Parenteral iron therapy and phosphorus homeostasis: A review.
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ABSTRACT:
SUBMITTER: Kalantar-Zadeh K
PROVIDER: S-EPMC8248123 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Iron deficiency anemia (IDA) is associated with decreased appetite. The ghrelin hormone is one of the major regulators of appetite. OBJECTIVES:To evaluate appetite and ghrelin levels in patients with IDA, and to investigate the change in appetite and ghrelin following intravenous iron therapy. METHODS:A total of 56 IDA patients and 51 controls were included in the study. Both appetite and ghrelin were assessed at baseline and following intravenous iron therapy. These were assessed at corresponding time intervals in the control group. Appetite was assessed by the SNAQ score (Simplified Nutritional Appetite Questionnaire) and fasting ghrelin levels were assessed by acylated ghrelin (AG), unacylated ghrelin (UAG) and their respective ratio AG/UAG. RESULTS:IDA patients had significantly lower SNAQ scores, yet higher AG levels and higher AG/UAG ratios compared to healthy controls; the mean SNAQ scores were 12.56 ± 3.45 and 16.1 ± 2, respectively (P<0.01); the median AG levels were 57.5 pg/ml and 43 pg/ml respectively (P = 0.007); and the median AG/UAG ratios were 0.48 and 0.25 respectively (P = 0.04). On multivariate linear regression analysis, IDA remained independently associated with decreased SNAQ score (β = -0.524, P<0.001) and increased acylated ghrelin (β = 0.289, P = 0.013). After IDA was treated, SNAQ scores increased significantly by a mean of 2 points. AG and AG/UAG ratios decreased significantly by a mean of -18.44 pg/ml and -0.2 respectively. The control group showed no significant change in SNAQ scores or ghrelin at corresponding time intervals. CONCLUSIONS:IDA patients have a reduced appetite and paradoxically elevated ghrelin hormone activity compared to healthy controls. Treating IDA enhances appetite and lowers ghrelin levels. Future studies are needed to explore the mechanism of this paradoxical ghrelin activity.
| S-EPMC7272047 | biostudies-literature
Project description:Purpose of reviewThe study of phosphorus physiology and investigations into clinical disorders of phosphorus metabolism has blossomed over the past decade. Recent work has confirmed and further extended our knowledge of basic mechanisms of phosphorus metabolism.Recent findingsThis review will focus on FGF-23 and Klotho, and on the recent further dissection of their roles in phosphorus and skeletal metabolism. Additionally, this review will detail recent studies that implicate a role for these phosphaturic and vitamin D regulating factors in extraskeletal calcification, including that occurring in soft tissue and vascular beds.SummaryThese findings in total provide fertile ground for investigations into the cause and treatment of abnormal skeletal and extraskeletal calcification in patients with inherited hypophosphatemic disorders. More importantly, and certainly with wider potential clinical application, these studies likewise imply a role for these factors in the pathogenesis of accelerated cardiovascular disease that occurs in patients with the most common hyperphosphatemic disorder, chronic kidney disease. Future studies are needed to confirm a harmful or possibly even beneficial role for FGF-23 and other factors in these disease states, and to determine whether therapeutic manipulation of these factors does truly affect clinical outcomes in patients with hypophosphatemia and hyperphosphatemia.
| S-EPMC3740176 | biostudies-literature
Project description:Introduction:The burden of iron deficiency anaemia during pregnancy and post-partum continues to remain high especially in India. Challenges to treatment include gastrointestinal side effects and non compliance to oral iron therapy. Newer parenteral formulations need to be explored as alternatives. Methods:Meta-analysis of randomized controlled trials published between years 2011 and 2018 comparing anaemic pregnant and post-partum women treated with intravenous iron sucrose versus oral iron was performed. The primary outcomes were mean maternal haemoglobin, serum ferritin and haematocrit at the end of 1st, 2nd, 4th and 6th weeks and comparison of adverse effects. Results:Eighteen studies including 1633 antenatal women were randomly assigned to intravenous iron sucrose (n?=?821) or oral iron [ferrous sulphate, ferrous ascorbate or fumarate] group (n?=?812) in ten trials . Another eight studies compared iron sucrose infusion with oral iron in 713 post-partum women who were randomly assigned to intravenous iron sucrose group (n?=?351) or oral iron group (n?=?362). Cumulative analysis of all the time points indicates that the estimated mean values of Hb in the intravenous iron sucrose and oral iron groups were 10.11 g/dl and 9.33 g/dl, respectively, in antenatal group, while it was 10.57 g/dl and 9.74 g/dl in post-partum. The estimated mean ferritin level from first week to six weeks was 63.1 ?g/l and 28.6 ?g/l, respectively, in intravenous and oral iron groups. Cumulative estimate of haematocrit in the intravenous sucrose and oral iron over 6 weeks showed that the mean values in the respective groups were 30.5% and 29.5% in antenatal and 33.8% and 31.6%, respectively, in post-partum groups. Sensitivity analysis confirmed the reliability and consistency of the results. Oral iron was associated with significant gastrointestinal side effects. There was no significant difference in birthweight between the groups. Conclusion:This meta-analysis demonstrates that intravenous iron sucrose is more effective than oral iron therapy for pregnant and post-partum women with iron deficiency anaemia. It is an effective and safe alternative to address the problem of iron deficiency especially in those who require rapid replacement of iron stores though medical personnel for intravenous administration of drug is required.Trial registration CRD42015024343.
| S-EPMC6361181 | biostudies-literature
Project description:Anaemia is a highly prevalent condition, which negatively impacts on patients' cardiovascular performance and quality of life. Anaemia is mainly caused by disturbances of iron homeostasis. While absolute iron deficiency mostly as a consequence of chronic blood loss or insufficient dietary iron absorption results in the emergence of iron deficiency anaemia, inflammation-driven iron retention in innate immune cells and blockade of iron absorption leads to the development of anaemia of chronic disease. Both, iron deficiency and anaemia have been linked to the clinical course of pulmonary hypertension. Various mechanistic links between iron homeostasis, anaemia, and pulmonary hypertension have been described and current treatment guidelines suggest regular iron status assessment and the implementation of iron supplementation strategies in these patients. The pathophysiology, diagnostic assessment as well as current and future treatment options concerning iron deficiency with or without anaemia in individuals suffering from pulmonary hypertension are discussed within this review.
| S-EPMC7289779 | biostudies-literature
Project description:ObjectivesA review of patients requiring lifelong antibiotics to control, rather than cure, infection was performed ['palliative outpatient parenteral antibiotic therapy (OPAT)']. This was to evaluate emerging themes and complications. The aim was to aid in the management of such patients.MethodsA retrospective review of the OPAT database over 5 years (2013-17) was performed. Of the 1438 patients, 9 were deemed to have received palliative OPAT.ResultsThe palliative cohort represented 0.6% of the total number of patients on OPAT and 8.6% of the bed days saved. Patients fell into two main groups: those with multiple comorbidities that precluded surgical management and those with a terminal condition. Both groups received IV antibiotics with no clear endpoint. The themes to emerge were: patients often had multiple comorbidities with a high operative risk to control the source of infection; a trial of no or oral antibiotics led to resurgence of the infection; vascular patients appeared to tolerate long-term antibiotics well; and conversely, antibiotic side effects were a significant issue in others. Patients with incurable cancer and a coincident infection can be given additional quality of life with the judicious use of appropriate therapy.ConclusionsThere are significant issues surrounding antimicrobial stewardship in the palliative OPAT group that should be considered. Excellent communication is required to deal with these often very complicated patients. There are considerable gains to be made both for patients and the number of bed days saved. The small number of patients accounted for a disproportionate number of bed days saved.
| S-EPMC8210122 | biostudies-literature
Project description:BACKGROUND:The kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) in vitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23. STUDY DESIGN:Cross-sectional. SETTING & PARTICIPANTS:980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTORS:Net acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimated from food frequency questionnaire responses, and serum bicarbonate concentration < 22 mEq/L. OUTCOME & MEASUREMENTS:24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations. RESULTS:Using linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P<0.05). Serum phosphorus concentration was also higher with higher net acid excretion and lower serum bicarbonate concentration (each P=0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion (P<0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but not FGF-23, concentration (P=0.2) was 26% (95% CI, 13%-40%) higher in participants with a serum bicarbonate concentration <22 versus ?22 mEq/L (P<0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n=359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available. LIMITATIONS:Possible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion. CONCLUSIONS:In CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials.
| S-EPMC5804342 | biostudies-other
Project description:BackgroundThere has been little detailed systematic consideration of the delivery, setting and outcomes of paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT), although individual studies report that it is a safe and effective treatment.ObjectiveThis scoping review aimed to examine what is known about the delivery, settings and outcomes of paediatric OPAT and to identify key knowledge deficits.DesignA scoping review using Arksey and O'Malley's framework was undertaken.Data sourcesKeywords were identified and used to search MEDLINE and CINAHL.Study appraisal methodsPrimary research studies were included if samples comprised children and young people 21 or under, who had received OPAT at home or in a day treatment centre. The Mixed Methods Appraisal Tool was used to review the methodological quality of the studies MAIN FINDINGS: From a preliminary pool of 157 articles, 51 papers were selected for full review. 19 studies fitted the inclusion criteria. Factors influencing delivery of OPAT were diverse and included child's condition, home environment, child-related factors, parental compliance, training and monitoring. There is little consensus as to what constitutes success of and adverse events in OPAT.ConclusionsFuture studies need to clearly define and use success indicators and adverse events in order to provide evidence that paediatric OPAT is safe and effective.ImplicationsConsensus outcomes that include child and parent perspectives need to be developed to allow a clearer appreciation of a successful paediatric OPAT service.
| S-EPMC6252693 | biostudies-literature
Project description:Nonheme food ferritin (FTN) iron minerals, nonheme iron complexes, and heme iron contribute to the balance between food iron absorption and body iron homeostasis. Iron absorption depends on membrane transporter proteins DMT1, PCP/HCP1, ferroportin (FPN), TRF2, and matriptase 2. Mutations in DMT1 and matriptase-2 cause iron deficiency; mutations in FPN, HFE, and TRF2 cause iron excess. Intracellular iron homeostasis depends on coordinated regulation of iron trafficking and storage proteins encoded in iron responsive element (IRE)-mRNA. The noncoding IRE-mRNA structures bind protein repressors, IRP1 or 2, during iron deficiency. Integration of the IRE-RNA in translation regulators (near the cap) or turnover elements (after the coding region) increases iron uptake (DMT1/TRF1) or decreases iron storage/efflux (FTN/FPN) when IRP binds. An antioxidant response element in FTN DNA binds Bach1, a heme-sensitive transcription factor that coordinates expression among antioxidant response proteins like FTN, thioredoxin reductase, and quinone reductase. FTN, an antioxidant because Fe(2+) and O(2) (reactive oxygen species generators) are consumed to make iron mineral, is also a nutritional iron concentrate that is an efficiently absorbed, nonheme source of iron from whole legumes. FTN protein cages contain thousands of mineralized iron atoms and enter cells by receptor-mediated endocytosis, an absorption mechanism distinct from transport of nonheme iron salts (ferrous sulfate), iron chelators (ferric-EDTA), or heme. Recognition of 2 nutritional nonheme iron sources, small and large (FTN), will aid the solution of iron deficiency, a major public health problem, and the development of new policies on iron nutrition.
| S-EPMC3056584 | biostudies-literature
Project description:Long-term parenteral nutrition (PN) administration can lead to PN-associated liver diseases (PNALD). Although multiple risk factors have been identified for PNALD, to date, the roles of bile acids (BAs) and the pathways involved in BA homeostasis in the development and progression of PNALD are still unclear. We have established a mouse PN model with IV infusion of PN solution containing soybean oil-based lipid emulsion (SOLE). Our results showed that PN altered the expression of genes involved in a variety of liver functions at the mRNA levels. PN increased liver gene expression of Cyp7a1 and markedly decreased that of Cyp8b1, Cyp7b1, Bsep, and Shp. CYP7A1 and CYP8B1 are important for synthesizing the total amount of BAs and regulating the hydrophobicity of BAs, respectively. Consistently, both the levels and the percentages of primary BAs as well as total non-12?-OH BAs increased significantly in the serum of PN mice compared with saline controls, whereas liver BA profiles were largely similar. The expression of several key liver-X receptor-? (LXR?) target genes involved in lipid synthesis was also increased in PN mouse livers. Retinoid acid-related orphan receptor-? (ROR?) has been shown to induce the expression of Cyp8b1 and Cyp7b1, as well as to suppress LXR? function. Western blot showed significantly reduced nuclear migration of ROR? protein in PN mouse livers. This study shows that continuous PN infusion with SOLE in mice leads to dysregulation of BA homeostasis. Alterations of liver ROR? signaling in PN mice may be one of the mechanisms implicated in the pathogenesis of PNALD.
| S-EPMC4719060 | biostudies-literature
Project description:Parenteral nutrition has evolved tremendously, with parenteral formulas now safer and more accessible than ever. "All-in-one" admixtures are now available, which simplify parenteral nutrition usage and decrease line infection rates alongside other methods of infectious control. Recently published data on the benefits of parenteral nutrition versus enteral nutrition together with the widespread use of indirect calorimetry solve many safety issues that have emerged over the years. All these advances, alongside a better understanding of glycemic control and lipid and protein formulation improvements, make parenteral nutrition a safe alternative to enteral nutrition.
| S-EPMC7146311 | biostudies-literature