Hepcidin helps!

Swelm , Van Rachel

In a recent publication in ‘The Journal of the American Society of Nephrology’ (JASN), Rachel van Swelm from the Dept. of Translational Metabolic Laboratory (Iron research group of Prof. Dorine Swinkels), theme Renal disorders demonstrated renal handling of circulating and renal-synthesized hepcidin and its protective effects against hemoglobin-mediated kidney injury.

Acute kidney injury (AKI) is an increasingly common complication in patients undergoing major surgery with cardiopulmonary bypass. It is now well-established that hemolysis is an essential mechanism that contributes to postoperative AKI. During hemolysis, reactive iron is released from hemoglobin, which damages the renal tissue. In several clinical observational studies an association was found between increased urinary levels of the iron-regulatory hormone hepcidin and reduced risk of postoperative AKI. 

As part of the Innovation Grant of the Dutch Kidney Foundation awarded to Prof. Dorine Swinkels, Prof. Jack Wetzels and Prof. Roos Masereeuw, the goal was to study renal handling of hepcidin and its potential protective mechanisms against AKI. Using megalin deficient mice, we demonstrated that circulating hepcidin is filtered by the glomerulus and partly reabsorbed in the proximal tubular epithelial cells via megalin-mediated endocytosis. Furthermore, systemic administration of hepcidin abolished hemoglobin-mediated early kidney injury in mice. Interestingly, we observed that not only circulating hepcidin that is reabsorbed in the proximal tubules, but also renal hepcidin synthesized in the distal nephron, is involved in renal protection against hemoglobin-mediated injury.

The next step is to investigate the protective molecular mechanisms of hepcidin in iron-mediated kidney injury and determine the role of locally synthesized hepcidin in kidney injury by unraveling the driving forces behind its transcription. Together, these insights will provide novel leads for protection against iron-mediated kidney injury. 


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