Background This study aimed to evaluate the erythropoietic response to parenteral iron in iron-deficient anaemic patients with normal and impaired kidney function and determine the factors that affect response. Method Recipients of parenteral iron from the CKD and pre-operative clinics of a tertiary kidney centre were evaluated. No patients were receiving erythropoiesis stimulating agents. The key outcome was the change in haemoglobin(∆Hb) defined as the difference between the pre-infusion and post-infusion haemoglobin(Hb) measured within 1- 3 months of iron infusion. Propensity-score matching, and multivariate linear regression adjusted for baseline demographics, comorbidities and iron indices were used to assess response to parenteral iron and the impact of kidney impairment versus the nature of iron deficiency (absolute iron deficiency [AID] vs functional iron deficiency [FID]) on response. Results 732 subjects (834 infusions) were included (mean age 66±17years, 56% females and 87% White). Median haemoglobin rise was significantly lower with lower kidney function (CKD0-2, 13[IQR, 2-23]g/l; CKD3-5; 7[IQR,1-15]g/L, P<0.001). When groups with different degrees of renal impairment were propensity-matched according to whether iron deficiency was due to AID or FID, the severity of renal impairment was no longer a factor affecting haemoglobin response (unmatched [14.2 vs 8.3]g/l, matched[14.1vs13.6] g/L). However, comparing AID and FID after propensity matching for the degree of renal impairment showed a significantly lower response in those with FID (unmatched AID vs FID 16.0 vs 6.6 g/L, matched 14.2 vs 6.6g/L). The multivariate analysis showed a positive association between ∆Hb and body mass index, total iron dose and glomerular filtration rate, whereas a negative association was observed between haemoglobin response and Black ethnicity, Asian ethnicity, diabetes, baseline Hb, mean corpuscular volume, and Functional iron deficiency Conclusion The nature of iron deficiency rather than the severity of CKD has a stronger impact on haemoglobin response with an attenuated response seen in functional iron deficiency irrespective of the degree of renal impairment

Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare and often fatal condition, frequently diagnosed in end-stage renal disease (ESRD) patients. Although exact pathogenesis remains unclear, iron supplementation is suggested as a potential risk factor. Iron and erythropoietin are the main stay of treatment for anaemia in ESRD patients. Few observational studies support the role of iron in the pathogenesis of calciphylaxis although data from the pivotal trial was not strongly supportive of this argument, i.e., no difference in incidence of calciphylaxis between the low-dose and high-dose iron treatment arms. Elevated levels of vascular cell adhesion molecules in association with iron excess were postulated to the pathogenesis of CUA by causing inflammation and calcification within the microvasculature. In-addition, oxidative stress generated because of iron deposition in cases of systemic inflammation, such as those seen in ESRD, may play a role in vascular calcification. Despite these arguments, a direct correlation between cumulative iron exposure with CUA incidence is not clearly demonstrated in the literature. Consequently, we do not have evidence to recommend iron reduction or cessation in ESRD patients that develop CUA.