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Serum hepcidin may be a novel uremic toxin, which might be related to erythropoietin resistance.

ABSTRACT: The clinical importance of serum hepcidin in non-dialysis chronic kidney disease (CKD) patients is unclear. The database of a large-scale multicentre prospective study in Korea of 2238 patients enrolled from 2011-2016 was analysed. After excluding patients with missing serum hepcidin (n?=?125) and haemoglobin (n?=?23) levels, the study included 2090 non-dialysis CKD patients. Markers of inflammation and iron status were positively associated with serum hepcidin level, regardless of CKD stage. However, estimated glomerular filtration rate was inversely associated with serum hepcidin level, particularly in patients with CKD stages 3b-5 but not in those with CKD stages 1-3a. Use of erythropoiesis-stimulating agents was associated with increased serum hepcidin levels, particularly in patients with CKD stages 3b-5 but not in those with CKD stages 1-3a, and serum hepcidin levels positively correlated with the dose of erythropoiesis-stimulating agent. These findings suggest that serum hepcidin may be a uremic toxin and play an important role in erythropoietin resistance. However, future prospective studies are needed to confirm our results.

SUBMITTER: Lee SW

PROVIDER: S-EPMC5484693 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Serum hepcidin may be a novel uremic toxin, which might be related to erythropoietin resistance.

Lee Sung Woo SW Kim Jeong Min JM Lim Hye Jin HJ Hwang Young-Hwan YH Kim Soo Wan SW Chung Wookyung W Oh Kook-Hwan KH Ahn Curie C Lee Kyu-Beck KB Sung Su Ah SA

Scientific reports 20170626 1

The clinical importance of serum hepcidin in non-dialysis chronic kidney disease (CKD) patients is unclear. The database of a large-scale multicentre prospective study in Korea of 2238 patients enrolled from 2011-2016 was analysed. After excluding patients with missing serum hepcidin (n = 125) and haemoglobin (n = 23) levels, the study included 2090 non-dialysis CKD patients. Markers of inflammation and iron status were positively associated with serum hepcidin level, regardless of CKD stage. Ho ...[more]

PMID: 28652624

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Project description:BACKGROUND:Hepcidin is an iron regulating hormone, and exercise-induced hepcidin elevation is suggested to increase the risk of iron deficiency among athletes. OBJECTIVE:We compared serum hepcidin responses to resistance exercise and endurance (cycling) exercise. METHODS:Ten males [mean ± standard error: 172 ± 2 cm, body weight: 70 ± 2 kg] performed three trials: a resistance exercise trial (RE), an endurance exercise trial (END), and a rest trial (REST). The RE consisted of 60 min of resistance exercise (3-5 sets × 12 repetitions, 8 exercises) at 65% of one repetition maximum, while 60 min of cycling exercise at 65% of [Formula: see text] was performed in the END. Blood samples were collected before exercise and during a 6-h post-exercise (0h, 1h, 2h, 3h, 6h after exercise). RESULTS:Both RE and END significantly increased blood lactate levels, with significantly higher in the RE (P < 0.001). Serum iron levels were significantly elevated immediately after exercise (P < 0.001), with no significant difference between RE and END. Both the RE and END significantly increased serum growth hormone (GH), cortisol, and myoglobin levels (P < 0.01). However, exercise-induced elevations of GH and cortisol were significantly greater in the RE (trial × time: P < 0.001). Plasma interleukin-6 (IL-6) levels were significantly elevated after exercise (P = 0.003), with no significant difference between the trials. Plasma hepcidin levels were elevated after exercise (P < 0.001), with significantly greater in the RE (463 ± 125%) than in the END (137 ± 27%, P = 0.03). During the REST, serum hepcidin and plasma IL-6 levels did not change significantly. CONCLUSION:Resistance exercise caused a greater exercise-induced elevation in hepcidin than did endurance (cycling) exercise. The present findings indicate that caution will be required to avoid iron deficiency even among athletes in strength (power) types of events who are regularly involved in resistance exercise.

Project description:Background and objectivesThe mechanisms underlying erythropoietin resistance are not fully understood. Carbamylation is a post-translational protein modification that can alter the function of proteins, such as erythropoietin. The hypothesis of this study is that carbamylation burden is independently associated with erythropoietin resistance.Design, setting, participants, & measurementsIn a nonconcurrent prospective cohort study of incident hemodialysis patients in the United States, carbamylated albumin, a surrogate of overall carbamylation burden, in 158 individuals at day 90 of dialysis initiation and erythropoietin resistance index (defined as average weekly erythropoietin dose [U] per kg body weight per hemoglobin [g/dl]) over the subsequent 90 days were measured. Linear regression was used to describe the relationship between carbamylated albumin and erythropoietin resistance index. Logistic regression characterized the relationship between erythropoietin resistance index, 1-year mortality, and carbamylation.ResultsThe median percent carbamylated albumin was 0.77% (interquartile range=0.58%-0.93%). Median erythropoietin resistance index was 18.7 units/kg per gram per deciliter (interquartile range=8.1-35.6 units/kg per gram per deciliter). Multivariable adjusted analysis showed that the highest quartile of carbamylated albumin was associated with a 72% higher erythropoietin resistance index compared with the lowest carbamylation quartile (P=0.01). Increasing erythropoietin resistance index was associated with a higher risk of death (odds ratio per unit increase in log-erythropoietin resistance index, 1.69; 95% confidence interval, 1.06 to 2.70). However, the association between erythropoietin resistance index and mortality was no longer statistically significant when carbamylation was included in the analysis (odds ratio, 1.44; 95% confidence interval, 0.87 to 2.37), with carbamylation showing the dominant association with death (odds ratio for high versus low carbamylation quartile, 4.53; 95% confidence interval, 1.20 to 17.10).ConclusionCarbamylation was associated with higher erythropoietin resistance index in incident dialysis patients and a better predictor of mortality than erythropoietin resistance index.

Project description:Prevalence of iron deficiency is commonly reported among athletic population groups. It impairs physical performance due to insufficient oxygen delivery to target organs and low energy production. This is due to the high demand of exercise on oxygen delivery for systemic metabolism by the erythrocytes in the blood. Hepcidin, the key regulator of iron homeostasis, decreases to facilitate iron efflux into the circulation during enhanced erythropoiesis. However, acute anaemia of exercise is caused by increased hepcidin expression that is induced by stress and inflammatory signal. The study aimed to systematically review changes in serum hepcidin levels during resistance and aerobic exercise programmes. A systemic literature search from 2010 to April 2020 across seven databases comprised of Cochrane library, PubMed, Web of Science, Scopus, Embase, MEDLINE, and OpenGrey. The primary outcome was increased or decreased serum hepcidin from baseline after the exercise activity. Risks of bias were evaluated by using the National Institutes of Health (NIH) for quality assessment of before and after different exercise programmes. Overall, twenty-three studies met the inclusion criteria. Out of the 23 studies, 16 studies reported significantly exercise-induced serum hepcidin elevation. Of the 17 studies that evaluated serum interleukin (IL)-6 levels, 14 studies showed significant exercise-induced serum IL-6 elevation. Changes in exercise-induced serum hepcidin and IL-6 levels were similar in both resistance and endurance exercise. Significant correlations were observed between post-exercise hepcidin and baseline ferritin levels (r = 0.69, p < 0.05) and between post-exercise hepcidin and post-exercise IL-6 (r = 0.625, p < 0.05). Resistance and endurance training showed significant increase in serum hepcidin and IL-6 levels in response to exercise. Baseline ferritin and post-exercise IL-6 elevation are key determining factors in the augmentation of hepcidin response to exercise.

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Serum hepcidin may be a novel uremic toxin, which might be related to erythropoietin resistance.

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Serum hepcidin may be a novel uremic toxin, which might be related to erythropoietin resistance.

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