Cardiovascular calcifications in dialysis patients / Calcifications cardiovasculaires chez le patient dialysé

Patients with advanced chronic kidney disease and those already on dialysis have an increased prevalence of cardiovascular calcifications. They are the cause of severe complications and are associated with a reduced life expectancy in these patients. Recommendations and imaging scores have been developed to detect and assess their importance, to guide and improve the management of cardiovascular risk. However, despite these recommendations, current practice teaches us that they are only partially applied. The prevention and treatment of cardiovascular calcifications go through the correction of classic risk factors associated with atherosclerosis, mineral and bone metabolism disorders and by optimizing the dose and the efficiency of dialysis. New therapeutic strategies are beginning to emerge, others are being evaluated, such as sodium thiosulfate, rheopheresis, vitamin K, magnesium supplementation, and SNF-472.

Les patients atteints de maladie rénale chronique (MRC) avancée et ceux déjà traités par dialyse présentent une prévalence accrue de calcifications cardiovasculaires. Elles sont à l'origine des complications sévères et s'associent à une diminution de l'espérance de vie chez ces patients. Des recommandations et des scores radiographiques ont été développés pour dépister et évaluer leur importance, afin d'orienter et améliorer la prise en charge du risque cardiovasculaire. Cependant, en dépit de ces recommandations, la pratique courante nous enseigne qu'elles ne sont que partiellement appliquées. La prévention et le traitement de calcifications cardiovasculaires passent par la correction des facteurs de risque classiques associés à l'athérosclérose, des troubles du métabolisme minéral et osseux et en optimisant la dose et l'efficacité de la dialyse. Des nouvelles stratégies thérapeutiques commencent à voir le jour, d'autres sont en cours d'évaluation, comme le thiosulfate de sodium, la rhéophérèse, la vitamine K, la supplémentation en magnésium et le SNF-472.

A meta-analysis of randomized controlled trials of tonifying kidney and strengthen bone therapy on nondialysis patients with chronic kidney disease-mineral and bone disorder.

BACKGROUND: Correction of calcium, phosphorus, and parathyroid hormone disorders is the standard of treatment in nondialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). However, the side effects and adverse reactions are still the main problems. Moreover, the lack of protection of kidney function in the treatment dramatically affects patients' health. Although Traditional Chinese Medicine, specifically tonifying kidney and strengthen bone (TKSB) therapy, is wildly applied to patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we conducted this meta-analysis to evaluate the efficacy and safety of TKSB therapy combined with Western medicine (WM) for nondialysis patients with CKD-MBD. METHODS: Two investigators conducted systematic research of randomized controlled trials of TKSB therapy for CKD-MBD from 7 electronic databases. Methodological quality evaluations were performed using the Cochrane collaboration tool, and data analysis was conducted by RevMan v5.3 software and STATA v15.0. RESULTS: In total, 8 randomized controlled trials involving 310 patients met the criteria of meta-analysis. The complete results showed that compared with WM alone, TKSB treatment could improve the clinical efficacy rate (risk ratio = 4.49, 95% confidence interval [CI]: [2.64, 7.61], P  .00001), calcium (weighted mean difference [WMD] = 0.11, 95% CI: [0.08, 0.14], P < .00001), serum creatinine (WMD = 45.58, 95% CI: [32.35, 58.8], P < .00001) phosphorus (WMD = 0.11, 95% CI: [0.08, 0.13], P < .00001), parathyroid hormone (WMD = 16.72, 95% CI: [12.89, 20.55], P < .00001), blood urea nitrogen levels (WMD = 0.95, 95% CI: [0.26, 1.64], P = .007) on nondialysis patients with CKD-MBD, which was beneficial to improve the patients' bone metabolic state and renal function. In addition, evidence shows that, compared with WM alone, TKSB treatment is safe and does not increase side effects. CONCLUSION: The systematic review found that TKSB therapy combined with WM has a positive effect on improving renal function and correcting bone metabolism disorder in nondialysis patients with CKD-MBD, which shows that Traditional Chinese Medicine is effective and safe in treating CKD-MBD. However, more high-quality, large-sample, multicenter clinical trials should be conducted to assess the safety and efficacy of TKSB therapy in treating nondialysis patients with CKD-MBD.Systematic review registration: INPLASY2020120086.

Dentoalveolar Alterations in an Adenine-Induced Chronic Kidney Disease Mouse Model.

Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD-MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD-MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)-induced CKD (AD-CKD) mouse model. Eight-week-old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high-phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro-computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp-dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue-nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD-CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD-associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effects of Plant-Based Protein Consumption on Kidney Function and Mineral Bone Disorder Outcomes in Adults With Stage 3-5 Chronic Kidney Disease: A Systematic Review.

INTRODUCTION: Plant-based protein is of growing interest for dietary management of chronic kidney disease (CKD) and is hypothesized to preserve kidney function and reduce CKD-mineral bone disorder (MBD) complications, among other benefits. This systematic review aimed to summarize the available clinical trial evidence for the effect of plant-based protein on kidney function and CKD-MBD outcomes in adults with stage 3-5 CKD not on dialysis. METHODS: Searches of Medline, Embase, Agricola, CAB abstracts, Web of Science, Scopus, and hand searching were performed. Clinical trials with ≥8 participants ≥18 years of age with an estimated glomerular filtration rate <60 mL/min/1.73 m2 but not on dialysis were included. Additionally, only clinical trials with ≥1-week interventions with ≥50% dietary protein from plant-based sources and reported at least one outcome for both kidney function and CKD-MBD outcomes were included. Of the 10,962 identified abstracts, 32 met inclusion criteria and were assessed for risk of bias. RESULTS: Results for kidney function and CKD-MBD outcomes were heterogenous, with most studies having suboptimal methodological quality. In most of the studies (27/32), protein source was altered only secondarily to low-protein diet interventions. Thus, data synthesis and interpretation were focused on a subset of five studies that investigated a change in protein source only (i.e., animal vs. plant). Of this subset, four studies reported no change in kidney function, while one study reported a decrease. Three studies reported no change in serum phosphorus, and one study reported lower serum phosphorus following a vegetarian diet. Further, limited data and inconclusive results were observed for phosphaturic hormones, parathyroid hormone, and fibroblast growth factor-23. CONCLUSION: Current clinical trial evidence on plant-based protein interventions for preserving kidney function and preventing CKD-MBD is limited to inform clinical guidelines at this time. This systematic review emphasizes the ongoing need to research the effects of plant-based protein on kidney function and CKD-MBD outcomes.

FGF23 Actions in CKD-MBD and other Organs During CKD.

Fibroblast growth factor 23 (FGF23) is a new endocrine product discovered in the past decade. In addition to being related to bone diseases, it has also been found to be related to kidney metabolism and parathyroid metabolism, especially as a biomarker and a key factor to be used in kidney diseases. FGF23 is upregulated as early as the second and third stages of chronic kidney disease (CKD) in response to relative phosphorus overload. The early rise of FGF23 has a protective effect on the body and is essential for maintaining phosphate balance. However, with the decline in renal function, eGFR (estimated glomerular filtration rate) declines, and the phosphorus excretion effect caused by FGF23 is weakened. It eventually leads to a variety of complications, such as bone disease (Chronic Kidney Disease-Mineral and Bone Metabolism Disorder), vascular calcification (VC), and more. Monoclonal antibodies against FGF23 are currently used to treat genetic diseases with increased FGF23. CKD is also a state of increased FGF23. This article reviews the current role of FGF23 in CKD and discusses the crosstalk between various organs under CKD conditions and FGF23. Studying the effect of hyperphosphatemia on different organs of CKD is important. The prospect of FGF23 for therapy is also discussed.

Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy.

Patients with advanced chronic kidney disease (CKD) often present with skeletal abnormalities, a condition known as renal osteodystrophy (ROD). While tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 are critical for bone mineralization, their role in the etiology of ROD is unclear. To address this, ROD was induced in both WT and Phospho1 knockout (P1KO) mice through dietary adenine supplementation. The mice presented with hyperphosphatemia, hyperparathyroidism, and elevated levels of FGF23 and bone turnover markers. In particular, we noted that in CKD mice, bone mineral density (BMD) was increased in cortical bone (P < 0.05) but decreased in trabecular bone (P < 0.05). These changes were accompanied by decreased TNAP (P < 0.01) and increased PHOSPHO1 (P < 0.001) expression in WT CKD bones. In P1KO CKD mice, the cortical BMD phenotype was rescued, suggesting that the increased cortical BMD of CKD mice was driven by increased PHOSPHO1 expression. Other structural parameters were also improved in P1KO CKD mice. We further investigated the driver of the mineralization defects, by studying the effects of FGF23, PTH, and phosphate administration on PHOSPHO1 and TNAP expression by primary murine osteoblasts. We found both PHOSPHO1 and TNAP expressions to be downregulated in response to phosphate and PTH. The in vitro data suggest that the TNAP reduction in CKD-MBD is driven by the hyperphosphatemia and/or hyperparathyroidism noted in these mice, while the higher PHOSPHO1 expression may be a compensatory mechanism. Increased PHOSPHO1 expression in ROD may contribute to the disordered skeletal mineralization characteristic of this progressive disorder.

Role of Vitamin K in Chronic Kidney Disease: A Focus on Bone and Cardiovascular Health.

Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease-mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications.

The Importance of Phosphate Control in Chronic Kidney Disease.

A series of problems including osteopathy, abnormal serum data, and vascular calcification associated with chronic kidney disease (CKD) are now collectively called CKD-mineral bone disease (CKD-MBD). The pathophysiology of CKD-MBD is becoming clear with the emerging of αKlotho, originally identified as a progeria-causing protein, and bone-derived phosphaturic fibroblast growth factor 23 (FGF23) as associated factors. Meanwhile, compared with calcium and parathyroid hormone, which have long been linked with CKD-MBD, phosphate is now attracting more attention because of its association with complications and outcomes. Incidentally, as the pivotal roles of FGF23 and αKlotho in phosphate metabolism have been unveiled, how phosphate metabolism and hyperphosphatemia are involved in CKD-MBD and how they can be clinically treated have become of great interest. Thus, the aim of this review is reconsider CKD-MBD from the viewpoint of phosphorus, its involvement in the pathophysiology, causing complications, therapeutic approach based on the clinical evidence, and clarifying the importance of phosphorus management.

Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review.

Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one's short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.

Cinacalcet use in paediatric dialysis: a position statement from the European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders Working Group of the ERA-EDTA.

Secondary hyperparathyroidism (SHPT) is an important complication of advanced chronic kidney disease (CKD) in children, which is often difficult to treat with conventional therapy. The calcimimetic cinacalcet is an allosteric modulator of the calcium-sensing receptor. It has proven to be effective and safe in adults to suppress parathyroid hormone (PTH), but data on its use in children are limited. To date, studies in children only consist of two randomized controlled trials, nine uncontrolled interventional or observational studies, and case reports that report the efficacy of cinacalcet as a PTH-lowering compound. In 2017, the European Medical Agency approved the use of cinacalcet for the treatment of SHPT in children on dialysis in whom SHPT is not adequately controlled with standard therapy. Since evidence-based guidelines are so far lacking, we present a position statement on the use of cinacalcet in paediatric dialysis patients based on the available evidence and opinion of experts from the European Society for Paediatric Nephrology, Chronic Kidney Disease-Mineral and Bone Disorder and Dialysis Working Groups, and the ERA-EDTA. Given the limited available evidence the strength of these statements are weak to moderate, and must be carefully considered by the treating physician and adapted to individual patient needs as appropriate. Audit and research recommendations to study key outcome measures in paediatric dialysis patients receiving cinacalcet are suggested.

[Complications and treatment of mineral and bone disorders in chronic kidney disease]. / Complications et prises en charge thérapeutiques des anomalies du métabolisme phosphocalcique de l'insuffisance rénale chronique.

Mineral and bone disorders are frequently observed in chronic kidney disease. Prevening these metabolic, bone and cardiovascular consequences requires a treatment strategy based on physiopathology and international recommendations. The precise diagnosis of these mineral and bone disorders is based on serum parathyroid hormone and alkaline phosphatases values allowing to identify secondary hyperparathyroidism and adynamic bone disease, that are both associated with cardiovascular complication together with calcium and phosphate imbalance. Chronic kidney disease-mineral and bone disorders are associated with bone disease and fractures. Bone biopsies are no longer performed and bone mineral density can be used in order to assess the risk for fractures. Vascular calcification is a major cardiovascular risk factor associated with chronic kidney disease-mineral and bone disorders and its prevention needs to normalized both serum calcium and phosphate values, to correct vitamin D deficiendy and to maintain an optimal bone turn over. The main treatments rely on are dietary counseling, dialysis prescription, calcium supplement, phosphate binders, vitamin D derivatives, calcimimetics and surgical parathyroidectomy. We suggest some treatments strategies based on diagnosis criteria in order to help the nephrologist to identify and treat mineral and bone disorders at all chronic kidney disease stages, to decrease complication frequency and to improve the bone and the cardiovascular prognosis of chronic kidney disease patients.

Peritoneal dialysis can alleviate the clinical course of hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

PURPOSE: It is unclear whether clinical courses of hungry bone syndrome (HBS) after parathyroidectomy (PTX) in peritoneal dialysis (PD) and hemodialysis (HD) patients are different. The present study aimed to investigate the possible differences of postoperative hypocalcemia and hyperkalemia between PD and HD patients. METHODS: We performed retrospectively 29 PD patients as the PD group and 169 HD patients as the HD group undergoing successful total PTX with autotransplantation. Calcium supplement after surgery was recorded. Higher levels of serum potassium during and immediately after surgery were recorded as K+d0. K+d3 was recorded as peak pre-dialysis serum potassium level 3 days post-surgery. RESULTS: There were 157 (92.90%) patients in HD group and 22 (75.86%) patients in PD group suffered from HBS after surgery, with significant difference between the groups (P = 0.004). Patients in PD group had significantly shorter intravenous calcium supplement duration (P = 0.037) and significantly smaller intravenous calcium supplement dosage (P = 0.042) and total calcium supplement dosage during hospitalization (P = 0.012) than patients in HD group. The levels of serum K+d0 (P < 0.001) and K+d3 (P < 0.001) were both significantly lower in PD group than those in HD group. Peritoneal dialysis was one of the independent influencing factors with negative correlation for calcium supplement, serum K+d0 and serum K+d3. CONCLUSIONS: Compared with HD patients, the clinical course of HBS after PTX in PD patients was alleviated. Efforts should be devoted to individual perioperative management for PD patients undergoing PTX.

Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease-mineral bone disorder parameters in dialysis patients.

BACKGROUND: Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or sevelamer carbonate ('sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia. METHODS: After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. RESULTS: Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. CONCLUSIONS: Overall, 1 year of sucroferric oxyhydroxide or sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.

Initial surgical results of 500 Parathyroidectomies for Hyperparathyroidism related to chronic kidney disease - mineral and bone disorder / Resultados cirúrgicos iniciais de 500 Paratireoidectomias por Hiperparatireoidismo relacionado a distúrbio mineral e ósseo da doença renal crônica

ABSTRACT Introduction: Surgical treatment of hyperparathyroidism related to chronic kidney disease is a challenging procedure even for experienced parathyroid surgeons. Over the years, adjuvant techniques have been developed to assist the medical team to improve surgical outcomes. However, medical staff in poor countries have less access to these techniques and the effectiveness of surgery in this context is unclear. Objective: verify the effectiveness of surgery for treatment of hyperparathyroidism related to chronic kidney disease without adjuvant techniques. Methods: Over a 5-years period, patients with hyperparathyroidism that had clinical therapeutic failure were evaluated for surgical treatment. Total parathyroidectomy with autograft or subtotal resection were the selected procedures. Surgeries were performed in a tertiary hospital in Brazil without the assistance of some of the adjuvant techniques that are usually applied, such as frozen section, nerve monitoring, and gamma probe. Intraoperative PTH and localization pre-operative exams were applied, but with huge restrictions. Results: A total of 518 patients with hyperparathyroidism (128 secondary and 390 tertiary) were surgically treated. Total parathyroidectomy were performed in 81.5%, subtotal in 12.4%, and 61% of patients had a surgical failure. Of all failures, only 1.4% needed a second surgery totaling 98.6% of successful initial surgical treatment. Neck hematoma and unilateral focal fold paralysis occurred in 1.9% and 1.5%, respectively. Conclusion: parathyroidectomy is a safe and reproducible surgical procedure even in the absence of adjuvant techniques.

RESUMO Introdução: O tratamento cirúrgico do hiperparatireoidismo relacionado à doença renal crônica é um procedimento desafiador mesmo para cirurgiões de paratireoide experientes. Ao longo dos anos, técnicas adjuvantes foram desenvolvidas para ajudar a equipe clínica a aprimorar os desfechos cirúrgicos. Contudo, as equipes clínicas de países mais pobres têm menor acesso a tais técnicas, o que faz com que a eficácia da cirurgia nesses contextos não seja tão evidente. Objetivo: Verificar a eficácia da cirurgia para tratamento do hiperparatireoidismo relacionado à doença renal crônica, sem técnicas adjuvantes. Métodos: Ao longo de período de cinco anos, pacientes com hiperparatireoidismo cujo tratamento clínico não resultou em melhora foram avaliados para resolução cirúrgica. Os procedimentos selecionados foram paratireoidectomia total com enxerto autólogo ou ressecção subtotal. As cirurgias foram realizadas em um hospital terciário no Brasil sem o auxílio de algumas das técnicas adjuvantes geralmente aplicadas, como exame de congelação, monitorização neurofisiológica e sonda gama. Exames intraoperatórios de PTH e pré-operatório de localização foram realizados, mas com grandes restrições. Resultados: Um total de 518 pacientes com hiperparatireoidismo (128 secundários e 390 terciários) foram tratados cirurgicamente. Paratireoidectomia total foi realizada em 81,5% e subtotal em 12,4% dos casos; 61% dos pacientes apresentaram falha cirúrgica. De todas as falhas, apenas 1,4% necessitaram de uma segunda cirurgia, totalizando 98,6% de sucesso no tratamento cirúrgico inicial. Hematoma cervical e paralisia unilateral de prega vocal ocorreram em 1,9% e 1,5% dos pacientes, respectivamente. Conclusão: A paratireoidectomia é um procedimento cirúrgico seguro e reprodutível, mesmo na ausência de técnicas adjuvantes.

Mineral bone disorders in chronic kidney disease.

As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling - scenario, which is known as CKD-mineral bone disease (MBD). CKD-MBD is characterized by : (i) abnormal metabolism of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; (ii) abnormalities in bone turnover, mineralization, volume linear growth or strength; (iii) soft-tissue calcifications, either vascular or extra-osseous. Uremic vascular calcification and osteoporosis are the most common complications related to CKD-MBD. Disregulated bone turnover by uremic toxin or secondary hyperparathyroidism disturbed bone mineralization and makes it difficult for calcium and inorganic phosphate to enter into bone, resulting in increased serum calcium and inorganic phosphate. Vascular calcification worsens by hyperphosphatemia and systemic inflammation. Since vitamin D deficiency plays an important role in renal osteodystrophy, supplement of nutritional vitamin D is important in treating uremic osteoporosis and vascular calcification at the same time. Its pleotropic effect improves the bone remodeling initiated by osteoblast and alleviates the risk factors for vascular calcification with less hypercalcemia than vitamin D receptor analogs. Therefore, nutritional vitamin D should be considered in managing CKDMBD.

Initial surgical results of 500 Parathyroidectomies for Hyperparathyroidism related to chronic kidney disease - mineral and bone disorder.

INTRODUCTION: Surgical treatment of hyperparathyroidism related to chronic kidney disease is a challenging procedure even for experienced parathyroid surgeons. Over the years, adjuvant techniques have been developed to assist the medical team to improve surgical outcomes. However, medical staff in poor countries have less access to these techniques and the effectiveness of surgery in this context is unclear. OBJECTIVE: verify the effectiveness of surgery for treatment of hyperparathyroidism related to chronic kidney disease without adjuvant techniques. METHODS: Over a 5-years period, patients with hyperparathyroidism that had clinical therapeutic failure were evaluated for surgical treatment. Total parathyroidectomy with autograft or subtotal resection were the selected procedures. Surgeries were performed in a tertiary hospital in Brazil without the assistance of some of the adjuvant techniques that are usually applied, such as frozen section, nerve monitoring, and gamma probe. Intraoperative PTH and localization pre-operative exams were applied, but with huge restrictions. RESULTS: A total of 518 patients with hyperparathyroidism (128 secondary and 390 tertiary) were surgically treated. Total parathyroidectomy were performed in 81.5%, subtotal in 12.4%, and 61% of patients had a surgical failure. Of all failures, only 1.4% needed a second surgery totaling 98.6% of successful initial surgical treatment. Neck hematoma and unilateral focal fold paralysis occurred in 1.9% and 1.5%, respectively. CONCLUSION: parathyroidectomy is a safe and reproducible surgical procedure even in the absence of adjuvant techniques.

Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders.

Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP's with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP's levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.

Fractures in patients with CKD-diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation.

Mineral and bone disease is omnipresent in patients with chronic kidney disease (CKD) and leads to a diverse range of clinical manifestations, including bone pain and fractures. The accumulation of traditional clinical risk factors, in addition to those related to CKD, enhances the risk of comorbidity and mortality. Despite significant advances in understanding bone disease in CKD, most clinical and biochemical targets used in clinical practice remain controversial, resulting in an undermanagement of bone fragility. Vitamin D supplementation is widely used, but only a few studies have shown beneficial effects and a reduced risk of fracture and mortality. The achievement of serum levels of 25-hydroxyvitamin D is recommended for CKD patients to reduce a high parathyroid hormone level, which is associated with skeletal fractures. Optimal control of parathyroid hormone also improves bone mineralization and lowers circulating bone biomarkers such as alkaline phosphatase and cross-linked collagen type I peptide. The potential value of more recent biomarkers such as sclerostin and fibroblast growth factor 23, as surrogates for bone fragility, is an encouraging new direction in clinical research but is far from being firmly established. This article reviews the literature related to the pathophysiological role of various mineral and biochemical factors involved in renal osteodystrophy. To better understand bone fragility in CKD, new information related to the impact of disturbances of mineral metabolism on bone strength is urgently needed. The combined expertise of clinicians from various medical disciplines appears crucial for the most successful prevention of fractures in these patients.

[CKD-MBD, cardiovascular involvement and prognosis].

Chronic low-grade inflammation is emerging as the pathophysiological mechanism underlying of the several chronic degenerative diseases. Atherosclerosis, inflammation and oxidative stress are some of the issues that arise from the general context of chronic inflammation. In this manuscript we analyzed the role of the immune system, metabolism and inflammation's molecular mediators in order to show an overview about only apparently different problems. Finally, we proposed some possible solutions to improve the survival and quality of life of patient with chronic kidney disease.

The Relation Between Variability of Intact Parathyroid Hormone, Calcium, and Cardiac Mortality in Hemodialysis Patients.

Chronic kidney disease-mineral and bone disorder (CKD-BMD) is a condition known to be associated with cardiovascular disease and mortality in hemodialysis (HD) patients. The relation between calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) variability in HD patients and cardiac mortality is unknown. The purpose of this study was to assess the relation between variability in these parameters and cardiac mortality. Baseline demographic and biochemical parameters of 218 HD patients together with Ca values corrected with albumin and P values measured on a monthly basis and iPTH levels measured at 3-monthly intervals were recorded over 2 years. Standard deviation (SD) and smoothness index (SI) for each parameter were calculated to assess Ca, P, and iPTH variability. The relations between all parameters and cardiac mortality were then analyzed. Cardiac mortality was observed in 38 patients in the 2-year study period. Nonsurviving patients' ages, systolic and diastolic blood pressure (DBP), high sensitivity C-reactive protein (HsCRP) levels, mean iPTH, and SD iPTH were significantly higher than those of surviving patients, while albumin levels, SI iPTH and SI Ca were significantly lower. Age, low albumin, high DBP, SI iPTH, and SI Ca were identified as independent predictors of cardiac mortality at multivariate analysis. Our study shows that Ca and iPTH variability affect cardiac mortality independently of mean and baseline values. When supported by further studies, the relation between Ca and iPTH variability and cardiac mortality in HD patients can lead to a new perspective in terms of prognosis and treatment planning.