The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment

Abstract

Background and objectives: Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Materials and methods: Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. Results: MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients’ 2-year survival. Conclusion: Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.

Calculated Whole Blood Viscosity and Albumin/Fibrinogen Ratio in Patients with a New Diagnosis of Multiple Myeloma: Relationships with Some Prognostic Predictors

“…Many papers in the literature underline the prognostic role of RDW in MM [ 17 , 40 , 41 ]. Indicating the heterogeneity of the volume of erythrocytes, RDW is a simple and immediately inflammatory marker and it reflects the increase of some cytokines, such as IL-6 and tumor necrosis factor-alpha (TNF-alpha), but also of hepcidin in the blood [ 42 , 43 ]. It is possible that the increase in this predictor may affect the erythrocyte deformability of MM patients, also considering that in some of our previous research [ 18 , 19 , 20 , 21 ], this hemorheological determinant was reduced compared with the control group.…”

New diagnostic strategy for multiple myeloma: A review

“…In addition, it was also related with poor response to MM treatment, revealing its potential being as survival predictor of MM. [ 15 ] Likewise, lower expression of GDF 15 was found in patients those received autologous stem cell transplantation compared to control groups, which indicated GDF 15 was able to predict response to treatment . Nevertheless, the predictive effect of GDF 15 on survival of MM patients is still in debate, because current research results were different.…”

Changes in RDW according to prognostic predictors in newly diagnosed multiple myeloma

“…Considering therefore the role of RDW in MM, it has meanwhile begun to analyse the possible causes responsible for the significant variation of this index. Several literature data are available about the relations between RDW and inflammatory markers, such as erythrocyte sedimentation ratio and C-reactive protein 21 but, in MM, is more plausible than the variation of RDW may mainly depend on high circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and hepcidin 22 – 24 . Interacting with each other, these factors tend to alter the erythropoiesis, causing significant variation in the erythrocyte maturation and, inevitably, contributing to the increase of the RDW.…”