Hepcidin Removal during Continuous Renal Replacement Therapy

Introduction: Patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) may require continuous renal replacement therapy (CRRT) as a supportive intervention. While CRRT is effective at achieving solute control and fluid balance, the indiscriminate nature of this procedure raises the possibility that beneficial substances may similarly be removed. Hepcidin, an antimicrobial peptide with pivotal roles in iron homeostasis and pathogen clearance, has biochemical properties amenable to direct removal via CRRT. We hypothesized that serum hepcidin levels would significantly decrease after initiation of CRRT. Methods: In this prospective, observational trial, we enrolled 13 patients who required CRRT: 11 due to stage 3 AKI, and 2 due to critical illness in the setting of ESKD. Plasma was collected at the time of enrollment, and then plasma and effluent were collected at 10:00 a.m. on the following 3 days. Plasma samples were also collected from healthy controls, and we compared hepcidin concentrations in those with renal disease compared to normal controls, evaluated trends in hepcidin levels over time, and calculated the hepcidin sieving coefficient. Results: Plasma hepcidin levels were significantly higher in patients initiating CRRT than in normal controls (158 +/- 60 vs. 17 +/- 3 ng/mL respectively, p < 0.001). Hepcidin levels were highest prior to CRRT initiation (158 +/- 60 ng/mL), and were significantly lower on day 1 (102 +/- 24 ng/mL, p < 0.001) and day 2 (56 +/- 14 ng/mL, p < 0.001) before leveling out on day 3 (51 +/- 11 ng/mL). The median sieving coefficient was consistent at 0.82-0.83 for each of 3 days. Conclusions: CRRT initiation is associated with significant decreases in plasma hepcidin levels over the first 2 days of treatment regardless of indication for CRRT, or presence of underlying ESKD. Since reduced hepcidin levels are associated with increased mortality and our data implicate CRRT in hepcidin removal, larger clinical studies evaluating relevant clinical outcomes based on hepcidin trends in this population should be pursued.