Vitamin D and chronic kidney disease-mineral bone disease (CKD-MBD).
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ABSTRACT:
SUBMITTER: Nigwekar SU
PROVIDER: S-EPMC3944129 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:Rationale & objectiveChronic kidney disease (CKD) in children is associated with cognitive dysfunction that affects school performance and quality of life. The relationship between CKD-mineral and bone disorder and cognitive function in children is unknown.Study designObservational study.Participants702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.PredictorsPlasma fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphorus, 25 hydroxyvitamin D (25[OH]D), and 1,25 dihydroxyvitamin D (1,25[OH]2D).OutcomesNeurocognitive tests of intelligence, academic achievement, and executive functions.Analytical approachLinear regression models to analyze the cross-sectional associations between log2FGF-23, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores and the cognitive test scores of interest after adjustment for demographics, blood pressure, proteinuria, and kidney function.ResultsAt baseline, median age was 12 (95% CI, 8.3, 15.2) years and estimated glomerular filtration rate was 54 (40.5, 67.8) mL/min/1.73 m2. In fully adjusted analyses, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores did not associate with cognitive test scores. In fully adjusted analyses, log2FGF-23 was associated with abnormal test scores for attention regulation (P < 0.05); specifically, Conners' Continuous Performance Test II Errors of Omission (β = 2.3 [1.0, 3.6]), Variability (β=1.4 [0.4, -2.4]), and Hit Reaction Time (β = 1.3 [0.2, 2.4]). Children in the highest FGF-23 tertile group had 7% and 9% greater cognitive risk for Hit Reaction Time and Errors of Omission compared with those in the lowest tertile, respectively. In fully adjusted analyses, higher FGF-23 tertile was associated with increased cognitive risk (P < 0.05) for Errors of Omission (β = 0.4 [0.1, 0.7]) and Hit Reaction Time (β = 0.4 [0.1, 0.7]).LimitationsThe study does not assess the cumulative effects of FGF-23 excess on cognitive function over time. Within-population stratified analyses were not performed due to limited sample size.ConclusionsIn children with CKD, higher plasma FGF-23 level is associated with lower performance in targeted tests of executive function, specifically attention regulation, independent of glomerular filtration rate.
| S-EPMC7406846 | biostudies-literature
Project description: Not available
| S-EPMC6513594 | biostudies-literature
Project description:BackgroundChronic kidney disease mineral bone disorder (CKD-MBD) is a condition characterized by alterations of calcium, phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23) metabolism that in turn promote bone disorders, vascular calcifications, and increase cardiovascular (CV) risk. Nephrologists' awareness of diagnostic, prognostic, and therapeutic tools to manage CKD-MBD plays a primary role in adequately preventing and managing this condition in clinical practice.MethodsA national survey (composed of 15 closed questions) was launched to inquire about the use of bone biomarkers in the management of CKD-MBD patients by nephrologists and to gain knowledge about the implementation of guideline recommendations in clinical practice.ResultsOne hundred and six Italian nephrologists participated in the survey for an overall response rate of about 10%. Nephrologists indicated that the laboratories of their hospitals were able to satisfy request of ionized calcium levels, 105 (99.1%) of both PTH and alkaline phosphatase (ALP), 100 (94.3%) of 25(OH)D, and 61 (57.5%) of 1.25(OH)2D; while most laboratories did not support the requests of biomarkers such as FGF-23 (intact: 88.7% and c-terminal: 93.4%), Klotho (95.3%; soluble form: 97.2%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (92.5%), C-terminal telopeptide (CTX) (71.7%), and pro-collagen type 1 N-terminal pro-peptide (P1NP) (88.7%). As interesting data regarding Italian nephrologists' behavior to start treatment of secondary hyperparathyroidism (sHPT), the majority of clinicians used KDOQI guidelines (n = 55, 51.9%). In contrast, only 40 nephrologists (37.7%) relied on KDIGO guidelines, which recommended referring to values of PTH between two and nine times the upper limit of the normal range.ConclusionResults point out a marked heterogeneity in the management of CKD-MBD by clinicians as well as a suboptimal implementation of guidelines in Italian clinical practice.
| S-EPMC10784916 | biostudies-literature
Project description:BackgroundVitamin D associates with the plasma concentration of the endogenous inhibitor of the nitric oxide system asymmetric dimethyl arginine (ADMA) and cross-sectional studies in CKD patients treated with the vitamin D receptor activator paricalcitol show that plasma ADMA is substantially less than in those not receiving this drug.MethodsIn the frame of a randomized, double-blind, placebo controlled trial, the Paracalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY), we investigated whether vitamin D receptor activation by paricalcitol (2 μg/day x 12 weeks) affects the plasma concentration of ADMA and symmetric dimethyl arginine (SDMA) in 88 patients with stage 3 to 4 CKD.ResultsParicalcitol produced the expected small rise in serum calcium and phosphate and a marked PTH suppression. However, ADMA [Paricalcitol: baseline 0.75 μMol/L (95%CI: 0.70-0.81), 12 week 0.72 μMol/L (95%CI: 0.66-0.78); Placebo: baseline 0.75 μMol/L (95%CI: 0.70-0.90) 12 weeks 0.70 μMol/L (95%CI: 0.66-0.74)] and SDMA [Paricalcitol: baseline 0.91 μMol/L (95%CI: 0.82-1.00), 12 week 0.94 μMol/L (95%CI: 0.82-0.1.06); Placebo: baseline 0.91 μMol/L (95%CI: 0.82-1.06) 12 weeks 0.99 μMol/L (95%CI: 0.88-1.10)] remained unchanged during the trial and 2 weeks after stopping these treatments.ConclusionsParicalcitol does not modify plasma ADMA and SDMA in patients with stage 3-4 CKD. The apparent beneficial effects of paricalcitol on ADMA registered in cross-sectional studies is likely attributable to confounding by indication rather than to a true effect of this drug on ADMA metabolism.
| S-EPMC5627906 | biostudies-literature
Project description:Childhood and adolescence are crucial times for the development of a healthy skeletal and cardiovascular system. Disordered mineral and bone metabolism accompany chronic kidney disease (CKD) and present significant obstacles to optimal bone strength, final adult height, and cardiovascular health. Decreased activity of renal 1 alpha hydroxylase results in decreased intestinal calcium absorption, increased serum parathyroid hormone levels, and high-turnover renal osteodystrophy, with subsequent growth failure. Simultaneously, phosphorus retention exacerbates secondary hyperparathyroidism, and elevated levels contribute to cardiovascular disease. Treatment of hyperphosphatemia and secondary hyperparathyroidism improves growth and high-turnover bone disease. However, target ranges for serum calcium, phosphorus, and parathyroid hormone (PTH) levels vary according to stage of CKD. Since over-treatment may result in adynamic bone disease, growth failure, hypercalcemia, and progression of cardiovascular calcifications, therapy must be carefully adjusted to maintain optimal serum biochemical parameters according to stage of CKD. Newer therapeutic agents, including calcium-free phosphate binding agents and new vitamin D analogues, effectively suppress serum PTH levels while limiting intestinal calcium absorption and may provide future therapeutic alternatives for children with CKD.
| S-EPMC2668632 | biostudies-other
Project description:Improving Global Outcomes (KDIGO) Clinical Practice Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) 2009 provided recommendations on the detection, evaluation, and treatment of CKD-MBD in patients CKD who are and are not undergoing dialysis. Because of the accumulation of evidence since this initial publication, the CKD-MBD Guideline underwent a selective update in 2017. In April 2018, KDIGO convened a CKD-MBD Guideline Implementation Summit in Japan with the key objective to discuss various barriers to the uptake and implementation of the CKD-MBD Guideline in 8 Asian countries/regions. These countries/regions were comparable according to their high-to-middle economic ranking assigned by the World Bank. The discussion took into account the availability of CKD-MBD medication therapies and government health policies that may influence reimbursement and practice patterns in the region. Most importantly, Summit participants developed a framework of multifaceted strategies aimed at overcoming barriers to guideline implementation. The Summit attendees suggested a shared decision-making approach between clinicians and patients in CKD-MBD management, as well as individualized care based on the treatment risk-benefit ratio. The Summit participants also discussed how KDIGO, as a guideline development organization, may work in partnership with local and national nephrology societies to provide education and facilitate implementation of the guideline by clinicians. The conclusions drawn from this Summit in Asia may serve as an important guide for other regions to follow.
| S-EPMC6933448 | biostudies-literature
Project description:microRNA in chronic kidney disease (CKD)
2017-01-01 | GSE80247 | GEO
Project description:Male Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone. Therefore, in this study, we aimed to determine the effect of ovariectomy (OVX) on the biochemical and skeletal manifestations of CKD-MBD in Cy/+ female rats. We hypothesized that OVX would accelerate development of the biochemical and skeletal features of CKD-MBD in female Cy/+ rats, similar to those seen in male Cy/+ rats. Female Cy/+ rats underwent OVX (n?=?8) or Sham (n?=?8) surgery at 15 weeks of age. Blood was collected every 5 weeks post-surgery until 35 weeks of age, when the rats underwent a 4-day metabolic balance, and the tibia and final blood were collected at the time of sacrifice. OVX produced the expected changes in trabecular and cortical parameters consistent with post-menopausal disease, and negative phosphorus balance compared with Sham. However, indicators of CKD-MBD were similar between OVX and Sham (similar kidney weight, plasma blood urea nitrogen, creatinine, creatinine clearance, phosphorus, calcium, parathyroid hormone, and no cortical porosity). Contrary to our hypothesis, OVX did not produce evidence of development of the CKD-MBD phenotype in female Cy/+ rats.
| S-EPMC6538713 | biostudies-literature
Project description:BackgroundIn the general population, the trabecular bone score (TBS) represents the bone microarchitecture and predicts fracture risk independent of bone mineral density (BMD). A few studies reported that TBS is significantly reduced in dialysis patients. Chronic kidney disease-mineral and bone disorder (CKD-MBD) are accompanied by increased fracture risk, cardiovascular morbidity, and mortality. We investigated whether TBS is associated with comorbidity related to CKD-MBD or frailty in hemodialysis patients.MethodsIn this prospective observational study, TBS was obtained using the TBS iNsight software program (Med-Imaps) with BMD dual energy x-ray absorptiometry (DXA) images (L1-L4) from prevalent hemodialysis patients. A Tilburg frailty indicator was used to evaluate frailty, and hand grip strength and bio-impedance (InBody) were measured. A patient-generated subjective global assessment (PG-SGA) was used for nutritional assessment. The history of cardiovascular events (CVE) and demographic, clinical, laboratory, and biomarker data were collated. We then followed up patients for the occurrence of CKD-MBD related complications.ResultsWe enrolled 57 patients in total. The mean age was 56.8 ± 15.9 years (50.9% female). Prevalence of Diabetes mellitus (DM) was 40.4% and CVE was 36.8%. Mean TBS was 1.44 ± 0.10. TBS significantly reduced in the CVE group (1.38 ± 0.08 vs. 1.48 ± 0.10, p < 0.001). Multivariable regression analysis was conducted adjusting for age, sex, dialysis vintage, DM, CVE, albumin, intact parathyroid hormone, fibroblast growth factor 23, handgrip strength, and phosphate binder dose. Age (ß = - 0.030; p = 0.001) and CVE (ß = - 0.055; p = 0.024) were significant predictors of TBS. During the follow up period after TBS measurements (about 20 months), four deaths, seven incident fractures, and six new onset CVE were recorded. Lower TBS was associated with mortality (p = 0.049) or new onset fracture (p = 0.007, by log-rank test).ConclusionLower TBS was independently associated with increased age and CVE prevalence in hemodialysis patients. Mortality and fracture incidence were significantly higher in patients with lower TBS values. These findings suggest that TBS may indicate a phenotype of frailty and also a CKD-MBD phenotype reciprocal to CVE.
| S-EPMC7382149 | biostudies-literature
Project description:The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an extremely important complication of kidney diseases. Here we tested whether CKD-MBD causes vascular calcification in early kidney failure by developing a mouse model of early CKD in a background of atherosclerosis-stimulated arterial calcification. CKD equivalent in glomerular filtration reduction to human CKD stage 2 stimulated early vascular calcification and inhibited the tissue expression of α-klotho (klotho) in the aorta. In addition, osteoblast transition in the aorta was stimulated by early CKD as shown by the expression of the critical transcription factor Runx2. The ligand associated with the klotho-fibroblast growth factor receptor complex, FGF23, was found to be expressed in the vascular media of sham-operated mice. Its expression was decreased in early CKD. Increased circulating levels of the osteocyte-secreted proteins, FGF23, and sclerostin may have been related to increased circulating klotho levels. Finally, we observed low-turnover bone disease with a reduction in bone formation rates more than bone resorption. Thus, the CKD-MBD, characterized by cardiovascular risk factors, vascular calcification, increased circulating klotho, FGF23 and sclerostin levels, and low-turnover renal osteodystrophy, was established in early CKD. Early CKD caused a reduction of vascular klotho, stimulated vascular osteoblastic transition, increased osteocytic secreted proteins, and inhibited skeletal modeling producing the CKD-MBD.
| S-EPMC3836911 | biostudies-literature