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 ◽  
...  

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.

2019 ◽  
Author(s):  
AISHATU MUHAMMAD NALADO ◽  
Gbenga Olorunfemi ◽  
Therese Dix-Peek ◽  
Caroline Dickens ◽  
Lungile Khambule ◽  
...  

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.


2020 ◽  
Author(s):  
Aishatu Muhammad Nalada ◽  
Gbenga Olorunfemi ◽  
Therese Dix-Peek ◽  
Caroline Dickens ◽  
Lungile Khambule ◽  
...  

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.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Aishatu M. Nalado ◽  
Gbenga Olorunfemi ◽  
Therese Dix-Peek ◽  
Caroline Dickens ◽  
Lungile Khambule ◽  
...  

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.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Boby Pratama Putra ◽  
Felix Nugraha Putra

Abstract Background and Aims Most of non-dialysis-dependent chronic kidney disease (NDD-CKD) patients will suffer from iron-deficiency anaemia (IDA) also mineral and bone disorders (CKD-MBD) as consequences of CKD progression. Ferric citrate (FC) is an iron-based phosphate binder that based on previous studies showed efficacies in improving IDA and CKD-MBD parameters although the results were still inconclusive. This study aims to establish the overall efficacies of FC in improving IDA and CKD-MBD parameters in NDD-CKD patients. Method We did comprehensive searching using predefined keywords in online databases of Pubmed, EMBASE, ScienceDirect, and The Cochrane Library, to include all relevant studies from 2000-2020. We included all randomized controlled trials (RCTs) accessing the efficacies of FC in improving IDA and CKD-MBD parameters compared with standard care (SC) in NDD-CKD patients. The CKD-MBD parameters analysed in this study are changes in serum phosphorus (P), serum calcium ions (Ca), alkaline phosphatase (ALP), intact fibroblast growth factors-23 (iFGF-23), C-terminal fibroblast growth factors-23 (cFGF-23), and intact parathyroid hormone (iPTH), while the IDA parameters analysed are changes of haemoglobin (Hb), serum iron (Fe), transferrin saturation (TSAT), and ferritin. Bias risk was accessed by using the revised Cochrane Risk-of-bias (RoB-2) tool. Analysis was performed to provide standard mean difference (SMD) with 95% confidence interval (CI) using random-effect heterogeneity test. Results We included six RCTs with total of 1,082 participants met our inclusion criteria. The FC significantly improve CKD-MBD parameters of P (SMD = -0.84. 95% CI = -1.21 to -0.07, p&lt;0.00001, I2 = 74%), iFGF-23 (SMD = -0.43. 95% CI = -0.73 to -0.13, p = 0.005, I2 = 73%), cFGF-23 (SMD = -0.74. 95% CI = -1.12 to -0.35, p = 0.0002, I2 = 78%), and iPTH (SMD = -0.23. 95% CI = -0.40 to -0.06, p = 0.008, I2 = 0%), while the improvement of Ca (SMD = 0.16. 95% CI = -0.07 to 0.38, p = 0.17, I2 = 0%) and ALP (SMD = 0.03. 95% CI = -0.22 to 0.28, p = 0.81, I2 = 14%) are not statistically significant compared with the SC group. The FC also significantly improve IDA parameters of Hb (SMD = 1.10. 95% CI = 0.06 to 2.14, p = 0.04, I2 = 97%), TSAT (SMD = 1.18. 95% CI = 0.67 to 1.69, p&lt;0.00001, I2 = 72%), and ferritin (SMD = 1.10. 95% CI = 0.34 to 1.86, p = 0.004, I2 = 87%) compared with the SC group, unless the improvement of Fe is not statistically significant (SMD = 1.34. 95% CI = -0.28 to 2.95, p = 0.11, I2 = 97%). Conclusion The ferric citrate shows potential benefits for improving iron-deficiency anaemia and CKD-MBD parameters in NDD-CKD patients. Nevertheless, further trials are needed to establish the efficacies.


Author(s):  
Kohila Kalimuthu ◽  
Vanusha Avudaithangam

Background: Moderate anaemia seen in about 15-20% of pregnant women. Iron sucrose complex which is used intravenously for the correction of Iron deficiency anaemia. The drug has been able to raise the haemoglobin to satisfactory level when used in moderately anaemic iron deficient pregnant women. The objective of this study was to study the improvement of Hb% after treatment with intravenous Iron sucrose complex in moderately anaemic pregnant women belonging to 24-32 weeks of gestational age.Methods: 50 antenatal patients between gestational age 24-32 weeks with hemoglobin between 8-9.5g/dl were selected and included in this study. They were subjected to blood hemoglobin estimation, hematocrit and peripheral smear study. In each infusion, the maximum total dose administered was 200 mg iron sucrose in 100 ml of normal saline, slow IV infused over 30 minutes. Monitoring was done throughout the infusion to observe for any side effects.Results: Mean hemoglobin among the 50 patients before starting the therapy was 8.172g/dl and the mean hemoglobin at the end of one month of completing the therapy was 11.066g/dl. The rise in mean hemoglobin i.e. the difference in the mean hemoglobin before and after treatment was 2.894g/dl. The p value is 0.0001 which is statistically significant. The mean hematocrit of the 50 patients studied before starting the treatment was 26.772% with a standard deviation of 1.914. The mean hematocrit after completing the therapy was 33.872% with a standard deviation of 1.321. The difference in the mean hematocrit was 7.100% with a p value of 0.0001 which is statistically significant.Conclusions: Intravenous iron sucrose complex is well tolerated and highly efficacious in improving hemoglobin, hematocrit in the treatment of iron deficiency anaemia in antenatal women.


Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 498 ◽  
Author(s):  
Faisal Nuhu ◽  
Anne-Marie Seymour ◽  
Sunil Bhandari

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.


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