Tubular reabsorption and local production of urine hepcidin-25

BMC Nephrology

Jack FM Wetzels¹  Dorine W Swinkels⁴  Elisabeth AM Cornelissen⁵  Annemarie Eek²  Otto C Boerman²  Rosalinde Masereeuw⁶  Peter Pickkers³  Coby MM Laarakkers⁴  Hilde PE Peters¹ 

[1]Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

[2]Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

[3]Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

[4]Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

[5]Pediatric Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

[6]Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

关键词: Kidney tubules;    Megalin;    Hepcidin;    β₂-microglobulin;    AKI;   

Others  :  1082969
DOI  :  10.1186/1471-2369-14-70

 received in 2012-06-25, accepted in 2013-02-19,  发布年份 2013

【 摘 要 】

Background

Hepcidin 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.

Methods

To 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.

Results

In 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.

Conclusions

Hepcidin-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.

【 授权许可】

   
2013 Peters et al.; licensee BioMed Central Ltd.

【 图 表 】

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