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Hematopoietic stem cell transplant (HSCT) is the treatment of choice in various hematologic diseases, and kidney transplantation (KTx) is the best therapy for end-stage kidney disease. Chronic kidney disease (CKD) occurs relatively often after both types of transplantations. Anemia after both HSCT and KTx may be due to CKD and other reasons. This study aimed to assess the prevalence of anemia to CKD in 156 prevalent patients after HSCT and 80 after KTx. According to the World Health Organization's definition (hemoglobin <13 g/dL for men and <12 g/dL for women), the prevalence of anemia in the studied cohort after HSCT was 13% in women and 35% in men and for those after KTx, it was29% in men and 11%. Anemia in KTx was found in 46% of patients, whereas CKD was present in 53%. After HSCT, anemia was associated with CKD in 56% of women and 17% of men. In KTx, anemia and CKD was diagnosed in 21% of patients. Patients with anemia after KTx had significantly lower glomerular filtration rate (GFR), hemoglobin, and significantly higher creatinine levels. Age was related to the estimated GFR (eGFR; r = -0.39, P < .001) in patients who underwent HSCT and had anemia. In patients without anemia, age was negatively related to eGFR (r = -0.56, P < .001) and the hemoglobin-to-platelet count (r = 0.62, P < .001). In KTx, hemoglobin was related to eGFR (r = 0.35, P < .001), and age was related to eGFR (r = -0.20, P < .05). The type of induction therapy immunosuppressive regimen (anti-thymocyte globulin vs basiliximab vs no induction) did not affect the prevalence of anemia in the KTx population studied. Anemia is relatively common in CKD after HSCT. In both CKD and coexistent anemia, nephrology referral is to be considered to optimize therapy, including nephroprotection., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

CKD is one of the fastest growing causes of death in the world and in 2040, it is estimated that it will be in the top five causes of death. In order to slow down this process, it is necessary to improve prevention, inhibit development and treat complications including anemia. Anemia is one of the common complication of chronic kidney disease (CKD), which is a significant clinical problem. It is most often the result of decreased renal production of erythropoietin and / or iron deficiency. Iron deficiency anemia is one of the most common problems in CKD that increases mortality. In order to successfully treat anemia in CKD with erythropoiesis-stimulating agentsand (ESA) and iron substitution, it is necessary to determine iron iron level. The diagnosis of iron deficiency anemia in patients with CKD is complicated due to the relatively low predictive ability of routine serum iron markers (e.g., ferritin and transferrin saturation) and more invasive measurements such as bone marrow iron stores. In the review novel biomarkers of iron metabolism are discussed such as hypoxia-inducible factor, erythroferon, growth differentiation factor 15 etc. with their possible clinical relevance.

Introduction: Anemia is a common manifestation of chronic kidney disease (CKD). The pathogenesis of CKD-associated anemia is multifactorial. Our understanding of the molecular control of iron metabolism has improved dramatically because of the discovery of hepcidin and attempts to introduce new drugs to stimulate erythropoiesis or affect the hepcidin-ferroportin pathway have recently emerged. Areas covered: We examine the possible role of hepcidin in iron metabolism and regulation and the potential therapeutic options involving hepcidin and hepcidin-ferroportin axis in renal anemia treatment. We focus on therapeutic targeting of hepcidin, the hepcidin-ferroportin axis and key molecules such as anti-hepcidin antibodies, spigelmers, and anticalins. We also discuss compounds affecting the bone morphogenetic protein receptor [BMP/BMPR] complex and molecules that influence hepcidin, such as hypoxia-inducible factor 1 stabilizers. Expert opinion: Hepcidin is a key regulator of iron availability and is a potential future therapeutic target for managing anemia that is associated with CKD. There are potential risks and benefits associated with novel sophisticated therapies and there are several novel options on the horizon; however, clinical data are currently limited and need development. Inhibition of hepcidin via various pathways might be a viable adjunctive therapeutic option in other clinical situations.

Introduction: Anemia has been remained one of the most characteristic and visible manifestations of chronic renal failure. Correction of anemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow., Areas Covered: Erythropoiesis activating agents became a mainstay in the treatment of renal anemia for more than 25 years. Recently, there have been several attempts to introduce new drugs to stimulate erythropoiesis or affect the hepcidin-ferroportin pathway. Orally available hypoxia-inducible factor (HIF) stabilizing compounds are attractive alternatives. They not only increase hemoglobin, but also suppress hepcidin production and improve iron availability. Novel iron preparations, may also help to ameliorate anemia, with acceptable safety profile and other beneficial properties such a phosphate binding., Expert Opinion: One should be aware of potential risks and benefits of novel sophisticated therapies and their role in the management of renal anemia remain to be established. In particular HIF stabilizers needs to be proven safe, or even safer than ESAs, in large long-term safety studies testing hard end points, due its ubiquitous nature and the regulation of variety of biological processes potentially leading to unexpected side effects. Besides safety, cost-effectiveness appears the major issue in the modern world, including nephrology.

The association between chronic kidney disease (CKD) and cardiovascular disease (CVD) is well established, and there is mounting evidence of interorgan cross talk that may accelerate pathologic processes and the progression of organ dysfunction in both systems. This process, termed cardiorenal syndrome (CRS) by the Acute Dialysis Quality Initiative, is considered a major health problem: patients with CKD and CVD are at much higher risk of mortality than patients with either condition alone. To date, the majority of CRS research has focused on neurohormonal mechanisms and hemodynamic alterations. However, mounting evidence suggests that abnormalities in the normal pathophysiology of the bone-mineral axis, iron, and erythropoietin play a role in accelerating CKD and CVD. The goal of this article is to review the role and interrelated effects of the bone-mineral axis and anemia in the pathogenesis of chronic CRS., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: In patients after kidney transplantation, anemia is relatively common and is associated with impaired kidney function, subclinical inflammatory state, and immunosuppressive treatment. Zonulin-prehaptoglobin-2, a newly discovered protein, is necessary for integrity of intracellular tight junctions in the gut. Taking into consideration iron metabolism, including its absorption in the gut, we designed a cross-sectional study to look for the possible interactions among zonulin, iron status, and anemia in kidney transplant recipients., Methods: The study was performed on 72 stable kidney transplant recipients and 22 healthy volunteers. Zonulin, iron status, and inflammatory markers were assessed with the use of commercially available kits., Results: Zonulin was significantly lower in kidney allograft recipients than in healthy volunteers (P < .001). Zonulin correlated with systolic blood pressure (r = -0.33; P < .05), thyroid-binding globulin (r = 0.24; P < .05), hematocrit (r = 0.28; P < .005), hemoglobin (r = 0.32; P < .01), total protein (r = -0.33; P < .01), erythrocyte count (r = 0.26; P < .05), and fasting glucose (r = -0.25; P < .05). Zonulin was not affected by sex, type of immunosuppressive therapy, presence of diabetes, coronary artery disease, heart failure, hypertension, or cause of end-stage renal disease. Zonulin was not related to any of the iron parameters studied. In multiple regression analysis, predictors of zonulin were total protein and thyroglobulin-binding protein, explaining 46% of variation., Conclusions: Zonulin, with its poorly defined function, does not seem to play a role in the anemia in kidney allograft recipients; however, it seems to be related to the absorption process in the gut.

Background: Chronic kidney disease is almost always accompanied by anaemia. Erythropoietin-stimulating agents (ESA) can increase haemoglobin concentration and thus reduce the frequency of anaemia-related complications including the cardiovascular events., Aim: The aim of the study was to collect prospective data on 12-month standard ESA therapy used in haemodialyzed patients in selected CEE countries as well as on cardiovascular complications, iron status and anaemia treatment., Patients and Methods: Fifty centres in 3 countries participated in the study. A group of 398 haemodialysed stable patients (M-231, F-167) aged 19-90 years (57.5 ± 14.7) on standard ESA therapy for chronic renal anaemia were recruited. Twelve-month prospective data on iron parameters, ESA therapy and cardiovascular events were collected. The use of iron, folic acid and blood transfusions were also assessed. Patient were divided into three groups according to ESA therapy start: group A-patients who received ESA after start of haemodialysis, group B-patients who received ESA within 3 months from the day of first haemodialysis and group C-patients who had received ESA more than 3 months before haemodialysis. Chi(2) test for qualitative data and Kruskall-Wallis test for quantitative data with p < 0.05 were used in statistical analysis., Results: At prestudy period, the mean weekly dose of ESA in group C was statistically lower than in the remaining two groups (3,823 ± 3,169 vs. 5,276 ± 2,915 and 6,427 ± 3,441 units/week, p < 0.001), but during prospective phase of the study the doses did not differ among groups A, B and C. No major fluctuation of ESA administration schedule was observed during the study in the groups; however, at majority of visits, the mean frequency of ESA administration in group C was statistically higher than in groups A and B. At baseline visit, the haemoglobin concentration in group A patients (10.86 ± 1.34 g/dL) was slightly lower than in group B (11.26 ± 1.43 g/dL) and group C (10.98 ± 1.35 g/dL) (p = 0.025), but at subsequent visits these differences disappeared and mean haemoglobin concentration was stable around 11 g/dL. Ferritin concentration increased from 280 ± 241 at baseline to 506 ± 405 at month 12, and no important differences in the groups were observed. The other haematological parameters (haematocrit, iron concentration) remained stable during the entire study. The frequency of blood transfusion and total volume of blood in group C were lower than in groups A and B. During the prospective 12-month follow-up, 23 (5.8 %) of the patients died and 35 (8.8 %) were transplanted. No differences in death or transplantation rate were observed among groups A, B and C. The number of patients with adverse events, serious adverse events or drug-related adverse events in all groups was similar. In conclusion, ESA therapy increased haemoglobin concentration and no major differences in haematological parameters among the groups were observed during the entire study irrespective of early versus late start. Mortality, cardiovascular events or other adverse events were similar among the groups during the observation period; however, the limitation of the study is the sample size.

Unlabelled: Anemia is more prevalent in renal transplant recipients than in GFR-matched chronic kidney disease patients. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia or inflammation. Growth differentiation factor 15 (GDF15) was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. The aim of the study was to assess GDF15 levels with relation to iron parameters in 62 stable kidney allograft recipients maintained on triple immunosuppressive therapy., Methods: Complete blood count, urea, creatinine, and iron status were assessed by standard methods. We measured GDF15, hepcidin, hemojuvelin, IL-6 and NGAL with commercially available assays., Results: Mean levels of GDF15, NGAL, hepcidin and hemojuvelin were significantly higher in kidney allograft recipients when compared to the control group (p < 0.001 for all). GDF15 was significantly higher in patients with anemia according to the WHO definition when compared to their nonanemic counterparts (p < 0.05). GDF15 levels were not dependent on the type of immunosuppressive therapy. In univariate analysis GDF15 was related to kidney function (creatinine r = 0.39, p < 0.01, eGFR by MDRD r = -0.37, p < 0.01), urea (r = 0.39, p < 0.01), uric acid (r = 0.42, p < 0.01), hepcidin (r = -0.32, p < 0.01), IL-6 (r = 0.28, p < 0.05), hemoglobin (r = -0.32, p < 0.05), and NGAL (r = -0.35, p < 0.01). GDF15 was not related to serum iron, or ferritin. In multivariate analysis, hepcidin was found to be a predictor of GDF15. In conclusion, our preliminary data may suggest possible mutual relations between GDF15 and hepcidin in patients with kidney disease and that GDF15 might be involved in the pathogenesis of anemia in kidney allograft recipients. However, the role of inflammation should be also elucidated., (Copyright © 2013 S. Karger AG, Basel.)

Anemia is a highly prevalent disorder in recipients of renal allografts. Despite its frequent occurrence, there is still uncertainty with regard to treatment targets and treatment options. This includes questions on appropriate iron management, the choice and dosage of erythropoietin stimulating agents, criteria for the timing of treatment initiation and the targeted hemoglobin values. The review summarizes available data on recent therapeutic strategies for post transplant anemia, as well as for post transplant erythrocytosis, another hematological disorder, that has decreased in recent years., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

The aim of the study was to collect retrospective data on renal anemia management, comorbidities and prospective data on 12-month standard care erythropoiesis-stimulating agent (ESA) therapy used in 398 hemodialyzed patients in selected Central and Eastern European countries (50 centers in 3 countries). Patients were divided into three groups according to ESA therapy start: group A-ESA (after start of hemodialysis, HD), B-ESA (within 3 months from start of HD), C-ESA (more than 3 months before HD). At the chronic kidney disease diagnosis, hemoglobin in all patients was 10.3 ± 2.3 g/dl; however, ferritin, iron, TSAT were within reference limits. Early ESA therapy (C) was administered to 10% of patients only. 47% of patients received ESA after start of dialysis. Before study, the mean weekly ESA dose in group C was statistically lower than in groups B and A (p < 0.001). At baseline visit, hemoglobin in group A patients was slightly lower than in group B and C patients (p = 0.025). In conclusion, in Central and Eastern European countries renal anemia therapy with ESA starts shortly before or after start of HD. This highlights important differences in standard care in Eastern Europe. However, paradoxically, due to the tight reimbursement policy we foresee the clinical implications of the TREAT trial for the chronic kidney disease population., (Copyright © 2011 S. Karger AG, Basel.)

Background: Kidney disease and cardiovascular disease seem to be lethally synergistic and both are approaching the epidemic level. A reduced glomerular filtration rate is associated with increased mortality risk in patients with heart failure. Many patients with congestive heart failure are anemic. Anemia is very often associated with chronic kidney disease., Objectives: To assess--in relation to New York Heart Association class--the prevalence of anemia and chronic kidney disease in patients with normal serum creatinine in a cohort of 526 consecutive patients with coronary artery disease undergoing percutaneous coronary interventions., Methods: GFR was estimated using the simplified MDRD formula, the Cockcroft-Gault formula, the Jeliffe and the novel CKD-EPI formula., Results: According to the WHO definition the prevalence of anemia in our study was 21%. We observed a progressive decline in GFR and hemoglobin concentration together with a rise in NYHA class. Significant correlations were observed between eGFR and systolic blood pressure, diastolic blood pressure, age, NYHA class, complications of PCI, including bleeding, and major adverse cardiac events., Conclusions: The prevalence of anemia and chronic kidney disease is high in patients undergoing PCI despite normal serum creatinine, particularly in higher NYHA class. Lower eGFR and hemoglobin are associated with more complications, including bleeding after PCI and higher prevalence of major adverse cardiac events. In patients with risk factors for cardiovascular disease, GFR should be estimated since renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality.

Maintaining the correct iron balance is crucial for health. Our understanding of the molecular control of iron metabolism has increased dramatically over the past 5 years due to the discovery of hepcidin. This is a circulating antimicrobial peptide mainly synthesized in the liver, which has been recently proposed as a factor regulating the uptake of dietary iron and its mobilization from macrophages and hepatic stores. Inflammation causes an increase of production of hepcidin, which is a potent mediator of anemia of chronic diseases. Anemia in chronic kidney disease is mainly due to erythropoietin deficiency but these patients often have a chronic inflammatory state. The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin in iron metabolism and its regulation, particularly in kidney disease. In addition, current methods of determination of hepcidin are reviewed., (Copyright 2007 S. Karger AG, Basel.)

Introduction: All living organisms have evolved sophisticated mechanisms to maintain appropriate iron levels in their cells and within their body. Recently our understanding of iron metabolism has dramatically increased. Overt labile plasma iron (LPI) represents a component of non-transferrin bound iron (NTBI) that is both redox active and chelatable, capable of permeating into organs and inducing tissue iron overload. The LPI measures the iron-specific capacity of a given sample to produce reactive oxygen species. We studied for the first time NTBI correlations with markers of iron status and inflammation in prevalent hemodialyzed patients. Material and methods: Complete blood count, urea, serum lipids, fasting glucose, creatinine, ferritin, serum iron, total iron binding capacity (TIBC) were studied by standard laboratory method. The NTBI was assessed commercially available kits from Aferrix Ltd in Tel Aviv, Israel. A test result of 0.6 units of LPI or more indicates a potential for iron-mediated production of reactive oxygen species in the sample. Results: Patients with LPI units ⩾ 0.6 had higher serum iron, erythropoiesis stimulating agents (ESA) dose, ferritin, high-sensitivity C-reactive protein (hsCRP), hepcidin and lower hemojuvelin. In hemodialyzed patients NTBI correlated with hsCRP (r = 0.37, p < 0.01), ferritin (r = 0.41, p < 0.001), IL-6 (r = 0.43, p < 0.001). In multivariate analysis predictors of NTBI were hemoglobin and alkaline phosphatase, explaining 58% of the variability Conclusions: Elevated NTBI in HD may be due to disturbed iron metabolism. Anemia and liver function might also contribute to the presence of NTBI in this population. [ABSTRACT FROM AUTHOR]

Hemojuvelin (HJV) is a membrane protein that is responsible for the iron overload condition known as juvenile hemochromatosis. HJV, highly expressed in the liver, skeletal muscle and heart, seems to play a role in iron absorption and release from cells and has anti-inflammatory properties. HJV is a bone morphogenetic protein (BMP) co-receptor and signals via the SMAD (human homolog of Drosophila mad – mother against decapentaplegic) pathway to regulate hepcidin expression. HJV acts as a BMP co-receptor. Moreover, HJV plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway, although through unknown mechanisms. Dietary iron sensing and inflammatory pathways converge in the regulation of the key regulator hepcidin, but how these two pathways intersect remains unclear. Inflammation, through downregulation of hepatic HJV, might induce temporary elimination of iron sensing. Despite enormous scientific achievements in explaining the pathogenetic mechanisms of iron metabolism, many questions still remain unanswered: What is the functional role of HJV in iron metabolism? How it is related to hepcidin expression in different settings? How do iron-sensing and inflammatory pathways cooperate in hepcidin gene expression? Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is one of the fastest-growing major causes of death internationally. Better treatment of CKD and its complications is crucial to reverse this negative trend. Anemia is a frequent complication of CKD and is associated with unfavorable clinical outcomes. It is a devastating complication of progressive kidney disease, that negatively affects also the quality of life. The prevalence of anemia increases in parallel with CKD progression. The aim of this review is to summarize the current knowledge on therapy of renal anemia. Iron therapy, blood transfusions, and erythropoietin stimulating agents are still the mainstay of renal anemia treatment. There are several novel agents on the horizon that might provide therapeutic opportunities in CKD. The potential therapeutic options target the hepcidin–ferroportin axis, which is the master regulator of iron homeostasis, and the BMP-SMAD pathway, which regulates hepcidin expression in the liver. An inhibition of prolyl hydroxylase is a new therapeutic option becoming available for the treatment of anemia in CKD patients. This new class of drugs stimulates the synthesis of endogenous erythropoietin and increases iron availability. We also summarized the effects of prolyl hydroxylase inhibitors on iron parameters, including hepcidin, as their action on the hematological parameters. They could be of particular interest in the out-patient population with CKD and patients with ESA hyporesponsiveness. However, current knowledge is limited and still awaits clinical validation. One should be aware of the potential risks and benefits of novel, sophisticated therapies. [ABSTRACT FROM AUTHOR]