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Erythropoietic drive is the strongest predictor of hepcidin level in adults with sickle cell disease.

ABSTRACT: Levels of hepcidin, a key modulator of iron metabolism, are influenced by erythropoiesis, iron, and inflammation, all of which may be increased in patients with sickle cell disease (SCD). The objectives of this study were to determine: 1) the variation in hepcidin level, and 2) the relative contribution of erythropoietic drive, iron, and inflammation to differences in hepcidin level in an adult cohort with SCD. In a prospective study, cross-sectional measurements of hepcidin, reticulocyte percentage, erythropoietin, ferritin, and high-sensitivity CRP were obtained. A regression tree analysis was used to measure the association between these interacting factors and hepcidin level. The cohort was comprised of 40 adults with SCD. Median age was 26years, 68% were female, and all had HbSS. Hepcidin values ranged from 30ng/ml to 326ng/ml, with a median of 87ng/ml. Regression tree analysis demonstrated that reticulocyte percentage, erythropoietin, ferritin and hs-CRP all were associated with hepcidin. The highest hepcidin values were found in subjects with low reticulocyte percentage and erythropoietin. In conclusion, erythropoietic drive, iron status, and inflammation all contribute to variation in hepcidin level. The strongest contributor is erythropoietic drive. Future studies could determine whether suppression of erythropoiesis with chronic transfusion influences hepcidin level.

SUBMITTER: Karafin MS

PROVIDER: S-EPMC4754107 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Erythropoietic drive is the strongest predictor of hepcidin level in adults with sickle cell disease.

Karafin Matthew S MS Koch Kathryn L KL Rankin Amy B AB Nischik Debora D Rahhal Ghady G Simpson Pippa P Field Joshua J JJ

Blood cells, molecules & diseases 20150717 4

Levels of hepcidin, a key modulator of iron metabolism, are influenced by erythropoiesis, iron, and inflammation, all of which may be increased in patients with sickle cell disease (SCD). The objectives of this study were to determine: 1) the variation in hepcidin level, and 2) the relative contribution of erythropoietic drive, iron, and inflammation to differences in hepcidin level in an adult cohort with SCD. In a prospective study, cross-sectional measurements of hepcidin, reticulocyte percen ...[more]

PMID: 26460251

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Project description:BACKGROUND AND OBJECTIVES:Metabolic acidosis is a frequent manifestation of sickle cell disease but the mechanisms and determinants of this disorder are unknown. Our aim was to characterize urinary acidification capacity in adults with sickle cell disease and to identify potential factors associated with decreased capacity to acidify urine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Among 25 adults with sickle cell disease and an eGFR of ?60 ml/min per 1.73 m2 from a single center in France, we performed an acute acidification test after simultaneous administration of furosemide and fludrocortisone. A normal response was defined as a decrease in urinary pH <5.3 and an increase in urinary ammonium excretion ?33 µEq/min at one or more of the six time points after furosemide and fludrocortisone administration. RESULTS:Of the participants (median [interquartile range] age of 36 [24-43] years old, 17 women), 12 had a normal and 13 had an abnormal response to the test. Among these 13 participants, nine had normal baseline plasma bicarbonate concentration. Plasma aldosterone was within the normal range for all 13 participants with an abnormal response, making the diagnosis of type 4 tubular acidosis unlikely. The participants with an abnormal response to the test were significantly older, more frequently treated with oral bicarbonate, had a higher plasma uric acid concentration, higher hemolysis activity, lower eGFR, lower baseline plasma bicarbonate concentration, higher urine pH, lower urine ammonium ion excretion, and lower fasting urine osmolality than those with a normal response. Considering both groups, the maximum urinary ammonium ion excretion was positively correlated with fasting urine osmolality (r 2=0.34, P=0.002), suggesting that participants with sickle cell disease and lower urine concentration capacity have lower urine acidification capacity. CONCLUSIONS:Among adults with sickle cell disease, impaired urinary acidification capacity attributable to distal tubular dysfunction is common and associated with the severity of hyposthenuria. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_12_10_CJN07830719.mp3.

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Erythropoietic drive is the strongest predictor of hepcidin level in adults with sickle cell disease.

Publications

Erythropoietic drive is the strongest predictor of hepcidin level in adults with sickle cell disease.

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