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American Journal of Kidney Diseases :... Nov 2023Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality,...
RATIONALE & OBJECTIVE
Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD.
STUDY DESIGN
Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023.
SETTING & STUDY POPULATIONS
Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded.
SELECTION CRITERIA FOR STUDIES
RCTs with≥3 months of follow-up evaluating a vitamin D compound.
DATA EXTRACTION
Data were extracted independently by three investigators.
ANALYTICAL APPROACH
Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE.
RESULTS
Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium.
LIMITATIONS
Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality.
CONCLUSIONS
Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture and cardiovascular and kidney outcomes were uncertain.
TRIAL REGISTRATION
Registered at PROSPERO with study number CRD42017057691.
PLAIN-LANGUAGE SUMMARY
Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.
PubMed: 37356648
DOI: 10.1053/j.ajkd.2023.04.003 -
Medical Sciences (Basel, Switzerland) Mar 2022: To date, there is no satisfactory treatment for patients with calcium and vitamin D supplementation refractive hypoparathyroidism. Parathyroid allotransplantation by... (Review)
Review
: To date, there is no satisfactory treatment for patients with calcium and vitamin D supplementation refractive hypoparathyroidism. Parathyroid allotransplantation by design is a one-time cure through its restoration of the parathyroid function and, therefore, could be the solution. A systematic literature review is conducted in the present paper, with the aim of outlining the possibilities of parathyroid allotransplantation and to calculate its efficacy. Additionally, various transplantation characteristics are linked to success. This review is carried out according to the PRISMA statement and checklist. Relevant articles were searched for in medical databases with the most recent literature search performed on 9 December 2021. In total, 24 articles involving 22 unique patient cohorts were identified with 203 transplantations performed on 148 patients. Numerous types of (exploratory) interventions were carried out with virtually no protocols that were alike: there was the use of (non-) cryopreserved parathyroid tissue combined with direct transplantation or pretreatment using in vitro techniques, such as culturing cells and macro-/microencapsulation. The variability increased further when considering immunosuppression, graft histology, and donor-recipient compatibility, but this was found to be reported in its entirety by exception. As a result of the large heterogeneity among studies, we constructed our own criterium for transplantation success. With only the studies eligible for our assessment, the pooled success rate for parathyroid allotransplantation emerged to be 46% (13/28 transplantations) with a median follow-up duration of 12 months (Q1-Q3: 8-24 months). Manifold possibilities have been explored around parathyroid allotransplantation but are presented as a double-edged sword due to high clinical diverseness, low expertise in carrying out the procedure, and unsatisfactory study quality. Transplantations carried out with permanent immunosuppression seem to be the most promising, but, in its current state, little could be said about the treatment efficacy with a high quality of evidence. Of foremost importance in pursuing the answer whether parathyroid allotransplantation is a suitable treatment for hypoparathyroidism, a standardized definition of transplantation success must be established with a high-quality trial.
Topics: Humans; Hypoparathyroidism; Immunosuppression Therapy; Parathyroid Glands; Tissue Donors; Treatment Outcome
PubMed: 35323218
DOI: 10.3390/medsci10010019 -
International Journal of Cardiology Jul 2017No consensus exists regarding the factors influencing mortality in patients undergoing hemodialysis (HD). This meta-analysis aimed to evaluate the impact of various... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
No consensus exists regarding the factors influencing mortality in patients undergoing hemodialysis (HD). This meta-analysis aimed to evaluate the impact of various patient characteristics on the risk of mortality in such patients.
METHODS
PubMed, Embase, and Cochrane Central were searched for studies evaluating the risk factors for mortality in patients undergoing HD. The factors included age, gender, diabetes mellitus (DM), body mass index (BMI), previous cardiovascular disease (CVD), HD duration, hemoglobin, albumin, white blood cell, C-reactive protein (CRP), parathyroid hormone, total iron binding capacity (TIBC), iron, ln ferritin, adiponectin, apolipoprotein A1 (ApoA1), ApoA2, ApoA3, high-density lipoprotein (HDL), total cholesterol, hemoglobin A1c (HbA1c), serum phosphate, troponin T (TnT), and B-type natriuretic peptide (BNP). Relative risks with 95% confidence intervals were derived. Data were synthesized using the random-effects model.
RESULTS
Age (per 1-year increment), DM, previous CVD, CRP (higher versus lower), ln ferritin, adiponectin (per 10.0μg/mL increment), HbA1c (higher versus lower), TnT, and BNP were associated with an increased risk of all-cause mortality. BMI (per 1kg/m increment), hemoglobin (per 1d/dL increment), albumin (higher versus lower), TIBC, iron, ApoA2, and ApoA3 were associated with reduced risk of all-cause mortality. Age (per 1-year increment), gender (women versus men), DM, previous CVD, HD duration, ln ferritin, HDL, and HbA1c (higher versus lower) significantly increased the risk of cardiac death. Albumin (higher versus lower), TIBC, and ApoA2 had a beneficial impact on the risk of cardiac death.
CONCLUSIONS
Multiple markers and factors influence the risk of mortality and cardiac death in patients undergoing HD.
Topics: Cardiovascular Diseases; Diabetes Mellitus; Humans; Kidney Failure, Chronic; Mortality; Renal Dialysis; Risk Factors
PubMed: 28341375
DOI: 10.1016/j.ijcard.2017.02.095 -
Genetics in Medicine : Official Journal... Mar 2023This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert...
This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.
Topics: Adult; Humans; Clinical Relevance; Consensus; DiGeorge Syndrome; Genetic Counseling; Surveys and Questionnaires
PubMed: 36729052
DOI: 10.1016/j.gim.2022.11.012 -
EBioMedicine Feb 2022Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for...
BACKGROUND
Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium.
METHODS
One-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings.
FINDINGS
Higher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings.
INTERPRETATION
This study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed.
FUNDING
ET is supported by a CRUK Career Development Fellowship (C31250/A22804). XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province. SCL acknowledges research funding from the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden).
Topics: Calcium; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Phenomics; Phenotype; Polymorphism, Single Nucleotide
PubMed: 35134646
DOI: 10.1016/j.ebiom.2022.103865 -
American Heart Journal May 2013Parathyroid hormone (PTH) excess might play a role in cardiovascular health. We therefore conducted a systematic review and meta-analysis to evaluate the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Parathyroid hormone (PTH) excess might play a role in cardiovascular health. We therefore conducted a systematic review and meta-analysis to evaluate the association between PTH and cardiovascular disease (CVD) events, and intermediate outcomes.
METHODS
We conducted a systematic and comprehensive database search using MEDLINE and Embase between 1947 and October 2012. We included English-language prospective studies that reported risk estimates for PTH and CVD events, and intermediate outcomes. The characteristics of study populations, exposure, and outcomes of total CVD events, fatal and non-fatal CVD events were reported, and a quality assessment was conducted. Results were extracted for the highest versus lowest PTH concentrations, and meta-analyses were carried out using random effects models.
RESULTS
The systematic literature search yielded 5770 articles, and 15 studies were included. Study duration ranged between 2 and 14 years. All studies were performed primarily in whites with a mean age between 55 and 75 years. The meta-analyses included 12 studies, of which 10 investigated total CVD events; 7, fatal CVD events; and 3, non-fatal CVD events. PTH excess indicated an increased risk for total CVD events: pooled HR (95% CI), 1.45 (1.24-1.71). The results for fatal CVD events and non-fatal CVD events were: HR 1.50 (1.18-1.91) and HR 1.48 (1.14-1.92). Heterogeneity was moderately present; however, sensitivity analyses for follow-up duration, prior CVD, or PTH as dichotomous values showed similar results.
CONCLUSIONS
The meta-analysis indicates that higher PTH concentrations are associated with increased risk of CVD events.
Topics: Cardiovascular Diseases; Humans; Morbidity; Parathyroid Hormone; Risk Factors
PubMed: 23622902
DOI: 10.1016/j.ahj.2013.02.014 -
Surgical Oncology Sep 2021The study aim was to systematically review literature evaluating surgeon volume-outcome relationships for thyroid and parathyroid operations in order to inform surgical...
BACKGROUND
The study aim was to systematically review literature evaluating surgeon volume-outcome relationships for thyroid and parathyroid operations in order to inform surgical quality improvement initiatives. Current literature suggests surgeons who perform a high volume of thyroid and/or parathyroid operations have better outcomes than low volume surgeons, though specific volume definition are not standardized.
METHODS
Eligible studies were selected through a literature search focused on the effect of surgeon volume on thyroid and parathyroid surgery patient outcomes. The literature search was conducted in accordance with the PRISMA guidelines. Publication dates extended from January 1998 to February 2021, and were limited to articles published in English.
RESULTS
A total of 33 studies were included: 25 studies evaluating thyroid surgery outcomes, 4 studies evaluating parathyroid surgery outcomes, and 4 studies evaluating both thyroid and parathyroid (mixed) surgery outcomes. Higher volume thyroid and parathyroid surgeons were found to be associated with fewer surgical and medical complications, shorter length of hospital stay, and reduced total cost when compared to lower volume surgeons. This volume-outcome relationship was also found to specifically affect the complication and recurrence rates for thyroid cancer patients undergoing surgery, especially for individuals with advanced stage disease.
CONCLUSION
The heterogeneity in cut-offs used for characterizing surgeons as high versus low volume, and also in subsequent patient outcome measures, limited direct study comparisons. The trend of improved patient outcomes with higher surgeon volume for both thyroid and parathyroid surgeries was consistently present in all studies reviewed.
Topics: Hospitals, High-Volume; Humans; Length of Stay; Outcome Assessment, Health Care; Parathyroid Neoplasms; Parathyroidectomy; Postoperative Complications; Prognosis; Thyroid Neoplasms; Thyroidectomy
PubMed: 33915486
DOI: 10.1016/j.suronc.2021.101550 -
European Journal of Endocrinology Mar 2013Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphataemia and hypomagnesaemia, and is exacerbated by... (Review)
Review
Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphataemia and hypomagnesaemia, and is exacerbated by suppressed parathyroid hormone (PTH) levels, which follows parathyroidectomy in patients with severe primary hyperparathyroidism (PHPT) and preoperative high bone turnover. It is a relatively uncommon, but serious adverse effect of parathyroidectomy. We conducted a literature search of all available studies reporting a 'hungry bone syndrome' in patients who had a parathyroidectomy for PHPT, to identify patients at risk and address the pitfalls in their management. The severe hypocalcaemia is believed to be due to increased influx of calcium into bone, due to the sudden removal of the effect of high circulating levels of PTH on osteoclastic resorption, leading to a decrease in the activation frequency of new remodelling sites and to a decrease in remodelling space, although there is no good documentation for this. Various risk factors have been suggested for the development of HBS, including older age, weight/volume of the resected parathyroid glands, radiological evidence of bone disease and vitamin D deficiency. The syndrome is reported in 25-90% of patients with radiological evidence of hyperparathyroid bone disease vs only 0-6% of patients without skeletal involvement. There is insufficient data-based evidence on the best means to treat, minimise or prevent this severe complication of parathyroidectomy. Treatment is aimed at replenishing the severe calcium deficit by using high doses of calcium supplemented by high doses of active metabolites of vitamin D. Adequate correction of magnesium deficiency and normalisation of bone turnover are required for resolution of the hypocalcaemia which may last for a number of months after successful surgery. Preoperative treatment with bisphosphonates has been suggested to reduce post-operative hypocalcaemia, but there are to date no prospective studies addressing this issue.
Topics: Bone Remodeling; Bone Resorption; Humans; Hyperparathyroidism, Primary; Hypocalcemia; Hypophosphatemia; Parathyroidectomy; Postoperative Complications; Risk Factors; Severity of Illness Index; Syndrome
PubMed: 23152439
DOI: 10.1530/EJE-12-0528 -
Head & Neck Mar 2022To evaluate the diagnostic accuracies of indocyanine green (ICG) fluorescence for identifying parathyroid glands during surgery and predicting the postoperative function. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the diagnostic accuracies of indocyanine green (ICG) fluorescence for identifying parathyroid glands during surgery and predicting the postoperative function.
METHODS
From six databases, 21 studies were finally included in the study. True-positive, true-negative, false-positive, and false-negative data were extracted for the analysis. The quality of each study was analyzed using the QUADAS-2 tool.
RESULTS
The sensitivity of ICG-based parathyroid gland identification was 0.9380 (95% CI [0.9003, 0.9621]). The diagnostic odds ratio for ICG-based prediction of parathyroid gland function was 54.5652 [13.2059, 225.4570]. The area under the summary receiver operating characteristic curve was 0.909. Fluorescence intensity-based prediction presented higher diagnostic accuracy than that of score-based prediction. The incidence of postoperative hypoparathyroidism was higher in the group with a zero ICG score compared to the high scored group.
CONCLUSIONS
Identification of parathyroid gland and prediction of postoperative function using ICG are valuable to patients undergoing thyroidectomy or parathyroidectomy.
Topics: Fluorescence; Humans; Hypoparathyroidism; Indocyanine Green; Parathyroid Glands; Postoperative Complications; Thyroidectomy
PubMed: 34908194
DOI: 10.1002/hed.26950 -
Journal of Renal Nutrition : the... Nov 2023Plant-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...
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 m 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.
Topics: Adult; Humans; Chronic Kidney Disease-Mineral and Bone Disorder; Plant Proteins; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Parathyroid Hormone; Minerals; Phosphorus; Dietary Proteins; Kidney
PubMed: 37116624
DOI: 10.1053/j.jrn.2023.04.004