This Delphi panel suggests that ID is a recognized problem also in PD patients. In particular, ID is independent from anaemia and iron status must be investigated in all PD patients, as guidelines generally recommend in CKD patients [1]. Indeed, it is known than ID is related to outcomes in PD patients [14]. However, an universal recommendation about how to measure it and which thresholds consider is still lacking [5]. As the panel answered, the majority of guidelines suggest the combination of ferritin and TSAT as the best tools to assess ID, since ferritin alone can be falsely elevated by the inflammatory status, but also hypochromic red cells and iron are cited [1, 5, 15,16,17,18]. Most commonly, ID should be treated when ferritin < 100 ng/mL and TSAT < 20% [1, 5, 15,16,17,18]: these were the two items with the higher confidence from the panel. However, a ferritin threshold of 200 ng/mL is also considered in haemodialysis patients [19], with less conviction received by the panel. The role of iron itself as a laboratory test is not cited by guidelines about ID management in CKD. However, probably thanks to its availability in most laboratories and the consequent widespread report, no consensus was reached by the panellists about its use in ID. Furthermore, the need of an internal shared protocol is claimed by the majority of respondents, since the common sense in clinical practice is not a valid strategy for them. In fact, since 1996 a consensus paper was published in Taiwan to solve this issue [20]. On the other hand, a greater randomness is expressed by the panel about how frequently search for and follow-up ID. Indeed, guidelines suggest when to test anaemia, but not ID [1, 5, 15,16,17,18]. In particular, the panel was more prone to test every 2–3 months, approaching a consensus. On the contrary, a screening is considered mandatory.
The present Delphi consensus highlights the higher confidence of nephrologists about I.V. than oral iron, focused on tailored targets different from patient to patient. In particular, high dose-low frequency strategy is preferred, which is typical of FCM. In general, the panel felt adequate the currently adopted approach (i.e., high dose-low frequency) for the majority of PD patients, but new molecules such as FCM may improve the logistics and the clinical response. Indeed, this was already demonstrated by Portolés-Pérez et al. in a multicentre retrospective real world study enrolling 91 PD patients: FCM was effective, safe and easy to administer during routine clinical visits, letting 68.6% of patients achieving ferritin levels of 200–800 ng/mL, 78.4% TSAT > 20%, and 62.8% TSAT > 20% and ferritin > 200 ng/mL after 12 months [21]. Ferritin between 200 and 800 ng/mL and TSAT > 20% were considered for drug efficacy. However, a greater variability is present among guidelines in this field, in part caused by the different cut-offs for patients in haemodialysis [1, 5, 15,16,17,18]. TSAT > 20% and ferritin up to 800 ng/mL are now considered safe. The last threshold, however, is more recent and an upper value of 500 ng/mL is the most cited by guidelines [1, 5, 15,16,17,18], as reflected by the agreement received by the panel. This explains the doubts of the panellists about this topic. Vice versa, nephrologists demonstrated a greater knowledge of the most recent trials about heart failure and ID; in particular, FCM reduced rehospitalizations in patients with a recent acute heart failure event [22]. However, when such complex patients are in PD, the panellists felt that their iron management should be shared with cardiologists, instead demanded to them.
ESA administration is crucial for anaemic CKD patients to correct EPO deficiency. On the other hand, ESA treatment increases the iron demand for erythropoiesis [6, 7], and about 90% of ESA-treated patients require iron supplementation to sustain an optimal haematological response to ESAs [8, 9]. Since nephrologists have been using FCM, the relationship and cost-effectiveness of ESAs and FCM itself has become more complex. The panellists agreed that a correct use of FCM can normalize the iron status and probably reduce the waste of costly ESAs, overruling the initially higher cost of FCM itself than other compounds. To summarize, they felt that I.V. iron can be prioritized than ESAs to reach the target haemoglobin also in PD patients, as already suggested by guidelines [1, 5, 15,16,17,18]. In particular, physiologically when the target haemoglobin is reached with iron supplementation and ESA, the last should be reduced, instead of iron stopped as more frequently happens in clinical practice. In addition, as already reported, the iron status in partly independent from the haemoglobin level and should be investigated with different exams (i.e., ferritin and TSAT). Notably, the target haemoglobin varies among guidelines, as reflected by the answers of the panel: values between 10 and 12 g/dL are generally considered adequate in PD since they are more stable than in haemodialysis thanks to a constant volaemia.
Finally, regarding pharmacoeconomic aspect the panel revealed to be quite imprecise, with contrasting answers. While an evaluation of cost-efficacy of I.V. iron, particularly FCM, should be performed, reducing costs and improving clinical outcomes, The panel retained that at the moment the data are already promising and quite reassuring about an advantage among different iron formulations.
Notably, the reduced use of ESAs may overrule the initially higher cost of FCM, but this field should be better investigated.
To the best of our knowledge, this is the first consensus Delphi about a highly specific topic such as ID in PD patients. The board of clinicians felt the necessity to have dedicated recommendations, not borrowed from general CKD guidelines or haemodialysis indications. Indeed, the major strengths of this paper is the rigorous method on its basis and its novelty. In addition, the 25 panellists were chosen among active nephrologists expert in PD. This explains the notable knowledge about iron management to treat ID, probably mediated by the haemodialysis field. Indeed, pharmacoeconomic and organizational aspects are mostly unknown for this kind of clinicians. Finally, being the respondents active in PD centres, the national representativeness on this Delphi is high, since PD centres are not extensively diffuse throughout the Country (Fig. 1).
