Abstract
BackgroundHepcidin is a central regulator of iron metabolism. Serum hepcidin levels are increased in patients with renal insufficiency, which may contribute to anemia. Urine hepcidin was found to be increased in some patients after cardiac surgery, and these patients were less likely to develop acute kidney injury. It has been suggested that urine hepcidin may protect by attenuating heme-mediated injury, but processes involved in urine hepcidin excretion are unknown.MethodsTo assess the role of tubular reabsorption we compared fractional excretion (FE) of hepcidin-25 with FE of β2-microglobulin (β2m) in 30 patients with various degrees of tubular impairment due to chronic renal disease. To prove that hepcidin is reabsorbed by the tubules in a megalin-dependent manner, we measured urine hepcidin-1 in wild-type and kidney specific megalin-deficient mice. Lastly, we evaluated FE of hepcidin-25 and β2m in 19 patients who underwent cardiopulmonary bypass surgery. Hepcidin was measured by a mass spectrometry assay (MS), whereas β2m was measured by ELISA.ResultsIn patients with chronic renal disease, FE of hepcidin-25 was strongly correlated with FE of β2m (r = 0.93, P <0.01). In megalin-deficient mice, urine hepcidin-1 was 7-fold increased compared to wild-type mice (p < 0.01) indicating that proximal tubular reabsorption occurs in a megalin- dependent manner. Following cardiac surgery, FE of hepcidin-25 increased despite a decline in FE of β2m, potentially indicating local production at 12–24 hours.ConclusionsHepcidin-25 is reabsorbed by the renal tubules and increased urine hepcidin-25 levels may reflect a reduction in tubular uptake. Uncoupling of FE of hepcidin-25 and β2m in cardiac surgery patients suggests local production.
Highlights
Hepcidin is a central regulator of iron metabolism
Serum hepcidin levels are increased in patients with renal insufficiency [7,8], and this may contribute to anemia and resistance to erythropoietin stimulating agents
Even more striking were the findings of Ho et al, who showed that patients with increased urine hepcidin levels were at lower risk to develop acute kidney injury (AKI) after cardiac surgery [10,11]
Summary
Serum hepcidin levels are increased in patients with renal insufficiency, which may contribute to anemia. Even more striking were the findings of Ho et al, who showed that patients with increased urine hepcidin levels were at lower risk to develop acute kidney injury (AKI) after cardiac surgery [10,11]. These results have recently been confirmed in a larger study that included 100 patients who had undergone cardiopulmonary bypass surgery (CABG) [12]. It was suggested that urine hepcidin may protect against AKI by attenuating heme-mediated injury
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