scholarly journals MO577EXPANDING THE POTENTIAL BENEFITS OF FERRIC CITRATE FOR IMPROVING IRON-DEFICIENCY ANAEMIA AND MINERAL BONE DISORDER PARAMETERS IN NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE PATIENTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

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<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<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.

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.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Philip A. Kalra ◽  
Sunil Bhandari ◽  
Michael Spyridon ◽  
Rachel Davison ◽  
Sarah Lawman ◽  
...  

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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