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• W2770265669 abstract "Over the past 3 decades, the routine use of erythropoeisis-stimulating agents (ESA) has enabled the correction of anemia in most patients with end-stage renal disease (ESRD), reducing the need for blood transfusions and improving the quality of life of severely anemic patients.1Hörl W.H. Clinical aspects of iron use in the anemia of kidney disease.J Am Soc Nephrol. 2007; 18: 382-393Crossref PubMed Scopus (121) Google Scholar Almost all ESA-treated hemodialysis patients receive parenteral iron to ensure sufficient available iron for ESA therapy.1Hörl W.H. Clinical aspects of iron use in the anemia of kidney disease.J Am Soc Nephrol. 2007; 18: 382-393Crossref PubMed Scopus (121) Google Scholar, 2KDOQI; National Kidney FoundationClinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults.Am J Kidney Dis. 2006; 47: Sl6-S85Google Scholar, 3Locatelli F. Covic A. Eckardt K.U. et al.on behalf of the ERA-EDTA ERBP Advisory BoardAnaemia management in patients with chronic kidney disease: a position statement by the Anaemia Working Group of European Renal Best Practice (ERBP).Nephrol Dial Transplant. 2009; 24: 348-354Crossref PubMed Scopus (179) Google Scholar, 4KDIGO Clinical practice guideline for anemia in chronic kidney disease.Kidney Int Suppl. 2012; 2: 279-335Abstract Full Text Full Text PDF Scopus (672) Google Scholar Iron deficiency is common in hemodialysis patients due to inadequate iron mobilization from repleted storage sites (functional iron deficiency) and blood loss related to the hemodialysis procedure itself, to routine blood sampling for laboratory tests (especially for monitoring of uremia), and to occult fecal bleeding due to uremic enteropathy.5Rottembourg J. Rostoker G. Use of intravenous iron supplementation in chronic kidney disease: interests, limits, and recommendations for a better practice.Nephrol Ther. 2015; 11: 531-542Crossref PubMed Scopus (16) Google Scholar, 6Macdougall I.C. Bircher A.J. Eckardt K.U. et al.conference participantsIron management in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.Kidney Int. 2016; 89: 28-39Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar Until recently, iron overload was considered to be very rare among hemodialysis patients, but it is now an increasingly recognized clinical problem.7Rostoker G. Griuncelli M. Loridon C. et al.Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study.Am J Med. 2012; 125: 991-999Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 8Ghoti H. Rachmilewitz E.A. Simon-Lopez R. et al.Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron.Eur J Haematol. 2012; 89: 87-93Crossref PubMed Scopus (74) Google Scholar, 9Canavese C. Bergamo D. Ciccone G. et al.Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients.Kidney Int. 2004; 65: 1091-1098Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 10Ferrari P. Kulkarni H. Dheda S. et al.Serum iron markers are inadequate for guiding iron repletion in chronic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 77-83Crossref PubMed Scopus (110) Google Scholar, 11Rostoker G. Vaziri N.D. Fishbane S. Iatrogenic iron overload in dialysis patients at the beginning of the 21st century.Drugs. 2016; 76: 741-757Crossref PubMed Scopus (44) Google Scholar The liver is the main site of iron storage, and the liver iron concentration (LIC) correlates closely with total iron stores in patients with genetic hemochromatosis and hemosiderosis secondary to hematological disorders.12Barton J.C. Edwards C.Q. Phatak P.D. et al.Handbook of Iron Overload Disorders. Cambridge University Press, New York, NY2010Crossref Google Scholar Magnetic resonance imaging (MRI) is now the gold standard method for LIC estimation in nonrenal patients with iron-overload disorders.12Barton J.C. Edwards C.Q. Phatak P.D. et al.Handbook of Iron Overload Disorders. Cambridge University Press, New York, NY2010Crossref Google Scholar A recent study of LIC in hemodialysis patients using quantitative MRI, and another study based on magnetic susceptometry a few years ago, demonstrated a strong link between infused iron dose and liver iron load in this setting.7Rostoker G. Griuncelli M. Loridon C. et al.Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study.Am J Med. 2012; 125: 991-999Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 9Canavese C. Bergamo D. Ciccone G. et al.Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients.Kidney Int. 2004; 65: 1091-1098Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar Compared to hemodialysis patients, patients undergoing peritoneal dialysis (PD) have fewer sources of blood loss,5Rottembourg J. Rostoker G. Use of intravenous iron supplementation in chronic kidney disease: interests, limits, and recommendations for a better practice.Nephrol Ther. 2015; 11: 531-542Crossref PubMed Scopus (16) Google Scholar, 6Macdougall I.C. Bircher A.J. Eckardt K.U. et al.conference participantsIron management in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.Kidney Int. 2016; 89: 28-39Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar, 11Rostoker G. Vaziri N.D. Fishbane S. Iatrogenic iron overload in dialysis patients at the beginning of the 21st century.Drugs. 2016; 76: 741-757Crossref PubMed Scopus (44) Google Scholar and guidelines therefore advocate oral iron as first-line therapy. Furthermore, the ferritin targets recommended in current guidelines are far lower and more physiological in PD than in hemodialysis patients.2KDOQI; National Kidney FoundationClinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults.Am J Kidney Dis. 2006; 47: Sl6-S85Google Scholar, 3Locatelli F. Covic A. Eckardt K.U. et al.on behalf of the ERA-EDTA ERBP Advisory BoardAnaemia management in patients with chronic kidney disease: a position statement by the Anaemia Working Group of European Renal Best Practice (ERBP).Nephrol Dial Transplant. 2009; 24: 348-354Crossref PubMed Scopus (179) Google Scholar, 4KDIGO Clinical practice guideline for anemia in chronic kidney disease.Kidney Int Suppl. 2012; 2: 279-335Abstract Full Text Full Text PDF Scopus (672) Google Scholar, 13Locatelli F. Bárány P. Covic A. et al.on behalf of the ERA-EDTA ERBP Advisory Board. Kidney DiseaseImproving Global Outcomes guidelines on anaemia management in chronic kidney disease: a European Renal Best Practice position statement.Nephrol Dial Transplant. 2013; 28: 1346-1359Crossref PubMed Scopus (282) Google Scholar Thus, almost all hemodialysis patients, but few PD patients, receive parenteral iron. In contrast to the situation regarding hemodialysis patients, there are no published data on liver iron content in PD patients. Moreover, given the major difference in iron therapy between hemodialysis and PD patients, an analysis of this specific population of patients with ESRD may give useful information on the influence of ESRD itself on liver iron load. The aim of this study was therefore to determine LIC in PD patients by MRI. This observational study was carried out between 17 June 2014 and 17 November 2015. A total of 32 adult patients receiving PD were recruited, and their LICs were analysed by MRI. The patients had been treated for at least 2 months in a PD unit belonging to 1 of 4 nephrology divisions in the Paris region (Hôpital Pitié-Salpêtrière; CHU Bicêtre, Kremlin-Bicêtre; CH Marc Jacquet, Melun; and HP Claude Galien, Quincy-sous-Sénart). The inclusion and exclusion criteria have been described elsewhere.7Rostoker G. Griuncelli M. Loridon C. et al.Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study.Am J Med. 2012; 125: 991-999Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar All participants gave their written informed consent after receiving a verbal explanation from their nephrologist of the reasons for the extra blood sampling, genetic testing in case of iron overload, and MRI scans. Ethical approval for the study was granted by the Drug, Devices and Clinical Trials Committee of Claude Galien hospital (COMEDIMS Claude Galien, 9 December 20047Rostoker G. Griuncelli M. Loridon C. et al.Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study.Am J Med. 2012; 125: 991-999Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar; in France, COMEDIMS follows the use of drugs and devices in hospitals and has the role of an institutional review board). The treatment of anemia in these patients was carried out according to usual practice and remained unchanged during the study; it followed European Renal Best Practice (ERBP) guidelines and comprised, if required, ESA, and iron.13Locatelli F. Bárány P. Covic A. et al.on behalf of the ERA-EDTA ERBP Advisory Board. Kidney DiseaseImproving Global Outcomes guidelines on anaemia management in chronic kidney disease: a European Renal Best Practice position statement.Nephrol Dial Transplant. 2013; 28: 1346-1359Crossref PubMed Scopus (282) Google Scholar In France, the first step in iron therapy is to advise patients to eat red meat. Oral iron therapy is prescribed only if dietary measures fail or if iron deficiency is substantial. We used i.v. iron only if oral iron was ineffective or poorly tolerated. A signal-intensity ratio method was used for MRI based on T1 and T2* contrast imaging without gadolinium, as established by Gandon et al. at Rennes University.14Gandon Y. Olivié D. Guyader D. et al.Non-invasive assessment of hepatic iron stores by MRI.Lancet. 2004; 363: 357-362Abstract Full Text Full Text PDF PubMed Scopus (536) Google Scholar Patients on iron therapy (i.v. or oral) received their iron dose at least 1 week before MRI. The MRI measurements were performed centrally at the Division of Radiology of Claude Galien hospital by the same senior radiologist (Y.C.). The efficacy of anemia treatment was determined using a hemoglobin assay and reticulocyte counts every month, as well as monthly or quarterly measurements (depending on local policy) of iron biomarkers (ferritin, transferrin, serum iron and transferrin saturation (TSAT), soluble transferrin receptors (sTfR), and C-reactive protein). The blood samples for measurement of biological markers of iron metabolism were obtained at least 7 days after the last iron infusion (in patients treated with i.v. iron) or 1 week after the last iron tablet. The closest biological markers of iron metabolism to MRI were analyzed. PD patients with abnormal iron load on MRI were screened for the C282Y HFE gene mutation (BIOMNIS, Lyon, France; and CERBA, Saint Ouen l’Aumone, France).7Rostoker G. Griuncelli M. Loridon C. et al.Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study.Am J Med. 2012; 125: 991-999Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar As values did not conform to a Gaussian distribution (Shapiro−Wilk normality test), according to Sheskin, all data are expressed as median and range.15Sheskin D.J. Handbook of Parametric and Nonparametric Statistical Procedures.4th ed. Chapman & Hall, Taylor & Francis Group, Boca Raton, FL2007Google Scholar Prism 6 software (GraphPad, San Diego, CA) was used for all statistical tests. The PD study cohort consisted of 32 French adult patients treated in the Paris region. Twelve other PD patients refused to participate in the study. Demographic, clinical, and biological characteristics of the patients are summarized in Tables 1 and 2. A total of 22 patients received automated PD, whereas the remaining 10 received continuous ambulatory peritoneal dialysis (CAPD) (nurse-assisted CAPD, n = 6; self-CAPD, n = 4). As we had no access to their medical records, before the initiation of dialysis, we were unable to analyze their exposure to therapeutic iron and blood transfusions before ESRD. The oral route was the preferred method of iron administration in these PD patients (8 of 32) (Table 1).Table 1Demographic and clinical characteristics of 32 patients treated by peritoneal dialysis and studied by MRI to determine liver iron contentVariablePeritoneal dialysis patients (N = 32)Age (yr)64.5 (34–92)Sex, female (%)46.9Duration of dialysis (mo)12.5 (2–52)ESA therapy (%)71.9Darbepoetin dose (μg/mo)59.1 (0–150)Iron therapy (i.v. or oral) (%)37.5Parenteral iron therapy (%)12.5Parenteral iron therapy (mg/PD mo)0 (0–112.5)Oral iron therapy (%)25Oral iron therapy ingested (mg/PD mo)0 (0–2560)Charlson Comorbidity Index5 (2–15)Diabetes (%)34.4Normal LIC at MRI (≤ 50 μmol/g), n26Abnormal LIC at MRI (> 50 μmol/g), n6Mild hepatic iron overload at MRI (51–100 μmol/g), n5Moderate hepatic iron overload (101–200 μmol/g), n0Severe hepatic iron overload (> 200 μmol/g), n1LIC, liver iron concentration; MRI, magnetic resonance imaging.Values shown are median (range), percentage (%) of patients, or number (n) of patients. Open table in a new tab Table 2Biochemical markers of iron metabolism in 32 patients treated by peritoneal dialysis and studied by MRI to determine liver iron contentVariablePatients treated by peritoneal dialysis (N = 32)Hemoglobin (g/dl)11.5 (8.7–16.2)Serum ferritin (μg/l)144 (11–885)Serum iron (μmol/l)13.2 (5.5–24.3)Serum transferrin (g/l)2.3 (1.5–3.6)Transferrin saturation (TSAT) (%)23.2 (1.1–50.0)Serum transferrin soluble receptors (sTfR) (mg/l)3.3 (2.3–7.9)C-reactive protein (mg/l)6.7 (1.3–67.6)MRI, magnetic resonance imaging.Values shown are median (range). Open table in a new tab LIC, liver iron concentration; MRI, magnetic resonance imaging. Values shown are median (range), percentage (%) of patients, or number (n) of patients. MRI, magnetic resonance imaging. Values shown are median (range). The LIC on MRI was normal (≤50 μmol/g) in 26 of 32 patients (Table 1, Figure 1). Iron overload on MRI was mild (50 < LIC ≤ 100 μmol/g) in 5 of 6 PD patients with hemosiderosis (Table 3). Only 1 PD patient had severe iron overload on MRI (> 200 μmol/g) and had received i.v. iron (Table 3). None of the PD patients had moderate iron overload (100 < LIC ≤ 200 μmol/g). Iron overload on MRI was not associated with the C282Y HFE gene mutation (homozygous or heterozygous) in these patients (Table 3).Table 3Characteristics of 9 peritoneal dialysis patients with either high LIC at MRI or having been treated by i.v. ironPatientSexAge at MRI (yr)LIC at MRI (μmol/g)Duration of PD before MRI (mo)Iron (i.v./oral) cumulative dose since initiation of PD (mg)Duration of iron exposure (d or mo)Time between iron oral tablet ingestion or i.v. iron infusion and MRI (d or mo)Blood transfusion since initiation of PD (mo)Serum ferritin (μg/l)Transferrin saturation (TSAT) (%)Genetic test HFE1F3423010i.v.300 mg3 mo6 mo010015Negative2F756521No iron0N/A (no iron therapy)088528Negative3M637014Oral14,480 mg7 mo8 mo015035Heterozygous CYS282-Tyr4M786028No iron0N/A (no iron therapy)048732Negative5M73553Oral7680 mg3 mo7 d012429.9Negative6M73704Oral3672.5 mg4 mo7 d015950Negative7F472035i.v.2000 mg2 mo30.5 mo011124Not done8F56542i.v.2000 mg21 d10 mo020128Not done9M4058i.v.900 mg8 mo7 d05717Not doneF, female; LIC, liver iron concentration; M, male; MRI, magnetic resonance imaging; N/A, not applicable; PD, peritoneal dialysis. Open table in a new tab F, female; LIC, liver iron concentration; M, male; MRI, magnetic resonance imaging; N/A, not applicable; PD, peritoneal dialysis. In this study, LIC was measured by MRI in a cohort of 32 adult patients receiving PD. By comparison with 2 cohorts of French patients receiving hemodialysis and studied in 2012 and 2014 by the same centralized radiological method and same radiology team,7Rostoker G. Griuncelli M. Loridon C. et al.Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study.Am J Med. 2012; 125: 991-999Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 16Rostoker G. Griuncelli M. Loridon C. et al.Maximal standard dose of parenteral iron for hemodialysis patients: an MRI-based decision tree learning analysis.PLoS One. 2014; 9: e115096Crossref PubMed Scopus (22) Google Scholar we observed striking differences in LIC between our PD patients and the historic hemodialysis cohorts. LIC was normal in most PD patients (26/32; 81.3%) compared to few hemodialysis patients (∼16% in the first hemodialysis cohort and 35% in the second hemodialysis cohort (which had a lower ferritin target of anemia treatment)). Only one PD patient (3.13%) had severe iron overload, compared to 30.3% of patients in the first hemodialysis cohort and 11.3% of those in the second cohort.7Rostoker G. Griuncelli M. Loridon C. et al.Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study.Am J Med. 2012; 125: 991-999Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 16Rostoker G. Griuncelli M. Loridon C. et al.Maximal standard dose of parenteral iron for hemodialysis patients: an MRI-based decision tree learning analysis.PLoS One. 2014; 9: e115096Crossref PubMed Scopus (22) Google Scholar We conclude that, in contrast to hemodialysis patients, iron overload on MRI is rare and mostly mild in patients receiving PD. All the authors declared no competing interests. Clinical trial registration: International Standard Randomized Controlled Trial Number (ISRCTN): 80100088. BI contributed to the conception, design, and supervision of the study, data acquisition, and planning and conduct of the study in the peritoneal dialysis unit of the Division of Nephrology and Dialysis, Département d’Urologie et de Néphrologie, Groupe Hospitalier Pitié-Salpétrière. He also participated in the writing of the article. NG contributed to the study design and data acquisition, and to the planning and conduct of the study in the peritoneal dialysis unit of the Centre Hospitalier Marc Jacquet Division of Nephrology and Dialysis. SB contributed to data acquisition and to the planning and conduct of the study in the peritoneal dialysis unit of the Bicêtre Hospital Division of Nephrology, Dialysis and Transplantation. MG contributed to data acquisition, analysis, and interpretation, and to the statistical analysis, and prepared the tables and figure. YC contributed to the acquisition and analysis of centralized MRI examinations. GR contributed to the conception, design, and supervision of the study, data acquisition, and planning and conduct of the study in the peritoneal dialysis unit of the Hôpital Privé Claude Galien Division of Nephrology and Dialysis. He supervised the statistical analysis, data interpretation, and reporting of the work, and wrote the article. Iron Overload in Dialysis Patients: Rust or Bust?Kidney International ReportsVol. 2Issue 6PreviewA recent study using magnetic resonance imaging (MRI) to assess liver iron content (LIC) by Issad and colleagues provides observational data from prevalent peritoneal dialysis patients, showing that few have iron overload.1 These results complement earlier MRI studies in hemodialysis patients by Rostoker et al. and other groups showing high MRI-estimated LIC in hemodialysis patients and a high incidence of moderate to severe iron overload. The discussions in these reports, and in several editorials and commentaries, have warned that our present i.v. Full-Text PDF Open AccessRe: Further Evidence Supporting the Accuracy of Quantitative Magnetic Resonance Imaging for Evaluating Iron Load in Dialysis PatientsKidney International ReportsVol. 3Issue 1PreviewIn his editorial accompanying our article, Daniel Coyne raises important issues regarding the validity of magnetic resonance imaging (MRI) for quantifying iron load in dialysis patients.1,2 We are disappointed that he did not analyze our article devoted to this topic, published in January 2017.3 There is indeed a need to validate these MRI techniques in dialysis patients, notably by comparison with liver biopsy.3 However, liver biopsy is an invasive and risky procedure, especially in frail patients with end-stage renal disease, and such studies therefore raise ethical concerns. Full-Text PDF Open AccessThe Author RepliesKidney International ReportsVol. 3Issue 1PreviewRostoker and colleagues1 do not contest my conclusion that applying the ratio of magnetic resonance imaging (MRI) estimate of liver iron content (LIC) to total body iron observed in hereditary and transfusional overload overestimates total body iron by a factor of 3 to 6 in dialysis patients.2 Unfortunately, this letter title states MRI-LIC is accurate for “evaluating iron load in dialysis patients.”1 A high MRI-LIC score is not the same as iron overload in dialysis patients.1,2 Based on the rate of decline in high MRI-LIC scores after halting iron therapy, most dialysis patients appear to have normal or mildly elevated total body iron. Full-Text PDF Open AccessThe Author RepliesKidney International ReportsVol. 3Issue 1PreviewDr. Rottembourg1 cites a 1981 paper by Brissot et al.2 stating that liver iron content (LIC) is related to the total body iron (TBI) by approximately each 130 μmol/g dry liver of LIC is equal to 1 g of TBI. Because Rostoker et al.3,4 found a yearly decrease in LIC of 270 μmol/g per year, corresponding to 1.68 g of TBI, they conclude that the magnetic resonance imaging (MRI) estimate of LIC (MRI-LIC) fits well with their calculated annual iron losses in hemodialysis and with the relationship of MRI-LIC to TBI seen in hemochromatosis patients. Full-Text PDF Open AccessOther Estimation of Blood Losses in Hemodialysis and Formula for Translating Liver Iron Concentration From Iron Balance Calculation Based on Iron Removal by PhlebotomyKidney International ReportsVol. 3Issue 1PreviewIn his recent editorial, Daniel Coyne1 raises concerns regarding iron overload detection in dialysis patients by quantitative magnetic resonance imaging (MRI). Using the equation established by Barry2 in 1974 (based on the relationship between liver iron content [LIC] and stored iron mobilized by phlebotomy in 12 patients with genetic hemochromatosis, where 30 μmol/g dry liver LIC equals 1 g of iron), Daniel Coyne calculates that the decline in LIC on MRI found by Rostoker et al.3 in their iron-overloaded hemodialysis patients after iron withdrawal (17.9 μmol/g dry liver/month or 215 μmol/g dry liver per year) “cannot match blood losses (7.16 g of iron lost per year with Barry’s formula). Full-Text PDF Open Access" @default.
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• W2770265669 title "Hepatic Iron Load at Magnetic Resonance Imaging Is Normal in Most Patients Receiving Peritoneal Dialysis" @default.
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