In my intern year while on the wards a patient of mine with normal kidney function on admission developed acute kidney injury (AKI) 48 hours after angiography; I thought I was confident about the diagnosis, it had to be from the contrast. That day I went home and read more about the causes of contrast induced-AKI (CI-AKI), only to find out that there is even controversy about its very existence. See this year’s #NephMadness contrast region.
The first report of CI-AKI was in 1954 which described acute anuria developing 48 hours post intravenous administration of Diodone (high osmolar agent). In 1963 Healey et al compared patients with AKI and exposure to contrast in patients with multiple myeloma. In the 1970s reports emerged describing diabetes mellitus as another risk factor for CI-AKI (Diaz-Buxo et al). Later Krumlovsky et al described the association of kidney hypoperfusion, preexisting chronic kidney disease (CKD) and hyperuricemia with CI-AKI.
It was not until the 1980s that prospective studies were published. Most studies were single centered, with less than 200 subjects, using different criteria to define AKI; such as creatinine increase of 0.5 mg/dL, or 25% to 50% increase of creatinine from baseline. Kumar et al reported a 1% incidence of CI-AKI in patients undergoing angiography whereas Teural et al reported a 23.8% incidence with exposure to intravenous contrast. The first controlled study was by Parfrey et al in NEJM in 1989 (220 contrast vs 268 without contrast). They reported a 5.5% incidence of CI-AKI among patients with preexisting CKD and a relative risk associated with contrast exposure of 4.7. In 1990 Rudnick et al studied 1196 patients undergoing cardiac angiography in a randomized, double blinded trial. They reported incidences of AKI of 3.2% and 7.1% after iohexol or diatrizoate contrast, respectively. After this study the low osmolality agents such as Iohexol was used predominantly.
The last year has seen the publication of several important studies. The POSEIDON trial (intraarterial non-ionic low osmolar Ioxilan) was a randomized, single-blind study of 396 patients comparing the impact of different hydration methods on CI-AKI. They reported an overall incidence of 11.4%. Subsequently, the AMACING trial (intravenous and intraarterial non-ionic low osmolar iopromide) studied intravenous hydration versus no prophylaxis in over 600 and found no difference in incidence (2.7%).
Recently two studies have intensified the CI-AKI debate. McDonald et al (Ioxehol if Cr <2 mg/dL or Iodixanol if Cr > 2 mg/dL, low-osmolar and iso-osmolar, respectively) performed a single-center retrospective study of just above 21,000 patients similarly divided between contrast vs non-contrast imaging. Incidence did not vary between groups for all outcomes studied. The biggest study to date is a retrospective study over 7 million patients from the NIS cohort. This study found no increase in CI-AKI risk associated with contrast. Published this year, the PRESERVE trial, was a randomized double-blind placebo study of 5000 patients at high risk for renal complications undergoing angiography. This was a 2×2 factorial design comparing prophylactic IV bicarbonate, IV normal saline and PO acetylcysteine. Incidence of AKI was between 8-10% and there were no between group differences with respect to CI-AKI.
There is no doubt that multiple factors influence AKI risk associated with contrast, such as charge (ionic or non-ionic), chemical structure (monomer or dimer), osmolality (high; 1400-1800 mOsm/kg, low; 600-850 mOsm/kg, iso-osmolar;280 mOsm/kg), viscosity, and contrast volume. The decreased incidences in later reports may be due to preventive measures such as avoidance in high risk patients and lower volumes used. Although recent retrospective studies have shown low incidence or no difference between control groups, we should be cautious about ignoring CI-AKI. New prospective studies using modern practices are needed to improve our understanding of the risks of CI-AKI. In fact, there is a move to change the naming convention from induced to contrast associated AKI (CA-AKI).
Mario Funes, MD @MarioFunesMD
Internal Medicine Resident
Saint Peter’s University Hospital/Rutger’s Robert Wood Johnson University.