Iron, Inflammation, Dialysis Adequacy, Nutritional Status, and Hyperparathyroidism Modify Erythropoietic Response

Background: Erythropoiesis-stimulating agent (ESA) resistance remains incompletely understood among hemodialysis (HD) patients. Method: A retrospective, multicenter study was designed to analyze data from 1,934 patients followed for up to two years. The outcome measure was the erythropoietin resistance index (ERI), defined as erythropoietin dosage over a week divided by the post-HD weight and hemoglobin value. Results: Multivariate analysis revealed albumin, Kt/V, transferrin saturation, statin use and male gender to be inversely related to ERI, whereas parathyroid hormone and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) use were associated with higher ESA resistance. ERI was statistically lower in patients with higher levels of albumin (p < 0.001) and with higher transferrin saturation levels (p < 0.05). Discussion: The results allow for a better understanding of predictors of erythropoietin resistance among HD patients including not extensively studied factors such as statin and ACEI/ARB use.

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“…Hgb sensitivity to erythropoietin decreases by about 30% as PTH increases from 0 through 1,000 pg/ml [56]. …”

Section: Discussionmentioning

confidence: 99%

Factors Predicting Erythropoietin Resistance among Maintenance Hemodialysis Patients

et al. 2012

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“…[12][13][14][15][16][17][18] Further, the systemic inflammatory response and increased oxidative stress are associated with poor response to erythropoietinstimulating agent (ESA) therapy. 19 Initiation of MHD does not improve biomarkers of oxidative stress or systemic inflammation, suggesting that maintenance dialysis alone is inadequate to control the proatherogenic metabolic milieu that accompanies uremia. 20 Emerging evidence associating oxidative stress biomarkers with inflammation and cardiovascular risk in patients undergoing MHD has led to several pilot trials of antioxidant regimens, with most studies focusing on use of tocopherols or thiol-containing antioxidants.…”

mentioning

confidence: 99%

Provision of Antioxidant Therapy in Hemodialysis (PATH)

Himmelfarb

İkizler²,

Ellis³

et al. 2014

Journal of the American Society of Nephrology

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Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients. In total, 353 patients were enrolled in a prospective, placebo-controlled, double-blind clinical trial and randomly assigned to receive a combination of mixed tocopherols (666 IU/d) plus a-lipoic acid (ALA; 600 mg/d) or matching placebos for 6 months (NCT00237718); 238 patients completed the study. High-sensitivity C-reactive protein (hsCRP) and IL-6 concentration were measured as biomarkers of systemic inflammation, and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress. The groups did not significantly differ at baseline. At 3 and 6 months, the treatment had no significant effect on plasma hsCRP, IL-6, F2 isoprostane, or isofuran concentrations and did not improve the erythropoietic response. No major adverse events were related to the study drug, and both groups had similar mortality and hospitalization rates during the study. In conclusion, the administration of mixed tocopherols and ALA was generally safe and well tolerated, but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response.

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“…Vitamin D deficiency may increase inflammatory cytokines production (interleukin-6, IFN-γ, TNF-α), which stimulate hepcidin production, thus inhibiting ferroportin activity and limiting iron usability [77,78]. In addition, secondary hyperparathyroidism will directly inhibit erythroid progenitors, endogenous erythropoietin synthesis, and red blood cell survival as well as indirectly promote bone marrow fibrosis and hyperphosphatemia [76,79]. All of these factors will lead to ESA hyporesponsiveness.…”

Section: Vitamin D and Anemiamentioning

confidence: 99%

Pleiotropic Effects of Vitamin D in Kidney Disease

Wu¹,

Lu²

2017

A Critical Evaluation of Vitamin D - Clinical Overview

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Vitamin D is metabolized in the liver and kidneys and then converted to the active form, 1.25-dihydroxyvitamin D [1.25(OH)2D]. Chronic kidney disease patients usually lack both 25-hydroxyvitamin D [25(OH)D] and 1.25(OH)2D due to impaired renal function and 1α-hydroxylase deficiency. Chronic kidney disease patients have a high incidence of cardiovascular and infectious morbidities. Increasing evidence indicates a relationship between vitamin D deficiency and cardiovascular and infectious mortality risks. Vitamin D may have significant biological effects beyond its traditional roles on mineral and bone metabolism. Many extrarenal cells have the capability to produce local active 1.25(OH)2D in an intracrine or paracrine fashion. Vitamin D has a significant association with nonskeletal diseases, such as immunodeficiency, metabolic syndrome, insulin resistance, diabetes, hyperlipidemia, cardiovascular disease, proteinuria, and acute kidney injury. This article aims to review and summarize the pleiotropic effects of vitamin D in patients with kidney disease, particularly the immunological, metabolic, cardiovascular, and renal effects.

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Iron, Inflammation, Dialysis Adequacy, Nutritional Status, and Hyperparathyroidism Modify Erythropoietic Response

Cited by 66 publications

References 26 publications

Factors Predicting Erythropoietin Resistance among Maintenance Hemodialysis Patients

Factors Predicting Erythropoietin Resistance among Maintenance Hemodialysis Patients

Provision of Antioxidant Therapy in Hemodialysis (PATH)

Pleiotropic Effects of Vitamin D in Kidney Disease

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