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Archives of Endocrinology and Metabolism May 2024Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We... (Comparative Study)
Comparative Study
Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.
Topics: Humans; Familial Hypophosphatemic Rickets; Antibodies, Monoclonal, Humanized; Fibroblast Growth Factor-23; Treatment Outcome; Calcitriol; Antibodies, Monoclonal; Phosphorus
PubMed: 38788147
DOI: 10.20945/2359-4292-2023-0242 -
Cureus Oct 2022The major cause of death in the United States is heart disease. The global burden of illness and mortality from heart failure is substantial. Despite recent innovations... (Review)
Review
The major cause of death in the United States is heart disease. The global burden of illness and mortality from heart failure is substantial. Despite recent innovations in the treatment of heart failure, the prognosis is still poor. To identify, evaluate, and summarize the findings of all relevant studies of a drug that is equally efficacious but rather cost-effective, empagliflozin compared to the other sodium-glucose cotransporter-2 (SGLT2) inhibitors was studied. It is licensed by the Food and Drug Administration (FDA), acts by preventing the reabsorption of glucose from the kidney, and exhibits promising advantages in heart failure. We systematically explored PubMed, PubMed Central (PMC), and Medical Literature Analysis and Retrieval System Online (MEDLINE) for randomized controlled trials (RCTs) and observational studies related to cardiovascular and renal outcomes of empagliflozin in patients with heart failure with reduced ejection fraction (HFrEF). After performing scoping search and search strategy, studies were screened for quality assessment using the Cochrane risk of bias assessment tool. We screened 60 articles by titles, abstract, and exclusion and inclusion criteria, after which eight final randomized controlled trials (RCTs) with 18,659 participants treated with empagliflozin and placebo were used for the systematic review. This systematic review's objective is to investigate and explore the full range of empagliflozin's effects and advantages on cardiac structure, function, and hemodynamics and renal function in patients with heart failure with reduced ejection fraction (EF) in order to better understand the drug's effects and related mechanisms.
PubMed: 36348895
DOI: 10.7759/cureus.29896 -
The Cochrane Database of Systematic... Oct 2021Conventional treatment of X-linked hypophosphatemia with oral phosphate and calcitriol can heal rickets, but it does not always raise serum phosphate concentrations... (Review)
Review
BACKGROUND
Conventional treatment of X-linked hypophosphatemia with oral phosphate and calcitriol can heal rickets, but it does not always raise serum phosphate concentrations significantly, nor does it always normalize linear growth. Some clinical trials suggest that combining recombinant human growth hormone therapy with conventional treatment improves growth velocity, phosphate retention, and bone mineral density, but some clinical trials suggest that it appears to aggravate the pre-existent disproportionate stature of such children. This is an updated version of a previously published review.
OBJECTIVES
To determine whether recombinant human growth hormone therapy for children with X-linked hypophosphatemia is associated with changes in longitudinal growth, mineral metabolism, endocrine function, renal function, bone mineral density, body proportions, and also with any adverse effects.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE and the reference lists of identified trials and other reviews. We also undertook some additional handsearching of relevant journals and conference proceedings. Date of the most recent search: 12 January 2021 SELECTION CRITERIA: All randomized controlled studies or quasi-randomized controlled studies comparing growth hormone (alone or combined with conventional treatment) with either placebo or conventional treatment alone in children with X-linked hypophosphatemia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for risk of bias and extracted data from eligible studies. GRADE criteria were used to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included two studies (20 participants) in the review. In one cross-over study, results showed that recombinant human growth hormone therapy may improve the height standard deviation (SDS) score (z score), but we are unsure whether the intervention was the reason behind a transient increase in serum phosphate and tubular maximum for phosphate reabsorption. In the second, parallel study, treatment may also have improved the height SDS from baseline in the rhGH group compared to the control group, although no significant difference was seen between groups after three years, MD 0.50 SDS (95 % CI -0.54 to 1.54) (low-certainty evidence). The treatment was possibly well-tolerated during both studies with only transient adverse effects seen in three participants (low-certainty evidence). We are uncertain whether growth hormone improves serum phosphate levels or change in TmP/GFR (very low-certainty evidence). The treatment may make little or no difference to alkaline phosphatase levels (low-certainty evidence).
AUTHORS' CONCLUSIONS
We do not have enough high-certainty evidence to recommend the use of recombinant human growth hormone therapy in children with X-linked hypophosphatemia.
Topics: Body Height; Child; Cross-Over Studies; Familial Hypophosphatemic Rickets; Growth Hormone; Human Growth Hormone; Humans
PubMed: 34618915
DOI: 10.1002/14651858.CD004447.pub3 -
Journal of Diabetes Research 2020Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose...
Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules. . A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance). . Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content; human studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with NaKATPase activity impacting on glucose transport. . Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.
Topics: Animals; Glucose; Humans; Insulin; Kidney Tubules, Proximal; Sodium-Glucose Transport Proteins
PubMed: 32377524
DOI: 10.1155/2020/8492467 -
Current Diabetes Reviews 2020The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the...
BACKGROUND
The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the pathophysiology of type 2 DM in children is paramount to devise an effective management plan.
OBJECTIVE
Discuss the pathophysiology of type 2 DM in children and adolescents.
METHODS AND RESULTS
This is a comprehensive review of the literature on this topic. Type 2 DM in childhood is viewed as a continuum of insulin resistance (IR) which is determined by an underlying genetic predisposition, intrauterine environment, excessive food consumption, continued rapid weight gain, and poor lifestyle. Besides IR, this is compounded by multiple metabolic defects including β-cell dysfunction and inadequate insulin secretion, α-cell dysfunction, hyperglucagonemia and increased hepatic glucose production, lipotoxicity, inflammation, deficiencies in incretin production and action, and increased renal glucose reabsorption. The confluence of genetic and environmental factors underscores the complexity in disease progression.
CONCLUSION
A consistent single risk factor for type 2 DM is obesity and related IR and therefore it is essential to curtail the progression of obesity. It is important to investigate the role of stringent dietary and nutritional approaches, medications that enhance β-cell function and insulin sensitivity.
Topics: Adolescent; Child; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Pediatric Obesity; Risk Factors
PubMed: 29879890
DOI: 10.2174/1573399814666180608074510