The Influence of Inflammatory Markers and CRP Predictive Value in Relation to the Target Hemoglobin Level in Patients on Chronic Hemodialysis

Musanovic, Adnan; Trnačević, Senaid; Mekic, Mevludin; Musanovic, Affan

doi:10.5455/medarh.2013.67.361-364

Cited by 4 publications

(6 citation statements)

References 13 publications

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“…Aggressive IIT has been used in HD patients of Western countries probably due to high prevalence of inflammation, which increases serum ferritin and hepcidin-25, thereby inhibiting iron efflux and absorption for erythropoiesis and requiring higher dose of IV iron. In support of this finding, it was shown that if the CRP increased by 1 mg/L, possibilities to achieve tHb were reduced by 7.5% in HD patients with IDA [ 37 ]. High dose of IIT may increase a risk of infection-related mortality [ 38 ], cardiovascular events and high mortality in HD patients [ 12 ], although it was challenged [ 11 ].…”

Section: Discussionmentioning

confidence: 82%

Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of Intravenous Iron Therapy for OIT-Nonresponders

et al. 2018

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Background: We determined optimal serum ferritin for oral iron therapy (OIT) in hemodialysis (HD) patients with iron deficiency anemia (IDA)/minor inflammation, and benefit of intravenous iron therapy (IIT) for OIT-nonresponders. Methods: Inclusion criteria were IDA (Hb <120 g/L, serum ferritin <227.4 pmol/L). Exclusion criteria were inflammation (C-reactive protein (CRP) ≥ 5 mg/L), bleeding, or cancer. IIT was withheld >3 months before the study. ΔHb ≥ 20 g/L above baseline or maintaining target Hb (tHB; 120–130 g/L) was considered responsive. Fifty-one patients received OIT (ferrous fumarate, 50 mg/day) for 3 months; this continued in OIT-responders but was switched to IIT (saccharated ferric oxide, 40 mg/week) in OIT-nonresponders for 4 months. All received continuous erythropoietin receptor activator (CERA). Hb, ferritin, hepcidin-25, and CERA dose were measured. Results: Demographics before OIT were similar between OIT-responders and OIT-nonresponders except low Hb and high triglycerides in OIT-nonresponders. Thirty-nine were OIT-responders with reduced CERA dose. Hb rose with a peak at 5 months. Ferritin and hepcidin-25 continuously increased. Hb positively correlated with ferritin in OIT-responders (r = 0.913, p = 0.03) till 5 months after OIT. The correlation equation estimated optimal ferritin of 30–40 ng/mL using tHb (120–130 g/L). Seven OIT-nonresponders were IIT-responders. Conclusions: Optimal serum ferritin for OIT is 67.4–89.9 pmol/L in HD patients with IDA/minor inflammation. IIT may be a second line of treatment for OIT-nonreponders.

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Section: Discussionmentioning

confidence: 82%

Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of Intravenous Iron Therapy for OIT-Nonresponders

et al. 2018

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“…These data suggest that under concomitant inflammation, ferritin is not a predictor of the response to iron therapy. In support of this, Musanovic et al reported that the predictive values of CRP to achieve tHb following IIT was ≤6.5 mg/dL and that serum ferritin levels failed to predict the response to IIT in highly inflamed HD patients with higher CRP levels [ 136 ]. In addition, in HD patients with high levels of serum ferritin (500–1200 ng/mL) and CRP (>20 mg/dL) and low TSAT (<25%), none of the iron indices (ferritin, CHr, TSAT or sTfR) was predictive of the response to IIT, while lower CRP levels of ≤14.0 mg/dL were predictive of the response to IIT [ 22 ].…”

Section: Impact Of Inflammation On Therapeutic Strategy With Iron mentioning

confidence: 97%

“…Furthermore, serum hepcidin was positively correlated with inflammation markers (CRP, IL-6 and TNF-α) and ferritin but inversely correlated with TIBC, Hb, Ht and GFR [ 50 , 134 , 135 ]. In contrast, relatively low CRP (≤6.5 mg/dL) was associated with more achievement of tHb and if CRP increased by 1 mg/dL, possibility to maintain tHb was reduced by 7.5% in HD patients [ 136 ]. These data suggest that inflammation is a confounding factor for maintenance of tHb probably due to increased ferritin and hepcidin which inhibit iron absorption and efflux, leading to reduced iron bioavailability for erythropoiesis.…”

Section: Impact Of Inflammation On Therapeutic Strategy With Iron mentioning

confidence: 99%

“…Our previous study showed that optimal serum ferritin levels were estimated to be 30–40 ng/mL in HD patients with normal CRP and that further increment of serum ferritin was associated with increased levels of serum hepcidin and decreased Hb levels [ 124 ]. As shown in Table 4 , optimal serum ferritin levels are significantly lower in HD patients with minor inflammation receiving IIT than achieved serum ferritin targets in those with apparent inflammation receiving IIT (mean serum ferritin, 340–810 ng/mL) [ 114 , 120 , 123 , 136 , 167 ] but similar to those (mean, 238.5 ng/mL) in ND-CKD patients with weakly positive CRP (mean, 1.3 mg/dL) receiving IIT [ 118 ]. Thus, concomitant inflammation increases serum ferritin targets to maintain tHb, making IIT more preferable than OIT to maintain tHb in CKD patients.…”

Section: What Are Optimal Levels Of Serum Ferritin For the Managemmentioning

confidence: 99%

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Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

2018

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Iron deficiency anemia (IDA) is a major problem in chronic kidney disease (CKD), causing increased mortality. Ferritin stores iron, representing iron status. Hepcidin binds to ferroportin, thereby inhibiting iron absorption/efflux. Inflammation in CKD increases ferritin and hepcidin independent of iron status, which reduce iron availability. While intravenous iron therapy (IIT) is superior to oral iron therapy (OIT) in CKD patients with inflammation, OIT is as effective as IIT in those without. Inflammation reduces predictive values of ferritin and hepcidin for iron status and responsiveness to iron therapy. Upper limit of ferritin to predict iron overload is higher in CKD patients with inflammation than in those without. However, magnetic resonance imaging studies show lower cutoff levels of serum ferritin to predict iron overload in dialysis patients with apparent inflammation than upper limit of ferritin proposed by international guidelines. Compared to CKD patients with inflammation, optimal ferritin levels for IDA are lower in those without, requiring reduced iron dose and leading to decreased mortality. The management of IDA should differ between CKD patients with and without inflammation and include minimization of inflammation. Further studies are needed to determine the impact of inflammation on ferritin, hepcidin and therapeutic strategy for IDA in CKD.

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“…Under concomitant inflammation, ferritin loses its predictive value of the response to iron therapy. Moreover, in highly inflamed patients, not only ferritin but also other biomarkers of iron metabolism (TSAT, CHr, or sTfR) lose their value in predicting treatment response [55][56][57]. In these patients, the values of CRP, but not indices of iron status may be predictive of the response to iron supplementation [55,57], and there is no correction factor that could applied in estimation of iron stores depending on ferritin concentration [48].…”

Section: Assessment Of Iron Statusmentioning

confidence: 99%

Biomarkers of iron metabolism in chronic kidney disease

2020

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Iron is the most abundant transition metal in the human body and an essential element required for growth and survival. Our understanding of the molecular control of iron metabolism has increased dramatically over the past 20 years due to the discovery of hepcidin, which regulates the uptake of dietary iron and its mobilization from macrophages and hepatic stores. Anemia and iron deficiency are common in chronic kidney disease. The pathogenesis of anemia of chronic kidney disease is multifactorial. Correction of anemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow. However, there are still many uncertainties in regard to iron metabolism in patients with chronic kidney disease and in renal replacement therapy. The aim of this review was to summarize the current knowledge on iron metabolism in this population, including new biomarkers of iron status. There is an area of uncertainty regarding diagnostic utility of both erythroferrone (ERFE) and hepcidin in end-stage renal disease (ESRD) patients. Higher concentration of hepcidin in oligoanuric patients may reflect decreased renal clearance. Furthermore, the hepcidin-lowering effect of ERFE in ESRD patients treated with erythropoiesis-stimulating agents (ESAs) may be blunted by underlying inflammation and concomitant iron treatment. Thus, future studies should validate the use of ERFE as a biomarker of erythropoiesis and predictor of response to iron and ESA therapy in dialysis-dependent patients.

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The Influence of Inflammatory Markers and CRP Predictive Value in Relation to the Target Hemoglobin Level in Patients on Chronic Hemodialysis

Abstract: The research results show how what looks as routine findings may be helpful in the timely detection of threatening complications and their treatment, and provide extended and improved quality of life for patients on hemodialysis.

Cited by 4 publications

References 13 publications

Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of Intravenous Iron Therapy for OIT-Nonresponders

Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of Intravenous Iron Therapy for OIT-Nonresponders

Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

Biomarkers of iron metabolism in chronic kidney disease

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