Contrast Induced Nephropathy
Last updated 22nd March 2023 - Tom Heaton
The idea of contrast induced nephropathy (CIN) seems to be one of the recurring concerns or questions in the critically ill.
Patients who are critically ill can often have an acute kidney injury (AKI) and may regularly need contrast enhanced imaging to guide diagnosis and management.
This could therefore pose a clinical challenge as to the risk vs benefit balance of the use of contrast.
However, there is great controversy about whether CIN even exists as an entity, and certainly when such a concern is used to prevent valuable clinical information being gained.
Patients who are critically ill can often have an acute kidney injury (AKI) and may regularly need contrast enhanced imaging to guide diagnosis and management.
This could therefore pose a clinical challenge as to the risk vs benefit balance of the use of contrast.
However, there is great controversy about whether CIN even exists as an entity, and certainly when such a concern is used to prevent valuable clinical information being gained.
Definition
Contrast induced nephropathy is commonly defined as an AKI arising within 48 hours of intravascular radiological contrast agent that is not attributable to another cause.
It is interesting to note that there has been some move to change the description to contrast-associated AKI to acknowledge some of the controversies that we will look at.
It is interesting to note that there has been some move to change the description to contrast-associated AKI to acknowledge some of the controversies that we will look at.
Mechanism
The exact mechanism of injury is not well understood.
There appear to be a number of mechanisms attributed to the contrast medium, working to cause different problems.
This includes:
However, there are important differences between the types of contrast agents used.
A common categorisation is based upon their osmolality:
These have clearly different impact on renal dysfunction, with high osmolality contrast agents being well recognised as higher risk.
These are not used anymore for IV contrast.
There appear to be a number of mechanisms attributed to the contrast medium, working to cause different problems.
This includes:
- Interfere with renal vasoconstriction and vasodilation
- Direct toxicity
- Induced diuresis
- Increased urinary viscosity
However, there are important differences between the types of contrast agents used.
A common categorisation is based upon their osmolality:
- High osmolality (approx 1500 mOsm)
- Diatrizoate (Gastrograffin, urograffin)
- Low osmolarity (320-800 mOsm)
- Iohexol (omnipaque)
- Ioversol (Optiray)
- Iso osmolar (290 mOsm)
- Iodixanol (Visipaque)
These have clearly different impact on renal dysfunction, with high osmolality contrast agents being well recognised as higher risk.
These are not used anymore for IV contrast.
Risk Factors
There are a number of risk factors described, with the majority of them simply being recognised vulnerability to any AKI.
These include.
Patient related:
Relating to this, the use of contrast for cardiac catheterisation does clearly seem to be higher risk than system use for CT imaging.
Part of this may also be related to microembolic effects of the intervention, alongside the other factors described above.
These include.
Patient related:
- Preexisting renal disease
- Diabetes
- Hypertension
- Increased age
- CCF
- Cirrhosis
- Hypovolaemia
- Sepsis
- Any nephrotoxins
- High doses
- Intra arterial
Relating to this, the use of contrast for cardiac catheterisation does clearly seem to be higher risk than system use for CT imaging.
Part of this may also be related to microembolic effects of the intervention, alongside the other factors described above.
Clinical Profile
There is usually no change in urine output, purely being seen in renal biomarkers.
The trend here is usually:
The trend here is usually:
- Start rising within 24H
- Peak at 3-5 days
- Resolve within 2 weeks
Management
The management is generally the same as for any other modality of AKI.
More specifically there is a focus on prevention.
General strategies here include:
Intravenous volume expansion remains a key component.
It isn’t clear if the choice of fluid matters here.
The choice of 0.9% NaCl would seem odd given the recognised adverse effects of chloride load on renal function.
Sodium bicarbonate might have some theoretical benefits (reduced formation of free radicals).
A variety of other preventative agents have been described but with limited or controversial evidence.
More specifically there is a focus on prevention.
General strategies here include:
- Alternative imaging modalities
- Non contrast
- MRI, US
- Non contrast
- Reduce dose to minimal
- Low osmolality or non-ionic contrast
- Avoid other nephrotoxins
Intravenous volume expansion remains a key component.
It isn’t clear if the choice of fluid matters here.
The choice of 0.9% NaCl would seem odd given the recognised adverse effects of chloride load on renal function.
Sodium bicarbonate might have some theoretical benefits (reduced formation of free radicals).
A variety of other preventative agents have been described but with limited or controversial evidence.
Controversy
The controversy around the concept of contrast induced nephropathy seems to centre around several ideas.
Many of this questions seem to be reflective of persisting poor research methodology than has inflated the risk of CIN.
It is very difficult to prove a negative and there may be some toxicity.
However, analysis of the research base suggests that there is little evidence for concern.
Different Agents
As noted above, there are a variety of different agents used as IV contrast.
These have different risk profiles which may not be well represented in the mental models of certain clinicians.
It seems clear that high osmolality agents carry higher risk, and hence there lack of current use.
However, the risk profiles vary across the low and iso-osmolar groups.
Iso-osmolar contrast agents appear to be low risk.
Most of the low osmolarity group also appear to be lower risk, with the exception of iohexol and ioxaglate.
Creatinine Rise
A rise in creatinine is a common feature of the type of patients that need a contrast CT scan (e.g. acute abdomen).
It appears there had previously been little work on actually identifying true correlation, never mind causation.
Some recent retrospective propensity matched studies looking at this question have suggested that there is actually no difference between non-contrast and contrast CT studies in terms of risk of renal injury.
One of these, by Davenport et al, suggested a potential contrast link in those with a pre-existing renal impairment (an eGFR <30ml/min).
However, the size of this subgroup (and other methodological limitations) question the strength of this conclusion.
This is especially true when compared with other research of greater strength, such as that of McDonald et al.
This is a major problem given the definition of CIN as requiring the absence of other causes.
This seems to have been forgotten in much of the early research on CIN that seemed to ignore the possibility that creatinine could rise for any other reason (and this in patients who have medical pathology warranting contrast-enhanced imaging!)
Creatinine Rises and AKI
Another concern is that rises in creatinine that are being studied may not actually be reflective of renal injury.
Whilst creatinine is a useful biomarker for monitoring kidney function, it has recognised limitation.
As such, there is incomplete correlation between its trend and renal function.
This is well described in some studies looking at how creatinine levels may just be undergoing fluctuations.
This is because some studies show no change in the average creatine levels of the population studied.
Instead, they showed a similar number of patients with a decrease in creatinine as those with the AKI-level increase, as would be expected from a normal distribution.
This is suggestive of either contradictory mechanisms of effect (causing both AKI and improved renal function) or, more plausibly, that these are actually representing variations in biomarkers rather than end organ effects.
Studies that have looked at more specific biomarkers of renal injury, such as neutrophil gelatinase-associated lipocalin, have not seen this marker rise with contrast.
Clinical Significance
All of this then begs the question as to the actual clinical significance of any renal effects.
Indeed, the general pattern described of CIN is one of a transient rise in biomarkers with a predictable return to normal.
If this is actually relevant to our patients then we need to see some impact on adverse outcomes, such as a need for renal replacement therapy or death.
Again, much of the research has no control group.
Here a CIN does have bad correlation but this is problematic when the interventions themselves are massively confounded (being sick enough to need coronary angiography is associated with worse outcomes).
When this specific question is asked, such as by McDonald, the relationship between AKI and bad outcomes is present but the relationship between contrast administration and bad outcomes disappears.
A recent multi-site retrospective propensity-adjusted analysis by Ehmann and colleagues looked at this specific question for those who actually had an AKI.
This again showed no link between contrast administration and outcomes of concern.
This effect was the same in those that were sick enough to need ICU.
- Newer agents having a different (better) risk profile
- Creatinine rises being related to contrast
- Creatinine rises reflecting AKI
- Clinical significance
Many of this questions seem to be reflective of persisting poor research methodology than has inflated the risk of CIN.
It is very difficult to prove a negative and there may be some toxicity.
However, analysis of the research base suggests that there is little evidence for concern.
Different Agents
As noted above, there are a variety of different agents used as IV contrast.
These have different risk profiles which may not be well represented in the mental models of certain clinicians.
It seems clear that high osmolality agents carry higher risk, and hence there lack of current use.
However, the risk profiles vary across the low and iso-osmolar groups.
Iso-osmolar contrast agents appear to be low risk.
Most of the low osmolarity group also appear to be lower risk, with the exception of iohexol and ioxaglate.
Creatinine Rise
A rise in creatinine is a common feature of the type of patients that need a contrast CT scan (e.g. acute abdomen).
It appears there had previously been little work on actually identifying true correlation, never mind causation.
Some recent retrospective propensity matched studies looking at this question have suggested that there is actually no difference between non-contrast and contrast CT studies in terms of risk of renal injury.
One of these, by Davenport et al, suggested a potential contrast link in those with a pre-existing renal impairment (an eGFR <30ml/min).
However, the size of this subgroup (and other methodological limitations) question the strength of this conclusion.
This is especially true when compared with other research of greater strength, such as that of McDonald et al.
This is a major problem given the definition of CIN as requiring the absence of other causes.
This seems to have been forgotten in much of the early research on CIN that seemed to ignore the possibility that creatinine could rise for any other reason (and this in patients who have medical pathology warranting contrast-enhanced imaging!)
Creatinine Rises and AKI
Another concern is that rises in creatinine that are being studied may not actually be reflective of renal injury.
Whilst creatinine is a useful biomarker for monitoring kidney function, it has recognised limitation.
As such, there is incomplete correlation between its trend and renal function.
This is well described in some studies looking at how creatinine levels may just be undergoing fluctuations.
This is because some studies show no change in the average creatine levels of the population studied.
Instead, they showed a similar number of patients with a decrease in creatinine as those with the AKI-level increase, as would be expected from a normal distribution.
This is suggestive of either contradictory mechanisms of effect (causing both AKI and improved renal function) or, more plausibly, that these are actually representing variations in biomarkers rather than end organ effects.
Studies that have looked at more specific biomarkers of renal injury, such as neutrophil gelatinase-associated lipocalin, have not seen this marker rise with contrast.
Clinical Significance
All of this then begs the question as to the actual clinical significance of any renal effects.
Indeed, the general pattern described of CIN is one of a transient rise in biomarkers with a predictable return to normal.
If this is actually relevant to our patients then we need to see some impact on adverse outcomes, such as a need for renal replacement therapy or death.
Again, much of the research has no control group.
Here a CIN does have bad correlation but this is problematic when the interventions themselves are massively confounded (being sick enough to need coronary angiography is associated with worse outcomes).
When this specific question is asked, such as by McDonald, the relationship between AKI and bad outcomes is present but the relationship between contrast administration and bad outcomes disappears.
A recent multi-site retrospective propensity-adjusted analysis by Ehmann and colleagues looked at this specific question for those who actually had an AKI.
This again showed no link between contrast administration and outcomes of concern.
This effect was the same in those that were sick enough to need ICU.
