Iron Deficiency After Kidney Transplantation

Joanna Sophia J. Vinke; Marith I. Francke; Michele F. Eisenga; Dennis A. Hesselink; Martin H. de Borst


Nephrol Dial Transplant. 2021;36(11):1976-1985. 

In This Article

Iron Supplementation in KTRs

ID can be treated with either oral or IV iron preparations. In the context of CHF and CKD, IV iron supplementation has a superior efficacy to correct iron parameters, compared with oral preparations.[5,110,111] A likely explanation for this phenomenon is that hepcidin, which is increased by inflammation, prevents intestinal iron absorption. Moreover, oral iron supplementation is associated with side effects such as abdominal pain, obstipation or diarrhoea, and compliance is notoriously poor.[112] Furthermore, different studies have demonstrated that oral iron supplements change the gut microbiome in favour of Bacteroides and Enterobacteria at the expense of symbiotic Bifidobacteria and Lactobacilli.[68]Lactobacilli are among the few species that do not rely on iron availability. Human microbiota have a major interaction with the immune system and recent studies in kidney transplantation suggest an important effect of the host microbiota profile on diarrhoea, graft survival, the incidence of infections and metabolism of immunosuppressive medication.[113–115]Vice versa, immunosuppression affects the microbiome. In the first months after kidney transplantation, the microbiota profile shifts in favour of pathogenic bacteria such as Escherichia, Salmonella, Yersinia, Campylobacter and Pseudomonas, while the diversity is significantly reduced.[113,116] The impact of iron on the microbiota after transplantation has not been studied systematically. However, because of overgrowth of the pathogenic species that are known to express siderophores and need iron at the expense of iron-independent Lactobacilli, it could be speculated that intra-intestinal iron supplementation has a detrimental effect on the microbiota in KTRs and that abundance of intra-intestinal iron increases the risk of enteritis or abdominal sepsis. In a small RCT assessing the effects of oral iron supplementation in recently transplanted KTRs, there was no sign of increased infection risk.[117]

The unfavourable effects of oral iron supplements can be avoided by IV iron administration. Although a single dose of oral iron sulphate (210 mg daily) may be as effective as a single dose of 500 mg IV iron polymaltose in patients with anaemia, IV iron supplementation may be more effective when given repeatedly.[32,118,119] FCM and iron sucrose (ISC) injections have been shown to be effective and safe in anaemic or iron-deficient KTRs.[118,120] IV iron supplementation compared with oral treatment did not increase the risk of infection in a study of 102 KTRs.[32] There was a non-significant trend towards less gastro-intestinal side effects in the intravenously treated group.[32]

A potential concern with the IV administration of iron in KTRs is the worsening of hypophosphataemia. Since ID is associated with increased FGF23 concentrations, it might be expected that iron supplementation reduces FGF23 and restores phosphate homoeostasis. Surprisingly, some IV iron preparations, such as iron polymaltose and FCM, are known to induce an acute rise in intact FGF23 and, as a result, a decrease in phosphate levels.[121–125] In a small cohort of 23 KTRs who had received up to 1000 mg FCM, mean serum phosphate concentrations decreased by 0.27 mmol/L on average, although only one patient needed short-term phosphate supplementation.[123] The relationship between use of different IV iron preparations and occurrence of hypophosphataemia needs to be delineated in more detail in future studies.