1. Imaging in acute kidney injury: how
to kill as few patients as possible
Imaging in acute kidney injury:
Joel Topf, M.D., JACN
Just another clinical neprhologist
Detroit, Michigan, USA
St John Hospital and Medical Center
http://www.PBfluids.com

2. Dopamine
ANZICS Clinical Trials Group. Lancet 2000;356:2139-47
Fenoldopam
Tumlin et al. Am J Kidney Dis (2005) vol. 46 (1) pp. 26-34
Anaritide
Allgren et al. N Engl J Med (1997) vol. 336 (12) pp. 828-34
High dose furosemide
Cantarovich et al. Am J Kidney Dis (2004) vol. 44 (3) pp. 402-9
High intensity dialysis
VA/NIH Acute Renal Failure Trial Network et al. N Engl J Med (2008) vol. 359 7-20

6. Patients with primary diagnosis of AKI have
higher mortality when they are:
admitted on week-ends
admitted to smaller hospitals
James et al. Weekend Hospital Admission, Acute Kidney Injury, and Mortality.
Journal of the American Society of Nephrology (2010) vol. 21 (5) pp. 845-851

7. We just don’t know what
that “good care” looks like
Despite the lack of
evidence
based success,
good care makes a
difference

8. • With out evidence we are left to wander with
only our clinical sense to guide us
– Avoid hypotension
– Maintain urine flow
– Avoid renal toxins
– Maintain electrolyte balance
– Maintain fluid balance

9. • Relate this to imaging
– Avoid contrast induced renal toxicity
– Avoid nephrogenic systemic fibrosis
• With out evidence we are left to wander with
only our clinical sense to guide us
– Avoid hypotension
– Maintain urine flow
– Avoid renal toxins
– Maintain electrolyte balance
– Maintain fluid balance

10. Contrast

11. Hydration
0.9 normal saline
+/- Isotonic bicarbonate
Minimize contrast exposure
Low or isosmolar contrast
+/- N-Acetylcysteine

12. • 2,308 patients randomized to
1,200 mg of N-acetylcysteine
x 4 doses
• No improvement in:
– Contrast induced nephropathy
– Change in Cr
– Need for dialysis
– 30 day mortality or CV mortality
• Sub group analysis looking
at:
– Age
– Creatinine
– Diabetes
– Gender

13. Hydration
0.9 normal saline
+/- Isotonic bicarbonate
Minimize contrast exposure
Low or isosmolar contrast
+/- N-Acetylcysteine
Techniques of particular interest to patients
with acute kidney injury
Dialysis
Hemofiltration

14. Hemodialysis following contrast
• Moon et al first demonstrated the ability to
remove contrast in patients with pre-ESRD
CKD by dialysis
• A 6 hour hemodialysis session was able to
remove 77% of the contrast load
Moon et al. Nephron (1995) vol. 70 (4) pp. 430-7

15. Cr (mg/dL) Diabetes
Contrast
volume (mL)
4.5 DM 470
3.5 DM 980
3.2 177
4.1 377
2.4 259
5.7 313
7.5 97
6.1 DM 176
3.7 DM 227
4.5 377
3.0 476
5.7 DM 264
5.8 237
4.6 38% 340

16. First randomized controlled trial
• N=30
• Cr 2.4 ±0.16
• DM 43%
• 3 hours of HD started 63±6 min after contrast
• Iopental, a low osmolar, non-ionic contrast
• CIN defined as an increase of creatinine of 0.5
mg/dL at 48 hours
Lehnert T, Et al Nephro Dial Transplant. 1998
13(2): 358-62.

17. Dialysis accelerated clearance
dialysis
• At 24 hours
– Dialysis: 89% of contrast was gone
– Control 83% of contrast was gone

18. But didn’t save the kidneys
dialysis

19. Second RCT, 3 times the size
• 113 patients
• Cr 3.5 ± 1 (GFR 21 mL/min)
• 33% diabetes
• Hemodialysis started 120 minutes after
contrast
• 3 hours of HD
Vogt et al. Am J Med (2001) vol. 111 (9) pp. 692-8

20. Solid line: dialysis
Dotted line: control
Contrast Dose (P=0.007)
Control: 143 ±115
Hemodialysis: 210 ±143
Contrast Nephropathy (P=0.35)
Control: 9 (16%)
Hemodialysis 13 (24%)
Hemodialysis (P=0.12)
Control: 3 (5%)
Hemodialysis 8 (15%)

21. Moon initiated dialysis 1.8 hours after exposure
Lehnert initiated dialysis 1 hour after exposure
Vogt initiated dialysis 2 hours after exposure
Could earlier hemodialysis make a
difference?

22. 7 patients with hemodialysis started 10 minutes prior to left heart cath
10 patients with IVF in the control group
No need for further dialysis in either group
No difference in the average serum Cr at 48 hours and 1 week
Frank et al. Clin Nephrol (2003) vol. 60 (3) pp. 176-82

23. Largest dialysis trial
• 424 patients
• 3x the size of Vogt
• Cr 1.3-3.5
• CIN defined as Cr rise of
0.5 at 48-72 hours
• Three arms
– Control 6.1%
– Dialysis 15.9%
– NAC 5.3%
P=0.008
• Cr was not different at
30-60 days
Reinecke H, Fobker M, Wellmann J, Et al. Clin Res Cardiol. 2007 Mar;96(3):130-9.

24. WHAT ABOUT THE WORST OF THE
WORST?
CKD stage 5 not on dialysis
Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20

25. Lehnert
Vogt
• Cr > 3.5
• 90 patients
randomized to dialysis
or usual care
– 4 hours, no UF
– 81±32 min after
contrast (45-180)
• 24 hour CrCl on 4th day
after contrast
Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20
• No ITT analysis
– 8 patient not analyzed
– Insufficient f/u, NSAIDs,
2nd contrast exposure
and NAC, off protocol

26. Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20
Cr and CrCl improved at 4 days

27. Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20
Cr is lower at day 4, peak and D/C

28. 1
14
0
5
2
18
Less temporary and permanent dialysis
Less cases of severe CIN
Lee et al. J Am Col Cardiol (2007) vol. 50 (11) pp. 1015-20

29. Dialysate
Conventional Dialysis
Diffusive Clearance

30. Ultrafilter 3+
liters/hour
Replace all ultrafiltrate
with sterile fluid at ideal
plasma concentrations
CVVH
Convective clearance

31. What about hemofiltration
• Marenzi et al.
– Removal
– Dilution
• 114 patients (Cr = 3,
30% DM) randomized to
– CVVH
• Began 4-6 hours before
contrast, continued for 24
hours
– Hydration
• CIN defined as an Cr
increase >25 % from
base-line
• Emergency dialysis was
protocolized:
– oligouria for more than
48 hours despite use of
more than 1 g of IV
furosemide
Marenzi et al. The prevention of radiocontrast-agent-induced nephropathy by
hemofiltration. N Engl J Med (2003) vol. 349 (14) pp. 1333-40

32. Contrast induced nephropathy
(P=0.001)
control: 28 (50%)
hemofiltration: 3 (5%)
Emergency HD
control: 10 (18%)
hemofiltration: 0
Hospital mortality (P=0.02)
control: 8 (14%)
hemodialysis: 1 (2%)
1 year mortality (P=0.01)
control: 17 (30%)
hemofiltration: 6 (10%)

33. • So the hemofiltration group differed from the
control group by receiving:
– More IVF
– Removal of contrast
– Anticoagulation
– IV Alkali in the form of replacement fluid
– ICU care

34. Follow up study
• 92 patients
• Three protocols
– IVF 12 hours before and after contrast
– CVVH for 18-24 hours after contrast
– CVVH for 6 hours before and 18-24 after contrast
• Designed to isolate contrast removal from
fluid administration
Marenzi G, Lauri G, Campodonico J, et al. Comparison of two
hemofiltration protocols for prevention of contrast-induced
nephropathy in high-risk patients. Am J Med 2006;119:155–162.

35. Contrast
nephropathy
Emergent
dialysis
Hospital
mortality
IVF alone 12/30 (40%) 9/30 (30%) 6/30 (20%)
CVVH after 8/31 (26%) 3/31 (10%) 3/31 (10%)
CVVH before
and after
1/31 (3%) 0/31 (0%) 0/31 (0%)
Between
group analysis
P=0.0013 P=0.002 P=0.03

36. Before and after
IVF

37. Pre/Post hemofiltration was 95%
protective for contrast nephropathy
compared to saline
Pre/Post hemofiltration was 90%
protective for contrast nephropathy
compared to post hemofiltration

38. • So the pre/post hemofiltration group received
– More IVF
– Removal of contrast
– Anticoagulation
– Alkali exposure
– ICU care

39. summary

40. • Hemodialysis is generally considered
ineffective at protecting the kidneys from
CIN
Cruz et al. Am J Kidney Dis (2006) vol. 48 (3) pp. 361-71

41. However…
• Data on the weakest
kidneys was positive
• Hemofiltration has been
effective in two RCTs

42. • Swollen and thickened skin
• Wood-like texture
• Decreased range of motion
• Presenting over days to weeks
Nephrogenic systemic fibrosis
Broome et al. AJR Am J Roentgenol
(2007) vol. 188 (2) pp. 586-92

43. Twenty-four– month mortality was 48% and 20% in
patients with and those without cutaneous changes
of NSF, respectively
Todd et al. Arthritis Rheum (2007) vol. 56 (10) pp. 3433-41

44. Novel Disease
First patients with dermal features suggestive
of scleromyxedema were identified in 1997
(published in 2000)
– Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta
S, LeBoit PE. The Lancet 2000; 356(9234):1000-1
19972001
A follow-up article on the same patient series.
Characterized the histology and identified it as
a novel disease they named Nephrogenic
Fibrosing Dermopathy
– Cowper SE, Su L, Robin H, Bhawan J, LeBoit PE.
Amer J Dermatopathol 2001; 23(5): 383-393

45. 2000-2006
No idea of what triggered NSF
• ACEi
• Sevelamer
• Epoetin
• Ischemia
• Clotting
abnormalities
–Anti-phospholipid
antibodies
• Abnormal Ca-
Phos metabolism
• Trauma
• Acidosis

46. 5Five patients who received
gadodiamide and developed NSF
4Four patients who also received
gadodiamide but did not develop NSF

47. 10 months later

48. …we have not observed a single
case of NSF among patients who
were not exposed to gadodiamide…

49. Boyd et al. Gadolinium deposition in nephrogenic fibrosing dermopathy. Journal of the
American Academy of Dermatology (2007) vol. 56 (1) pp. 27-30

50. Gadopentetate (magnevest) introduced
1988
Gadodiamide (Omniscan) approved
1993
1997
First case of NSF 1997
Galan A, Cowper SE, Bucala R: Nephrogenic systemic fibrosis (nephrogenic
fibrosing dermopathy). Curr Opin Rheumatol 18: 614–617, 2006
Examined two tissue repositories to find unrecognized cases prior to 1997.

51. Co-factor to trigger NSF?
• ACEi
• Sevelamer
• Epoetin
• Ischemia
• Clotting
abnormalities
–Anti-phospholipid
antibodies
• Abnormal Ca-
Phos metabolism
• Trauma
• Acidosis

52. RISK OF NSF FOLLOWING
GADOLINIUM

53. Not all gadolinium are equal
• Gadolinium is insoluble in water and
highly toxic
• For human use gadolinium needs to
be chelated
• All the brands of gadolinium differ in
the nature of the chelation molecule

54. Brand name generic
Class of chelation
agent
K (log dissociation
constant)
Optimark Gadoversetamide
Linear, non-ionic
16.8
Omniscan Gadodiamide 16.9
Vasovist Gadofosveset
Linear, ionic
22.1
Magnesvist Gadopentetate 22.5
Multihance Gadobenate 22.6
Eovist Gadoxetate 23.5
Gadovist Gadobutrol 21.8
Prohance Gadoteridol Cyclic, ionic 23.8

55. Gadodiamide
K=16.9
Gadoteridol
K=23.8
1,000,000x more free, toxic Gd

56. Gadodiamide Gadoteridol
1,000,000x as tall
Mount Elbert 14,440 feet Thickness of an iPod, 0.26 inches

57. 13
23
4.7
2.6
2.2Omniscan
Magnevist
Optimark
Multihance
Prohance
Adapted from data presented at Joint Meeting of
the Cardiovascular and Renal Drugs and Drug Safety
and Risk Management Advisory Committees
Estimated doses (millions)*
The gadolinium matters
*2005-2008 IMS National Sales Perspectives™, Year 2005- 2009
** post marketing adverse events. FDA Office of Surveillance and Epidemiology

58. • 2.4% risk
– 3 patients of 87 who received
123 exposures
– Deo A, Fogel M, Cowper SE. Clin J
Am Soc Nephrol 2007;2:264–7.
• 18% risk
– 18/102 patients exposures to
gadodiamide exposure
– Rydahl C, Thomsen HS,
Marckmann P. Invest Radiol
2008;43:141– 4.
• 0% risk
– 0 of 141 exposures to
gadoteridol (ProHance)
– Reilly RF. Clin J AmSoc Nephrol
2008;3:747–51.
• 30% risk
– 16/54. Prospectively examined
patients for dermatologic signs of NSF
after exposure to gadopentetate
– Todd DJ, Kagan A, Chibnik LB, et al.
Arthritis Rheum 2007;56:3433–41.
• 8.4% risk
– Patients with a GFR <15 mL/min (not
on dialysis) receiving gadolinium
developed NSF
– Prince MR, Zhang H, Morris M, et al.
Radiology 2008;248:807–16.
• 0.05% risk with gadodiamide
• 0.002% risk with gadopentetate
– Used all MRI scans as the denominator
– Wertman R, Altun E, Martin DR, et al.
Radiology 2008;248:799 – 806

59. NSF in acute renal failure
• The condition occurs in acute renal failure but
much of the focus has been on chronic dialysis
patients
Todd DJ, Kagan A, Chibnik
LB, et al. Arthritis Rheum
2007;56:3433–41.

60. • Perez-Rodriguez looked at 33 cases of biopsy
proven NSF from a single center
– 7 were AKI (21%)
– 5 subsequently recovered renal function,
– That did not lead to improved symptoms
Perez-Rodriguez J, Lai S, Ehst BD, Fine DM, Bluemke DA 2009 Radiology, 250, 371-377

61. Prince et al. Radiology (2008) vol. 248 (3) pp. 807-16
11 of 15
(73%)patients were
in acute kidney
injury

62. • 4 of 12 cases (33%) from a single institution
were in acute renal failure
• 3 of the 4 were due to hepatorenal syndrome
Broome et al. AJR Am J Roentgenol (2007) vol. 188 (2) pp. 586-92

63. Avoiding NSF
• Because there is no effective therapy for NSF,
avoidance of exposure is the best option
• View the unenhanced images to verify the
need for gadolinium enhancement
• Minimize dose
– avoid MR angiogram
• Low risk gadolinium- containing contrast agent

64. Brand name generic
Class of chelation
agent
K (log dissociation
constant)
Optimark Gadoversetamide
Linear, non-ionic
16.8
Omniscan Gadodiamide 16.9
Vasovist Gadofosveset
Linear, ionic
22.1
Magnesvist Gadopentetate 22.5
Multihance Gadobenate 22.6
Eovist Gadoxetate 23.5
Gadovist Gadobutrol 21.8
Prohance Gadoteridol Cyclic, ionic 23.8

66. • Gadolinium contrast
agents are rapidly
cleared
– half life of 1.3 hours in
healthy volunteers.
– In CKD the half-life can be
extended from 30 to 120
hours.
• 70 dialysis patients, 4
hours hemodialysis
session
Okada S, Katagiri K, Et al. Acta Radiol 2001; 42: 339-341.

67. Prince et al. Radiology (2008) vol. 248 (3) pp. 807-16
14 of 15 patients had
either no dialysis or
delayed dialysis

68. • 33 cases of NSF
– 8 not on dialysis
– 5 on peritoneal dialysis
– 20 on hemodialysis
• 7 received HD on the day of exposure
• 13 unable to determine the timing of dialysis in regards
to gadolinium exposure
Perez-Rodriguez et al. Radiology (2009) vol. 250 (2) pp. 371-7

69. • 3 of 12 cases (33%) received dialysis on the
day of exposure and then daily for three days
• And they developed NSF
Broome et al. AJR Am J Roentgenol (2007) vol. 188 (2) pp. 586-92

70. Recovery of renal function
• Some authors report improvement in
symptoms with improvement in renal function
– Cowper. Am J Kidney Dis (2005) vol. 46 (4) pp. 763-5
• Perez-Rodriguez reported on 5 cases of NSF in
association with renal failure with a liver
transplant.
– Every patient recovered renal function within 6
weeks, none had improvement in NSF
– One patient’s kidney function recovered days prior
to developing skin changes
Perez-Rodriguez et al. Radiology (2009) vol. 250 (2) pp. 371-7

71. Summary
• Nephrogenic Systemic Fibrosis is a devastating
complication
• The risk, in patients with decreased renal
function and inflammatory insults, likely runs
from 5 to 30% following a single Gd exposure
• Though dialysis if suggested as a way to
reduce harm, there are case reports of
patients who have developed NSF despite this

72. Summary
• Avoid gadolinium
• Use safer formulations of gadolinium,
Gadovist, ProHance if necessary

73. DOES ANYBODY HAVE ANY
QUESTIONS?
The big finish