1. IV contrast and Contrast-Induced Acute Kidney Injury.
Dr Sarah Constantine FRANZCR
The Queen Elizabeth Hospital
University of Adelaide, SA.

2. Contrast-induced acute kidney injury.
CI-AKI is defined as an acute decrease in renal function, occurring within 3 days of administration of iodinated contrast, (in the absence of an alternative aetiology).1
transient event
serum creatinine peaks at approx. 72 hours
slowly returns to normal over 2 weeks
small number will progress to established renal failure
1. RANZCR Guidelines 2009

3. Contrast-induced acute kidney injury.
15% of ICU patients2, 1.5% of unselected patients3
a deterioration in serum markers of renal function after administration of iodinated contrast is very common
almost always an “alternative aetiology” - or compounding factors
How do we know the decline in renal function is due to iodinated contrast?
2. Hoste et al 2011 Intensive Care Med
3. Laskey et al 2007 J Am Coll Cardiol

4. Contrast-induced acute kidney injury.
it doesn’t matter!!
the end result is the same regardless of the cause

5. Other Risks of Poor Renal Function
reduced success of procedures
increased bleeding
increased MI
increased number of deaths
3. Laskey et al 2007 J Am Coll Cardiol

6. Risk Factors for CI-AKI.
advanced age (over 75 years)
pre-existing renal disease
prolonged hypotension (systolic BP less than 80mmHg for 1 hour or more within 48 hours of contrast administration)
congestive cardiac failure
diabetes mellitus
cirrhosis
multiple myeloma

7. Risk Factors for CI-AKI.
dehydration
anaemia
low serum albumin (< 35 g/L)
medications – ACE inhibitors, angiotensin II blockers, NSAIDs, diuretics, nephrotoxic antibiotics eg gentamicin

8. Reducing the risk of CI-AKI.
identify and modify risk factors (where possible)
defer scan
alternative imaging technique
involve renal physicians
monitor renal function

9. SA Renal Network

10. Outpatient Risk Assessment
ask about risk factors
recent serum creatinine/eGFR (within 3 months)
oral hydration if necessary
rebook with more aggressive prevention if necessary

11. Inpatient Risk Assessment
check renal function and risk factors at time of scan request
organise hydration, NAC, cease medication etc
ensure renal function is rechecked within 72 hours post scan

12. 4. SA Renal Network 2010

13. Proven methods of reducing the risk of CI-AKI.
adequate hydration5 – easy, cheap, quick, safe, take care in CCF
volume of contrast6 – use the minimum necessary to obtain a diagnostic scan
5. Balemans et al 2012 Radiology
6. Gurm et al 2011 Am J Coll Cardiol

14. Hydration 747 patients receiving IV contrast
high risk patients hydrated, low risk patients not hydrated
serum creatinine rechecked 3 – 5 days later
incidence of CI-AKI was 2.5%
5. Balemans et al 2012 Radiology

15. Hydration
5. Balemans et al 2012 Radiology

16. Methods of possibly reducing the risk of CI-AKI.
N-acetylcysteine7 – conflicting evidence as to its success, does no harm, expensive
sodium bicarbonate8 – thought to be effective by some authors
7. Sergie 2012 Catheter Cardiovasc Interv
8. Hiremath 2010 Nephrol Dial Transplant

17. Experimental/non-proven methods
statins
ascorbic acid (vitamin C)
β1 blockers
loop diuretics
theophylline
5HT receptor blockers
systemic hypothermia

18. Special Situations: Code Stroke, STEMI
time is critical in this patient group
life potentially at risk
assess risk factors AFTER scan, modify where possible
no significant decreases in renal function in our experience

19. Special Situations: CRF patients
unique group with severe, chronic renal impairment
liase with renal physicians
background renal function may be important in this group
transplant patients

20. Estimating Renal Function
serum creatinine measures the effect of both production (from muscle) and excretion (by the kidneys)
creatinine clearance provides a good estimate of GFR
calculated via the Cockcroft – Gault equation
accuracy has been verified9
not reliable in extremes of body size, rapidly changing renal function eg ARF
9. Faull Aust Presc 2007

21. Calculated GFR and CrCL
Cockcroft-Gault Equation*:
Age = years
Weight = kg
Creatinine = μmol/L
Creatinine clearance =
(mL/min)
(140 – age) x weight
serum creatinine x 0.815
* multiply by 0.85 for females
overestimates GFR in severely impaired renal function (< 20mL/min), unreliable in morbid obesity or severe malnutrition1
9. Faull Aust Presc 2007

22. Estimated Glomerular Filtration Rate
assumes patient is average body size (what is average??)
surface area of 1.73m2, hence the units mL/min/1.73m2
screening tool
overdose small patients, underdose large patients

23. Contrast Dose to Cr Ratio
Cigarroa formula: 5ml per kg divided by serum creatinine (mg/dL)3
in patients with normal renal function, a ratio of 1:1 is considered safe, higher ratios are associated with a higher risk
increasing evidence that this is effective
ratio in Australia : 1 (μmol/L)

24. Why not just use serum creatinine?
creatinine rise from 60 to 120 is still in the normal range, although GFR has halved
as renal function declines with age, an 80 year old with the same creatinine as a 20 year old will have about half the renal function

25. GFR or CrCL? not the same entity
CrCL is an indirect measure of renal function, the rate at which creatinine is removed from the body
CrCL requires blood sample + 24 hour urine collection
GFR is a direct measure of renal function, the rate at which ultrafiltrate is formed by the glomerulus.
GFR requires injection of radioisotope, then 2 blood samples to measure plasma clearance
calculated methods less accurate but more practical
9. Faull Aust Presc 2007

26. Contrast Dose to CrCL Ratio
several studies now published
iodinated contrast has linear pharmacokinetics: systemic clearance of contrast equals glomerular filtration rate
plot serum contrast concentration vs time
area under the curve (AUC) represents systemic exposure (and therefore toxicity)
ratio of contrast dose to eGFR or CrCL approximates AUC10
10. Sherwin et al 2005 Invest Radiol

27. Blood Concentration vs Time11
contrast dose
CrCL
AUC ≈

28. Contrast Dose to CrCL Ratio
several studies now published
iodinated contrast has linear pharmacokinetics: systemic clearance of contrast equals glomerular filtration rate
plot serum contrast concentration vs time
area under the curve (AUC) represents systemic exposure (and therefore toxicity)
ratio of contrast dose to eGFR or CrCL approximates AUC10
10. Sherwin et al 2005 Invest Radiol

29. Contrast Volume to Cr CL Ratio.
Gurm et al 2011 Am J Coll Cardiol

30. Contrast Dose to GFR Ratio.
Nyman et al 2005 Acta Radiol

31. Contrast Dose to Cr CL Ratio
Author
Ratio
Low Risk
High Risk
Laskey et al3
volume
CrCL
Not stated
≥ 3.7
Gurm et al6
< 2
> 3
Altmann et al13
≤ (4%)
> 6 (14%)
Nyman et al12
gm-Iodine
eGFR
< (2%)
> 1 (25%)
Nyman et al14
< (3%)
≥1 (25%)

32. Summary screen patients for CI-AKI risk – history, blood results
consider non-contrast scan, other tests
minimise risk with prevention protocol
HYDRATION is important
role for contrast to renal function ratios?

33. References
RANZCR Guidelines for Iodinated Contrast Administration. March 2009, RANZCR Website.
Hoste EA et al. Epidemiology of contrast-associated acute kidney injury in ICU patients: a retrospective cohort analysis. Intensive Care Med 2011; 37: 1921 – 31.
Laskey WK et al. Volume-to-Creatinine Clearance Ratio. J Am Coll Cardiol 2007; 50: 584 – 90.
SA Renal Network. Protocol For Prevention Of Contrast-induced Acute Kidney Injury, 2010.
Balemans CE et al. Epidemiology of contrast material-induced nephropathy in the era of hydration. Radiology 2012; 263:
Gurm HS et al. Renal Function-Based Contrast Dosing to Define Safe Limits of Radiographic Contrast Media in Patients Undergoing Percutaneous Coronary Interventions. J Am Coll Cardiol 2011; 58: 907 – 14.
Sergie Z, Mehran R. NAC and CIN Prevention: Mounting Evidence of Inefficacy. Catheter Cardiovasc Interv 2012; 79: 927 – 8.
Hiremath S, Brar SS. The evidence for sodium bicarbonate therapy for contrast-associated acute kidney injury: far from settled science. Nephrol Dial Transplant 2010; 25: 2802 – 4.
Faull R, Lee L. Prescribing in renal disease. Aust Prescr 2007; 30: 17 – 20.
Sherwin PF et al. Contrast Dose–to–Creatinine Clearance Ratio as a Potential Indicator of Risk for Radiocontrast-Induced Nephropathy. Invest Radiol 2005; 40: 598 – 603.
DiPiro JT et al. Pharmacotherapy: A pathophysiologic Approach. 7th Edn.
Nyman U et al. Contrast-Medium-Induced Nephropathy Correlated to the Ratio Between Dose in Gram Iodine and Estimated GFR in ml/min. Acta Radiol 2005; 46: 830 – 42.
Altmann DB et al. Use of the Contrast Volume to Estimated Creatinine Clearance Ratio to Predict Renal Failure After Angiography. J Interven Cardiol 1997; 10: 113 – 9.
Nyman U et al. Contrast Medium Dose-to-GFR Ratio: A Measure of Systemic Exposure to Predict Contrast-Induced Nephropathy after Percutaneous Coronary Intervention. Acta Radiol 2008; 49: 658 – 67.