos sutrikimu paplitimas, pobudis bei kontroles kokybe tarp Lietuvos hemodializuojamu ligoniu (2004-2005 metu duomenimis).

UNLABELLED: The aim of the study was to determine the prevalence and quality of control of disorders of calcium and phosphorus metabolism among patients on hemodialysis in Lithuania during the period of 2004-2005 and to assess rarely used methods of treatment such as parathyroidectomy and administration of calcimimetics. MATERIAL AND METHODS: All Lithuanian hemodialysis centers were visited, and data on disorders of calcium-phosphorus metabolism were collected in December 2004 and 2005. The quality of control was evaluated according to Kidney Disease Outcome Quality Initiative recommendations. RESULTS: According to Kidney Disease Outcome Quality Initiative guidelines, normal parathyroid hormone levels were found in 20.4% of hemodialysis patients in 2004 and 18.8% of hemodialysis patients in 2005; normal levels of phosphate were in 41.9% and 39.4%, respectively; normal levels of calcium were observed in 44.7% of patients in 2004 and in 42.3% of patients in 2005. In 2005 as compared to 2004, there were statistically significantly more patients with low parathyroid hormone level (39.9% and 45.8%, respectively, P<0.05). Only in 5.6% of patients in 2004 and 3.9% of patients in 2005, all four parameters of calcium-phosphate metabolism (calcium, phosphate, and of parathyroid hormone levels and calcium-phosphate product) were within the normal range. No parameters in the normal range were found in 17-20% of patients. The use of alfacalcidol significantly increased: 316 (30.8%) patients in 2004 and 388 (35.7%) patients in 2005 were treated with alfacalcidol (P<0.05). Alfacalcidol was prescribed for 16.5% of patients in 2004 and for 17% of patients in 2005, in whom parathyroid hormone level was below the normal range in the presence of hypercalcemia and hyperphosphatemia. The use of calcimimetics was considered rational in 142 (13.8%) patients in 2004 and 119 (10.9%) patients in 2005. According to the data of our study, parathyroidectomy was indicated in 19 (1.85%) patients in 2004 and 17 (1.56%) patients in 2005. CONCLUSIONS: According to Kidney Disease Outcome Quality Initiative recommendations, the control of disorders of calcium-phosphate metabolism in Lithuanian hemodialysis patients was insufficient in 2004 and 2005. One-third of the patients were treated with alfacalcidol when parathyroid hormone level was low and hypercalcemia and hyperphosphatemia persisted. Calcimimetics for the treatment of secondary hyperparathyroidism were administered in about 10% of patients.

Vitamin D receptor modulators for inflammation and cancer.

1alpha, 25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active form of vitamin D, is an important hormone that is critically required for the maintenance of mineral homeostasis and structural integrity of bones. 1,25-(OH)2D3 accomplishes this by facilitating calcium absorption from the gut and by a direct action on osteoblasts, the bone forming cells. Apart form its classical actions on the gut and bone, 1,25-(OH)2D3 and its synthetic analogs also possess potent anti-proliferative, differentiative and immunomodulatory activities. 1,25-(OH)2D3 exerts these effects through vitamin D receptor (VDR), a ligand-dependent transcription factor that belongs to the superfamily of steroid/thyroid hormone/retinoid nuclear receptors. The presence of VDR in various tissues other than gut and bone, along with their ability to exert differentiation, growth inhibitory and anti-inflammatory action, has set the stage for therapeutic exploitation of VDR ligands for the treatment of various inflammatory indications and cancer. However, the use of VDR ligands in clinic is limited by their major dose-related side effect, namely hypercalcemia/hypercalciuria. Efforts are being undertaken to develop vitamin D receptor modulators (VDRMs) that are tissue-selective and/or gene-selective in their action and these ligands may exhibit increased therapeutic indices. This review explores the recent advances in VDR biology, non-secosteroidal VDR ligands and the current and potential clinical applications of VDR ligands in inflammation and cancer.

Costs and consequences of using pamidronate compared with zoledronic acid in the management of breast cancer patients in the UK.

OBJECTIVE: To estimate the costs and consequences of using pamidronate compared to zoledronic acid in the prophylactic management of skeletal morbidity among breast cancer patients in the UK. DESIGN AND SETTING: This was a modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: Published clinical outcomes from a comparative study were combined with resource utilisation estimates derived from a panel of clinicians. This enabled the construction of a decision model depicting the management of patients with breast cancer receiving antineoplastic therapy who are 18 years of age or above and who have at least one bone metastasis (lytic or mixed). There are no significant differences in outcome between using pamidronate and zoledronic acid in breast cancer patients. Therefore, a cost minimisation analysis was performed to identify the treatment strategy that achieves the same outcome for least cost. The expected time attributable to a pamidronate and zoledronic acid infusion was also estimated. MAIN OUTCOME MEASURES AND RESULTS: Starting treatment with pamidronate among patients receiving chemotherapy is expected to lead to a healthcare cost of 6046 pounds over 12 months compared to 6981 pounds with zoledronic acid. In comparison, for patients receiving hormonal therapy, starting treatment with pamidronate is expected to lead to a healthcare cost of 5401 pounds over 12 months compared to 6043 pounds with zoledronic acid. This cost difference is primarily due to the lower acquisition cost of pamidronate and fewer tests among pamidronate-treated patients. Accordingly, pamidronate affords a less expensive management modality. Multivariate analysis showed the expected time attributable to a pamidronate infusion to be 110 to 277 minutes compared with 136 to 296 minutes for a zoledronic acid infusion. CONCLUSION: Use of pamidronate instead of zoledronic acid affords an economic benefit to the NHS. Moreover, published clinical trials show no statistical difference between pamidronate and zoledronic acid at 1 year. Hence, within the limitations of our model and the published evidence, pamidronate is the preferred first-line intravenous bisphosphonate for use in breast cancer patients receiving antineoplastic therapy who are 18 years of age or above and who have at least one bone metastasis (lytic or mixed).

[The antioxidant prevention of disorders in calcium ion metabolism under the action of glutamate on the synaptosomes of the rat cerebral cortex]. / Predotvrashchenie antioksidantami narushenii obmena ionov kal'tsiia pri deistvii glutamata na sinaptosomy kory mozga krys.

An increase of intracellular calcium ion concentration and of the 45Ca2+ entry, a decrease in Na+,K(+)-ATPase activity, and activation of Na+/Ca2+ exchange were shown to be initiated by glutamate in the rat brain cortex synaptosomes. These effects could be prevented with antagonists and blocking agents of the NMDA receptors. Pre-incubation of the synaptosomes with alpha-tocopherol, superoxide dismutase, and ganglioside GM1 was shown to normalise [45Ca2+], the rate of 45Ca2+ entry, and the activity of Na+,K(+)-ATPase in the synaptosomes. The data obtained suggest that calcium ions entering the brain cortex neurones via the NMDA receptors in presence of excessive glutamate, trigger activation of free radical reactions damaging the neurones in ischemia, cerebral lesions, and other pathological conditions.

Hipercalcemia, hipercalciuria: en pacientes con tuberculosis pulmonar activa / Hypercalcemia, hypercalciuria: in patients with active pulmonary tuberculosis

Dada la relación existente entre hipercalcemia, hipercalciuria con enfermedades granulomatosas, se presenta un estudio de 10 pacientes con tuberculosis (TBCP), donde se midió calcio sérico corregido por albúmina, calciuria, paratohormona, fósforo, ingesta de calcio, índice de masa corporal (I.M.C) y radiología de tórax. Se encontró en todos ellos un 80 por ciento de desnutrido, 60 por ciento de baciloscopia ++; radiología entre lesión moderada y avanzada sin evidenciar hipercalcemia. Se concluye que los transtornos del calcio asociados a TBCP no es un mecanismo constante sino más bien un proceso no bien conocido

[Effect of hydrochlorothiazide on calcium metabolism in postoperative hypoparathyroidism]. / Wplyw hydrochlorotiazydu na metabolizm wapnia w pooperacyjnej niedoczynnosci tarczycy.

Vitamin D3 administered to patients with postoperative hypoparathyroidism increases calcium absorption from the gut and calcium blood levels but leads to hypercalciuria and may produce renal lithiasis. Thiazides decrease calcium excretion with the urine. Therefore, an effect of combined therapy with hydrochlorothiazide, vitamin D3 and calcium on hypoparathyroidism was investigated. Twenty one women were selected out of 135 patients with postoperative hypoparathyroidism. These women were constantly given vitamin D3 (30,000-225,000 IU daily) and calcium. Normocalcemia, hyperphosphatemia and hypercalciuria were noted before the treatment with hydrochlorothiazide. Therapy normalized hypercalciuria but did not change mean differences in calcemia, phosphatemia, magnesemia, blood alkaline phosphatase and phosphates and magnesium clearance factors. Hypercalcemia and necessity to withdraw hydrochlorothiazide together with change of either doses or preparation of vitamin D3 were noted in three patients, including one patient in whom both hypercalcemia and hypercalciuria with the symptoms of vitamin D3 poisoning were observed. The author suggests that combined therapy with hydrochlorothiazide, vitamin D3 and calcium prevents hypercalciuria but may require changes in vitamin D3 dosage and withdrawal of hydrochlorothiazide in some patients.

[Use of xidifon for prevention and treatment of nephropathies with metabolic disorders in children]. / Ispol'zovanie ksidifona dlia profilaktiki i lecheniia dismetabolicheskikh nefropatii u detei.

Xydofon was applied to the treatment of 68 children suffering from different renal diseases associated with metabolic disorders. The latter ones involved oxaluria (28 children), uraturia (17 children), cystinuria (14 children), and phosphaturia (9 children). To appraise the action of xydofon, use was made of the indicators of membranolysis, cellular homeostasis of calcium, lipid peroxidation, and of the level of beta 2-microglobulin in urine. The results obtained indicate that xydofon can be used as an effective remedy for the treatment of children suffering from nephropathies associated with metabolic disorders.

Aplicacao de Calcarea phosphorica na osteodistrofia fibrosa em frangos de corte / Calcarea phosphorica utilization in fibrous osteodystrophy in young chicken

Pintinhos de um dia da linhagem Cobb foram distribuidosem 6 grupos experimentais com 4 repeticoes, sendo 2 de cada sexo. Cada grupo recebeu Arsenicum album 30 CH, nosodio P.B.S. 30 CH, Calcarea phosphorica 30 CH, Arsenicum album + nosodio P.B.S. 30 CH e Colibacillinum C200, respectivamente e o ultimo grupo foi o controle que recebeu agua. Estes animais foram tratados com racao de milho e farelo, "ad libidum" e receberam os tratamentos na agua de beber. No decorrer da experimentacao, as aves apresentaram a sindrome da oeteodistrofia fibrosa por baixa disponibilidade de calcio e fosforo, na racao. Porem, as aves tratadas com Calcarea phosphorica 30 CH tiveram o seu peso dentro do normal, nao apresentando sintomas caracteristicos da deficiencia de fosforo. Por outro lado, os outros grupos nao foram beneficiados pelos tratamentos recebidos apresentando deficiencia no dsenvolvimento e ganho do peso