The problem with transferrin saturation as an indicator of iron ‘sufficiency’ in chronic kidney disease

Author(s):  
Anatole Besarab ◽  
Tilman B Drueke

Abstract After a brief review of physiological iron metabolism, we describe diagnostic tests for iron status and iron deficiency anemia in patients without chronic kidney disease (CKD) or inflammation. Thereafter we review the dysregulation of iron metabolism in CKD. Specific emphasis is placed on the role of the ‘inflammatory’ state that develops with the progression of CKD. It invokes changes in iron metabolism that are the exact opposite of those occurring during pure iron deficiency. As a result, transferrin saturation (TSAT) becomes a poorer index of iron availability to the bone marrow and serum ferritin no longer represents iron that can be used during erythropoiesis. We argue that serum iron may provide more information to guide iron therapy than TSAT. In other words, the emphasis on TSAT is misplaced. With the development of a number of hypoxia-inducible factor prolyl hydroxylase inhibitors, which restore iron metabolism toward the ‘physiologic state’, the iron indices indicating sufficient iron availability to avoid functional iron deficiency during therapy of CKD-associated anemia are likely to change. We summarize these changes in the section ‘A peek into things to come!’, citing the available data.

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 465-470
Author(s):  
Maria Domenica Cappellini ◽  
Roberta Russo ◽  
Immacolata Andolfo ◽  
Achille Iolascon

Abstract Inherited microcytic anemias can be broadly classified into 3 subgroups: (1) defects in globin chains (hemoglobinopathies or thalassemias), (2) defects in heme synthesis, and (3) defects in iron availability or iron acquisition by the erythroid precursors. These conditions are characterized by a decreased availability of hemoglobin (Hb) components (globins, iron, and heme) that in turn causes a reduced Hb content in red cell precursors with subsequent delayed erythroid differentiation. Iron metabolism alterations remain central to the diagnosis of microcytic anemia, and, in general, the iron status has to be evaluated in cases of microcytosis. Besides the very common microcytic anemia due to acquired iron deficiency, a range of hereditary abnormalities that result in actual or functional iron deficiency are now being recognized. Atransferrinemia, DMT1 deficiency, ferroportin disease, and iron-refractory iron deficiency anemia are hereditary disorders due to iron metabolism abnormalities, some of which are associated with iron overload. Because causes of microcytosis other than iron deficiency should be considered, it is important to evaluate several other red blood cell and iron parameters in patients with a reduced mean corpuscular volume (MCV), including mean corpuscular hemoglobin, red blood cell distribution width, reticulocyte hemoglobin content, serum iron and serum ferritin levels, total iron-binding capacity, transferrin saturation, hemoglobin electrophoresis, and sometimes reticulocyte count. From the epidemiological perspective, hemoglobinopathies/thalassemias are the most common forms of hereditary microcytic anemia, ranging from inconsequential changes in MCV to severe anemia syndromes.


e-CliniC ◽  
2013 ◽  
Vol 1 (1) ◽  
Author(s):  
Cynthia Ombuh

ABSTRACTBackground: Chronic Kidney Disease (CKD) is kidney damage that occurred during the three months or more with a glomerular filtration rate less than 60 ml/men./1, 73 m2. One complication that often occurs in patients with CKD is anemia. Anemia in CKD can be caused by several factors such as EPO deficiency, Iron Deficiency, etc. and one of the parameters commonly examined in patients with CKD who are undergoing hemodialysis is composed of iron status Serum Iron(SI), TIBC, Transferrin Saturation, Ferritin.Objective: Looking iron status in CKD patientsMethods: The study design was a descriptive look at the medical records of the patients who are undergoing hemodialysis with purposive sampling technique.Results: In patients with CKD undergoing hemodialysis anemia. Anemia all experienced that often caused by the presence of erythropoietin deficiency. But there are also caused by iron deficiency from a status marked where the iron transferrin saturation <20%. There was also found an increase in ferritin> 400 ng / ml caused by the presence of an infection such as anemia or chronic disease can also be caused due to frequent blood transfusions. Treatment for iron overload in patients with CKD, especially regular hemodialysis patients who undergo repeated blood transfusions can be re-utilization by the use of ESA, anemia in CKD caused by deficiency erythropoietin.ESA therapy may also be given.Conclusion: Based on the results of research in the department of hemodialysis room Prof.Dr.RD Kandou obtained all patients with chronic kidney disease decreased hemoglobin, and Serum Iron which fell by 40%, the normal 60%, and ferritin were increased by 46.7% , that no data 53.3% and TIBC were decreased by 80%, as much as 20% of normal and Transferrin Saturation fell by 6.7%, which increased by 3.3% and as much as 90% of normal.Keywords: CKD, iron statusABSTRAKLatar Belakang : Penyakit Ginjal Kronik (PGK) adalah kerusakan ginjal yang terjadi selama atau lebih tiga bulan dengan laju filtrasi glomerulus kurang dari 60 ml/men./1,73 m2. Salah satu komplikasi yang sering terjadi pada pasien PGK adalah anemia. Anemia pada PGK dapat disebabkan oleh beberapa faktor seperti: Defisiensi EPO, Defisiensi Besi, dll dan salah satu parameter yang biasa diperiksa pada pasien PGK yang sedang menjalani hemodialisis adalah status besi yang terdiri dari Serum Iron (SI), TIBC, Saturasi Transferin, Feritin.Tujuan : Melihat Status besi pada pasien PGKMetode : Desain penelitian adalah deskriptif dengan melihat data rekam medik para pasien yang sedang menjalani hemodialisis dengan teknik purposive sampling.Hasil : Pada pasien PGK yang menjalani hemodialisis semuanya mengalami anemia.Anemia yang sering terjadi disebabkan oleh karena adanya defisiensi eritropoetin. Namun ada juga yang disebabkan oleh defisiensi besi yang ditandai dari pemeriksaan status besi dimana saturasi transferin < 20%. Ada juga didapatkan peningkatan Feritin > 400 ng/ml yang disebabkan oleh karena adanya infeksi seperti pada anemia penyakit kronis atau juga bisa disebabkan karena seringnya transfusi darah. Penatalaksanaan untuk kelebihan zat besi pada pasien PGK terutama pasien hemodialisis reguler yang mengalami transfusi darah berulang dapat dire-utilisasi dengan pemakaian ESA, anemia pada PGK yang disebabkan oleh dekfisiensi eritopoetin juga dapat diberikan terapi ESA.Kesimpulan : Berdasarkan hasil penelitian di ruangan hemodialisis di RSUP Prof.Dr.R.D Kandou didapatkan semua pasien penyakit ginjal kronik mengalami penurunan Hb,dan Serum Iron yang menurun sebanyak 40%, yang normal sebanyak 60%, dan Feritin yang meningkat sebanyak 46,7%, yang tidak ada data sebanyak 53,3% dan TIBC yang menurun sebanyak 80%, yang normal sebanyak 20% dan Saturasi Transferin yang menurun sebanyak 6,7% yang meningkat sebanyak 3,3% dan yang normal sebanyak 90%.Kata Kunci: PGK, Status Besi


Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1173 ◽  
Author(s):  
Norishi Ueda ◽  
Kazuya Takasawa

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.


2013 ◽  
Vol 70 (4) ◽  
pp. 368-373 ◽  
Author(s):  
Marija Jelic ◽  
Tatjana Cvetkovic ◽  
Vidojko Djordjevic ◽  
Goran Damnjanovic ◽  
Predrag Vlahovic ◽  
...  

Bacground/Aim. Hepcidin may play a pathogenetic role in iron metobolism disorders. The aim of this study was to determine the correlation between hepcidin concentration and parameters of iron metabolism in patients with different stage of chronic kidney disease (CKD). Methods. The study involved 104 patients with CKD: 64 on hemodialysis (HD) and 40 patients in pre-dialysis stadium (pre-HD) with adequate erythropoetin therapy and iron supplementation. The HD group was divided in four subgroups according to the level of serum ferritin (up to 100; 100-199; 200-499 and over 500 ng/mL). Parameters of anemia, iron status, inflamation and hepcidin level were evaluated. Results. The HD patients had a significantly lower eritrocyte count, erythrocytes indexes, hemoglobin and transferrin saturation and significantly higher iron, ferritin, hepcidin and total iron binding capacity (TIBC). The HD subgroups up to 199 ng/mL of serum feritin had lower high-sensitivity Creactive protein (hsCRP), iron and higher unbuffered iron binding capacity (UIBC), transferrin saturation and TIBC compared to the HD subgroups over 200 ng/mL. The lowest and the highest ferritin subgroups had the highest hepcidin level and it showed significant correlation with ferritin. Conclusion. Hepcidin may serve as a marker for better diagnosing and monitoring anemia and iron metabolism disorders in CKD.


2021 ◽  
pp. 1-10
Author(s):  
Pablo E. Pergola ◽  
Diogo Belo ◽  
Paul Crawford ◽  
Moustafa Moustafa ◽  
Wenli Luo ◽  
...  

<b><i>Introduction:</i></b> Ferric citrate (FC) is indicated as an oral iron replacement for iron deficiency anemia in adult patients with chronic kidney disease (CKD) not on dialysis. The recommended starting dose is one 1-g tablet three times daily (TID). This study investigated long-term efficacy and safety of different FC dosing regimens for treating anemia in nondialysis-dependent CKD (NDD-CKD). <b><i>Methods:</i></b> In this phase 4, randomized, open-label, multicenter study, patients with anemia with NDD-CKD (estimated glomerular filtration rate, ≥20 mL/min and &#x3c;60 mL/min) were randomized 1:1 to one FC tablet (1-g equivalent to 210 mg ferric iron) TID (3 g/day) or 2 tablets twice daily (BID; 4 g/day). At week 12, dosage was increased to 2 tablets TID (6 g/day) or 3 tablets BID (6 g/day) in patients whose hemoglobin (Hb) levels increased &#x3c;0.5 g/dL or were &#x3c;10 g/dL. Primary endpoint was mean change in Hb from baseline to week 24. <b><i>Results:</i></b> Of 484 patients screened, 206 were randomized and 205 received FC. Mean (standard deviation) changes from baseline in Hb at week 24 were 0.77 (0.84) g/dL with FC TID 3 g/day and 0.70 (0.98) g/dL with FC BID 4 g/day. <b><i>Discussion/Conclusions:</i></b> FC administered BID and TID for 48 weeks was safe and effective for treating anemia in this population, supporting potentially increased dosing flexibility.


2017 ◽  
Vol 7 (2) ◽  
pp. 132-137
Author(s):  
Abdul Latif ◽  
Muhammad Rafiqul Alam ◽  
Asia Khanam ◽  
Farhana Hoque ◽  
Muhammad Abdur Rahim ◽  
...  

Background: Anemia is common in patients with chronic kidney disease (CKD) and this is generally anemia of chronic disease, but iron deficiency anemia (IDA) is also common. Soluble transferrin receptor (sTfR) is a useful marker for IDA. Present study was undertaken to assess the utility of sTfR as a marker of IDA in selected group of Bangladeshi patients with CKD.Methods: This cross-sectional study was conducted in the Department of Nephrology, BSMMU, Dhaka, Bangladesh from January 2013 to December 2014. Patients with anemia admitted in nephrology department whether on hemodialysis or not and medicine department of BSMMU were taken for study. The study population was further divided into two groups; Group A, patients who are having IDA and Group B, patients with ACD and a control group was also selected. Data were collected by face to face interview and laboratory investigations with a self-administered questionnaire.Results: The mean age of the patients in two study groups were 38.40±13.23 and 34.85±10.52 years respectively and male-female ratio were 0.5:1 and 1:0.5. Mean sTfR level was higher (4.81± 1.64 ?g/ml) in patients with IDA than (2.89±1.40 ?g/ml) in patients with ACD (p <0.0001). In our study mean ferritin level was 599.59± 449.15?g/L in ACD patients whereas 101.23±119.42 in IDA patients (p<0.0001). Total iron binding capacity (TIBC) was more in ACD patients with sTfRe”3?g/ml as compared to ACD patients with sTfR<3?g/ml. Transferrin saturation (TSAT) level was significantly decreased in ACD patients with sTfR ?3?g/ml as compared to ACD patients with sTfR<3?g/ml.Conclusion: sTfR has a comparable ability to S. ferritin in diagnosing IDA and ACD. However, sTfR and serum ferritin alone cannot definitely exclude co-existing iron deficiency in ACD. As sTfR is not affected by infection and/or inflammation, thus providing a non-invasive alternative to bone marrow study.Birdem Med J 2017; 7(2): 132-137


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Takahiro Imaizumi ◽  
Kenta Murotani ◽  
Takayuki Hamano ◽  
Masafumi Fukagawa

Abstract Background and Aims Patients with predialysis chronic kidney disease (CKD) have a greater risk of developing cardiovascular disease (CVD) events than the general population. Anaemia is the most frequent comorbidity in pre-dialysis CKD patients and is associated with an increase in CVD events. Iron deficiency is the most frequent cause of erythropoiesis-stimulating agents (ESAs) resistant anaemia in CKD patients and is modifiable by therapeutic intervention. However, the optimal ranges of iron markers are uncertain in predialysis CKD patients. Therefore, we aimed to investigate the association between serum indices of iron metabolism and the incidence of CVD events in patients with predialysis CKD using the CKD-Japan Cohort (CKD-JAC) data. Method We prospectively followed 1550 CKD patients aged 20-75 years with an estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m2 for a mean of 4.21 years. We set serum transferrin saturation (TSAT) and ferritin levels as the main exposures to be tested. Our main outcome measures were any of the CVD events including fatal or non-fatal myocardial infarction, congestive heart failure (CHF), angina pectoris, arrhythmia, aorta dissection, cerebrovascular disorder, and peripheral artery diseases identified at each facility and adjudicated by the independent cardiac function evaluation committee. Multivariable Cox proportional hazards regression models were employed to examine the association between serum TSAT or ferritin levels with time to events. Death was considered as a competing risk with the Fine and Gray model. All models were stratified by facilities and adjusted for potential confounders as follows: age, sex, systolic blood pressure, diabetes mellitus, history of CHF, haemoglobin, serum calcium, serum phosphorus, intact parathyroid hormone, eGFR, proteinuria, ESAs, iron supplementation, renin-angiotensin system inhibitors, and beta-blockers. We also applied the multivariable fractional polynomial interaction (MFPI) approach to investigate whether TSAT levels are the effect modifier of the association between iron supplementation and the outcomes. Results In the overall cohort, 208 (13.4 %) patients developed CVD events (including 97 CHF) during the follow-up period (26.6 events/1000 person-year). The incidence rate of CVD events was the highest in the TSAT &lt; 20% category (33.0 events/1000 person-year). Compared to patients in the TSAT &gt; 40% category, those in the TSAT &lt; 20% category demonstrated an increased risk of CVD events (adjusted hazard ratio (AHR): 1.86, 95% confidence interval (CI): 1.06-3.26) and CHF events (AHR: 2.82, 95% CI: 1.15-6.89), respectively. Meanwhile, there was no association between serum ferritin levels and the risk of developing CVD or CHF events. MFPI analyses showed a reduced risk of CVD in patients receiving iron supplementation only in patients with TSAT &lt;20% (P for interaction=0.02). Conclusion Maintaining TSAT &gt;20% could be effective to reduce the risk of developing CVD events (especially CHF) in patients with predialysis CKD. Our analyses also suggest that iron-deficient patients with predialysis CKD may benefit from iron supplementation for reduced risk of CVD events.


2019 ◽  
Vol 12 (1) ◽  
pp. 77-82
Author(s):  
Ewa Kwiatkowska ◽  
Martyna Opara ◽  
Sebastian Kwiatkowski ◽  
Leszek Domański ◽  
Małgorzata Marchelek-Myśliwiec ◽  
...  

Background: According to the currently applicable KDIGO-2012 and ERBP 2013 guidelines, iron metabolism assessments for patients with Chronic Kidney Disease (CKD) are performed using such parameters as ferritin concentration and Transferrin Saturation (TSAT). Their values are to be treated as a basis on which to decide on providing iron substitution. Patients with Stage 5 CKD on maintenance hemodialysis commonly suffer from malnutrition syndrome and inflammation. One of the markers for malnutrition and inflammation is low transferrin concentration. Our study focused on establishing what percentage of patients this applied to and whether or not the transferrin saturation figure was artificially inflated in such cases. Materials and Methods: The study group included 66 patients with Stage 5 CKD on maintenance hemodialysis. Such data were analyzed as complete blood count, iron and ferritin concentrations, and Transferrin Saturation (TSAT). Other parameters - age, sex, time from their first hemodialysis, and the quality of their dialysis in the last six months – the Kt/V average. Results: It was found that only 12% of the study group patients had their transferrin concentrations above the lower limit of normal. The TSAT value correlated negatively with transferrin concentration. Transferrin concentration correlated negatively with time from first hemodialysis or ferritin concentration, and positively with body weight. Normal transferrin concentration was only seen in patients with ferritin concentrations of up to 400 μg/L. The group was divided according to transferrin concentration of <1.5 g/L or >1.5 g/L. These groups differed significantly in ferritin concentration and transferrin saturation. (p = 0.0005 and p = 0.004, respectively). The 1.5 g/L transferrin concentration point divides patients with mild and medium malnutrition. It is also the minimum transferrin content necessary to achieve hemoglobin values ≥10 g/dL determined using the ROC curve. Conclusion: Low transferrin concentrations cause abnormally high TSAT values. In most patients on maintenance hemodialysis, this marker is not useful for assessing the availability of iron for erythropoiesis.


2018 ◽  
Vol 2 (3and4) ◽  
pp. 85-89
Author(s):  
Garima Sharma ◽  
Richa Saxena ◽  
Nikhita Gulati

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Xin Li ◽  
Kristin Danielson ◽  
Innas Forsal ◽  
Ken Iseri ◽  
Lu Dai ◽  
...  

Abstract Background and Aims Transferrin saturation (TSAT) is an indicator of iron deficiency or overload, but its relationship with mortality in patients with different stages of chronic kidney disease (CKD) is unclear. We investigated the association of TSAT with mortality in CKD patients. Method In 479 CKD patients (97 CKD3-4 patients, 298 CKD5 non-dialysis patients and 84 peritoneal dialysis patients; median age 58 years, 67% males, 33% cardiovascular disease, CVD, and 29% diabetes), biomarkers of iron status (plasma iron, TSAT, transferrin and ferritin), systemic inflammation (high sensitivity C-reactive protein, hsCRP, and interleukin-6, IL-6) and nutritional status were assessed. During median follow-up of 35.6 months, 139 (29%) patients died, and 176 (37%) patients underwent renal transplantation. Patients were stratified into low (n=157) and high (n=322) TSAT tertile groups. All-cause and CVD mortality risk were analyzed with competing risk regression with renal transplantation as competing risk. Results TSAT [median 23% (IQR 17-30%)] was negatively associated with presence of DM and CVD, body mass index, hsCRP, IL-6, Framingham´s CVD risk score (FRS), erythropoietin resistance index (ERI) and iron supplementation, and positively associated with hemoglobin, ferritin and s-albumin. In competing risk analysis, low tertile of TSAT was independently associated with increased all-cause mortality risk (sHR=1.50, 95%CI 1.05-2.14) after adjusting for CKD stages, 1-SD of FRS, 1-SD of hemoglobin, 1-SD of hsCRP, 1-SD of ESA dose and iron supplementation (Figure 1). Conclusion TSAT was inversely associated with mortality risk in CKD patients. When evaluating clinical outcomes of CKD patients, iron status using TSAT as a predictive marker, should be considered.


Sign in / Sign up

Export Citation Format

Share Document