2. Session Name: Proffered papers - CT Scanning
Presentation Title: Efforts to Prevent Contrast-Induced Acute Kidney Injury. Presenter Name: Dr Sarah Constantine FRANZCR The Queen Elizabeth Hospital University of Adelaide, SA.

3. Session Name: Proffered papers - CT Scanning
The presenter has advised that the following presentation will NOT include discussion on any commercial products or service and that there are NO financial interests or relationships with any of the Commercial Supporters of the 2014 Combined Scientific Meeting.

4. Efforts to Prevent Contrast-Induced Acute Kidney Injury.
Dr Sarah Constantine FRANZCR
The Queen Elizabeth Hospital
University of Adelaide, SA.

5. 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

6. RANZCR Guidelines introduced in 2009
provide detailed information for the management of patients with impaired renal function who require iodinated contrast
clinician and radiologist awareness of updated guidelines is variable
Our College has guidelines for the administration of of iodinated contrast.
The current guidelines were formalised in March 2009, and are based on guidelines from other international Colleges, as well as numerous published studies.
They provide detailed, evidence-based guidelines for the management of patients with impaired renal function who require iodinated contrast as part of a radiological study or procedure.
The recommendations have changed over the years, and the awareness of both radiologists and referrers of these changes seems quite variable.
One of the most important changes from the previous guidelines is the use of the estimated glomerular filtration rate which provides a more accurate measure of a patient’s renal function than the serum creatinine alone. This is because it takes into account the patient’s age, gender and race, as well as their serum creatinine level.

7. 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
2. Hoste Intensive Care Med 2011
3. Laskey J Am Coll Cardiol 2007

8. 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

9. 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

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

11. Methods of Risk Reduction in CI-AKI.
adequate hydration4 – easy, cheap, quick, safe, take care in CCF
volume of contrast5 – use the minimum necessary to obtain a diagnostic scan
4. Balemans Radiology 2012
5. Gurm Am J Coll Cardiol 2011

12. The Queen Elizabeth Hospital
350 bed adult teaching hospital
only renal transplant unit in SA until 2010, large renal medicine/dialysis unit
busy emergency department, medical and surgical units, intensive care unit
I work at the QEH, which is a 350 bed adult teaching hospital in the western suburbs of Adelaide, about 10 km from the CBD.
Until recently, the QEH was SA’s only renal transplant hospital, and has a large renal medicine unit, as well as a busy emergency department, medical , surgical and intensive care units.
As such, we are possibly more aware than other Adelaide hospitals of the need to protect renal function in our patient population.

13. Renal Protection Audit 2010
retrospective audit of CT scans in 2010 ( scans, (52%) with IV contrast)
identified patients with eGFR ≤ 60 mL/min/1.73m2 who received contrast (957, 7.2%)
patients on long term dialysis (61) and those who died within 24 hours (2) were excluded
data collected on a total of 894 patients
To evaluate our efforts in preventing CIN, a retrospective audit of CT scans performed in 2010 was undertaken. We have 2 multislice CT scanners which service the hospital inpatients and outpatients, as well as a limited number of referrals from local GPs and specialists.
The patients with an eGFR of 60 or less were identified, who received an intravenous contrast injection as part of their CT scan.
Through a review of the hospital computer systems (OACIS), radiology reports and patient case notes, it was recorded which patients received a renal protection protocol, and the renal function (where available) was recorded at 24, 48 and 72 hours post injection.
Patients on dialysis were excluded as their serum creatinine/eGFR fluctuates wildly with dialysis, and there is usually no concern about preserving any renal function in this group.
Patients who died within 24 hours of their scan were also excluded as there could not be any follow up data.

14. Results
7.2% were contrast scans performed on renally-impaired patients
despite these patients having Stage 3, 4 or 5 Chronic Kidney Disease6, only 18% received renal protection
59% of patients did not have their renal function rechecked within the danger period
7.2% of all CT scans were contrasted scans performed on renally-impaired patients
One third were CT angiograms, which requires a higher contrast load than non-angiographic studies.
Despite these patients having suboptimal renal function (Stage 3, 4 or 5 Chronic Kidney Disease3), only 18% received renal protection.
Renal protection was considered to have been given if: it was reported as such in the radiology report, the renal protection form was filled out and in the case notes, or a reference was made in the medical or nursing notes to renal protection associated with the IV contrast and a corresponding fluid and/or NAC order was filled out.
It was reassuring that a higher percentage of patients receiving a higher contrast dose received renal protection, but the number was still low.
Almost 2/3 of all patients did not have a blood test within 3 days of the scan to recheck renal function.
6. Adair W Clin Radiol 2006

15. Results mean eGFR stable for most groups
very large standard deviations
No renal protection
Renal protection
The mean eGFR in each patient group remained stable over 72 hours, whether renal protection was provided or not.
Amongst the patients in each group, however, there were extreme fluctuations in eGFR, with some patients having a marked drop in renal function, while others showed a marked improvement. I suspect that dehydration had a significant impact in several of these cases.

16. Results
 Serum creatinine ≥ 25%
Renal Protection
Required Dialysis
eGFR 45 – 60
17/601 = 2.8%
2/17 = 11%
eGFR 30 – 44
10/252 = 4%
3/10 = 30%
2 (1 RP)
eGFR < 30
6/41 = 14.6%
3/6 = 50%
2 (no RP)
most patients had numerous risk factors of a decrease in renal function eg sepsis, diabetes
several were also on potentially nephrotoxic drugs eg gentamicin
Although we now use eGFR as a measure of renal function, CIN is still defined in terms of serum creatinine as a rise of 25% or more.
As expected, the high risk group had the most patients whose renal function deteriorated significantly; 15% compared with 4% in group B and 3% in group A.
Renal protection protocols were less protective in the higher risk group than the lower risk group.
Only one patient who had renal protection required dialysis.

17. Results 1 patient died of renal failure 5 weeks after a contrast scan
2 patients became dialysis-dependent after a contrast scan
0.3% of cases studied
1 patient died of renal failure 5 weeks after his contrasted scan. He was also on gentamicin, and was diabetic on metformin. He was in group A with an initial eGFR of 56, and his renal function was not rechecked until 72 hours after his scan, when his eGFR was 17. He did receive renal protection.
1 patient who became dialysis dependent was in group C, with a baseline eGFR of 29.
The other had no past history of renal impairment, but had a long ICU stay for the admission diagnosis of rhabdomyolysis, which was the initial cause of his deteriorated renal function.
Neither of these patients received renal protection.

18. Are doing our best to prevent AKI?
NO!
inadequate renal follow up
under utilization of renal protection
?? overuse of IV contrast
60% of patients do not have their renal function followed up - ? Assumed protection will work
Low number of patients receiving renal protection – partly due to creatinine being used as measure of renal function, giving a false sense of security, especially in the elderly.
Whether IV contrast was indicated, or another test could have been substituted is beyond the limitations of this study

19. Conclusion CI-AKI is a complicated issue
a number of at-risk patients are not being adequately managed
new procedures and a more formalised protocol

20. How Can We Improve?
use eGFR, not serum creatinine as a measure of renal function
Check the eGFR not the serum creatinine for each patient when required.
At the QEH, we are now using this stamp, which is placed in the patient’s case notes, and on the back of the request form. We encourage all radiologists to include this information in the report.

21. SA Renal Network

22. 7. SA Renal Network 2010

23. Possible Risk Reduction in CI-AKI.
N-acetylcysteine8 – conflicting evidence as to its success, does no harm, expensive
sodium bicarbonate9 – thought to be effective by some authors
8. Sergie Catheter Cardiovasc Interv 2012
9. Hiremath Nephrol Dial Transplant 2010

24. Renal Protection Audit 2012
retrospective audit of CT scans in 2012 ( scans, (49%) with IV contrast)
identified patients with eGFR ≤ 60 mL/min/1.73m2 who received contrast (903, 6.9%)
patients on long term dialysis (27) and those who died within 24 hours (4) were excluded
data collected on a total of 872 patients
To evaluate our efforts in preventing CIN, a retrospective audit of CT scans performed in 2010 was undertaken. We have 2 multislice CT scanners which service the hospital inpatients and outpatients, as well as a limited number of referrals from local GPs and specialists.
The patients with an eGFR of 60 or less were identified, who received an intravenous contrast injection as part of their CT scan.
Through a review of the hospital computer systems (OACIS), radiology reports and patient case notes, it was recorded which patients received a renal protection protocol, and the renal function (where available) was recorded at 24, 48 and 72 hours post injection.
Patients on dialysis were excluded as their serum creatinine/eGFR fluctuates wildly with dialysis, and there is usually no concern about preserving any renal function in this group.
Patients who died within 24 hours of their scan were also excluded as there could not be any follow up data. 24

25. Results
 Serum creatinine ≥ 25%
Renal Protection
Required Dialysis
eGFR 45 – 60
28/682 = 4.1% [2.8%]
25/28 = 89% [11%]
[0]
eGFR 30 – 44
16/174 = 9.2% [4%]
10/16 = 63% [30%]
2 (no RP) [2, 1RP]
eGFR < 30
3/20 = 15% [14.6%]
0/3 = 100% [50%]
2 (no RP) [2, no RP]
most patients had numerous risk factors of a decrease in renal function eg sepsis, diabetes
several were also on potentially nephrotoxic drugs eg gentamicin
Although we now use eGFR as a measure of renal function, CIN is still defined in terms of serum creatinine as a rise of 25% or more.
As expected, the high risk group had the most patients whose renal function deteriorated significantly; 15% compared with 4% in group B and 3% in group A.
Renal protection protocols were less protective in the higher risk group than the lower risk group.
Only one patient who had renal protection required dialysis.

26. Results 1 patient died of renal failure 4 weeks after a contrast scan
4 patients had significantly and permanently impaired renal function after a contrast scan
0.5% of cases studied
1 patient died of renal failure 5 weeks after his contrasted scan. He was also on gentamicin, and was diabetic on metformin. He was in group A with an initial eGFR of 56, and his renal function was not rechecked until 72 hours after his scan, when his eGFR was 17. He did receive renal protection.
1 patient who became dialysis dependent was in group C, with a baseline eGFR of 29.
The other had no past history of renal impairment, but had a long ICU stay for the admission diagnosis of rhabdomyolysis, which was the initial cause of his deteriorated renal function.
Neither of these patients received renal protection.

27. Renal Protection Audits
did not take into account the indications for scanning
decision to give contrast was based on the clinical indication and patient’s renal function combined

28. Results similar numbers of patients scanned in each year
patient group was slightly older in 2012 (mean age 76 years vs 74 years 2010)
around 40% of all patients were referred by 3 units: haematology/oncology, urology, vascular surgery

29. 2012 group was lower risk over all than 2010 group
There were far fewer patients in the high and very high risk groups in 2012.

30. Results
after the introduction of a targeted renal protection protocol, there was a very significant increase in the number of patients being pre-hydrated (80% vs 19%)
more patients had their renal function rechecked after contrast administration
25% of high or very high risk patients still did not have their eGFR rechecked

31. Results
the use of the renal protection protocol was found to be efficacious in those patients with an eGFR of < 50 (p = 0.008)
there was no efficacy in those with an eGFR of 50 and over unless they were hypotensive
the most significant risk factors for developing AKI were hypotension (P< 0.001) and CCF

32. Results
4% of patients in 2010 and 7% of patients in 2012 developed AKI
almost all of these patients had unstable renal function prior to contrast administration

33. Literature Review
750 patients with an eGFR < 60 who had an iodinated IV contrast scan
they found IV hydration to be effective in protecting against AKI
they also identified heart failure, low BMI and repeated doses of contrast to be significant risk factors
4. Balemans Radiology 2012

34. Literature Review
compared contrast and non-contrast scans in , using propensity score analysis to remove selection bias
they found patients to be at risk of AKI only if their serum creatinine was > 130
no association with the volume or concentration of contrast
they also identified unstable renal function (improving AND declining) and loop diuretics as significant risk factors
10. Davenport Radiology 2013

35. Literature Review
contrasted CT scans in patients with stable renal function
they found that using the eGFR measurement was more reliable than serum creatinine measurements for screening patients at risk of AKI
11. Davenport Radiology 2013

36. Recommendations screen all patients referred for contrasted CT
history of renal disease
history of cardiac impairment
history of diabetes
patient age 75 years and older
if no history of the above, then a biochemical renal function screen is not necessary

37. Recommendations
eGFR check for patients with any of the 4 main risk factors
utilise the “risk score” to determine level of hydration/renal protection required
liase with referrers to ensure renal function is checked within 72 hours of contrast administration

38. Contrast Dose to Cr Ratio
Cigarroa formula3: 5ml/kg
Cr (mg/dL)
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)
3. Laskey J Am Coll Cardiol 2007

39. Contrast Dose to GFR Ratio.
iodinated contrast has linear pharmacokinetics: systemic clearance of contrast equals glomerular filtration rate
12. Nyman Acta Radiol 2005

40. Contrast Dose to Cr CL Ratio
Author
Ratio
Low Risk
High Risk
Laskey et al3
volume
CrCL
Not stated
≥ 3.7
Gurm et al5
< 2
> 3
Altmann et al13
≤ (4%)
> 6 (14%)
Nyman et al12
gm-Iodine
eGFR
< (2%)
> 1 (25%)
Nyman et al14
< (3%)
≥1 (25%)

41. Results “safe” ratio was not able to be determined low contrast doses
lack of biochemical follow-up data

42. Contrast Dose vs Creatinine Clearance

43. 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?

44. Future Directions further investigation of the “safe” contrast dose
does CI-AKI really exist?
3 recent high quality papers suggesting the relationship is coincidental rather than causal
15. McDonald R Radiology 2013
16. McDonald J Radiology 2013
17. McDonald J Radiology 2014

45. 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.
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.
Adair W, Harris K, Entwisle J. Use of estimated eGFR values to identify patients at risk from iodinated contrast induces nephropathy. Clin Radiol 2006; 61: 714 – 715.
SA Renal Network. Protocol For Prevention Of Contrast-induced Acute Kidney Injury, 2010.
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.
Davenport MS et al. Contrast Material–induced Nephrotoxicity and Intravenous Low-Osmolality Iodinated Contrast Material: Risk Stratification by Using Estimated Glomerular Filtration Rate. Radiology 2013; 268: 719 – 728.
Davenport MS et al. Contrast Medium–induced Nephrotoxicity Risk Assessment in Adult Inpatients: A Comparison of Serum Creatinine Level– and Estimated Glomerular Filtration Rate–based Screening Methods. Radiology 2013;269: 92 – 100.
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.
McDonald RJ et al. Intravenous Contrast Material–induced Nephropathy: Causal or Coincident Phenomenon? Radiology 2013; 267: 106 – 118.
McDonald JS et al. Frequency of Acute Kidney Injury Following Intravenous Contrast Medium Administration: A Systematic Review and Meta-Analysis. Radiology 2013; 267: 119 – 128.
McDonald JS et al. Risk of Intravenous Contrast Material–mediated Acute Kidney Injury: A Propensity Score–matched Study Stratified by Baseline-estimated Glomerular Filtration Rate. Radiology 2014; 271: 65 – 73.