Iron Deficiency and Erythropoietin Excess: Two Sides of the Same Coin?:studies in patients with chronic kidney disease and in the general population

Anemia of chronic kidney disease (CKD) is an important complication in patients with CKD and in renal transplant recipients (RTRs). An important cause of anemia of CKD is iron deficiency. The general aim of this thesis was to assess the consequences of iron deficiency in CKD patients, RTRs, and in the general population. We identified in this thesis that iron deficiency independently of anemia is associated with adverse outcomes in RTRs. This is contrary to daily clinical practice, where iron deficiency is generally considered only relevant in presence of anemia. Importantly, in the following chapters we showed that the detrimental effects of iron deficiency seem, at least to a large extent, attributable to increased levels of fibroblast growth factor 23 (FGF23) in CKD patients, RTRs and in the general population. FGF23 is an osteocyte-derived hormone which is an essential regulator of phosphate and vitamin D metabolism. Similarly, we showed that the associations between erythropoietin (EPO), both endogenous as exogenous, and adverse outcomes are related to increased FGF23 levels. This thesis highlights the importance of iron deficiency, and unravels that both iron deficiency as high EPO levels are associated with increased levels of FGF23. Finally, this thesis contains the rationale and design study of TransplantLines, the largest biobank worldwide that comprises all types of solid organ transplant recipients. This study will be of uttermost importance in upcoming years for further unraveling the interplay between iron deficiency, high levels of EPO and FGF23, and outcomes