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NIHR Signal Iron deficiency in people with chronic kidney disease can be managed with either oral or IV therapy

Published on 4 June 2019

doi: 10.3310/signal-000773

For people with chronic kidney disease who are also iron deficient, intravenous iron improves haemoglobin levels and iron stores faster than oral iron. However, the evidence is inconclusive about whether it influences survival, cardiovascular death, or quality of life. Adverse effects and such as allergic reactions or gastrointestinal side effects and other practicalities are likely to determine the choice of a route of administration.

Chronic kidney disease is a long-term condition categorised into five stages as the kidneys progressively lose function. Anaemia is common and can be made worse by iron deficiency. When levels are low, there is uncertainty about which form of iron therapy brings greatest benefit.

This Cochrane review update included 39 trials comparing intravenous to oral iron therapy in both adults and children with chronic kidney disease.

The findings support existing NICE guidance regarding the choice of route for iron therapy for people with CKD.

  •   Child Health, Haematological and immunological disorders, Medicines, Renal and urogenital disorders, Acute and general medicine
Iron deficiency in people with chronic kidney disease can be managed with either oral or IV therapy

Why was this study needed?

Around three million people have chronic kidney disease in the UK, and about 61,000 of these have kidney failure (stage 5 disease).

Anaemia is twice as likely for people with chronic kidney disease as the general population, and for those with kidney failure over half will be anaemic. Chronic kidney disease impairs production of red blood cells, and the problem is often exacerbated by iron deficiency.

This review update adds a further 11 studies to the previous review from 2012. The researchers aimed to assess potential benefits and harms of intravenous and oral iron therapy for people with chronic kidney disease. This update brings an increased focus on patient-centred outcomes such as quality of life.

What did this study do?

In this systematic review, researchers looked at 39 randomised and quasi-randomised controlled trials (3,852 participants). These trials compared intravenous and oral iron therapy in adults and children with stages 3 to 5 disease, including some trials with patients on haemodialysis. There was considerable variation in the formulations and doses of intravenous and oral iron preparations used. Follow up lasted from 35 days to 26 months.

The review’s primary outcomes were death from any cause, cardiovascular death, and quality of life.

Certainty around these outcomes is limited by the quality of included studies, short durations of treatment and follow-up, and the lack of inclusion of patient-centred outcome measures in many of the studies.

What did it find?

  • Deaths from all causes during the trial periods were not found to be different, between patients given intravenous (3.3%) and oral iron therapy (3.1%) (risk ratio [RR] 1.12, 95% confidence interval [CI] 0.64 to 1.94;).
  • Cardiovascular deaths during the trial periods were not found to be different between intravenous (3.4%) and oral iron therapy (2.0%) groups (RR 1.71, 95% CI 0.41 to 7.18).
  • Quality of life was not found to be different between the two groups.
  • Target haemoglobin levels were more likely to be achieved by people receiving intravenous (54%) than oral iron therapy (32%) (RR 1.71, 95% CI 1.43 to 2.04).
  • Allergic reactions or low blood pressure were three times as likely in those receiving intravenous (2.4%) than oral iron therapy (0.7%) (RR 3.56, 95% CI 1.88 to 6.74).
  • Gastrointestinal adverse effects were less common with intravenous than oral iron therapy, particularly constipation which was one third as likely, occurring in 3% compared with 11% on oral iron (RR 0.32, 95% CI 0.18 to 0.57).

What does current guidance say on this issue?

The NICE 2015 guideline and 2017 treatment pathway recommend that for anaemic patients with chronic kidney disease, iron therapy should be offered before erythropoietic stimulating agents are considered for treating anaemia.

The guidelines recommend taking account of patient choice following discussion or the risks and benefits of treatment options. Generally, for people not receiving haemodialysis oral iron should be the first line therapy, with intravenous therapy offered if this is not tolerated or target haemoglobin levels are not reached within three months. For people who are receiving haemodialysis, intravenous iron should be the first line therapy.

What are the implications?

This review found no evidence of a difference in patient-centred outcomes between people with chronic kidney disease receiving intravenous or oral iron therapy. Doubts remain over the relative benefits for patients in terms of overall deaths, deaths caused by heart disease and quality of life.

There were greater improvements in haemoglobin levels and laboratory iron markers when using intravenous iron. Intravenous iron therapy led to more allergic reactions but fewer gastrointestinal side effects than oral therapy.

The findings are in keeping with existing NICE guidance. An approach balancing risks of adverse effects and the practicalities of delivering intravenous and oral iron therapy continues to be appropriate.

Citation and Funding

O'Lone E. L., Hodson E.M., Nistor, I et al. Parenteral versus oral iron therapy for adults and children with chronic kidney disease. Cochrane Database Syst Rev. 2019;(2):CD007857.

No external funding sources were reported.

Bibliography

NICE. Chronic kidney disease: managing anaemia. NG8. London: National Institute for Health and Care Excellence; 2015.

NICE Pathways. Managing anaemia in people with chronic kidney disease. London: National Institute for Health and Care Excellence; 2017.

NHS Choices. Chronic Kidney Disease. London: NHS England; 2016.

Kidney Care UK. Anaemia. Alton: Kidney Care UK; 2019.

Kidney Care UK. Facts and Stats. Alton: Kidney Care UK; 2019.

Expert commentary

This Cochrane review provides reassurance to clinicians and patients that IV iron is effective at least in improving laboratory markers of anaemia and iron deficiency.

Questions remain about cost-effectiveness and tolerability of both oral and IV therapies. It seems reasonable to continue the widespread practice of administering IV iron when haemodialysis patients attend their dialysis unit regularly.

It remains less clear whether IV iron is cost-effective and preferable to patients who do not attend hospital so frequently, such as patients with chronic kidney disease who do not receive dialysis and patients treated with peritoneal dialysis. These groups require further study.

Mark Devonald, Consultant Nephrologist, Nottingham University Hospitals NHS Trust

The commentator declares no conflicting interests

Definitions

A blood test called eGFR (estimated glomerular filtration rate) indicates roughly how well the kidneys are working to filter out waste from your blood. This function of your kidneys is categorised into five stages of chronic kidney disease.

Stages from 1 to 5 indicate a range on this blood test result:

  • Stage 1 indicates a normal eGFR (above 90ml/min), but other tests have detected signs of kidney damage
  • Stage 2 indicates a slightly reduced eGFR (60-89ml/min), with other signs of kidney damage
  • Stage 3a indicates an eGFR of 45-59ml/min
  • Stage 3b indicates an eGFR of 30-44ml/min
  • Stage 4 indicates an eGFR of 15-29ml/min
  • Stage 5 indicates an eGFR below 15ml/min, meaning the kidneys have lost almost all of their function. Patients with this kidney function will usually need the support of haemodialysis or transplant