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 Nalada ◽  
Gbenga Olorunfemi ◽  
Therese Dix-Peek ◽  
Caroline Dickens ◽  
Lungile Khambule ◽  
...  
Keyword(s):  
South Africa ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Predictive Value ◽  
Iron Deficiency Anaemia ◽  
P Value ◽  
Diagnostic Validity ◽  
Deficiency Anaemia ◽  
Ckd Stage

Abstract Background Anaemia is a common presenting feature among patients with chronic kidney disease (CKD) and it is associated with poor clinical outcomes and quality of life. It is not clear if growth differentiation factor-15 (GDF-15) or hepcidin are useful as early markers of iron deficiency anaemia (IDA) among non-dialysis CKD patients. We therefore evaluated the diagnostic validity of GDF-15 and hepcidin as biomarkers of IDA among non-dialysis CKD patients in Johannesburg, South Africa. Method An analytic cross-sectional study was conducted among non-dialysis CKD patients (n=312) and apparently healthy controls (n=184) from June to December 2016 at an Academic Hospital, in Johannesburg, South Africa. An interviewer administered proforma was used to obtain the Socio-biological and clinical characteristics of the participants. Serum levels of GDF-15 and hepcidin were determined Predictive logistic regression models were built and post estimation receiver operator characteristics was determined to evaluate diagnostic validity of hepcidin and GDF-15 for absolute and functional iron deficiency anaemia. Results About half (50.6%) of the participants were female while the participants’ mean age was 49.7 ±15.8 years. The predictive value of diagnosing absolute IDA among CKD patients using GDF-15 was 74.02% (95% CI: 67.62% - 80.42%) while the predictive value of diagnosing functional IDA 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.Conclusion Serum GDF-15 is a potential biomarker of absolute IDA, while hepcidin levels can predict functional IDA among CKD patients.

scholarly journals Hepcidin and GDF-15 are potential biomarkers of iron deficiency anaemia in chronic kidney disease patients in South Africa

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Aishatu M. Nalado ◽  
Gbenga Olorunfemi ◽  
Therese Dix-Peek ◽  
Caroline Dickens ◽  
Lungile Khambule ◽  
...  
Keyword(s):  
South Africa ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Predictive Value ◽  
Iron Deficiency Anaemia ◽  
P Value ◽  
Diagnostic Validity ◽  
Deficiency Anaemia ◽  
Ckd Stage

Abstract Background Anaemia is a common presenting feature among patients with chronic kidney disease (CKD) and it is associated with poor clinical outcomes and quality of life. It is not clear if growth differentiation factor-15 (GDF-15) or hepcidin are useful as early markers of iron deficiency anaemia (IDA) among non-dialysis CKD patients. We therefore evaluated the diagnostic validity of GDF-15 and hepcidin as biomarkers of IDA among non-dialysis CKD patients in Johannesburg, South Africa. Method An analytic cross-sectional study was conducted among non-dialysis CKD patients (n = 312) and apparently healthy controls (n = 184) from June to December 2016 at an Academic Hospital, in Johannesburg, South Africa. An interviewer administered proforma was used to obtain the socio-biological and clinical characteristics of the participants. Serum levels of GDF-15 and hepcidin were determined. Predictive logistic regression models were built and post estimation receiver operator characteristics were determined to evaluate diagnostic validity of hepcidin and GDF-15 for absolute and functional iron deficiency anaemia. Results About half (50.6%) of the participants were female while the participants’ mean age was 49.7 ± 15.8 years. The predictive value of diagnosing absolute IDA among CKD patients using GDF-15 was 74.02% (95% CI: 67.62–80.42%) while the predictive value of diagnosing functional IDA 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. Conclusion Serum GDF-15 is a potential biomarker of absolute IDA, while hepcidin levels can predict functional IDA among CKD patients.

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

2019 ◽  
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 ◽  
And Gender ◽  
Potential Biomarkers

Abstract BackgroundIron 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. MethodA 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. ResultsThe mean age of participants was 49.7 ±15.8 years, and 50.6% of them were females. The predictive value of diagnosing iron deficiency anaemia among CKD patients using GDF-15 and hepcidin was high (AUC=0.723 and 0.714, respectively). 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=0.005, P-value<0.001), MCV (β=0.0276, P-value=0.029) and gender (β=-0.2188, P-value=0.042) were predictors of log hepcidin. Urea (β=0.0062, P-value=0.044), MCHC (β= -0.0816, P-value<0.001) and gender (β=-0.0755, P-value=0.001) were predictors of logGDF-15. Both GDF-15 (P=0.028) and hepcidin (P=0.049) were associated with iron deficiency anaemia. Subgroup analysis showed that GDF-15 predicted absolute iron deficiency, while hepcidin predicted functional iron deficiency anaemiaConclusionGDF-15 and hepcidin are potential predictors of iron deficiency anaemia among CKD patients.

scholarly journals Impact of Intravenous Iron on Oxidative Stress and Mitochondrial Function in Experimental Chronic Kidney Disease

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 498 ◽  
Author(s):  
Faisal Nuhu ◽  
Anne-Marie Seymour ◽  
Sunil Bhandari
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Glutathione Peroxidase ◽  
Mitochondrial Function ◽  
Iron Deficiency Anaemia ◽  
Deficiency Anaemia ◽  
Iv Iron

Background: Mitochondrial dysfunction is observed in chronic kidney disease (CKD). Iron deficiency anaemia (IDA), a common complication in CKD, is associated with poor clinical outcomes affecting mitochondrial function and exacerbating oxidative stress. Intravenous (iv) iron, that is used to treat anaemia, may lead to acute systemic oxidative stress. This study evaluated the impact of iv iron on mitochondrial function and oxidative stress. Methods: Uraemia was induced surgically in male Sprague-Dawley rats and studies were carried out 12 weeks later in two groups sham operated and uraemic (5/6 nephrectomy) rats not exposed to i.v. iron versus sham operated and uraemic rats with iv iron. Results: Induction of uraemia resulted in reduced iron availability (serum iron: 31.1 ± 1.8 versus 46.4 ± 1.4 µM), low total iron binding capacity (26.4 ± 0.7 versus 29.5 ± 0.8 µM), anaemia (haematocrit: 42.5 ± 3.0 versus 55.0 ± 3.0%), cardiac hypertrophy, reduced systemic glutathione peroxidase activity (1.12 ± 0.11 versus 1.48 ± 0.12 U/mL), tissue oxidative stress (oxidised glutathione: 0.50 ± 0.03 versus 0.36 ± 0.04 nmol/mg of tissue), renal mitochondrial dysfunction (proton/electron leak: 61.8 ± 8.0 versus 22.7 ± 5.77) and complex I respiration (134.6 ± 31.4 versus 267.6 ± 26.4 pmol/min/µg). Iron therapy had no effect on renal function and cardiac hypertrophy but improved anaemia and systemic glutathione peroxidase (GPx) activity. There was increased renal iron content and complex II and complex IV dysfunction. Conclusion: Iron therapy improved iron deficiency anaemia in CKD without significant impact on renal function or oxidant status.

scholarly journals NIMO-CKD-UK: a real-world, observational study of iron isomaltoside in patients with iron deficiency anaemia and chronic kidney disease

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Philip A. Kalra ◽  
Sunil Bhandari ◽  
Michael Spyridon ◽  
Rachel Davison ◽  
Sarah Lawman ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Observational Study ◽  
Adverse Drug Reactions ◽  
Real World ◽  
Iron Deficiency Anaemia ◽  
Intravenous Iron ◽  
Drug Reactions ◽  
Deficiency Anaemia

Abstract Background Intravenous iron is often used to treat iron deficiency anaemia in non-dialysis chronic kidney disease (ND-CKD), but the optimal dosing regimen remains unclear. We evaluated the impact of high- versus low-dose intravenous iron isomaltoside on the probability of retreatment with intravenous iron in iron-deficient ND-CKD patients. Methods This real-world, prospective, observational study collected data from 256 ND-CKD patients treated for anaemia in the UK. Following an initial course of iron isomaltoside, patients were followed for ≥12 months. Iron dose and the need for retreatment were determined at the investigators’ discretion. The primary study outcome was the need for retreatment at 52 weeks compared between patients who received >1000 mg of iron during Course 1 and those who received ≤1000 mg. Safety was evaluated through adverse drug reactions. Results The probability of retreatment at Week 52 was significantly lower in the >1000 mg iron group (n = 58) versus the ≤1000 mg group (n = 198); hazard ratio (95% confidence interval [CI]): 0.46 (0.20, 0.91); p = 0.012. Mean (95% CI) haemoglobin increased by 6.58 (4.94, 8.21) g/L in the ≤1000 mg group and by 10.59 (7.52, 13.66) g/L in the >1000 mg group (p = 0.024). Changes in other blood and iron parameters were not significantly different between the two groups. Administering >1000 mg of iron isomaltoside saved 8.6 appointments per 100 patients compared to ≤1000 mg. No serious adverse drug reactions were reported. Of the patients who received ≤1000 mg of iron in this study, 82.3% were eligible for a dose >1000 mg. Conclusions The >1000 mg iron isomaltoside regimen reduced the probability of retreatment, achieved a greater haemoglobin response irrespective of erythropoiesis-stimulating agent treatment, and reduced the total number of appointments required, compared to the ≤1000 mg regimen. Many of the patients who received ≤1000 mg of iron were eligible for >1000 mg, indicating that there was considerable underdosing in this study. Trial registration ClinicalTrials.gov NCT02546154, 10 September 2015.

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