A more cautious approach to excess ESA dosing has been adopted dasatinib IC50 since randomized trials in CKD populations indicated an increased risk of stroke and venous thromboembolism when ESA therapy is used to target high Hb levels [22�C24], especially in relatively unresponsive patients [55, 56]. In kidney transplantation, a large retrospective study has demonstrated that reaching an Hb level of 14.0g/dL during ESA therapy is associated with increased mortality compared to 12.5g/dL [21]. In the current study, fewer than 15% of patients had an Hb level > 13g/dL at any time point during C.E.R.A. administration. The recent KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease advises that iron deficiency should be addressed prior to initiation of ESA therapy [57].

In our cohort of patients, the documented use of iron supplementation was low (21.5%), but unfortunately medication reporting and the assessment of iron status seem unlikely to have been comprehensive or fell outside the prespecified windows for study visits. For example, immunosuppressive agents were listed by investigators in only 15% of patients, another clear limitation of the study. Serum ferritin levels, however, indicated the presence of low iron stores in many patients with available data, with median values consistently below the lower recommended limit of 100ng/mL [32]. Additionally, approximately 25% of patients were below the recommended minimum TSAT level of 20% [32], a level frequently considered to represent functional iron deficiency.

While data are incomplete, it appears that iron indices are not routinely monitored or managed at all centers. Thus, our observational study has identified some marked areas of concern where there is room for improvement in patient management, upon which future studies should focus. Adverse events and serious events judged by the investigator to have at least a possible relation to C.E.R.A. were reported in 2.5% and 1.4% of patients, respectively. Taking into account the comorbidities and multiple concomitant medications given to kidney transplant patients, it is difficult to accurately assign causality to a specific drug. Of the expected adverse events listed in the summary of product characteristics for C.E.R.A., only headache (0.70%) and hypertension (1.10%) were observed, with hypertension contributing to discontinuation in two cases.

There were no hematological or biochemical concerns. An observational study design was chosen to document ��real-world�� outcomes when patients were selected for C.E.R.A. therapy and Carfilzomib managed according to local center practice at a large number of transplant centers. Randomized trials in dialysis-dependent and nondialysis CKD populations have previously shown Hb control to be similar with once-month C.E.R.A.