Hepcidin for clinicians.
ABSTRACT Despite the use of erythropoiesis-stimulating agents (ESAs), the anemia of chronic kidney disease (CKD) can be resistant to therapy. Both absolute and functional iron deficiency along with inflammation can contribute to ESA resistance and can be difficult to identify with current-day markers of iron storage. Hepcidin, a small peptide produced by the liver, is a recently discovered key regulator of iron homeostasis. Via regulation of ferroportin, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. Because of its renal elimination and regulation by inflammation, it is possible that progressive renal insufficiency leads to altered hepcidin metabolism, subsequently affecting enteric absorption of iron and the availability of iron stores. Thus, hepcidin likely plays a major role in the anemia of CKD as well as ESA resistance. This article discusses the biologic actions and regulation of hepcidin along with reviewing studies of hepcidin in CKD.
Article: Impact of C-reactive protein on absolute reticulocyte count in haemodialysis patients: the role of iron status.[show abstract] [hide abstract]
ABSTRACT: The exact mechanisms by which the effects of inflammation on erythropoiesis occur are still to be determined. We aimed to examine the relation between C-reactive protein (CRP) and erythropoiesis as quantified by the absolute reticulocyte count (RTC) and the possible effect of iron status on this relationship. As part of a study that follows the changes of haematologic parameters after the intravenous (IV) administration of iron in 93 stable haemodialysis (HD) patients, we made a cross-sectional analysis of baseline measurements and an analysis of changes in RTC 1 week after baseline measurements and iron administration. Multiple linear regression analysis revealed that RTC had a positive correlation with CRP; RTC had a negative correlation with reticulocyte haemoglobin content (CHr). An interaction was also found between CRP and CHr in that CRP had a significant relation to RTC only in those patients whose CHr was more than 31.2 pg. At lower values of CHr, the correlation between CRP and RTC was not significant. Five days after the IV administration of 200 mg iron sucrose, a significant increase of RTC was observed, only in those patients with elevated baseline CRP levels who also showed an increase in CHr levels from ≤ 31.2 pg at baseline to ≥ 31.2 pg post-administration, supporting the presence of an independent positive correlation between CRP and RTC when iron is adequate. It is indicated that, in HD patients, elevated CRP values are associated with increased erythroid production only when CHr is quite satisfactory.Nephrology Dialysis Transplantation 03/2011; 26(3):992-7. · 3.40 Impact Factor
Article: Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease.[show abstract] [hide abstract]
ABSTRACT: To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin) and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis. We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group). Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment. The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group. By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease. Trial registration: ISRCTN59866656.Clinics (São Paulo, Brazil) 01/2011; 66(4):657-62. · 1.59 Impact Factor