Safety and Effectiveness of Ferric Carboxymaltose Intravenous Therapy in Pediatric Patients with Kidney Transplant

Safety and Effectiveness of Ferric Carboxymaltose Intravenous Therapy in Pediatric Patients with Kidney Transplant | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Safety and Effectiveness of Ferric Carboxymaltose Intravenous Therapy in Pediatric Patients with Kidney Transplant Diletta Domenica Torres, Luigi Antonio Moscogiuri, Giulia Fontò, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5052408/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Jul, 2025 Read the published version in Pediatric Nephrology → Version 1 posted 5 You are reading this latest preprint version Abstract Anemia is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence between 20 and 80% depending on its definition. Causes of and risk factors for post-transplantation anemia (PTA) are multifactorial with iron deficiency being the primary cause of early PTA. Post transplant anemia therapy may be challenging and should be directed to the underlying causes. Iron supplementation may be indicated. Oral iron supplementation could be ineffective, and some studies demonstrated superior performance of intravenous iron over oral therapy. Ferric carboxymaltose (FCM) is an intravenous iron formulation allowing large single doses and rapid infusion time; its safety and efficacy has not been demonstrated so far in pediatric KTR. We report our experience with the use of FCM, effective and well-tolerated therapeutic option for KT pediatric patients affected by iron deficiency anemia. Figures Figure 1 Introduction Post transplant anemia (PTA) is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence between 20 and 80% depending on its definition, that is still very controversial. The most widely accepted definition is the one provided by the Improving Global Outcomes (KDIGO) guidelines on anemia management in CKD, which considers different hemoglobin cut-off values matching to age [1]. Children undergoing KT often present anemia induced by iron deficiency, the prevalence would seem to be rather high (from 22 to 85%). The etiology can be multifactorial: the use of immunosuppressive agents, anemia before transplantation, sudden interruption of treatment with exogenous EPO in the post-transplant period, advanced age of the donor, acute or chronic rejection episode, susceptibility to opportunistic infections, repeated transplant, inadequate diet, as well underlined by P.G. Galutira et al. [2].Also an Epo resistance could play a role in PTA [3]. Very few clinical studies have dealt with PTA, even fewer in the pediatric age group. Correction of anemia in these patients could improve quality of life and potentially preserve the integrity of the transplanted kidney, as well as reduce the risk of heart failure or death [4]. For this reason, it is mandatory to identify transplant patients suffering from anemia through specific serum markers and start adequate therapies [5]. Oral iron supplementation may be considered first line therapy, although intolerance and non-adherence to prolonged treatment courses often impair therapeutic success. Moreover, it usually takes several weeks of therapy to obtain an increase in Hb levels and even a few months to restore iron deposits. To overcome these limitations, it may be necessary to use iron intravenous IV therapies [6]. Iron IV therapies are divided in two categories: dextran derivative (like ferumoxytol) which are no longer use in clinical practice for the higher risk of anaphylactic reaction related do dextran component and no dextran derived iron (such as iron sucrose, sodium ferric gluconate and ferric carboxymaltose) which are more safety and have less adverse effects [7-8]. Bamgbola et al explored the efficacy of routine use of iron sucrose in pediatric KT patients, in the early post-transplant period [9]. Ferric carboxymaltose (FCM) is an IV iron formulation allowing large single intravenous doses and rapid infusion time (over 15-20 min) with a better safety and efficacy profile than iron dextran and other previous generation agents [10]. FCM has been shown to be safe and effective in adults; however, hypophosphatemia and skeletal complications were described with this and other IV iron formulation [11-15]. In pediatric populations very few studies have examined the role of this drug for correction of iron deficiency anemia because it is only licensed for use in children older than 14 years. Therefore, data in younger children remains scarce particularly in children with CKD and only some off-label use of FCM is reported in children below 14 years, especially for those with inflammatory bowel disease [16-18]. Side effects such as hypophosphatemia are also described in pediatric patients [19,20]. A recent publication reported the successful use of FCM in patients with CKD, but not yet undergoing a KT [21]. Guzzo et al recently reviewed the literature about anemia after KT, concluding for no evidence coming from prospective studies in pediatric KT to evaluate the effectiveness and safety of IV iron therapies [22]. We report our experience with the administration of FCM (Ferinject®) in children diagnosed with PTA. In particular, the aim of our study is to demonstrate for the first time that in pediatric KTR with iron deficiency anemia resistant to oral supplementation, the use of iron treatment with FCM is safe and effective to improve this clinical condition. Methods Study design Retrospective cohort study conducted by electronic chart review. Study population Were eligible all KT patients diagnosed with iron deficiency (ID) and/or iron deficiency anemia (IDA) who received FCM during the observation period from December 2016 to November 2022, in absence of other acute diseases. Anemia and ID were defined was defined according to KDIGO guidelines by Hb levels for age, Tsat levels <20% and ferritin <100 ng/ml. A total of 15 patients were included in the study; thirteen underwent two administrations, according to drug schedule after 30 days from the first one; only two patients received a single dose (for a total of 28 infusions). All patients had received first-line oral iron therapy without success. No patients received oral iron supplementation during the study period. Just one patient of ours had therapy with erythropoiesis-stimulating agents (ESAs). Patients younger than 14 years received FCM as an off-label indication, after obtaining a written informed consent from parents. This single-center case series was based on registry data and was analyzed retrospectively. All procedures performed were in accordance with the 1964 Helsinki Declaration and its later amendments. Ethical approval was obtained from the Institutional Review Board of the University Hospital “Policlinico Consorziale” of Bari (Italy) (Prot. 1624/2018). All the minors’ legal guardians signed a written informed consent to collect their clinical data at the time of hospital access and for the publication of any potentially identifiable images or data included in this article. Primary outcome FCM is effective to improve IDA in pediatric KTR Secondary outcomes FCM is effective in iron status change, does not affect phosphorus levels and it’s safe in the study population. Statistical analysis Data were expressed as absolute frequencies and percentages, mean and standard deviations, median and interquartile ranges. The behavior of the main parameters over time has been analyzed by the Student T-test for paired data and the Wilcoxon test, as appropriate. Statistical analysis was carried out with software SPSS Statistics 17.0. Results Demographic and clinical characteristics of the study population are reported in Table1 . All 15 patients showed ID and 10 of them showed also IDA. Median post-transplant follow up was 41.8 months (11.3-72.6). Patients were 6 (40%) males, 9 (60%) females. Mean age was 15.4 years (SD +/- 3.11).All patients had undergone KT following end-stage kidney disease for the following nephropathies:6 had nephronophthisis (40%), 2 glomerulonephritis (13.3%), 2 congenital kidney hypoplasia (13.3%), 1 chronic kidney disease secondary to hemolytic uremic syndrome (HUS) (6.6%), 1 ciliopathy (6.6%) and finally 3 children with congenital anomalies of the kidney and urinary tract (CAKUT) (20%). Kidney transplant was in 11 patients from deceased (73.3%) and 4 from living donors (26.7%). Six (40%) patients received a preemptive KT. For 2 of our patients, we started an off-label procedure for the authorization of the administration (age <14 years). The mean weight of patients was 44.6 kg (SD +/- 15.9). The median pre-infusion hemoglobin (HB) was 11.6 g/dL (10.6-12), one month after the first infusion the median HB was 12.8 g/dL (11.8-13.6); three months after treatment, it was 13.1 g/dl (12.4-13.5); after six months the median HB was 12.8 g/dl (12.1-13.6), finally after one year the median HB was 13 g/dl (12-13.8). Therefore, the statistical analysis of our data confirmed a statistically significant increase in the median hemoglobin level 30 days after infusion (p=0.0018), at three (p=0.0016), six (p=0.0083) and twelve (p=0.0175) months. There was a normalization of HB levels in all treated patients. We identified a statistically significant increase in serum ferritin one month, three and six months after the first infusion, but it was not statistically significant one year after the first infusion. Non-parametric method showed a statistically significant increase in the baseline value of iron blood levels one and three months after the first infusion (p <0.05); this increase did not appear to be statistically significant after six months. The Tsat was analyzed with the same method, the increase was statistically significant (p <0.05) one month after the infusion, however after three and six months there was no longer statistically significant. Median baseline phosphate concentration was 4.2 (3.9-5) mg/dl; our sample did not show statistically significant differences before and one month after the infusion (p=0.802). The main results in the changes of hematologic parameters during follow-up are reported in Figure 1 . No significant adverse reactions occurred in any of the subjects analyzed during the subsequent hospital observation period (2 hours). Discussion Recent published studies indicate that FCM is an effective and well-tolerated treatment for iron deficiency and iron deficiency anemia of various etiologies in children and adolescence. Garcia-Ortega P. et al have published the first study dealing with effectiveness and safety of FCM in pediatric patients with CKD (not on hemodialysis) at the end of 2022 [20]. This evidence is not yet present in pediatric KTR as underlined by Guzzo et al. [22]. Our study is the first that describe the use of FCM in pediatric patients with PTA diagnosed during the post-transplant follow up period, demonstrating effectiveness and safety in this very delicate population study. A recent narrative review by Aksan et al. [8]. has provided an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents, concluding that FCM is effective and generally well-tolerated treatment for ID or IDA in children and adolescent, but despite the wealth of retrospective evidence, prospective, randomized controlled trials in the pediatric setting are necessary. Our data support the hypothesis that the use of FCM in pediatric patients with CKD and successful KT is safe and effective. Compared with previous, our study shows a significant median increase of Hb levels at one, three, six and twelve months, compared to baseline, after treatment with FCM, in most cases with two FCM administration, with an absolute median increase of Hb levels of 1.2 g/dl from baseline onwards. Similar results were obtained for ferritin levels with a significant median increase at one, three and six months after the first FCM infusion. Iron median levels increased significantly at one and three months of follow-up. Transferrin saturation percentage showed a statistically significant increase only at one months after therapy, but median Tsat% was never above 20% during the hole follow up. We evaluated the significant change in hematological parameters, comparing levels between paired groups of patients and not considering only the median increase in the different parameters. Moreover, most patients have data registered at a follow up of twelve months, longer than in previous studies on FCM use. Other publications evaluated ESAs prescription modification after FCM; in our study only one patient was in therapy with ESAs, that was withdrawn after the first infusion of FCM. The rapid hematological response after the first infusion of FCM underlines the ability to correct these parameters faster than with oral preparations. All patients in our study had undergone therapy with oral iron preparations, of these 5 (33%) had shown minor gastrointestinal symptoms (nausea, epigastric pain, diarrhea) and 3 (20%) had therefore withdrawn therapies. FCM is administered intravenously, avoiding gastrointestinal absorption; for this reason, has an optimal gastrointestinal tolerance. Moreover, FCM can be administered at higher doses compared to other formulations, because of its chemical stability. In KTR, infusions may coincide with routine outpatient visits using, for drug infusion, the same needle used to take blood samples. In these patients who have very complex therapies, this allows to reduce the pills to be taken. Patients and caregivers showed good compliance thanks to the improvement in quality of life. Several studies show a possible correlation between the administration of FCM and hypophosphatemia. The incidence of hypophosphatemia following FCM treatment in children (23,24) is lower than in adults (17,18). We evaluated phosphorus levels at baseline and at different follow up times, showing no change in phosphorus levels at 1,6 and 12 months of follow-up. However, further studies are necessary with appropriate sample size to answer correctly to this research question. In studies published so far, the incidence and types of adverse events (AEs) of FCM is reported in the review of Aksan et al [8], this data is in line with other previous papers and with those described in prescribing information [23-24]. None of our fifteen treated patients, including those younger than fourteen years, showed adverse drug reactions in the post-infusion period, with the drug showing the same efficacy and tolerability. However, this study has several limitations; first the retrospective and observational design of the study; moreover, the low number of included patients. The strengths of our work are the availability of clinical and laboratory data necessary for analysis in an electronic database for all patients, with follow-up visits established at the beginning of the study and a median follow up duration of 12 months, longer than in previous studies on FCM. In conclusion, this study provide evidence that FCM is an effective and well-tolerated therapeutic option also for KT pediatric patients affected by iron deficiency and iron deficiency anemia. Declarations Acknowledgement We would like to acknowledge all our little patients and their families for the collaboration to our study. Conflict of interest The authors declare that they have no conflict of interest Data availability The datasets generated during and/or analyzed during the current study are available from the corresponding authors on reasonable request. References Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. (2012) KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney International Supplements 2, 281-335; doi:10.1038/kisup.2012.39 Galutira PJ and Del Rio M (2012) Understanding renal post-transplantation anemia in the pediatric population. Pediatr Nephrol. 27:1079-1085. doi: 10.1007/s00467-011-2036-1 Krause I, Davidovits M, Tamary H, Yutcis M, Dagan A. (2016) Anemia and markers of erythropoiesis in pediatric kidney transplant recipients compared to children with chronic renal failure. Pediatr Transplant. 20(7):958-962. doi: 10.1111/petr.12792. Epub 2016 Sep 12. PMID: 27620552. Schechter A, Gafter-Gvili A, Shepshelovich D, Rahamimov R, Gafter U, Mor E, Chagnac A, Rozen-Zvi B. (2019) Post renal transplant anemia: severity, causes and their association with graft and patient survival. BMC Nephrol. 20:51. doi: 10.1186/s12882-019-1244-y Kouri A, Balani S, Kizilbash S. (2022) Anemia in Pediatric Kidney Transplant Recipients Etiologies and Management. Front Pediatr. 10:929504. doi: 10.3389/fped.2022.929504 Macdougall CI, Geisser P (2013) Use of Intravenous Iron Supplementation in Chronic Kidney Disease An Update. IJKD 7:9-22. PMID: 23314137 Drüeke TB, Parfrey PS (2012) Summary of the KDIGO guideline on anemia and comment: reading between the (guide)line(s). Kidney Int. 82:952-960. doi: 10.1038/ki.2012.270 Aksan A, Zepp F, Anand S, Stein J. (2022) Intravenous ferric carboxymaltose for the management of iron deficiency and iron deficiency anaemia in children and adolescents: a review. Eur J Pediatr. 181:3781-3793. doi: 10.1007/s00431-022-04582-w Iorember F, Aviles D, Bamgbola O. (2020) Impact of immediate post-transplant parenteral iron therapy on the prevalence of anemia and short-term allograft function in a cohort of pediatric and adolescent renal transplant recipients. Pediatr Transplant 24:e13787. doi: 10.1111/petr.13787 Tan MLN, Windscheif PM, Thornton G, Gaynor E, Rodrigues A, Howarth L (2017) Retrospective review of effectiveness and safety of intravenous ferric carboxymaltose given to children with iron deficiency anaemia in one UK tertiary centre. Eur J Pediatr. 176:1419-1423. doi: 10.1007/s00431-017-2995-8 Zoller H, Schaefer B, Glodny B. (2017) Iron-induced hypophosphatemia: an emerging complication. Curr Opin Nephrol Hypertens. 26:266-275. doi: 10.1097/MNH.0000000000000329 Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. (2018) Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight 3:e124486. doi: 10.1172/jci.insight.124486 Klein K, Asaad S,Econs M, Rubin J E. (2018) Severe FGF23-based hypophosphataemic osteomalacia due to ferric carboxymaltose administration. BMJ Case Rep. 2018: bcr-2017-222851. doi: 10.1136/bcr-2017-222851 Wolf M, Rubin J, Achebe M, Econs MJ, Peacock M, Imel EA, Thomsen LL, Carpenter TO, Weber T, Brandenburg V, Zoller H (2020) Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA 323:432-443. doi: 10.1001/jama.2019.22450 Schaefer B, Tobiasch M, Viveiros A, Tilg H, Kennedy NA, Wolf M, Zoller H. (2021) Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside-a systematic review and meta-analysis. Br J Clin Pharmacol. 87:2256-2273. doi: 10.1111/bcp.14643 Laass MW, Straub S, Chainey S, Virgin G, Cushway T (2014) Effectiveness and safety of ferric carboxymaltose treatment in children and adolescents with inflammatory bowel disease and other gastrointestinal diseases. BMC Gastroenterology 14:184. doi: 10.1186/1471-230X-14-184 Carman N., Muir R., Lewindon P. (2019) Ferric carboxymaltose in the treatment of iron deficiency in pediatric inflammatory bowel disease. Transl Pediatr 8:28-34. doi: 10.21037/tp.2019.01.01 Papadopoulos M., Patel D, Korologou-Linden R., Goto E. (2018) Safety and efficacy of parenteral iron in children with inflammatory bowel disease. Br J Clin Pharmacol 84: 694–699. doi: 10.1111/bcp.13493 Kirk SE, Scheurer ME, Bernhardt MB, Mahoney DH, Powers JM. (2021) Phosphorus levels in children treated with intravenous ferric carboxymaltose. Am J Hematol. 96: E215-E218. doi: 10.1002/ajh.26165. Posod A, Schaefer B, Mueller T, Zoller H, Kiechl-Kohlendorfer U. (2020) Hypophosphatemia in children treated with ferric carboxymaltose. Acta Paediatr. 109:1491-1492. doi: 10.1111/apa.15178 Garcia-Ortega P, Jimenez-Lozano I, Cruz Á, Polo AF, Lopez M, Ariceta G (2022) Safety and effectiveness of ferric carboxymaltose intravenous therapy in pediatric patients with chronic kidney disease. Front Pediatr. 10:967233. doi: 10.3389/fped.2022.967233 Guzzo I, Atkinson MA. (2023) Anemia after kidney transplantation. Pediatr Nephrol. 38:3265-3273. doi: 10.1007/s00467-022-05743-7 Ferinject (ferric carboxymaltose) summary of product characteristics (2021) Available at: https://www.medicines.org.uk/emc/product/ 5910/smpc Injectafer prescribing information (2022) Available at: https:// injectafer.com/. (Accessed May 2022) Tables Tables 1 and 2 are available in the Supplementary Files section. Supplementary Files Visualabstract.pptx table1.docx Cite Share Download PDF Status: Published Journal Publication published 26 Jul, 2025 Read the published version in Pediatric Nephrology → Version 1 posted Reviewers agreed at journal 03 Dec, 2024 Reviewers invited by journal 02 Dec, 2024 Editor assigned by journal 02 Dec, 2024 First submitted to journal 02 Dec, 2024 Editorial decision: Major Revisions Needed 07 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5052408","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":385392577,"identity":"f04a8ad3-73b1-4172-81f5-aca14e567037","order_by":0,"name":"Diletta Domenica Torres","email":"","orcid":"","institution":"Policlinico di Bari Ospedale Giovanni XXIII: Azienda Ospedale Policlinico","correspondingAuthor":false,"prefix":"","firstName":"Diletta","middleName":"Domenica","lastName":"Torres","suffix":""},{"id":385392578,"identity":"164affb6-e711-4563-bd21-f37ce5ef3a91","order_by":1,"name":"Luigi Antonio Moscogiuri","email":"","orcid":"","institution":"Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari","correspondingAuthor":false,"prefix":"","firstName":"Luigi","middleName":"Antonio","lastName":"Moscogiuri","suffix":""},{"id":385392579,"identity":"2737a81c-2281-462c-80b6-940a3736999b","order_by":2,"name":"Giulia Fontò","email":"","orcid":"","institution":"Azienda Sanitaria Locale Lecce: ASL Lecce","correspondingAuthor":false,"prefix":"","firstName":"Giulia","middleName":"","lastName":"Fontò","suffix":""},{"id":385392580,"identity":"e5813ade-e2c4-4027-a502-d1e8ac7797cd","order_by":3,"name":"Paolo Giordano","email":"","orcid":"","institution":"Central Hospital SS Annunziata: Presidio Ospedaliero Centrale SS Annunziata","correspondingAuthor":false,"prefix":"","firstName":"Paolo","middleName":"","lastName":"Giordano","suffix":""},{"id":385392581,"identity":"7decd7c0-4c48-44c6-876f-ac5fa99098e7","order_by":4,"name":"Vincenza Carbone","email":"","orcid":"","institution":"Policlinico di Bari Ospedale Giovanni XXIII: Azienda Ospedale Policlinico","correspondingAuthor":false,"prefix":"","firstName":"Vincenza","middleName":"","lastName":"Carbone","suffix":""},{"id":385392582,"identity":"194fae7c-e35a-4a3d-a8f5-0ed2fcea0973","order_by":5,"name":"Marida Martino","email":"","orcid":"","institution":"Policlinico di Bari Ospedale Giovanni XXIII: Azienda Ospedale Policlinico","correspondingAuthor":false,"prefix":"","firstName":"Marida","middleName":"","lastName":"Martino","suffix":""},{"id":385392583,"identity":"66ed6382-024d-420e-9acb-38afce12dbd6","order_by":6,"name":"Luisa Santangelo","email":"","orcid":"","institution":"Policlinico di Bari Ospedale Giovanni XXIII: Azienda Ospedale Policlinico","correspondingAuthor":false,"prefix":"","firstName":"Luisa","middleName":"","lastName":"Santangelo","suffix":""},{"id":385392584,"identity":"47ecdfb7-36d7-4e5f-8845-797e4cbcb5a4","order_by":7,"name":"Mario Giordano","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-4224-636X","institution":"Ospedale Pediatrico Giovanni XXIII, Bari","correspondingAuthor":true,"prefix":"","firstName":"Mario","middleName":"","lastName":"Giordano","suffix":""}],"badges":[],"createdAt":"2024-09-08 11:30:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5052408/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5052408/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-025-06869-0","type":"published","date":"2025-07-26T15:58:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":70946414,"identity":"73602d20-e046-4305-91da-54fd6d7212c4","added_by":"auto","created_at":"2024-12-09 13:08:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":52110,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBox plot with median values ​​and interquartile range of Hb, Ferritin, Tsat, S-Phosphorus (S-P) at baseline (T0), one (T1), three (T3), six (T6) months and one year (T12) after the infusion.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA.\u003c/strong\u003e The median Hb value was statistically significantly increased compared to the baseline at 1,3,6 months and one year (p\u0026lt;0.05). \u003cstrong\u003eB.\u003c/strong\u003e The median ferritin value was statistically significantly increased compared to the baseline at 1,3,6 months (p\u0026lt;0.05). There is no statistically significant increase one year after infusion. \u003cstrong\u003eC.\u003c/strong\u003e The median Tsat value was statistically significantly increased compared to the baseline at 1 months (p\u0026lt;0.05). There is no statistically significant increase 3,6 months and 1 year after infusion. \u003cstrong\u003eD.\u003c/strong\u003e There were no statistically significant changes in S-phosphorus values ​​during the study period.\u003c/p\u003e\n\u003cp\u003eHb (0) 13.4/9.7; Hb (1) 14/11.1; Hb (3) 14.7/11.5 Hb (6) 14.4/11.2 Hb (12) 14.5/11.2\u003c/p\u003e\n\u003cp\u003eFerritin (0) 227/4; Ferritin (1) 410/15.5; Ferritin (3) 171/7; Ferritin (6) 144/5.3; Ferritin (12) 132/40\u003c/p\u003e\n\u003cp\u003eTsat (0) 41/4.4; Tsat (1) …..5.8; tsat (3) 24.3/2.9; tsat (6) 36/7.6; tsat (12) 35.7/7.1\u003c/p\u003e\n\u003cp\u003eFosforo (0) 6.2/2.8; Fosforo (1) 6.2/3; fosforo (3) 5.6/3.5; fosforo (6) 6.7/3; fosforo (12)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5052408/v1/7be8aceb933e82674fbc6d9a.png"},{"id":87756871,"identity":"4d9c24a8-4a95-4bd3-8b91-23529314c6ee","added_by":"auto","created_at":"2025-07-28 16:10:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":485167,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5052408/v1/a20d64be-ca61-4fe3-9e82-0f0cabbffeb9.pdf"},{"id":70945799,"identity":"cc8ffb02-a686-4580-b023-3d2f9df533a2","added_by":"auto","created_at":"2024-12-09 13:00:10","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":151286,"visible":true,"origin":"","legend":"","description":"","filename":"Visualabstract.pptx","url":"https://assets-eu.researchsquare.com/files/rs-5052408/v1/d556bd8c62be094d1b0eaeee.pptx"},{"id":70946415,"identity":"ac444e9e-1436-4077-8500-10935c00095a","added_by":"auto","created_at":"2024-12-09 13:08:10","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16422,"visible":true,"origin":"","legend":"","description":"","filename":"table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5052408/v1/42702c72d1f9a0b059a82bfe.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eSafety and Effectiveness of Ferric Carboxymaltose Intravenous Therapy in Pediatric Patients with Kidney Transplant\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePost transplant anemia (PTA) is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence between 20 and 80% depending on its definition, that is still very controversial. \u0026nbsp;The most widely accepted definition is the one provided by the Improving Global Outcomes (KDIGO) guidelines on anemia management in CKD, which considers different hemoglobin cut-off values matching to age [1].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChildren undergoing KT often present anemia induced by iron deficiency, the prevalence would seem to be rather high (from 22 to 85%). The etiology can be multifactorial: the use of immunosuppressive agents, anemia before transplantation, sudden interruption of treatment with exogenous EPO in the post-transplant period, advanced age of the donor, acute or chronic rejection episode, susceptibility to opportunistic infections, repeated transplant, inadequate diet, as well underlined by P.G. Galutira et al. [2].Also an Epo resistance could play a role in PTA [3].\u003c/p\u003e\n\u003cp\u003eVery few clinical studies have dealt with PTA, even fewer in the pediatric age group. Correction of anemia in these patients could improve quality of life and potentially preserve the integrity of the transplanted kidney, as well as reduce the risk of heart failure or death [4]. For this reason, it is mandatory to identify transplant patients suffering from anemia through specific serum markers and start adequate therapies [5].\u003c/p\u003e\n\u003cp\u003eOral iron supplementation may be considered first line therapy, although intolerance and non-adherence to prolonged treatment courses often impair therapeutic success. Moreover, it usually takes several weeks of therapy to obtain an increase in Hb levels and even a few months to restore iron deposits. To overcome these limitations, it may be necessary to use iron intravenous IV therapies [6]. Iron IV therapies are divided in two categories: dextran derivative (like ferumoxytol) which are no longer use in clinical practice for the higher risk of anaphylactic reaction related do dextran component and no dextran derived iron (such as iron sucrose, sodium ferric gluconate and ferric carboxymaltose) which are more safety and have less adverse effects [7-8].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBamgbola et al explored the efficacy of routine use of iron sucrose in pediatric KT patients, in the early post-transplant period [9].\u003c/p\u003e\n\u003cp\u003eFerric carboxymaltose (FCM) is an IV iron formulation allowing large single intravenous doses and rapid infusion time (over 15-20 min) with a better safety and efficacy profile than iron dextran and other previous generation agents [10]. FCM has been shown to be safe and effective in adults; however, hypophosphatemia and skeletal complications were described with this and other IV iron formulation [11-15]. In pediatric populations very few studies have examined the role of this drug for correction of iron deficiency anemia because it is only licensed for use in children older than 14 years. Therefore, data in younger children remains scarce particularly in children with CKD and only some off-label use of FCM is reported in children below 14 years, especially for those with inflammatory bowel disease [16-18]. Side effects such as hypophosphatemia are also described in pediatric patients [19,20]. A recent\u0026nbsp;publication reported the successful use of FCM in patients with CKD, but not yet undergoing a KT [21]. Guzzo et al recently reviewed the literature about anemia after KT, concluding for no evidence\u0026nbsp;coming from prospective studies in pediatric KT to evaluate the effectiveness and safety of IV iron therapies [22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe report our experience with the administration of FCM (Ferinject®) in children diagnosed with PTA. In particular, the aim of our study is to demonstrate for the first time that in pediatric KTR with iron deficiency anemia resistant to oral supplementation, the use of iron treatment with FCM is safe and effective to improve this clinical condition.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRetrospective cohort study conducted by electronic chart review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy population\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWere eligible all KT patients diagnosed with iron deficiency (ID) and/or iron deficiency anemia (IDA) who received FCM during the observation period from December 2016 to November 2022, in absence of other acute diseases.\u003c/p\u003e\n\u003cp\u003eAnemia and ID were defined \u0026nbsp;was defined according to KDIGO guidelines by Hb levels for age, Tsat levels \u0026lt;20% and ferritin \u0026lt;100 ng/ml.\u003c/p\u003e\n\u003cp\u003eA total of 15 patients were included in the study; thirteen underwent two administrations, according to drug schedule after 30 days from the first one; only two patients received a single dose (for a total of 28 infusions). All patients had received first-line oral iron therapy without success. No patients received oral iron supplementation during the study period. Just one patient of ours had therapy with erythropoiesis-stimulating agents (ESAs).\u003c/p\u003e\n\u003cp\u003ePatients younger than 14 years received FCM as an off-label indication, after obtaining a written informed consent from parents.\u003c/p\u003e\n\u003cp\u003eThis single-center case series was based on registry data and was analyzed retrospectively. All procedures performed were in accordance with the 1964 Helsinki Declaration and its later amendments. Ethical approval was obtained from the Institutional Review Board of the University Hospital “Policlinico Consorziale” of Bari (Italy) (Prot. 1624/2018). All the minors’ legal guardians signed a written informed consent to collect their clinical data at the time of hospital access and for the publication of any potentially identifiable images or data included in this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFCM is effective to improve IDA in pediatric KTR\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFCM is effective in iron status change, does not affect phosphorus levels and it’s safe in the study population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were expressed as absolute frequencies and percentages, mean and standard deviations, median and interquartile ranges. The behavior of the main parameters over time has been analyzed by the Student T-test for paired data and the Wilcoxon test, as appropriate. Statistical analysis was carried out with software SPSS Statistics 17.0.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDemographic and clinical characteristics of the study population are reported in \u003cstrong\u003eTable1\u003c/strong\u003e. All 15 patients showed ID and 10 of them showed also IDA. Median post-transplant follow up was 41.8 months (11.3-72.6). Patients were 6 (40%) males, 9 (60%) females. Mean age was 15.4 years (SD +/- 3.11).All patients had undergone KT following end-stage kidney disease for the following nephropathies:6 had nephronophthisis (40%), 2 glomerulonephritis (13.3%), 2 congenital kidney hypoplasia (13.3%), 1 chronic kidney disease secondary to hemolytic uremic syndrome (HUS) (6.6%), 1 ciliopathy (6.6%) and finally 3 children with congenital anomalies of the kidney and urinary tract (CAKUT) (20%). Kidney transplant was in 11 patients from deceased (73.3%) and 4 from living donors (26.7%). Six (40%) patients received a preemptive KT.\u003c/p\u003e\n\u003cp\u003eFor 2 of our patients, we started an off-label procedure for the authorization of the administration (age \u0026lt;14 years). The mean weight of patients was 44.6 kg (SD +/- 15.9). \u003c/p\u003e\n\u003cp\u003eThe median pre-infusion hemoglobin (HB) was 11.6 g/dL (10.6-12), one month after the first infusion the median HB was 12.8 g/dL (11.8-13.6); three months after treatment, it was 13.1 g/dl (12.4-13.5); after six months the median HB was 12.8 g/dl (12.1-13.6), finally after one year the median HB was 13 g/dl (12-13.8). Therefore, the statistical analysis of our data confirmed a statistically significant increase in the median hemoglobin level 30 days after infusion (p=0.0018), at three (p=0.0016), six (p=0.0083) and twelve (p=0.0175) months. There was a normalization of HB levels in all treated patients. We identified a statistically significant increase in serum ferritin one month, three and six months after the first infusion, but it was not statistically significant one year after the first infusion. Non-parametric method showed a statistically significant increase in the baseline value of iron blood levels one and three months after the first infusion (p \u0026lt;0.05); this increase did not appear to be statistically significant after six months. The Tsat was analyzed with the same method, the increase was statistically significant (p \u0026lt;0.05) one month after the infusion, however after three and six months there was no longer statistically significant. Median baseline phosphate concentration was 4.2 (3.9-5) mg/dl; our sample did not show statistically significant differences before and one month after the infusion (p=0.802). The main results in the changes of hematologic parameters during follow-up are reported in \u003cstrong\u003eFigure 1\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eNo significant adverse reactions occurred in any of the subjects analyzed during the subsequent hospital observation period (2 hours). \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRecent published studies indicate that FCM is an effective and well-tolerated treatment for iron deficiency and iron deficiency anemia of various etiologies in children and adolescence.\u003c/p\u003e\n\u003cp\u003eGarcia-Ortega P. et al have published the first study dealing with effectiveness and safety of FCM in pediatric patients with CKD (not on hemodialysis) at the end of 2022 [20]. This evidence is not yet present in pediatric KTR as underlined by Guzzo et al. [22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study is the first that describe the use of FCM in pediatric patients with PTA diagnosed during the post-transplant follow up period, demonstrating effectiveness and safety in this very delicate population study.\u003c/p\u003e\n\u003cp\u003eA recent narrative review by Aksan et al. [8].\u0026nbsp; has provided an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents, concluding that FCM is effective and generally well-tolerated treatment for ID or IDA in children and adolescent, but despite the wealth of retrospective evidence, prospective, randomized controlled trials in the pediatric setting are necessary. Our data support the hypothesis that the use of FCM in pediatric patients with CKD and successful KT is safe and effective.\u003c/p\u003e\n\u003cp\u003eCompared with previous, our study shows a significant median increase of Hb levels at one, three, six and twelve months, compared to baseline, after treatment with FCM, in most cases with two FCM administration, with an absolute median increase of Hb levels of 1.2 g/dl from baseline onwards.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSimilar results were obtained for ferritin levels with a significant median increase at one, three and six months after the first FCM infusion. Iron median levels increased significantly at one and three months of follow-up. Transferrin saturation percentage showed a statistically significant increase only at one months after therapy, but median Tsat% was never above 20% during the hole follow up. We evaluated the significant change in hematological parameters, comparing levels between paired groups of patients and not considering only the median increase in the different parameters. Moreover, most patients have data registered at a follow up of twelve months, longer than in previous studies on FCM use.\u003c/p\u003e\n\u003cp\u003eOther publications evaluated ESAs prescription modification after FCM; in our study only one patient was in therapy with ESAs, that was withdrawn after the first infusion of FCM.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe rapid hematological response after the first infusion of FCM underlines the ability to correct these parameters faster than with oral preparations. All patients in our study had undergone therapy with oral iron preparations, of these 5 (33%) had shown minor gastrointestinal symptoms (nausea, epigastric pain, diarrhea) and 3 (20%) had therefore withdrawn therapies. FCM is administered intravenously, avoiding gastrointestinal absorption; for this reason, has an optimal gastrointestinal tolerance. Moreover, FCM can be administered at higher doses compared to other formulations, because of its chemical stability. In KTR, infusions may coincide with routine outpatient visits using, for drug infusion, the same needle used to take blood samples. In these patients who have very complex therapies, this allows to reduce the pills to be taken. Patients and caregivers showed good compliance thanks to the improvement in quality of life.\u003c/p\u003e\n\u003cp\u003eSeveral studies show a possible correlation between the administration of FCM and hypophosphatemia. The incidence of hypophosphatemia following FCM treatment in children (23,24) is lower than in adults (17,18). We evaluated phosphorus levels at baseline and at different follow up times, showing no change in phosphorus levels at 1,6 and 12 months of follow-up.\u003c/p\u003e\n\u003cp\u003eHowever, further studies are necessary with appropriate sample size to answer correctly to this research question.\u003c/p\u003e\n\u003cp\u003eIn studies published so far, the incidence and types of adverse events (AEs) of FCM is reported in the review of Aksan et al [8], this data is in line with other previous papers and with those described in prescribing information [23-24].\u003c/p\u003e\n\u003cp\u003eNone of our fifteen treated patients, including those younger than fourteen years, showed adverse drug reactions in the post-infusion period, with the drug showing the same efficacy and tolerability.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, this study has several limitations; first the retrospective and observational design of the study; moreover, the low number of included patients.\u003c/p\u003e\n\u003cp\u003eThe strengths of our work are the availability of clinical and laboratory data necessary for analysis in an electronic database for all patients, with follow-up visits established at the beginning of the study and a median follow up duration of 12 months, longer than in previous studies on FCM.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study provide evidence that FCM is an effective and well-tolerated therapeutic option also for KT pediatric patients affected by iron deficiency and iron deficiency anemia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge all our little patients and their families for the collaboration to our study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding authors on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. (2012) KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney International Supplements 2, 281-335; doi:10.1038/kisup.2012.39 \u003c/li\u003e\n\u003cli\u003eGalutira PJ and Del Rio M (2012) Understanding renal post-transplantation anemia in the pediatric population. Pediatr Nephrol. 27:1079-1085. doi: 10.1007/s00467-011-2036-1\u003c/li\u003e\n\u003cli\u003eKrause I, Davidovits M, Tamary H, Yutcis M, Dagan A. (2016) Anemia and markers of erythropoiesis in pediatric kidney transplant recipients compared to children with chronic renal failure. Pediatr Transplant. 20(7):958-962. doi: 10.1111/petr.12792. Epub 2016 Sep 12. PMID: 27620552.\u003c/li\u003e\n\u003cli\u003eSchechter A, Gafter-Gvili A, Shepshelovich D, Rahamimov R, Gafter U, Mor E, Chagnac A, Rozen-Zvi B. (2019) Post renal transplant anemia: severity, causes and their association with graft and patient survival. BMC Nephrol. 20:51. doi: 10.1186/s12882-019-1244-y\u003c/li\u003e\n\u003cli\u003eKouri A, Balani S, Kizilbash S. (2022) Anemia in Pediatric Kidney Transplant Recipients Etiologies and Management. Front Pediatr. 10:929504. doi: 10.3389/fped.2022.929504\u003c/li\u003e\n\u003cli\u003eMacdougall CI, Geisser P (2013) Use of Intravenous Iron Supplementation in Chronic Kidney Disease An Update. IJKD 7:9-22. PMID: 23314137\u003c/li\u003e\n\u003cli\u003eDr\u0026uuml;eke TB, Parfrey PS (2012) Summary of the KDIGO guideline on anemia and comment: reading between the (guide)line(s). Kidney Int. 82:952-960. doi: 10.1038/ki.2012.270\u003c/li\u003e\n\u003cli\u003eAksan A, Zepp F, Anand S, Stein J. (2022) Intravenous ferric carboxymaltose for the management of iron deficiency and iron deficiency anaemia in children and adolescents: a review. Eur J Pediatr. 181:3781-3793. doi: 10.1007/s00431-022-04582-w\u003c/li\u003e\n\u003cli\u003eIorember F, Aviles D, Bamgbola O. (2020) Impact of immediate post-transplant parenteral iron therapy on the prevalence of anemia and short-term allograft function in a cohort of pediatric and adolescent renal transplant recipients. Pediatr Transplant 24:e13787. doi: 10.1111/petr.13787\u003c/li\u003e\n\u003cli\u003eTan MLN, Windscheif PM, Thornton G, Gaynor E, Rodrigues A, Howarth L (2017) Retrospective review of effectiveness and safety of intravenous ferric carboxymaltose given to children with iron deficiency anaemia in one UK tertiary centre. Eur J Pediatr. 176:1419-1423. doi: 10.1007/s00431-017-2995-8\u003c/li\u003e\n\u003cli\u003eZoller H, Schaefer B, Glodny B. (2017) Iron-induced hypophosphatemia: an emerging complication. Curr Opin Nephrol Hypertens. 26:266-275. doi: 10.1097/MNH.0000000000000329\u003c/li\u003e\n\u003cli\u003eWolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. (2018) Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight 3:e124486. doi: 10.1172/jci.insight.124486\u003c/li\u003e\n\u003cli\u003eKlein K, Asaad S,Econs M, Rubin J E. (2018) Severe FGF23-based hypophosphataemic osteomalacia due to ferric carboxymaltose administration. BMJ Case Rep. 2018: bcr-2017-222851. doi: 10.1136/bcr-2017-222851\u003c/li\u003e\n\u003cli\u003eWolf M, Rubin J, Achebe M, Econs MJ, Peacock M, Imel EA, Thomsen LL, Carpenter TO, Weber T, Brandenburg V, Zoller H (2020) Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA 323:432-443. doi: 10.1001/jama.2019.22450\u003c/li\u003e\n\u003cli\u003eSchaefer B, Tobiasch M, Viveiros A, Tilg H, Kennedy NA, Wolf M, Zoller H. (2021) Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside-a systematic review and meta-analysis. Br J Clin Pharmacol. 87:2256-2273. doi: 10.1111/bcp.14643\u003c/li\u003e\n\u003cli\u003eLaass MW, Straub S, Chainey S, Virgin G, Cushway T (2014) Effectiveness and safety of ferric carboxymaltose treatment in children and adolescents with inflammatory bowel disease and other gastrointestinal diseases. BMC Gastroenterology 14:184. doi: 10.1186/1471-230X-14-184\u003c/li\u003e\n\u003cli\u003eCarman N., Muir R., Lewindon P. (2019) Ferric carboxymaltose in the treatment of iron deficiency in pediatric inflammatory bowel disease. Transl Pediatr 8:28-34. doi: 10.21037/tp.2019.01.01\u003c/li\u003e\n\u003cli\u003ePapadopoulos M., Patel D, Korologou-Linden R., Goto E. (2018) Safety and efficacy of parenteral iron in children with inflammatory bowel disease. Br J Clin Pharmacol 84: 694\u0026ndash;699. doi: 10.1111/bcp.13493\u003c/li\u003e\n\u003cli\u003eKirk SE, Scheurer ME, Bernhardt MB, Mahoney DH, Powers JM. (2021) Phosphorus levels in children treated with intravenous ferric carboxymaltose. Am J Hematol. 96: E215-E218. doi: 10.1002/ajh.26165. \u003c/li\u003e\n\u003cli\u003ePosod A, Schaefer B, Mueller T, Zoller H, Kiechl-Kohlendorfer U. (2020) Hypophosphatemia in children treated with ferric carboxymaltose. Acta Paediatr. 109:1491-1492. doi: 10.1111/apa.15178\u003c/li\u003e\n\u003cli\u003eGarcia-Ortega P, Jimenez-Lozano I, Cruz \u0026Aacute;, Polo AF, Lopez M, Ariceta G (2022) Safety and effectiveness of ferric carboxymaltose intravenous therapy in pediatric patients with chronic kidney disease. Front Pediatr. 10:967233. doi: 10.3389/fped.2022.967233\u003c/li\u003e\n\u003cli\u003eGuzzo I, Atkinson MA. (2023) Anemia after kidney transplantation. Pediatr Nephrol. 38:3265-3273. doi: 10.1007/s00467-022-05743-7\u003c/li\u003e\n\u003cli\u003eFerinject (ferric carboxymaltose) summary of product characteristics (2021) Available at: https://www.medicines.org.uk/emc/product/ 5910/smpc \u003c/li\u003e\n\u003cli\u003eInjectafer prescribing information (2022) Available at: https:// injectafer.com/. (Accessed May 2022)\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5052408/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5052408/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAnemia is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence between 20 and 80% depending on its definition. Causes of and risk factors for post-transplantation anemia (PTA) are multifactorial with iron deficiency being the primary cause of early PTA. Post transplant anemia therapy may be challenging and should be directed to the underlying causes. Iron supplementation may be indicated. Oral iron supplementation could be ineffective, and some studies demonstrated superior performance of intravenous iron over oral therapy. Ferric carboxymaltose (FCM) is an intravenous iron formulation allowing large single doses and rapid infusion time; its safety and efficacy has not been demonstrated so far in pediatric KTR. We report our experience with the use of FCM, effective and well-tolerated therapeutic option for KT pediatric patients affected by iron deficiency anemia.\u003c/p\u003e","manuscriptTitle":"Safety and Effectiveness of Ferric Carboxymaltose Intravenous Therapy in Pediatric Patients with Kidney Transplant","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-09 13:00:05","doi":"10.21203/rs.3.rs-5052408/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-12-03T11:11:58+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-12-03T00:11:23+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-12-03T00:10:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2024-12-02T16:57:55+00:00","index":"","fulltext":""},{"type":"decision","content":"Major Revisions Needed","date":"2024-10-07T14:09:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"43b92310-258c-4091-ba7d-386fe24b64d7","owner":[],"postedDate":"December 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-28T16:07:04+00:00","versionOfRecord":{"articleIdentity":"rs-5052408","link":"https://doi.org/10.1007/s00467-025-06869-0","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2025-07-26 15:58:28","publishedOnDateReadable":"July 26th, 2025"},"versionCreatedAt":"2024-12-09 13:00:05","video":"","vorDoi":"10.1007/s00467-025-06869-0","vorDoiUrl":"https://doi.org/10.1007/s00467-025-06869-0","workflowStages":[]},"version":"v1","identity":"rs-5052408","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5052408","identity":"rs-5052408","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}