Type of renal replacement therapy and residual renal function may affect prohepcidin and hepcidin

Abstract

Hepcidin is a small defensin-like peptide, the production of which by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Kidneys are involved in not only the synthesis of hepcidin, but they also may be involved in its elimination. A cross-sectional study was performed to assess prohepcidin and hepcidin in serum, urine, and ultrafiltrate/peritoneal effluent in relation to type of renal replacement therapy and prohepcidin and hepcidin correlations with renal function, iron status, and markers of inflammation.

Methods: Prohepcidin and hepcidin high-sensitivity CRP, TNF alpha, and IL-6 were measured using commercially available kits in 102 patients on hemodialyses, 17 on hemodiafiltration, 44 on peritoneal dialyses, and 22 healthy volunteers.

Results: In hemodialyzed and peritoneally dialyzed patients with residual renal function, serum prohepcidin (264.21 +/- 95.84 vs. 341.84 +/- 90.45 ng/mL, p < 0.01; 142.76 +/- 57.87 vs. 238.42 +/- 84.32 ng/mL, p < 0.01, respectively) and hepcidin (178.89 +/- 89.87 vs. 295.76 +/- 129.65 ng/mL, p < 0.01; 108.43 +/- 75.49 vs. 186.53 +/- 119.62 ng/mL, p < 0.01, respectively) were significantly lower than in anuric patients. In peritoneal effluent, prohepcidin level was significantly higher than in ultrafiltrate of HD/HDF patients. In multiple regression analysis, residual renal function, ferritin, and hsCRP were predictors of hepcidin in hemodialyzed patients, while residual renal function and ferritin were predictors of hepcidin in peritoneally dialyzed patients.

Conclusions: Residual renal function seems to play a pivotal role in hepcidin levels in dialyzed patients. In addition, the presence of low-grade inflammation, more pronounced in anuric patients, and functional iron deficiency may also contribute to the elevated hepcidin. The removal of prohepcidin with ultrafiltrate/peritoneal effluent may partially explain its lower concentration in peritoneal dialysis and hemodiafiltration.