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Title: Assessment of ferric management in multiple myeloma in relationship to stage of kidney failure


Multiple myeloma, which represents 10% of haematological neoplasms, mainly affects the elderly. In recent years the age limit for MM diagnosis has been gradually edging towards the younger population. The most common manifestations of MM are: predominantly anaemia and consequent symptoms due to bone and kidney failure. Anaemia, which is an early complication of MM, has multifactorial pathogenesis. The predominant causes are due to: overexpression of cytokines pathway which contribute to development of ACD, displacement of normal bone marrow cells by myeloma cells, disturbance of normal ferritic management and reduced EPO secretion due to renal failure. Anaemia correlates with worse prognosis; moreover it may be an independent predictor of development of impaired kidney function in multiple myeloma. In treatment of anaemia, classic methods are used such as iron supplementation, blood transfusions (which require frequent hospitalizations) and the use of EPO (associated with increased risk of thromboembolism). Currently new forms of anaemia pharmacotherapy are being studied (recombinant, soluble activin type-II receptor–IgG-Fc fusion proteins). Concentrations of HGB, haematocrit, RBC, MCH, MCHC, MCV, RDW-CV and iron are used for classical assessment of anaemia. Presently there are new biomarkers of ferritic management (GDF15, sTfR or hepcidin 25) which can improve the recognition ; of anaemia. This doctoral dissertation is based on the cycle of 3 publications that evaluate the use of new biomarkers of ferritic management (GDF15, sTfR and hepcidin 25) in patients with multiple myeloma and renal failure. The relationship between markers and neoplasm advancement, anaemia, kidney failure, mortality, as well as the associations between indicators were compared and studied. 73 patients were included into the study with MM or SMM. Blood and urine samples were drawn from each patient. Biomarkers of ferritic management (GDF15, sTfR, hepcidin 25), as well as standard indicators of anaemia and iron deficiency, markers of MM advancement, renal failure and inflammation were assayed. After an interval of 27 months from the start of the study, laboratory test results from the last visit (mainly markers of anaemia) were evaluated and mortality data were completed. After evaluation of the studied markers, Serum GDF15 concentrations had the best correlations with advancement of MM (ISS stage, as well as serum levels of FLC, urine LC, serum β2-microglobulin and serum albumin) and treatment response. Meanwhile, serum hepcidin 25 concentrations were additionally associated with the type of treatment prescription. Serum levels of all markers were higher in patients with anaemia; while only GDF15 and hepcidin 25 showed correlation with HGB concentrations. Associations betwee ; n serum GDF15 concentrations and markers of glomerular filtration impairment and renal tubular damage were observed. GDF15 presented most frequent associations with other biomarkers. Serum levels of hepcidin 25 have been predictors of mortality in MM patients independently of kidney injury and HGB concentrations. Taking into consideration the above results, it seems reasonable to assay biomarkers of ferritic management in the MM population to predict development of anaemia, as well as to assess patients prognosis independently of concomitant complications of multiple myeloma. These markers may serve to be helping tools in earlier intervention, prevention implementation and pharmacotherapy. In turn they may prevent the development of such consequences as: cardiovascular complications, cognitive deterioration or frequent hospitalizations associated with blood transfusions; and very importantly increase patients quality of life. One must emphasis the necessity to continue studies concerning these markers in order to exclude the influence of other factors and to precisely assess the effectiveness in their use in MM.

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2 - studia doktoranckie

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Wydział Lekarski


Krzanowska, Katarzyna

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pol; eng

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tylko w bibliotece

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Mar 10, 2023

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Mar 2, 2023

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Edition name Date
ZB-136330 Mar 10, 2023


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