Predictors of iron versus erythropoietin responsiveness in anemic hemodialysis patients.

Anemia protocols for hemodialysis patients usually titrate erythropoietin (ESA) according to hemoglobin and iron according to a threshold of ferritin, with variable response seen. A universally optimum threshold for ferritin may be incorrect, and another view is that ESA and iron are alternative anemia treatments, which should be selected based on the likely response to each. Hemodialysis patients developing moderate anemia were randomised to treatment with either an increase in ESA or a course of intravenous iron.

Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men.

Context: Osteoporosis results from disturbances in bone formation and resorption. Recent nonhuman data suggest that the reproductive hormone kisspeptin directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown.

Hepcidin secretion was not directly proportional to intracellular iron-loading in recombinant-TfR1 HepG2 cells: short communication.

Hepcidin is the master regulator of systemic iron homeostasis and its dysregulation is observed in several chronic liver diseases. Unlike the extracellular iron-sensing mechanisms, the intracellular iron-sensing mechanisms in the hepatocytes that lead to hepcidin induction and secretion are incompletely understood. Here, we aimed to understand the direct role of intracellular iron-loading on hepcidin mRNA and peptide secretion using our previously characterised recombinant HepG2 cells that over-express the cell-surface iron-importer protein transferrin receptor-1.

Hepcidin clearance is associated with erythropoietin requirement in stable hemodialysis patients .

Background: The discovery of hepcidin, the hormone regulating iron absorption and transport, has improved the understanding of anemia and erythropoietin treatment. Excessive hepcidin signaling causes anemia in chronic inflammatory conditions by restricting iron delivery to the bone marrow. Hepcidin is normally eliminated in the urine, and the high levels seen in renal failure are thought to contribute to renal anemia and resistance to erythropoietin.

Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia?

Objectives/hypothesis: To examine whether there is a rationale for iron treatments precipitating nosebleeds (epistaxis) in a subgroup of patients with hereditary hemorrhagic telangiectasia (HHT).

Study Design: Survey evaluation of HHT patients, and a randomized control trial in healthy volunteers.

Methods: Nosebleed severity in response to iron treatments and standard investigations were evaluated by unbiased surveys in patients with HHT.

Characterization of hepcidin response to holotransferrin in novel recombinant TfR1 HepG2 cells.

Hepcidin is the key regulator of systemic iron homeostasis. The iron-sensing mechanisms and the role of intracellular iron in modulating hepatic hepcidin secretion are unclear. Therefore, we created a novel cell line, recombinant-TfR1 HepG2, expressing iron-response-element-independent TFRC mRNA to promote cellular iron-overload and examined the effect of excess holotransferrin (5g/L) on cell-surface TfR1, iron content, hepcidin secretion and mRNA expressions of TFRC, HAMP, SLC40A1, HFE and TFR2.

Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells.

Iron overload coupled with low hepcidin levels are characteristics of hereditary haemochromatosis. To understand the role of transferrin receptor (TFR) and intracellular iron in hepcidin secretion, Chinese hamster ovary transferrin receptor variant (CHO TRVb-1) cells were used that express iron-response-element-depleted human TFRC mRNA (TFRC∆IRE). Results showed that CHO TRVb-1 cells expressed higher basal levels of cell-surface TFR1 than HepG2 cells (2.

Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease.

Background: Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25--the key hormone of iron-metabolism--on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.

Iron homeostasis and pulmonary hypertension: iron deficiency leads to pulmonary vascular remodeling in the rat.

Rationale: Iron deficiency without anemia is prevalent in patients with idiopathic pulmonary arterial hypertension and associated with reduced exercise capacity and survival.

Objectives: We hypothesized that iron deficiency is involved in the pathogenesis of pulmonary hypertension and iron replacement is a possible therapeutic strategy.

Methods And Results: Rats were fed an iron-deficient diet (IDD, 7 mg/kg) and investigated for 4 weeks.

Circulating pancreatic polypeptide concentrations predict visceral and liver fat content.

Context And Objective: No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control.

Effect of Intravenous Iron on Aerobic Capacity and Iron Metabolism in Elite Athletes.

Purpose: Iron-deficient athletes are often treated with long-term, low-dose iron therapy. Such treatments may be efficacious in correcting iron deficiency; however, the effect on acute and chronic iron metabolism and subsequent endurance capacity is less clear.

Methods: Fifteen national and international standard runners were identified as iron deficient nonanemic (IDNA) and assigned to either an intravenous iron treatment group or placebo group.

Acute and chronic effects of kisspeptin-54 administration on GH, prolactin and TSH secretion in healthy women.

Background: The peptide hormone kisspeptin is essential for human reproduction, acting on the hypothalamus to stimulate gonadotrophin-releasing hormone (GnRH) secretion. Kisspeptin is currently being evaluated as a novel therapeutic for women with infertility. However, some animal studies suggest that kisspeptin may also stimulate growth hormone (GH), prolactin and thyroid-stimulating hormone (TSH) secretion, with implications for its safety; no previous study has investigated whether kisspeptin stimulates these pituitary hormones in humans.

Cardiopulmonary exercise testing demonstrates maintenance of exercise capacity in patients with hypoxemia and pulmonary arteriovenous malformations.

Background: Patients with pulmonary arteriovenous malformations (PAVMs) are unusual because hypoxemia results from right-to-left shunting and not airway or alveolar disease. Their surprisingly well-preserved exercise capacity is not generally appreciated.

Methods: To examine why exercise tolerance is preserved, cardiopulmonary exercise tests were performed while breathing room air in 21 patients with radiologically proven PAVMs, including five restudied 3 to 12 months after embolization when their PAVMs had regressed.

Hemorrhage-adjusted iron requirements, hematinics and hepcidin define hereditary hemorrhagic telangiectasia as a model of hemorrhagic iron deficiency.

Background: Iron deficiency anemia remains a major global health problem. Higher iron demands provide the potential for a targeted preventative approach before anemia develops. The primary study objective was to develop and validate a metric that stratifies recommended dietary iron intake to compensate for patient-specific non-menstrual hemorrhagic losses.

Optimal iron fortification of maternal diet during pregnancy and nursing for investigating and preventing iron deficiency in young rhesus monkeys.

The realization that pregnant and infant monkeys were challenged by high nutritional needs for iron led vendors to markedly increase iron concentrations in commercial diets. Yet, no systematic research was conducted to investigate the consequences of this important dietary change. Hematology and iron panels were determined for 142 infant rhesus monkeys gestated and reared on 3 different diets varying in iron concentration (180, 225 or 380 mg Fe/kg).

Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension: clinical prevalence, outcomes, and mechanistic insights.

Objectives: This study sought to understand the prevalence and clinical relevance of iron deficiency in patients with idiopathic pulmonary arterial hypertension (IPAH).

Background: Iron availability influences the pulmonary vascular response to hypoxia in humans and may be significant in the pathogenesis of IPAH.

Methods: Iron deficiency, defined by raised levels of soluble transferrin receptor (sTfR), was investigated in 98 patients with IPAH.

Blunted increase in serum hepcidin as response to oral iron in HFE-hemochromatosis.

Background: HFE hemochromatosis (HFE-H) is the most common and well-defined inherited cause for iron-related morbidity and mortality. Majority of patients with HFE-H are homozygote for C282Y mutation. Recent studies suggest that iron accumulation in most types of hemochromatosis is due to deficiency of hepcidin, a central iron regulator.

Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension.

Background: Anaemia is common in left heart failure and is associated with a poorer outcome. Many patients with pulmonary arterial hypertension (PAH) are anaemic or iron-deficient. This study was performed to investigate the prevalence of iron deficiency in PAH and to identify possible causes.

Hepcidin levels in hereditary hyperferritinemia: Insights into the iron-sensing mechanism in hepatocytes.

Aim: To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome (HHCS).

Methods: Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position +40 in the L-ferritin gene, were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay, respectively, and measurements were compared with levels in serum from 25 healthy volunteers (14 females), mean age 36 +/- 11.9 years.

Presence of hepcidin-25 in biological fluids: bile, ascitic and pleural fluids.

Aim: To examine body fluids such as ascitic fluid (AF), saliva, bile and pleural effusions for the presence of hepcidin using a novel radioimmunoassay (RIA).

Methods: Serum samples were collected from 25 healthy volunteers (mean age: 36 +/- 11.9 years, 11 males, 14 females).

Results of the first international round robin for the quantification of urinary and plasma hepcidin assays: need for standardization.

The recently discovered iron regulatory peptide hormone hepcidin holds promise as a novel biomarker in iron metabolism disorders. To date, various mass spectrometry and immunochemical methods have been developed for its quantification in plasma and urine. Differences in methodology and analytical performance hinder the comparability of data.

Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin.

Expression of hepcidin, the key hormone governing iron transport, is reduced by anemia in a manner which appears dependent on increased bone marrow activity. The temporal associations between plasma hepcidin and other iron parameters were examined in healthy humans after erythropoietin administration and venesection. Profound hepcidin suppression appeared abruptly 24 hours after subcutaneous erythropoietin (P=0.

Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment.

Malnutrition is a common complication in patients on dialysis and is strongly associated with poor prognosis. Effective therapy could substantially improve morbidity and mortality, but neither enteral nor parenteral supplementation provide long-term benefit because of the strong appetite suppression seen in such patients. We performed a double-blinded randomized crossover study of a week-long treatment with daily subcutaneous ghrelin, a gut hormone that regulates hunger through the hypothalamus, in a group of 12 malnourished dialysis patients.

Hepcidin and inflammatory bowel disease: dual role in host defence and iron homoeostasis.

Objective: Hepcidin is an endogenous antimicrobial peptide with a key role in iron homoeostasis. Hepcidin is similar to defensin, the deficiency of which is associated with Crohn's disease. To date there has been no validated method to reliably assay serum hepcidin.