Use Of Active Vitamin Research Articles

Hypoparathyroidism and mortality after total thyroidectomy: A nationwide matched cohort study.

Total thyroidectomy (TT) carries a risk of hypoparathyroidism (hypoPT). Recently, hypoPT has been associated with higher overall mortality rates. We aimed to evaluate the frequency of hypoPT and mortality in patients undergoing TT in Denmark covering 20 years. Retrospective Cohort study. Using population-based registries, we identified all Danish individuals who had undergone TT between January 1998 and December 2017. We included a comparison cohort by randomly selecting 10 citizens for each patient, matched on sex and birth year. HypoPT was defined as treatment with active vitamin D after 12 months postoperatively. We used cumulative incidence to calculate risks and Cox regression to compare the rate of mortality between patients and the comparison cohort. We evaluated patients in different comorbidity groups using the Charlson Comorbidity Index and by different indications for surgery. 7912 patients underwent TT in the period. The prevalence of hypoPT in the study period was 16.6%, 12 months postoperatively. After adjusting for potential confounders the risk of death due to any causes (hazard ratio; 95% confidence intervals) following TT was significantly increased (1.34; 1.15-1.56) for patients who developed hypoPT. However, subgroup analysis revealed mortality was only increased in malignancy cases (2.48; 1.99-3.10) whereas mortality was not increased when surgery was due to benign indications such as goitre (0.88; 0.68-1.15) or thyrotoxicosis (0.86; 0.57-1.28). The use of active vitamin D for hypoPT was prevalent one year after TT. Patients with hypoPT did not have an increased risk of mortality following TT unless the indication was due to malignancy.

Effects of active vitamin D analogues on muscle strength and falls in elderly people: an updated meta-analysis.

Elderly people are at high risk of falls due to decreased muscle strength. So far, there is currently no officially approved medication for treating muscle strength loss. The active vitamin D analogues are promising but inconsistent results have been reported in previous studies. The present study was to meta-analyze the effect of active vitamin D analogues on muscle strength and falls in elderly people. The protocol was registered with PROSPERO (record number: CRD42021266978). We searched two databases including PubMed and Cochrane Library up until August 2023. Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence intervals (95% CI) were used to assess the effects of active vitamin D analogues on muscle strength or falls. Regarding the effects of calcitriol (n= 1), alfacalcidol (n= 1) and eldecalcitol (n= 1) on falls, all included randomized controlled trials (RCT) recruited 771 participants. Regarding the effects of the effects of calcitriol (n= 4), alfacalcidol (n= 3) and eldecalcitol (n= 3) on muscle strength, all included RCTs recruited 2431 participants. The results showed that in the pooled analysis of three active vitamin D analogues, active vitamin D analogues reduced the risk of fall by 19%. Due to a lack of sufficient data, no separate subgroup analysis was conducted on the effect of each active vitamin D analogue on falls. In the pooled and separate analysis of active vitamin D analogues, no significant effects were found on global muscle, hand grip, and back extensor strength. However, a significant enhancement of quadriceps strength was observed in the pooled analysis and separate analysis of alfacalcidol and eldecalcitol. The separate subgroup analysis on the impact of calcitriol on the quadriceps strength was not performed due to the lack to sufficient data. The results of pooled and separate subgroup analysis of active vitamin D analogues with or without calcium supplementation showed that calcium supplementation did not affect the effect of vitamin D on muscle strength. The use of active vitamin D analogues does not improve global muscle, hand grip, and back extensor strength but improves quadriceps strength and reduces risk of falls in elderly population.

Active Vitamin D Use and Fractures in Hemodialysis Patients: Results from the International DOPPS.

Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independently of its ability to suppress parathyroid hormone (PTH). We analyzed the association between the prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in-center hemodialysis patients from 21 countries in phases 3 to 6 (2005 to 2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per-protocol approach to censor patients at treatment switch during follow-up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient-year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed versus not prescribed active vitamin D was 1.02 (0.90 to 1.17) for any fracture and 1.00 (0.81 to 1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher versus lower active vitamin D prescriptions. Thus, our results do not suggest a PTH-independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. © 2023 American Society for Bone and Mineral Research (ASBMR).

Treatment of secondary hyperparathyroidism in non-dialysis CKD: an appraisal 2022s.

The situation of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients not on dialysis (ND-CKD) is probably best characterised by the Kidney Disease: Improving Global Outcomes Chronic Kidney Disease-Mineral and Bone Disorder Update 2017 guideline 4.2.1 stating that the optimal parathyroid hormone levels are not known in these stages. Furthermore, new caution became recommended with regard to the routine use of active vitamin D analogues in early CKD stages and moderate SHPT phenotypes, due to their potential risks for hypercalcaemia and hyperphosphataemia aggravation. Nevertheless, there is still a substantial clinical need to prevent the development of parathyroid gland autonomy, with its associated consequences of bone and vascular damage, including fracture risks and cardiovascular events. Therefore we now attempt to review the current guideline-based and clinical practice management of SHPT in ND-CKD, including their strengths and weaknesses, favouring individualised approaches respecting calcium and phosphate homeostasis. We further comment on extended-release calcifediol (ERC) as a new differential therapeutic option now also available in Europe and on a potentially novel understanding of a required vitamin D saturation in more advanced CKD stages. There is no doubt, however, that knowledge gaps will remain unless powerful randomised controlled trials with hard and meaningful endpoints are performed.

Serum Phosphorus and Pill Burden Among Hemodialysis Patients Prescribed Sucroferric Oxyhydroxide: One-Year Follow-Up on a Contemporary Cohort.

PurposeIn prior analyses of real-world cohorts of hemodialysis patients switched from one phosphate binder (PB) to sucroferric oxyhydroxide (SO), SO therapy has been associated with improvements in serum phosphorus (sP) and reductions in daily PB pill burden. To characterize how SO initiation patterns have changed over time, we examined the long-term effectiveness of SO in a contemporary (2018–2019) cohort.Patients and MethodsAdult Fresenius Kidney Care hemodialysis patients first prescribed SO monotherapy as part of routine care between May 2018 and May 2019 (N = 1792) were followed for 1 year. All patients received a non-SO PB during a 91-day baseline period before SO prescription. Mean PB pills/day and laboratory parameters were compared before and during SO treatment. Results were divided into consecutive 91-day intervals (Q1–Q4) and analyzed using linear mixed-effects regression and Cochran’s Q test. These results were contrasted with findings from a historical (2014–2015) cohort (N = 530).ResultsThe proportion of patients achieving sP ≤5.5 mg/dl increased after switching to SO (from 27.0% at baseline to 37.8%, 45.1%, 44.7%, and 44.0% at Q1, Q2, Q3, and Q4, respectively; P < 0.0001 for all). The mean daily PB pill burden decreased from a baseline of 7.7 to 4.4, 4.6, 4.8, and 4.9, respectively, across quarters (P < 0.0001 for all). Patients in the contemporary cohort had improved sP control (27.0% achieving sP ≤5.5 mg/dl vs 17.7%) and lower daily PB pill burden (mean 7.7 vs 8.5 pills/day) at baseline than those in the historical cohort. Overall use of active vitamin D was similar between cohorts, although higher use of oral active vitamin D (63.9% vs 15.7%) and lower use of IV active vitamin D lower (23.4% vs 74.2%) was observed in the contemporary cohort.ConclusionDespite evolving treatment patterns, switching to SO resulted in improved sP control with fewer pills per day in this contemporary hemodialysis cohort.

Effects of romosozumab with and without active vitamin D analog supplementation for postmenopausal osteoporosis.

Although romosozumab is attracting attentions as one of favorably used drugs in today's osteoporosis treatment, there has been no report discussing the differences in the efficacy of romosozumab in the presence or absence of combined use of active vitamin D analog yet. This prospective cohort investigation compared the effects of 12-month romosozumab treatment to increase bone mineral density (BMD) for postmenopausal osteoporosis to observe the influence of combined vitamin D supplementation. During 12-month romosozumab treatment, 175 patients were divided into the VD group (with vitamin D analog: N=88) and the NVD group (without vitamin D analog: N=87), and the change in BMD from baseline was measured at 6 and 12 months as well as alterations in bone turnover markers, serum calcium, and the incidence of adverse events during the administration period. The average 12-month percentage change from baseline level for lumbar spine BMD was comparable at 12.3% in the VD group and 12.1% in the NVD group. The changes in BMD at the total hip and femoral neck showed no significant differences between the groups. The VD group exhibited a significantly smaller increase in procollagen type 1N-terminal propeptide 1 (P1NP) and larger decrease in tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) versus the NVD group. The reduction rate of serum-corrected calcium was significantly less in the VD group than in the NVD group. Adverse events were minor in both groups, with no significant difference in the frequency of new fractures. Romosozumab may significantly increase BMD regardless of the addition of an active vitamin D analog.

Long-term cholecalciferol supplementation in hemodialysis patients: Effects on mineral metabolism, inflammation, and cardiac parameters.

Low levels of 25-hydroxyvitamin D [25(OH)D] are frequent in chronic kidney disease and are associated with adverse outcomes. The aim of this 5-year prospective study was to evaluate the effects of cholecalciferol supplementation on mineral metabolism, inflammation and cardiac parameters in hemodialysis (HD) patients. The study included 97 patients. Cholecalciferol was given after HD according to 25(OH)D baseline levels measured twice (end of winter and of summer). The 25(OH)D levels, circulating bone metabolism, inflammation parameters, brain natriuretic peptide (BNP), pulse pressure (PP), and left ventricular mass index (LVMI) were evaluated before and after supplementation. There was a significant increase in 25(OH)D levels after supplementation (p < 0.001); however, serum calcium (p = 0.02), phosphorus (p = 0.018), and iPTH (p = 0.03) were decreased. Magnesium levels increased during the study (p = 0.03). A reduction in the number of patients under active vitamin D (p < 0.001) and in the dose and number of patients treated with darbepoetin (p = 0.02) was observed. Serum albumin increased (p < 0.001), and C-reactive protein decreased (p = 0.01). BNP (p < 0.001), PP (p = 0.007), and LVMI (p = 0.02) were significantly reduced after supplementation. Long-term cholecalciferol supplementation allowed correction of 25(OH)D deficiency, improved mineral metabolism with less use of active vitamin D, attenuated inflammation, reduced the dose of the erythropoiesis-stimulating agent, and improved cardiac dysfunction.

Etelcalcetide Utilization, Dosing Titration, and Chronic Kidney Disease–Mineral and Bone Disease (CKD-MBD) Marker Responses in US Hemodialysis Patients

Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April2017. New-user design within prospective cohort. 2,596 new users of etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS). Baseline PTH, prior cinacalcet use, initial etelcalcetide dose. Trajectories of etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after etelcalcetide initiation. Cumulative incidence methods for etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses. By August 2019, etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium< 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after etelcalcetide initiation. Data are unavailable for provider dosing protocols, dose holds, or reasons for discontinuation. In the 12 months after etelcalcetide initiation, patients had large and sustained reductions in PTH levels. These results support the utility of etelcalcetide as an effective therapy to achieve the KDIGO-recommended guidelines for CKD-MBD markers in HD patients.

Risk Factors for Fracture Events in Maintenance Hemodialysis Patients

Objective: To explore risk factors for fracture events in maintenance hemodialysis patients. Methods: The study population was obtained from the hospital in patient database in China. There were 654 eligible patients with hemodialysis from 2018 – 2020. Other patient-related variables collected include gender, age, history of hypertension, history of diabetes mellitus, dialysis age, active vitamin D, hemoglobin, serum albumin, total cholesterol, triglyceride, serum corrected calcium. The primary outcome was any factors of fracture. Patients were followed until complete treatment or death. Besides, we performed subgroup analyses and used generalized linear models to assess interaction effects in logistic regressions. To clarify the relationship between fracture and risk factors, logistic regression was used. Result: By comparing non-fracture group and fracture group, we found that some factors were significantly difference, including gender, age, active vitamin D, and albumin (p = 0.001, p = 0.001, p < 0.001, p < 0.001). base on multivariate Logistic regression analysis of fracture occurrence in hemodialysis patients, older age, female, and low albumin were independent risk factors for fracture (p < 0.05). Also, the use of active vitamin D is a protective factor for fractures (p < 0.05). Conclusion: the risk factors for fracture events in maintenance hemodialysis patients included older age, female, low albumin, and active vitamin D.

The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation.

BackgroundOptimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation.MethodsWe studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4–6 (2009–18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9–12 months on HD.ResultsThe 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9–12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150–300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9–12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation.ConclusionsIncreased PTH before HD start predicted a higher PTH level 9–12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients.

Evaluation of factors affecting the occurrence of second atypical fracture after bone union of the first atypical fracture.

Teriparatide is sometimes used in the treatment of atypical femoral fracture (AFF). Even if bone union is achieved, orthopedic physicians must consider the risk of relapse. This study aimed to investigate the factors affecting AFF recurrence, and to determine the appropriate treatment for osteoporosis after bone union. One hundred thirty-one consecutive AFFs in 113 Japanese patients were included. Eleven patients had AFF in the unaffected limb (9 patients) after the first AFF or re-fracture at the original fracture site (2 patients) after bone union of the first AFF was confirmed. We divided all patients into two groups: the second fracture group (22 AFFs in 11 patients) and non-second fracture group (109 AFFs in 102 patients). We compared clinical information between the 2 groups and investigated the factors affecting AFF recurrence using the Student t-, Welch t-, and chi-square tests. Although there was no significant difference in clinical characteristics between the 2 groups, multivariate analysis of factors associated with AFF recurrence identified short duration of treatment with teriparatide and active vitamin D3 (p=0.0408 and 0.0366, respectively) as risk factors. Even in the analysis excluding subtrochanteric AFF, short periods of teriparatide and active vitamin D3 administration were observed as risk factors (p=0.0484 and 0.0346, respectively). The administration of teriparatide for as long as possible after occurrence first AFF and the use of active vitamin D3 after completion of teriparatide therapy may be the most effective strategy to prevent the recurrence of AFF.

Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD. Retrospective analysis nested in a cohort study. Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n= 847). Years before ESKD. Serial FGF-23, PTH, serum phosphate, and serum calcium levels. To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used "ESKD-anchored longitudinal analyses" to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD. Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased. Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.

Explore new approaches to prevent and treat type 2 diabetes with vitamin D and its active analogues——From somewhat disappointing clinical trials results to promising basic researches

The prevalence of diabetes is increasing rapidly which becomes a serious economic burden to society. The effects of vitamin D beyond bone are increasingly recognized. Circulating level of vitamin D is associated with the development of obesity and type 2 diabetes in cross-sectional human studies. However, as to the therapeutic efficacy of vitamin D supplementation on the prevention of diabetes, the results derived from randomized controlled clinical trials were disappointing, probably due to variations in the vitamin D receptor genotypes, the dosages and courses of vitamin D treatments. However, two recent basic studies found that central administration of active vitamin D can improve glucose metabolism in diet induced obesity rats; and the combining use of active vitamin D analogue and BRD9 inhibitor rendered the chromatin of vitamin D response elements more accessible, thus more efficiently exerted its anti-inflammatory efficacy and protected islet β cell function in obese and diabetic mice models. Thus it is paramount important to explore some new approaches to prevent and treat diabetes with vitamin D and its active analogues. (Chin J Endocrinol Metab, 2018, 34: 992-996) Key words: Vitamin D; Vitamin D receptor; Diabetes mellitus, type 2

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis

Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Treatment with 0.5 μg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. UMIN-CTR Identifier: UMIN000001194.

Impact of Vitamin D on the Cardiovascular System in Advanced Chronic Kidney Disease (CKD) and Dialysis Patients.

In patients suffering from chronic kidney disease (CKD), the prevalence of cardiovascular disease is much more common than in the general population. The role of vitamin D deficiency had been underestimated until a significant association was found between vitamin D therapy and survival benefit in haemodialysis patients. Vitamin D deficiency is present even in the early stages of chronic kidney disease. The results of experimental studies have revealed the relationship between vitamin D deficiency and impairment of cardiac contractile function, higher cardiac mass and increased myocardial collagen content. Experimental models propose that intermediate end points for the relationship between vitamin D deficiency and higher risk of cardiovascular disease comprise diminished left ventricular hypertrophy (LVH), enhanced left ventricular diastolic function, and decreased frequency of heart failure. Multiple observational studies have demonstrated an association between the use of active vitamin D therapy in patients on dialysis and with CKD and improved survival. However, there are also many studies indicating important adverse effects of such treatment. Therefore, large randomized trials are required to analyze whether supplementation of vitamin D may affect outcomes and whether it is safe to be used in CKD patients.

Current and potential therapeutic strategies for the management of vascular calcification in patients with chronic kidney disease including those on dialysis.

Patients with CKD have accelerated vascular stiffening contributing significantly to excess cardiovascular morbidity and mortality. Much of the arterial stiffening is thought to involve vascular calcification (VC), but the pathogenesis of this phenomenon is complex, resulting from a disruption of the balance between promoters and inhibitors of calcification in a uremic milieu, along with derangements in calcium and phosphate metabolic pathways. Management of traditional cardiovascular risk factors to reduce VC may be influential but has not been shown to significantly improve mortality. Control of mineral metabolism may potentially reduce the burden of VC, although using conventional approaches of restricting dietary phosphate, administering phosphate binders, and use of active vitamin D and calcimimetics, remains controversial because recommended biochemical targets are hard to achieve and clinical relevance hard to define. Increasing time on dialysis is perhaps another therapy with potential effectiveness in this area. Despite current treatments, cardiovascular morbidity and mortality remain high in this group. Novel therapies for addressing VC include magnesium and vitamin K supplementation, which are currently being investigated in large randomized control trials. Other therapeutic targets include crystallization inhibitors, ligand trap for activin receptors and BMP-7. This review summarizes current treatment strategies and therapeutic targets for the future management of VC in patients with CKD.

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

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). 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. 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. Recent changes in clinical practice are associated with reductions in pretransplant and posttransplant hyperparathyroidism, vitamin D deficiency, and fracture risk after KT.

Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease Stages 2-5 and on dialysis.

In patients with chronic kidney disease (CKD), renal synthesis of active vitamin D [1,25-dihydroxyvitamin D (1,25(OH)2D)] declines and is associated with hypocalcaemia, secondary hyperparathyroidism and the spectrum of CKD-mineral and bone disorder (MBD). In advanced CKD, active vitamin D analogues, including alfacalcidol, calcitriol and paricalcitol, are routinely administered. There are few studies on the use of vitamin D analogues in children with CKD and on dialysis. It is difficult to define bone-specific outcomes that can guide treatment with active vitamin D analogues in children with CKD-MBD. A core working group (WG) of the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis WGs has developed recommendations for the use of active vitamin D therapy in children with CKD and on dialysis. A second document in parallel with this one covers treatment recommendations for native vitamin D therapy. The WGs have performed an extensive literature review to include systematic reviews and randomized controlled trials in adults and children with CKD and prospective observational studies in children with CKD. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system was used to develop and grade the recommendations. In the absence of applicable study data, the opinion of experts from the ESPN CKD-MBD and Dialysis WGs is provided, but clearly GRADE-ed as such and must be carefully considered by the treating physician and adapted to individual patient needs as appropriate.

Vitamin D, phosphate, and vasculotoxicity.

Vascular calcification is a complex process that results in the ectopic deposition of calcium-phosphate hydroxyapatite. Medial and intimal vascular calcification is frequently present in patients with diabetes mellitus and chronic kidney disease (CKD), and markedly increases the morbidity and mortality of these patients. Increased serum levels of calcium and phosphate, along with the use of active vitamin D metabolites, are commonly implicated in the evolvement of vascular wall mineralization in CKD patients. Because CKD patients have lower serum levels of vitamin D, they are routinely prescribed vitamin D supplements that exert a dualistic role that is both healthful and harmful in these patients, perhaps protecting bone health, but at the expense of promoting vascular pathology. This review briefly explains how reducing the phosphate burden in CKD patients could minimize vitamin-D-associated vascular wall calcification.

Mineral and bone disorder after kidney transplantation.

After successful kidney transplantation, accumulated waste products and electrolytes are excreted and regulatory hormones return to normal levels. Despite the improvement in mineral metabolites and mineral regulating hormones after kidney transplantation, abnormal bone and mineral metabolism continues to present in most patients. During the first 3 mo, fibroblast growth factor-23 (FGF-23) and parathyroid hormone levels decrease rapidly in association with an increase in 1,25-dihydroxyvitamin D production. Renal phosphate excretion resumes and serum calcium, if elevated before, returns toward normal levels. FGF-23 excess during the first 3-12 mo results in exaggerated renal phosphate loss and hypophosphatemia occurs in some patients. After 1 year, FGF-23 and serum phosphate return to normal levels but persistent hyperparathyroidism remains in some patients. The progression of vascular calcification also attenuates. High dose corticosteroid and persistent hyperparathyroidism are the most important factors influencing abnormal bone and mineral metabolism in long-term kidney transplant (KT) recipients. Bone loss occurs at a highest rate during the first 6-12 mo after transplantation. Measurement of bone mineral density is recommended in patients with estimated glomerular filtration rate > 30 mL/min. The use of active vitamin D with or without bisphosphonate is effective in preventing early post-transplant bone loss. Steroid withdrawal regimen is also beneficial in preservation of bone mass in long-term. Calcimimetic is an alternative therapy to parathyroidectomy in KT recipients with persistent hyperparathyroidism. If parathyroidectomy is required, subtotal to near total parathyroidectomy is recommended. Performing parathyroidectomy during the waiting period prior to transplantation is also preferred in patients with severe hyperparathyroidism associated with hypercalcemia.