Rachel van Swelm, theme Renal Disorders has been awarded a Kolff Junior Postdoc Grant from the Dutch Kidney Foundation (Nierstichting) to perform innovative research in the field of nephrology. Her project is entitled 'Strike while the iron is hot: hepcidin-mediated protection against hemoglobin-induced acute kidney injury'.
Postoperative acute kidney injury (AKI) is an increasingly common life-threatening complication in up to 30% of the patients undergoing major surgery with cardiopulmonary bypass. Patients with postoperative AKI are at increased risk for mortality and morbidity, including chronic kidney disease. Currently, adequate preventive measures or specific treatment modalities are lacking. It is now well-established that hemolysis is an essential mechanism that contributes to postoperative AKI. During hemolysis, levels of circulating iron-containing hemoglobin increase, leading to accumulation in the kidney. Reactive iron released from hemoglobin subsequently damages the renal tissue. In line with clinical observations we have recently demonstrated in vivo that the iron-regulatory hormone hepcidin protects against hemoglobin-induced AKI. In order to move these findings forward towards a targeted treatment against AKI, it is essential to elucidate the molecular mechanisms and dynamics of hepcidin-mediated renal protection, which are currently unknown. Interestingly, during hepcidin-mediated protection against hemoglobin-induced AKI we observed reabsorption of systemically circulating hepcidin in the proximal tubules as well as enhanced synthesis of renal hepcidin in the distal tubules. The question remains whether both of these distinct hepcidin sources are essential for the protection of the entire nephron against hemoglobin-induced AKI and if there is a coordinated interaction between different nephron segments. Rachel will set up an inducible kidney-specific hepcidin knockout mouse model and innovative renal 3D co-culture system to answer her research questions, which will define our approach towards hepcidin-based treatment modalities against AKI.
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