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

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 (??=?0.00389, P-value

SUBMITTER: Nalado A

PROVIDER: S-EPMC7523312 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundWHO recommends daily iron supplementation for pregnant women, but adherence is poor because of side-effects, effectiveness is low, and there are concerns about possible harm. The iron-regulatory hormone hepcidin can signal when an individual is ready-and-safe to receive iron. We tested whether a hepcidin-guided screen-and-treat approach to combat iron-deficiency anaemia could achieve equivalent efficacy to universal administration, but with lower exposure to iron.MethodsWe did a three-arm, randomised, double-blind, non-inferiority trial in 19 rural communities in the Jarra West and Kiang East districts of The Gambia. Eligible participants were pregnant women aged 18-45 years at between 14 weeks and 22 weeks of gestation. We randomly allocated women to either WHO's recommended regimen (ie, a daily UN University, UNICEF, and WHO international multiple-micronutrient preparation [UNIMMAP] containing 60 mg iron), a 60 mg screen-and-treat approach (ie, daily UNIMMAP containing 60 mg iron for 7 days if weekly hepcidin was <2·5 μg/L or UNIMMAP without iron if hepcidin was ≥2·5 μg/L), or a 30 mg screen-and-treat approach (ie, daily UNIMMAP containing 30 mg iron for 7 days if weekly hepcidin was <2·5 μg/L or UNIMMAP without iron if hepcidin was ≥2·5 μg/L). We used a block design stratified by amount of haemoglobin at enrolment (above and below the median amount of haemoglobin on every enrolment day) and stage of gestation (14-18 weeks vs 19-22 weeks). Participants and investigators were unaware of the random allocation. The primary outcome was the amount of haemoglobin at day 84 and was measured as the difference in haemoglobin in each screen-and-treat group compared with WHO's recommended regimen; the non-inferiority margin was set at -5·0 g/L. The primary outcome was assessed in the per-protocol population, which comprised all women who completed the study. This trial is registered with the ISRCTN registry, number ISRCTN21955180.FindingsBetween June 16, 2014, and March 3, 2016, 498 participants were randomised, of whom 167 were allocated to WHO's recommended regimen, 166 were allocated to the 60 mg per day screen-and-treat approach, and 165 were allocated to the 30 mg per day screen-and-treat approach. 78 participants were withdrawn or lost to follow-up during the study; thus, the per-protocol population comprised 140 women assigned to WHO's recommended regimen, 133 allocated to the 60 mg screen-and-treat approach, and 147 allocated to the 30 mg screen-and-treat approach. The screen-and-treat approaches did not exceed the non-inferiority margin. Compared with WHO's recommended regimen, the difference in the amount of haemoglobin at day 84 was -2·2 g/L (95% CI -4·6 to 0·1) with the 60 mg screen-and-treat approach and -2·7 g/L (-5·0 to -0·5) with the 30 mg screen-and-treat approach. Adherence, reported side-effects, and adverse events were similar between the three groups. The most frequent side-effect was stomachache, which was similar in the 60 mg screen-and-treat group (82 cases per 1906 person-weeks) and with WHO's recommended regimen (81 cases per 1974 person-weeks; effect 1·0, 95% CI 0·7 to 1·6); in the 30 mg screen-and-treat group the frequency of stomachache was slightly lower than with WHO's recommended regimen (58 cases per 2009 person-weeks; effect 0·7, 95% CI 0·5 to 1·1). No participants died during the study.InterpretationThe hepcidin-guided screen-and-treat approaches had no advantages over WHO's recommended regimen in terms of adherence, side-effects, or safety outcomes. Our results suggest that the current WHO policy for iron administration to pregnant women should remain unchanged while more effective approaches continue to be sought.FundingBill & Melinda Gates Foundation and the UK Medical Research Council.

Project description:INTRODUCTION:Iron deficiency anaemia (IDA) worsens the prognosis and outcomes of chronic kidney disease (CKD). However, while the haemoglobin level is unreliable for early detection of IDA, reticulocyte haemoglobin content (CHr) and hypochromic red cells (%HYPO) are early markers of IDA. METHODS:This was a cross sectional study of black adult participants (n = 258) with CKD and apparently healthy members of staff and patients' relatives (n = 141) at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa, between 1 June 2016 and 31 December 2016. Serum iron, serum ferritin and transferrin were measured using standard laboratory methods, while the haematology analyser was employed to measure CHr and %HYPO. The validity of CHr and %HYPO as markers of IDA were evaluated. Multivariable binary logistic regression was conducted to determine predictors of the relationship between IDA, CHr and %HYPO. The area under the receiver operator characteristics (ROC) curve (AUC) of the final models were utilised to evaluate the discriminatory value of CHr and %HYPO respectively. RESULTS:About one-quarter (26.1%) of the participants had IDA which was more than three times more frequent among CKD patients, compared to controls (35.3% vs 9.2%); 32.3% (95%CI: 27.90%- 37.10%) of the study population had iron deficiency without anaemia and the prevalence of iron deficiency without anaemia was lower in CKD patients compared to controls (29.5% vs 37.6%). The mean age of CKD patients was higher than in controls (52.7 ±14.3 vs 40.4 ±12.6 years, P-value<0.001). The sensitivity and specificity for diagnosing IDA among CKD participants was 62.6% and 80.2% respectively for CHr (at a cut-off value of <28pg) and 63.3% and 79.8% respectively for %HYPO. CKD participants with CHr levels >28pg were 82% less likely to be diagnosed as having IDA as compared to those with CHr levels ? 28pg) (adj odds ratio = 0.18, 95% CI: 0.09-0.37). The AUC of CHr (0.81, 95% CI: 0.76-0.87) was higher than the AUC of %HYPO (0.76, 95%CI: 0.70-0.82). CONCLUSION:The diagnostic usefulness of CHr and the screening performance of %HYPO in predicting IDA among CKD patients are high. Their lower cost compared to conventional markers of ID recommend their use in clinical practice. Further cost effectiveness studies of these parameters are warranted.

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.

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

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