Professor Phil Kalra, Consultant Nephrologist

Iron trial delivers significant results for haemodialysis patients

A major study has given doctors new guidance on how much iron can safely be given to anaemic kidney patients receiving haemodialysis.

The four and a half year PIVOTAL study showed that the higher dose iron treatment significantly reduced the risk of death or nonfatal cardiovascular events. It reduced the risk of heart attack and hospitalisation for heart failure and led to a reduction in dose of erythropoietin and transfusion rate, and there was no increase in infection.

Until now the amount of iron which could safely be given was largely based on anecdotal evidence, with clinicians reluctant to give high doses of iron for fear of causing serious infections, such as pneumonia and sepsis, leading to patients being given less iron and more EPO (the hormone that stimulates the body to produce red blood cells).

Salford Royal’s Professor Phil Kalra co-designed the study, was on the trial steering committee and was Principal Investigator for the study at the dialysis units at Salford, Oldham, Rochdale, Bolton and Wigan. It was facilitated by Kidney Research UK and led by Chief Investigator, Professor Iain Macdougall at King’s College Hospital, London, in partnership with Glasgow University Clinical Trials Unit.

Professor Kalra said: “These results will, for the first time, give healthcare professionals clear guidance on best practice of use of intravenous iron in haemodialysis patients.

“Kidney patients who receive dialysis are deficient in iron because they lose more iron than they absorb from the gut. Added to this, their kidneys no longer produce enough of the red blood cell-forming hormone, EPO.

“All patients are given iron intravenously via their dialysis machines because iron tablets don’t work for them.

“Currently, clinicians use both EPO and iron to treat anaemia in haemodialysis patients. Giving more iron allows us to use less EPO – very high doses of EPO have been associated with an increased risk of cardiovascular events, such as strokes. This is why we like to minimise the EPO dose by giving more iron and the PIVOTAL trial has given us good evidence that this is a safe and beneficial approach.

“Another outcome of the study is a reduction in blood transfusions for those patients receiving high-dose iron. This is potentially positive news as blood transfusions can lead to the production of antibodies, which could increase the likelihood of kidney transplant rejection further down the line.”

‘’We sincerely thank the patients treated at Salford Royal and its satellite dialysis units for their participation in what has proved to be a very successful trial that will change the approach to treatment throughout the world. Our research trials team also deserve special praise for their quality work on the study.’’

More than 70 patients from Salford Royal’s dialysis units took part in the study, making the Trust the fifth highest recruiter of the 50 NHS organisations involved. Altogether more than 2,100 kidney patients took part in the UK.

 In the UK alone, there are 29,000 people receiving dialysis of whom 25,000 are treated with haemodialysis.

It is anticipated that the results of the PIVOTAL trial, which have been published in the highest regarded journal in medicine, the New England Journal of Medicine, will lead to a review of national and international clinical practice guidelines.

Kidney Research UK helped to deliver and drive the study, supported by an unrestricted grant of just under £3.5million from Vifor Fresenius Medical Care Renal Pharma Ltd. The company also provided all the iron for the study, free of charge.