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Anaemia and iron dysregulation: untapped therapeutic targets in chronic lung disease?

ABSTRACT: Hypoxia is common in many chronic lung diseases. Beyond pulmonary considerations, delivery of oxygen (O2) to the tissues and subsequent O2 utilisation is also determined by other factors including red blood cell mass and iron status; consequently, disruption to these mechanisms provides further physiological strains on an already stressed system. O2 availability influences ventilation, regulates pulmonary blood flow and impacts gene expression throughout the body. Deleterious effects of poor tissue oxygenation include decreased exercise tolerance, increased cardiac strain and pulmonary hypertension in addition to pathophysiological involvement of multiple other organs resulting in progressive frailty. Increasing inspired O2 is expensive, disliked by patients and does not normalise tissue oxygenation; thus, other strategies that improve O2 delivery and utilisation may provide novel therapeutic opportunities in patients with lung disease. In this review, we focus on the rationale and possibilities for doing this by increasing haemoglobin availability or improving iron regulation.

SUBMITTER: Patel MS

PROVIDER: S-EPMC6733331 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Anaemia and iron dysregulation: untapped therapeutic targets in chronic lung disease?

Patel Mehul S MS McKie Elizabeth E Steiner Michael C MC Pascoe Steven J SJ Polkey Michael I MI

BMJ open respiratory research 20190830 1

Hypoxia is common in many chronic lung diseases. Beyond pulmonary considerations, delivery of oxygen (O2) to the tissues and subsequent O2 utilisation is also determined by other factors including red blood cell mass and iron status; consequently, disruption to these mechanisms provides further physiological strains on an already stressed system. O2 availability influences ventilation, regulates pulmonary blood flow and impacts gene expression throughout the body ...[more]

PMID: 31548896

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Project description:BackgroundIntravenous 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.MethodsThis 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.ResultsThe 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.ConclusionsThe >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 registrationClinicalTrials.gov NCT02546154 , 10 September 2015.

Project description: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 (??=?0.00389, P-value<?0.001), was a predictor of log hepcidin. MCHC (??=???0.0220, P-value 0.005) and CKD stage (??=?0.4761, P-value <?0.001), race (??=?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.

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Anaemia and iron dysregulation: untapped therapeutic targets in chronic lung disease?

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Anaemia and iron dysregulation: untapped therapeutic targets in chronic lung disease?

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