Residual confounding in the prognostic interpretation of iron deficiency in incident peritoneal dialysis

Dear Editor,

We read with interest the recent article by Rigodon et al. reporting an anemia-independent prognostic value of iron deficiency in incident peritoneal dialysis (PD) patients. ¹ The topic is clinically relevant, and the findings contribute to the ongoing discussion on iron metabolism and outcome stratification in kidney disease. We would like to highlight several issues that may influence the interpretation of the reported association.

First, the definition of iron deficiency in incident PD patients remains challenging. Transferrin saturation and ferritin are affected not only by iron status but also by inflammation, infection, and nutritional condition, all of which are common during the early phase of PD treatment.^2,3 Reliance on baseline iron indices alone may therefore increase the risk of misclassification.

Second, residual confounding deserves careful attention. Iron deficiency may coexist with protein-energy wasting, systemic inflammation, greater comorbidity burden, and poorer functional reserve, ⁴ factors that are themselves associated with adverse outcomes. Accordingly, the observed relationship may not fully represent an independent prognostic role of iron deficiency itself.

Finally, the clinical implications should be interpreted cautiously. Although the findings are hypothesis-generating, an observational association may not yet support more intensive iron intervention, particularly when the balance of benefit and risk may vary across PD subgroups.

We believe this study is valuable and clinically relevant. Future studies incorporating longitudinal iron markers and more comprehensive adjustment for inflammatory and nutritional variables may help clarify the true prognostic significance of iron deficiency in incident PD patients.