Iron status, inflammation and hepcidin in ESRD patients: The confounding role of intravenous iron therapy

Abstract

Uremia is a state of heightened inflammatory activation. This might have an impact on several parameters including anemia management. Inflammation interferes with iron utilization in chronic kidney disease through hepcidin. We studied the body iron stores, degree of inflammatory activation, and pro-hepcidin levels in newly diagnosed patients with end-stage renal disease (ESRD), and compared them with normal population. In addition to clinical examination and anthropometry, the levels of iron, ferritin, C-reactive protein, tumor necrosis factor alfa, interleukin-6, and prohepcidin were estimated. A total of 74 ESRD patients and 52 healthy controls were studied. The ESRD patients had a significantly lower estimated body fat percentage, muscle mass, and albumin; and higher transferrin saturation (TSAT) and raised serum ferritin. Inflammatory activation was evident in the ESRD group as shown by the significantly higher CRP, IL-6, and TNF-α levels. The pro-hepcidin levels were also increased in this group. Half of the ESRD patients had received parenteral iron before referral. Patients who had received intravenous iron showed higher iron, ferritin, and TSAT levels. These patients also showed more marked inflammatory activation, as shown by the significantly higher CRP, TNF-α, and IL-6 levels. We conclude that our ESRD patients showed marked inflammatory activation, which was more pronounced in patients who had received IV iron. High hepcidin levels could explain the functional iron deficiency. The cause of the relatively greater degree of inflammatory activation as well as the relationship with IV iron administration needs further studies.

Keywords: Anemia; end-stage renal disease; hepcidin; inflammation; intravenous iron.

Figure 1

Histogram showing transferrin saturation in ESRD patients. The vertical blue lines indicate normal distribution

Figure 2

Box-and-whisker plots showing the serum iron (microgm/dl), transferrin saturation (TSAT, %), ferritin (ng/ml), albumin (g/dl), C-reactive protein (mg/l), TNF-a (pg/ml) IL-6 (pg/ml), and hepcidin (ng/ml) in ESRD patients (solid blue line) and healthy controls (dashed red line). Log-transformed data, with the solid horizontal line denoting the median along with the interquartile range

Figure 3

Box-and-whisker plots showing the serum iron (microgm/dl), transferrin saturation (TSAT, %), ferritin (ng/ml), albumin (g/dl), C-reactive protein (mg/l), TNF-a (pg/ml), IL-6 (pg/ml), and hepcidin (ng/ml) in ESRD patients who did not receive IV iron (solid blue line) and those who did (dashed red line). Log-transformed data, with the solid horizontal line denoting the median along with the interquartile range