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.

Diagnosis and management of mineral and bone disorders in infants with CKD: clinical practice points from the ESPN CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce.

BACKGROUND: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. METHODS: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2-5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. RESULTS: We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). CONCLUSION: As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. A higher resolution version of the Graphical abstract is available as Supplementary information.

Phosphate, Microbiota and CKD.

Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms.

Effects of tonifying kidney and strengthen bone therapy on non-dialysis patients with chronic kidney disease-mineral and bone disorder: A protocol for the systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Correction of calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) disorders is the standard of treatment in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), but the side effects and adverse reactions brought by western medicine (WM) are still the main problems. More importantly, the lack of protection of kidney function in the treatment greatly affects the health of patients. Although traditional Chinese medicine (TCM), specifically tonifying kidney and strengthen bone (TKSB) therapy is wildly applied for patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we pretent to conduct this protocol to evaluate the efficacy and safety of TKSB therapy combined with WM for non-dialysis patients with CKD-MBD. METHODS: A system research of randomized controlled trials (RCTs) of TKSB therapy for CKD-MBD will be conducted by 2 investigators from 7 electronic databases. Methodological quality evaluations will be performed by using the Cochrane collaboration tool and data analysis will be conducted by RevMan V5.3 software and STATA v15.0. RESULTS: The results of this paper will be submitted to a peer-reviewed journal for publication. CONCLUSION: This research will determine the safety and efficacy of TKSB therapy in treating non-dialysis patients with CKD-MBD. INPLASY REGISTRATION NUMBER: INPLASY2020120086.

Effect of cholecalciferol on serum hepcidin and parameters of anaemia and CKD-MBD among haemodialysis patients: a randomized clinical trial.

In this multicentre double-blind randomized clinical trial, we investigated the effects of oral cholecalciferol supplementation on serum hepcidin and parameters related to anaemia and CKD-MBD among haemodialysis patients. Participants were assigned in a 2:2:1:1 ratio to either (1) thrice-weekly 3,000-IU cholecalciferol, (2) once-monthly cholecalciferol (equivalent to 9,000 IU/week), (3) thrice-weekly placebo, or (4) once-monthly placebo. We also examined the effect modifications by selected single nucleotide polymorphisms in vitamin D-related genes. Out of 96 participants, 94 were available at Month 3, and 88 completed the 6-month study. After adjustment for baseline values, serum hepcidin levels were higher at Day 3 in the combined cholecalciferol (vs. placebo) group, but were lower at Month 6 with increased erythropoietin resistance. Cholecalciferol increased serum 1,25(OH)2D levels, resulting in a greater proportion of patients who reduced the dose of active vitamin D at Month 6 (31% vs. 10% in the placebo group). Cholecalciferol also suppressed intact PTH only among patients with severe vitamin D deficiency. In conclusion, cholecalciferol supplementation increases serum hepcidin-25 levels in the short term and may increase erythropoietin resistance in the long term among haemodialysis patients. Both thrice-weekly and once-monthly supplementation effectively increases serum 1,25(OH)2D levels, and hence, reduces active vitamin D drugs.Clinical Trial Registry: This study was registered at ClinicalTrials.gov and University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as NCT02214563 (registration date: 12/08/2014) and UMIN000011786 (registration date: 15/08/2014), respectively (please refer to the links below). ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/record/NCT02214563 . UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000017152&language=E .

Circadian rhythms of mineral metabolism in chronic kidney disease-mineral bone disorder.

PURPOSE OF REVIEW: The circadian rhythms have a systemic impact on all aspects of physiology. Kidney diseases are associated with extremely high-cardiovascular mortality, related to chronic kidney disease-mineral bone disorder (CKD-MBD), involving bone, parathyroids and vascular calcification. Disruption of circadian rhythms may cause serious health problems, contributing to development of cardiovascular diseases, metabolic syndrome, cancer, organ fibrosis, osteopenia and aging. Evidence of disturbed circadian rhythms in CKD-MBD parameters and organs involved is emerging and will be discussed in this review. RECENT FINDINGS: Kidney injury induces unstable behavioral circadian rhythm. Potentially, uremic toxins may affect the master-pacemaker of circadian rhythm in hypothalamus. In CKD disturbances in the circadian rhythms of CKD-MBD plasma-parameters, activin A, fibroblast growth factor 23, parathyroid hormone, phosphate have been demonstrated. A molecular circadian clock is also expressed in peripheral tissues, involved in CKD-MBD; vasculature, parathyroids and bone. Expression of the core circadian clock genes in the different tissues is disrupted in CKD-MBD. SUMMARY: Disturbed circadian rhythms is a novel feature of CKD-MBD. There is a need to establish which specific input determines the phase of the local molecular clock and to characterize its regulation and deregulation in tissues involved in CKD-MBD. Finally, it is important to establish what are the implications for treatment including the potential applications for chronotherapy.

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.

Native vitamin D in pre-dialysis chronic kidney disease.

Chronic kidney disease patients have a high prevalence of vitamin D insufficiency/deficiency. Vitamin D deficiency has been associated with a variety of bone, metabolic and cardiovascular disorders. However, the role of native vitamin D supplementation (ergocalciferol, cholecalciferol or calcifediol) remains unclear in chronic kidney disease (CKD), particularly in the pre-dialytic phase. Several international guidelines have been developed on CKD-Mineral and Bone Disorder, but the optimal strategy for native vitamin D supplementation and its clinical benefit remains a subject of debate in the scientific community. This paper aims to review the available literature, including randomized clinical trials that evaluated the effects of native vitamin D supplementation on pre-dialysis CKD on biochemical and clinically relevant outcomes.

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.

Periarticular calcification mimicking inflammatory polyarthritis in chronic kidney disease.

Periarticular calcification is a frequent radiographic manifestation in chronic kidney disease (CKD). However, clinical presentation as inflammatory periarthritis, tenosynovitis, and bursitis is unusual. A 34-year-old man with CKD on dialysis for three years presented with painful swollen joints. His adherence to regular dialysis, phosphate binders, Vitamin D supplements, and antihypertension therapy was poor. He had swelling of the right thumb, index, and little fingers; periarticular swelling of the left middle finger and right little toe; and extensor tenosynovitis of the wrists and right olecranon bursitis. Laboratory investigations showed the following: urea 36 mmol/L; creatinine 1764 umol/L; serum urate 0.37 mmol/L; corrected calcium 1.76 mmol/L; phosphate 4.32 mmol/L; 25-dihydroxycholecalciferol 30 ng/mL; and parathyroid hormone 104 pmol/L. Radiographs showed periarticular calcification corresponding to the sites of inflammation. The inflammation resolved with oral steroids. In our patient, deranged mineral and bone metabolism contributed to periarticular calcification at multiple sites, mimicking inflammatory polyarthritis.

CKD-MBD: from the Pathogenesis to the Identification and Development of Potential Novel Therapeutic Targets.

PURPOSE OF REVIEW: Although we have seen tremendous advances in the comprehension of CKD-MBD pathophysiology during the last few years, this was not accompanied by a significant change in mortality rate and quality of life. This review will address the traditional and updated pathophysiology of CKD-MBD along with the therapeutic limitations that affect CKD-MBD and proposed alternative treatment targets. RECENT FINDINGS: An innovative concept brings the osteocyte to the center of CKD-MBD pathophysiology, in contrast to the traditional view of the skeleton as a target organ for disturbances in calcium, phosphate, parathyroid hormone, and vitamin D. Osteocytes, through the synthesis of FGF-23, sclerostin, among others, are able to interact with other organs, making bone an endocrine organ. Thus, osteocyte dysregulation might be an early event during the course of CKD. This review will revisit general concepts on the pathophysiology of CKD-MBD and discuss new perspectives for its treatment.

Bone and mineral metabolism at 55 haemodialysis centres in Lima. / Influencia de la sobrecarga de calcio sobre el metabolismo óseo y mineral en 55 centros de hemodiálisis de Lima.

BACKGROUND: Mineral and bone metabolism disorders are common complications in haemodialysis patients that present significant geographical variability. OBJECTIVES: The objective of this study was to assess these disorders for the first time in haemodialysis patients from Peru. METHODS: The study included 1551 haemodialysis patients from 55 centres affiliated with the Social Health System of Peru in the city of Lima. Demographic data, comorbidities, treatments and biochemical parameters were collected from each patient. Serum calcium, phosphorus and PTH levels were categorised according to the recommended ranges in the KDOQI and KDIGO guidelines. RESULTS: The mean age of the patients was 59.5±15.6 years, with a mean time on haemodialysis of 58.0±54.2 months. All patients were dialysed with a calcium concentration in the dialysis fluid of 3.5 mEq/l and 68.9% of patients were prescribed phosphate-binding agents (98.4% of them calcium carbonate). A high percentage of patients showed serum calcium above, and serum phosphorus below, the recommended ranges in the KDOQI guidelines (32.8% and 37.3%, respectively). More than half of the patients had serum PTH values below the recommended ranges of both the KDOQI and KDIGO guidelines (56.4% and 51.6%, respectively). CONCLUSIONS: Patients included in this study were younger than those from other studies and showed both hypophosphataemia and suppressed PTH, probably due to an excessive calcium overload through dialysis fluid and the use of calcium-containing phosphate binding agents.

Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: Synopsis of the Kidney Disease: Improving Global Outcomes 2017 Clinical Practice Guideline Update.

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a selective update of the prior CKD-MBD guideline published in 2009. The guideline update and the original publication are intended to assist practitioners caring for adults with CKD and those receiving long-term dialysis. Methods: Development of the guideline update followed an explicit process of evidence review and appraisal. The approach adopted by the Work Group and the evidence review team was based on systematic reviews of relevant trials, appraisal of the quality of the evidence, and rating of the strength of recommendations according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Searches of the English-language literature were conducted through September 2015 and were supplemented with targeted searches through February 2017. Final modification of the guidelines was informed by a public review process involving numerous stakeholders, including patients, subject matter experts, and industry and national organizations. Recommendations: The update process resulted in the revision of 15 recommendations. This synopsis focuses primarily on recommendations for diagnosis of and testing for CKD-MBD and treatment of CKD-MBD that emphasizes decreasing phosphate levels, maintaining calcium levels, and addressing elevated parathyroid hormone levels in adults with CKD stage G3a to G5 and those receiving dialysis. Key elements include basing treatment on trends in laboratory values rather than a single abnormal result and being cautious to avoid hypercalcemia when treating secondary hyperparathyroidism.

[Effect of Ronghuang Granule on serum FGF23, FGFRs and Klotho in non-dialysis patients with CKD-MBD and kidney deficiency and damp-heat syndrome].

OBJECTIVE: To observe the effect of Ronghuang granule on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptor (FGFRs) and Klotho protein levels in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and kidney deficiency and damp heat syndrome. METHODS: Seventy non-dialysis CKD-MBD patients with kidney deficiency and dampness-heat syndrome were randomized into control group (n=35) and treatment group (n=35). All the patients were given routine treatment combined with traditional Chinese medicine retention enema, and the patients in the treatment group received additional Ronghuang granule treatment (3 times a day). After the 12-week treatments, the patients were examined for changes of TCM syndromes. Serum levels of Ca, P, parathyroid hormone (iPTH), FGF23, FGFRs and Klotho proteins were detected before and after treatment. These parameters were also examined in 20 healthy volunteers. RESULTS: Sixty-five patients completed the study, including 33 in the control group and 32 in the treatment group. The patients in the treatment group showed significantly better treatment responses than those in the control group (P < 0.05 or 0.01). At 4, 8, and 12 weeks of treatment, the patients in the treatment group had significantly lowered scores of TCM syndromes compared with the score before treatment (P < 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks (P < 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group (P < 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group (P < 0.05) but only at 12 weeks in the control group (P < 0.05). The patients in the control and treatment groups all showed elevated serum levels of FGF23, FGFRs and Klotho protein compared with the normal subjects (P < 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group (P < 0.05) but remained unchanged in the control group (P>0.05), showing significant differences between the two groups. CONCLUSIONS: Ronghuang granule improves the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and dampness heat syndrome by reducing serum levels of FGF23, FGFRs and Klotho, improving calcium and phosphorus metabolism disorder, and inhibiting secondary hyperparathyroidism.

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.

[Management of bone and mineral metabolism disorders before the dialysis stage remains still perfectible. Data from the French Phosphorus and Calcium Survey Photo-Graphe]. / La prise en charge des troubles du métabolisme minéral et osseux avant le stade de la dialyse reste encore perfectible. À partir des données de l'Observatoire national du métabolisme minéral et osseux Photo-Graphe.

Only limited data is available on the management of the chronic kidney disease-associated bone and mineral metabolism disorder (CKD-MBD) in the pre-dialysis stages of CKD in France. A better knowledge of current management habits could lead to an improvement in the implementation of international recommendations (KDIGO). The 3rd version of the French Phosphorus and Calcium Survey Photo-Graphe (Sanofi) included a cohort of CKD stages 4 and 5 patients, whose aim was to examine the prevalence of CKD-MBD and the quality of its management in patients under the care of 62 nephrologists from over 20 geographical regions in France. The study started in October 2011, i.e. one year after patient enrollment. We examined in particular the percentage of patients presenting with laboratory parameter abnormalities indicative of CKD-MBD who were not receiving adequate treatment. A total of 456 patients with CKD stage 4 and 154 with CKD stage 5 were studied. Their mean age was 72.9±14.2 years, and male/female ratio was 58/42. KDIGO targets of serum PTH for CKD stages 4 and 5 were not achieved in respectively 80 and 84% of the patients, for serum calcium in 8 and 22% and for serum phosphate in 12 and 46%. As a potential explanation, insufficient therapy was estimated to account for respectively 45 and 60% of insufficiently controlled secondary hyperparathyroidism, and for 36% of persistent hyperphosphatemia in stage 5. It should be noted that 55.5 and 57.5% of patients were receiving native vitamin D. In this national observatory, the management of CKD-MBD stages 4 and 5 appears suboptimal, especially as regards the control of secondary hyperparathyroidism, which remained untreated in nearly 50% of the patients. Hyperphosphatemia was also common and inadequately controlled in CKD stage 5. To improve the management of CKD-MBD, nephrologists need to be more aware of the importance of aiming for recommended laboratory targets and how this can be achieved.

Clinical Epidemiology of Mineral Bone Disorder Markers in Prevalent Hemodialysis Patients in the Xinjiang Uyghur Autonomous Region in China.

We investigated the clinical epidemiology of mineral bone disorder markers in prevalent hemodialysis (HD) patients in Xinjiang, the largest province in China. Data were obtained from 59 hospitals. A total of 3725 patients tracked from January 1 to December 31, 2014, were enrolled. Serum calcium (Ca) levels, phosphorus (P) levels, and intact parathyroid hormone (iPTH) levels were analyzed. Serum Ca levels were lower compared to the International Dialysis Outcomes and Practice Patterns Study (DOPPS4) and the Chinese DOPPS. The hypercalcemia rate was similar to DOPPS4 and lower than in the Chinese DOPPS. Serum P levels were higher than in DOPPS4 and lower than those in the Chinese DOPPS. Hyperphosphatemia rates were higher than DOPPS4 and lower than Chinese DOPPS. Serum iPTH levels were higher than in DOPPS4 and the Chinese DOPPS. We demonstrated higher serum P and iPTH levels in Xinjiang HD patients than in the DOPPS4 and Chinese DOPPS. In contrast, serum Ca levels were lower than the other two studies. High hypocalcemia and hyperphosphatemia rates may suggest that HD services in Xinjiang are inadequate. A multidiscipline chronic kidney disease (CKD) care program needs to be established to improve chronic kidney disease-mineral and bone disorder (CKD-MBD) target achievement in Xinjiang.

Recent Changes in Chronic Kidney Disease-Mineral and Bone Disorders and Associated Fractures After Kidney Transplantation.

BACKGROUND: The management of chronic kidney disease-mineral and bone disorders has recently changed. We investigated the modifications of chronic kidney disease-mineral and bone disorder with a special focus on the incidence of fractures in the first year after kidney transplantation (KT). METHODS: We retrospectively compared 2 groups of patients who consecutively underwent transplantation at our center 5 years from each other. Group 1 consisted of patients (n = 152) transplanted between 2004 and 2006, whereas patients in group 2 (n = 137) underwent KT between 2009 and 2011. RESULTS: During the end-stage renal disease phase at the time of transplant, cinacalcet, and native vitamin D were used significantly more frequently in group 2. Median intact parathyroid hormone levels were lower and severe hyperparathyroidism decreased significantly. Vitamin D deficiency dropped from 64% to 20%. After transplantation, persistent hyperparathyroidism (parathyroid hormone > 130 ng/L) and bone turnover markers were significantly reduced in group 2. Native vitamin D supplementation increased over time, whereas the use of active vitamin D was unchanged. The 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were significantly higher. The fracture incidence at 1 year decreased significantly (3.1% vs 9.1%; P = 0.047). No steroid sparing was observed in group 2. Bisphosphonates after KT were more frequently used in group 2. CONCLUSIONS: Recent changes in clinical practice are associated with reductions in pretransplant and posttransplant hyperparathyroidism, vitamin D deficiency, and fracture risk after KT.