Iron metabolism in chronic kidney disease

2015 ◽  
Author(s):  
Jolanta Malyszko ◽  
Iain C. Macdougall
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Iron Metabolism ◽  
Ferritin Level ◽  
Negative Regulator ◽  
Whole Body ◽  
Main Function ◽  
Functional Iron Deficiency ◽  
Absolute Iron Deficiency

While whole-body (‘absolute’) iron deficiency is common and probably increased in frequency in chronic kidney disease (CKD), functional iron deficiency is a particular problem in CKD. Absolute iron deficiency is likely to be present in advanced CKD when the ferritin falls below 100 ng/mL and the TSAT falls below 20%. Functional iron deficiency is characterized by the presence of adequate iron stores (as defined by conventional criteria), but with an inability to mobilize this iron rapidly enough to adequately support erythropoiesis with the administration of erythropoietin. Among such patients, the serum ferritin level is either normal or elevated (usually between 100 and 800 ng/mL), with a TSAT typically ≤20%. Hepcidin, a novel peptide discovered at the turn of the twenty-first century, is an iron gatekeeper that plays a key role in functional iron deficiency, and the ‘anaemia of chronic disease’. The main function of hepcidin is homeostatic regulation of iron metabolism and mediation of host defence and inflammation. Hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron transport across the placenta, and iron release from the macrophages. Novel strategies that modulate hepcidin and its target ferroportin for the treatment of anaemia of chronic diseases are currently undergoing extensive research.

scholarly journals Iron Deficiency Anemia in Chronic Kidney Disease

2019 ◽  
Vol 142 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Anat Gafter-Gvili ◽  
Amir Schechter ◽  
Benaya Rozen-Zvi
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Supplementation ◽  
Deficiency Anemia ◽  
Functional Iron Deficiency ◽  
Iron Stores ◽  
Ckd Stage ◽  
Absolute Iron Deficiency

Iron deficiency anemia is a common complication of chronic kidney disease (CKD). CKD patients suffer from both absolute and functional iron deficiency. Absolute iron deficiency is defined by severely reduced or absent iron stores, while functional iron deficiency is defined by adequate iron stores but insufficient iron availability for incorporation into erythroid precursors. This is due to increased levels of hepcidin. Anemia in CKD is associated with an increased risk of morbidity and mortality. The association between anemia and mortality may be related to the severity of anemia. All CKD patients should be screened for anemia during the initial evaluation for CKD. Criteria used to define iron deficiency are different among CKD compared to normal renal function. Among CKD patients, absolute iron deficiency is defined when the transferrin saturation (TSAT) is ≤20% and the serum ferritin concentration is ≤100 ng/mL among predialysis and peritoneal dialysis patients or ≤200 ng/mL among hemodialysis patients. Functional iron deficiency, also known as iron-restricted erythropoiesis, is characterized by TSAT ≤20% and elevated ferritin levels. Iron supplementation is recommended for all CKD patients with anemia. There is general agreement according to guidelines that intravenous (i.v.) iron supplementation is the preferred method for CKD patients on dialysis (CKD stage 5D) and either i.v. or oral iron is recommended for patients with CKD ND (CKD stages 3–5). In this review we discuss the evidence base for these recommendations.

scholarly journals Serum ferritin <70 μg/L predicts functional iron deficiency in patients with chronic kidney disease

2018 ◽  
Vol 29 (5) ◽  
pp. 1035 ◽  
Author(s):  
Mrinalini Kotru ◽  
Neha Garg ◽  
Anil Yadav ◽  
Usha Rusia ◽  
Meera Sikka ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Serum Ferritin ◽  
Functional Iron Deficiency

scholarly journals P0867ANEMIA AND IRON DEFICIENCY IN NON-DIALYISIS CHRONIC KIDNEY DISEASE: A LINK WITH ADVERSE OUTOCOMES?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sara Fernandes ◽  
Luis Falcao ◽  
Adriana Paixão Fernandes ◽  
Beatriz Donato ◽  
Ana Cortesão Costa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Clinical Outcomes ◽  
Cardiovascular Events ◽  
Deficiency Anemia ◽  
Similar Distribution ◽  
Cardiovascular Comorbidities ◽  
Absolute Iron Deficiency

Abstract Background and Aims Anemia is a major complication of Chronic Kidney Disease (CKD). There are few large observational studies analyzing the association between anemia and significant clinical outcomes in non-dialysis dependent CKD (ND-CKD) patients. Our aim was to evaluate the prevalence of anemia and iron deficiency and their association with mortality, cardiovascular events, need for renal replacement therapy and hospitalizations in an outpatient ND-CKD population. Method A patient-level, retrospective, cohort analysis of all adult ND-CKD patients evaluated in an outpatient nephrology clinic between January 2012 to December 2017 with at least one year follow up. Anemia (defined according to the WHO definition - Hemoglobin [Hb] &lt; 13.0 g/dL in men and 12.0g/dL in women), absolute iron deficiency (ferritin &lt; 100 ng/mL), other demographic and clinical data (CKD staging and etiology, comorbidities) were assessed at the first visit through individual consultation of electronic medical records. Results During the 6-year period, 3008 patients were identified (mean age 70.9±14.1 years; 54.5% male; 91.7% white) with a mean follow-up of 3.3±2.0 years. The most frequent cardiovascular comorbidities were arterial hypertension (81.9%), obesity (58%), diabetes mellitus (57.9%) and dyslipidemia (43.9%). The mean Hb was 11.8 ±1.9 g/dL. Anemia was present in 49.9 % of patients, with similar distribution between genders (50.4% in men vs 49.6% in women) and more frequent in white patients (92% vs 8% p= 0.019). Anemia prevalence increased across CKD stages - 12.9%, 25.9%, 57.2%, 72.7% and 86.4% for stages 1 to 5, respectively (p&lt;0,001 for the trend). Anemia was associated with cardiovascular comorbidities, such as diabetes (52% vs 32%, p&lt;0.001), hypertension (86.7% vs 77.7%, p&lt;0.001), obesity (65.5% vs 60.8 %, p=0.012) and dyslipidemia (46% vs 41.2%, p=0.01). Among patients with ferritin levels available (1638), 41.7% had absolute iron deficiency. Anemia was associated with increased mortality (74% vs 26%, p &lt;0,001) and hospitalization (61,8% vs 38.2%, p &lt;0.001). In multivariate logistic regression analysis, anemia (OR 1,923; 95%IC 1,362-2.716; p&lt;0,001) and absolute iron deficiency (OR 0.531 95% IC 0.348-0.809; p=0.003) emerged as independent predictors of death. Cardiovascular events were more prevalent in the group of patients with Hb levels 10-12 g/dL (4.1 vs2.3% 2p=0.006). Conclusion As expected, anemia prevalence increases across CKD stages and, as well as absolute iron deficiency, is independently associated with adverse clinical outcomes in ND-CKD patients, including death. Future studies should be developed to investigate if correction of these factors improves adverse outcomes.

scholarly journals Hepcidin and GDF-15 are potential biomarkers of Iron Deficiency Anaemia in Chronic Kidney Disease Patients in South Africa

2020 ◽  
Author(s):  
AISHATU MUHAMMAD NALADO ◽  
Gbenga Olorunfemi ◽  
Therese Dix-Peek ◽  
Caroline Dickens ◽  
Lungile Khambule ◽  
...  
Keyword(s):  
South Africa ◽  
Chronic Kidney Disease ◽  
Iron Deficiency ◽  
Iron Deficiency Anaemia ◽  
P Value ◽  
Academic Hospital ◽  
Functional Iron Deficiency ◽  
Deficiency Anaemia ◽  
Absolute Iron Deficiency ◽  
Potential Biomarkers

Abstract Background Iron deficiency anaemia is a significant cause of morbidity and mortality among chronic kidney disease (CKD) patients. There is a paucity of information on the role of hepcidin and growth differentiation factor-15 (GDF-15) as potential biomarkers of iron deficiency anaemia among non-dialysis CKD patients. This study aimed to determine the utility of hepcidin and GDF-15 as biomarkers of iron deficiency among non-dialysis CKD patients at an academic hospital in Johannesburg, South Africa. Method A cross-sectional study of 312 consecutive consenting non-dialysis CKD patients and 184 controls at Charlotte Maxeke Academic Hospital was conducted from June 2016 to December 2016. Socio-demographic and clinical characteristics were recorded. Plasma hepcidin and GDF-15 were measured using mass spectrometry and ELISA, respectively. Spearman rank correlation, linear and logistic regression and receiver operator curves were utilised to evaluate the predictive and diagnostic/reference values of hepcidin and GDF-15 in absolute and functional iron deficiency anaemia. Results The mean age of participants was 49.7 ±15.8 years, and 50.6% of them were females. The predictive value of diagnosing absolute iron deficiency anaemia among CKD patients using GDF-15 was 74.02% (95% CI: 67.62% - 80.42%) while the predictive value of diagnosing functional iron deficiency anaemia among CKD patients using hepcidin was 70.1% (95% CI: 62.79% - 77.49%).There was a weak negative correlation between hepcidin levels and GFR (r=-0.19, p=0.04) in anaemic CKD patients, and between serum GDF-15 and haemoglobin (r=-0.34, p=0.001). Serum ferritin (β=0.00389, P-value<0.001), was a predictor of log hepcidin. MCHC (β= -0.0220, P-value 0.005) and CKD stage (β=0.4761, P-value <0.001), race (β = 0.3429, P-value = 0.018) were predictors of log GDF-15. Both GDF-15 (adj OR: 1.0003, 95%CI: 1.0001 – 1.0005, P=0.017) and hepcidin (adj OR: 1.003, 95%CI: 1.0004 – 1.0055, P=0.023) were associated with iron deficiency anaemia after multiple linear regression modelling. Subgroup analysis showed that GDF-15 predicted absolute iron deficiency, while hepcidin predicted functional iron deficiency anaemiaConclusion GDF-15 and hepcidin are potential predictors of iron deficiency anaemia among CKD patients.

scholarly journals Prevalence, correlates and outcomes of absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease

2019 ◽  
Vol 36 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Ahmed A Awan ◽  
Carl P Walther ◽  
Peter A Richardson ◽  
Maulin Shah ◽  
Wolfgang C Winkelmayer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Large Population ◽  
Adverse Outcomes ◽  
Deficiency Anemia ◽  
Functional Iron Deficiency ◽  
Risk Of Mortality ◽  
Increased Risk

Abstract Background Anemia is associated with adverse outcomes in those with chronic kidney disease (CKD). We examined the association of absolute and functional iron deficiency anemia (IDA) with adverse outcomes (cardiovascular hospitalization, dialysis and mortality) in those with nondialysis-dependent CKD. Methods Nondialysis-dependent CKD patients followed in the US Veterans Administration with hemoglobin level measured within 90 days of the date of the second estimated glomerular filtration rate &lt;60 mL/min/1.73 m2 were included. Logistic regression, multivariate Cox proportional hazards and Poisson regression models adjusted for demographics and comorbidities were used to assess the prevalence and correlates of absolute [transferrin saturation (TSAT) ≤20%, ferritin &lt;100 ng/mL] and functional (TSA T≤20%, ferritin &gt;100–500 ng/mL) IDA and the associations of absolute and functional IDA with mortality, dialysis and cardiovascular hospitalization. Results Of 933 463 patients with CKD, 20.6% had anemia. Among those with anemia, 23.6% of patients had both TSAT and ferritin level measured, of whom 30% had absolute IDA and 19% had functional IDA. Absolute IDA in CKD was not associated with an increased risk of mortality or dialysis but was associated with a higher risk of 1-year {risk ratio [RR] 1.20 [95% confidence interval (CI) 1.12–1.28]} and 2-year cardiovascular hospitalization [RR 1.11 (95% CI 1.05–1.17)]. CKD patients with functional IDA had a higher risk of mortality [hazard ratio (HR) 1.11 (95% CI 1.07–1.14)] along with a higher risk of 1-year [RR 1.21 (95% CI 1.1–1.30)] and 2-year cardiovascular hospitalization [RR 1.13 (95% CI 1.07–1.21)]. Ferritin &gt;500 ng/mL (treated as a separate category) was only associated with an increased risk of mortality [HR 1.38 (95% CI 1.26–1.51)]. Conclusions In a large population of CKD patients with anemia, absolute and functional IDA were associated with various clinical covariates. Functional IDA was associated with an increased risk of mortality and cardiovascular hospitalization, but absolute IDA was associated only with a higher risk of hospitalization.

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

2020 ◽  
Author(s):  
Anatole Besarab ◽  
Tilman B Drueke
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Iron Metabolism ◽  
Iron Status ◽  
Hypoxia Inducible Factor ◽  
Transferrin Saturation ◽  
Deficiency Anemia ◽  
Iron Availability ◽  
Inflammatory State

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.

Abbott Alinity hq reticulocyte hemoglobin cutoff for diagnosing functional iron deficiency in chronic kidney disease

2019 ◽  
Vol 493 ◽  
pp. S430
Author(s):  
Z. Mukhtar ◽  
B.A. Wevers ◽  
C.L. Slim ◽  
M.W.H.J. Demmers ◽  
H.J. Adriaansen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Functional Iron Deficiency
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