First do no harm…. What now for contrast-induced AKI prophylaxis?

It has been widely agreed for many years that iodine-based radiological contrast can cause AKI, particularly in those patients who are deemed high risk.  However, as newer research is published, the risk of developing AKI from contrast, may now not be as significant as first thought, with some authors even questioning its existence!  Part of the problem is that many studies in the past, attributed any change in creatinine in the days following contrast exposure, to the contrast, rather than taking into account other factors e.g. critical illness or simply that the creatinine variation seen, was a normal fluctuation.  This may have overestimated the incidence of contrast-induced AKI (CI-AKI).  Also, with greater awareness of AKI and patient risk factors nowadays and the universal use of safer lower osmolar contrast agents, the risk that contrast poses, has reduced even further.

In the CG169 document in 2013, NICE recommended that intravenous volume expansion should be offered as prophylaxis to anyone who was to receive iodinated contrast agents, if they were at increased risk of AKI or had acute illness.1  The recommendations were made to use a regimen of 0.9% saline or sodium bicarbonate.  The exact fluid and fluid rates, unfortunately, were never standardised, with considerable variation seen in prophylactic regimens offered globally.  No proposed prophylactic intervention had ever been compared to that of placebo, with many studies producing conflicting results. Also, patients with low eGFR <30 ml/min/1.73m3 and those who were critically ill, were often excluded from such studies.

In late 2017, the AMACING study compared no CI-AKI prophylaxis to intravenous fluid expansion with 0.9% saline in patients who were high risk for AKI (eGFR of 30-59 ml/min/1.73m3).2  In this single centre study, 660 patients were recruited who received contrast selectively as part of their investigations.  Serum creatinine was observed between day 2 to 6 and day 26 to 35 and compared to baseline pre-procedure.  The results showed that CI-AKI was recorded in 2.6% of the no prophylaxis group and in 2.7% in those who received 0.9% saline hydration.  No difference in outcomes was found between the two groups with no prophylaxis being cost saving through reduced treatment and hospitalisation costs.  No haemodialysis or related deaths occurred within 35 days.  5.5% of patients, however, had complications associated with IV hydration, such as symptomatic heart failure (4.0%), hyponatraemia (0.3%) and arrhythmias (1.2%).  Not receiving prophylaxis was non-inferior and cost saving in preventing CI-AKI compared with IV hydration.

This study prompted an amendment to NICE guidance, which highlighted that routine use of intravenous hydration therapy prior to contrast in high-risk patients (eGFR 30-59 ml/min/1.73m3) may not be beneficial and may inadvertently cause harm through fluid overload.

In another trial, the PRESERVE study recruited nearly 5000 patients from the US, Australia, Malaysia, and New Zealand scheduled to undergo angiography.3  All patients were randomly assigned, in a 2-by-2 factorial design, to receive intravenous 1.26% sodium bicarbonate or 0.9% saline plus oral N-acetylcysteine (NAC) or placebo.  The primary outcome was a composite of death, need for dialysis, or an increase over baseline of at least 50% in serum-creatinine level 90 days post-angiography.  The study concluded that among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral NAC over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of CI-AKI.

What do we do now?   It is likely that routine CI-AKI prophylaxis through intravenous fluid expansion is harmful and costly if done as a ‘blanket rule’ for any patients’ who have risk factors for AKI.  No hydration overall was associated with much less patient morbidity and cost!  It therefore cannot be recommended for use in everyone.  However, CI-AKI probably does exist but is not as prevalent as first thought.  Efforts should still be made to limit contrast exposure if appropriate and to individualise preventative measures to those with multiple risk factors, although more research is needed on what effective preventative measures should be offered!  The PRESERVE study would suggest that there is no role for sodium bicarbonate and/or NAC over saline therapy.

In patients with low eGFR <30 ml/min/1.73m3 and those who are critically ill, it is difficult to know exactly what to do.  Such patients have been excluded from many studies and results cannot be easily extrapolated.  It would be reasonable until further research is conducted, to try and limit contrast exposure to only when necessary and to ensure that critically ill patients are at least euvolemic and that IV hydration is offered peri-procedure using a crystalloid.  In critically ill patients at risk of fluid overload, judicious use of volume replacement is recommended.  Routine AKI preventative measures should still be continued such as good medicines management (e.g. avoiding NSAIDS) and optimising blood pressure.

First do no harm!  In our efforts to reduce or stop CI-AKI, it is such a shame, despite best intentions, that we have this double-edged sword and have inadvertently caused significant harm through fluid overload, which may be worse and more prevalent than the CI-AKI that we are trying to prevent!



1.  National Institute for Health and Care Excellence (NICE).  Acute kidney injury: prevention, detection and management.  Clinical guideline [CG169] Published date: August 2013.

2.  Nijssen EC, Rennenberg RJ, Nelemans PJ, et al.   Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial.  Lancet. 2017 Apr 1;389(10076):1312-1322. doi: 10.1016/S0140-6736(17)30057-0. Epub 2017 Feb 21.

3.  Weisbord SD, Gallagher M, Jneid H, et al. for the PRESERVE Trial Group.  Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.  N Engl J Med 2018; 378:603-614. doi: 10.1056/NEJMoa1710933


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