An insight into contrast induced nephropathy

1. “Prevention is easier than solving
the problem”
An insight into contrast induced
nephropathy
Dr. Buddhika Illeperuma
Senior Registrar in Nephrology

2. Questions to be answered
1. What is contrast induced nephropathy ?
2. How significant is the problem in routine clinical practice ?
3. Can it be prevented ?
4. Is it difficult to treat once occurred ?

3. Contrast induced nephropathy (CIN)
Why CIN is an important topic?
• 3rd most common cause of hospital-acquired renal dysfunction after
surgery and hypotension.
• Contrast related investigations and therapeutic procedures are utilized
widely and incidence of CIN is on the rise
• Some patients require renal replacement temporarily

4. Contrast induced nephropathy (CIN)
Why CIN is an important topic?
• There are preventable and modifiable risk factors
• In established CKD patients, CIN may cause progression of CKD
• Known to cause excessive mortality rates, independent of other risk
factors.

5. DEFINITION
Impairment of renal function measured as either a 25% increase in serum
creatinine from baseline or a 0.5 mg/dL (44 µmol/L) increase in absolute
serum creatinine value, within 48-72 hours after intravenous contrast
administration, in the absence of other identifiable cause*
*Contrast-induced nephropathy:Definition, epidemiology, and patients at risk. Mehran R. et
al.Kidney International,Vol 69 ,S11-S15

6. History and Epidemiology
• Fatal AKI occurred in patients with myeloma related renal disease
following intravenous pyelography (1950s)
• Incidence among moderate diabetic CKD patients was 9–40% and severe
CKD 50–90% *
• These figures are from the era which used ionic hyperosmolar contrast
agents which are obsolete in current clinical practice.
* Harkonen S, Kjellstrand CM. Exacerbation of diabetic renal failure following intravenous pyelography. Am J
Med 1977; 63:939 –946

7. Epidemiology in 21st century
• Among patients who have no risk factors (particularly no CKD), the risk of
contrast nephropathy is negligible ( < 1%)*
• Among at-risk patients (especially those with diabetes and CKD), the
reported risk following coronary angiography with or without intervention
is 10 to 30 percent.**
* Wilhelm-Leen E, Montez-Rath ME, Chertow G. Estimating the Risk of Radiocontrast-Associated Nephropathy.
J Am Soc Nephrol 2017; 28:653.
** Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N
Engl J Med 2003; 348:491.

8. Pathophysiology

9. Clinical features of CIN
• Rise in serum creatinine and, less commonly oliguria.
• Serum creatinine rise within the first 24 h in 80% of cases (PRINCE Study
1999)
• Serum creatinine typically peaks in 3–5 days and returns to baseline or
near baseline within 1–3 weeks.
• Relatively rapid recovery of renal function compared with other types of
ATN ( Due to less severe tubular necrosis)

10. Reversible !! Why so much fuss?
• 20% suffer persistent worsening of renal function after CM exposure
• Five times higher in-hospital mortality shown in observational studies
• Approximately four times higher mortality rates at 1 and 5 years with
some demonstrating 1-year mortality rates of between 20%and 38%.
Rear R, Bell RM, Hausenloy DJ Contrast-induced nephropathy following angiography and cardiac interventions
Heart BMJ 2016;102:638-648.

11. Reversible !! Why so much fuss?
• CKD patients with small amount of residual renal function might need
initiation or increasing the required frequency of dialysis.
• In AKI, contrast media may jeopardize the reversal of renal impairment.
• Risks should be weighed against the likely diagnostic benefit of contrast
administration.
• Those with true dialysis dependent ESKD, may tolerate contrast studies
without much issues.

12. Risk factors

13. Contrast medium and CIN
• Non ionic low/iso-osmolar media are proven to be less nephrotoxic.
• Iohexol is the universal contrast medium used in Sri Lankan setup.
• Lower doses (<125 mL) of contrast are proven to be safer.*
• Average volumes used
Contrast CT 50-60ml
Angiographies ( Cerebral/Celiac/aortic) 100-120ml
Coronary angiography < 50ml
Coronary intervention Average 250ml
(Can go up to 400-500ml)
• Intra-arterial injection poses higher risk than intra-venous.**
*Cigarroa RG, Lange RA, Williams RH, et al. Dosing of contrast material to prevent contrast nephropathy in patients with renal disease. Am J
Med 1989; 86: 649–652.
**Byrd L, Sherman RL. Radiocontrast-induced acute renal failure: a clinical and pathophysiologic review. Medicine 1979; 58:270 –
279

14. Diagnosis of CIN
• Demonstration of typical timing of onset with the exclusion of other
causes of AKI
• Classic findings of muddy brown granular and epithelial cell casts and free
renal tubular epithelial cells.
• Absence of these urinary findings does not exclude the diagnosis.
• Presence of WBCs, WBC casts, dysmorphic RBCs, or RBC casts suggests
causes other than CIN.
Eg : Interstitial nephritis / Glomerulonephritis

15. Prevention of CIN – Pathophysiological basis

16. Suggested preventive measures and
mechanisms of action
1. Use the lowest possible dose of CM
2. Use non ionic iso-osmolar CM
3. Prevent renal vasoconstriction
Stopping NSAIDS, ACE inhibitors and ARBs
4. Reduce blood viscosity & increase renal blood flow
Prevent dehydration, Intravenous fluid (Isotonic saline/isotonic
sodium bicarbonate) administration
5. Counteract reactive oxygen species
N-Acetyl cysteine, Sodium bicarbonate

17. IV fluids in prevention of CIN
• Standard of care, though not proven by large RCTs.
• Number of studies done to compare between different fluids and
combinations show a significant benefit from IV fluids.
• Both 0.9% saline and 1.26% sodium bicarbonate are equally effective and
recommended in KDIGO guidelines 2012.

18. IV fluids in prevention of CIN
Dose
• No clear evidence from the literature to guide optimal rate and duration of
fluid infusion.
• Usual recommended regime is to give fluids 1ml/kg/hr 6-12 hours
preprocedure, intraprocedure, and for 6 to 12 hours postprocedure.
• In patients with advanced kidney disease or heart failure, fluid treatment
would be difficult.
• Left ventricular end diastolic pressure guided fluid therapy was proven to
be better in POSEIDON trial (May 2014)

19. PRESERVE trial (Prevention of Serious Adverse Events
Following Angiography) November 2017

20. PRESERVE trial
• Largest trial ever tested sodium bicarbonate and acetyl cysteine with
isotonic saline.
• Double-blind, placebo and comparator-drug–controlled, randomized trial
• eGFR of 15 to 44.9 ml/min or 45 to 59.9 ml/min among those with
diabetes mellitus
• 4993 patients
• No difference was shown in saline vs bicarbonate arm or NAC vs placebo
arm

21. N-Acetyl cysteine in prevention of CIN
• Both oral and intravenous forms are tested in number of studies with
inconsistent results.
• Side effects of IV NAC are unacceptably high to use as a prophylactic agent
and not recommended in KDIGO guidelines 2012.
• Combination of NAC with IV fluids has not shown benefits in PRESERVE
trial.

22. AMACING TRIAL - April 2017
• 660 patients with eGFR 30-59 randomized into saline and no treatment
groups.
• No difference of CIN in both groups.

23. Limitations of AMACING trial
• Relatively small number of patients
• Less severe baseline CKD
• Relatively healthy outpatients presenting for elective imaging would have
been a relatively well hydrated group.
• Usage of relatively low volumes of contrast media
• Relatively low incidence of AKI within control group

24. Prevention of CIN
Other measures
1. Prophylactic hemofiltration and hemodialysis
• A 2012 meta-analysis assessing eight studies of prior hemodialysis and
three studies of prior hemofiltration showed no benefit.
• Number of studies failed to show benefit from immediate dialysis
after intravascular contrast media administration
• KDIGO guidelines 2012 advises against.

25. Prevention of CIN
Other measures
2. Withholding ACE inhibitors and/or ARBs
• Some studies suggested higher risk compared with those who are not
• Other studies show no such evidence.
• Decision depends on clinical judgment

26. Take home messages
• Patients with near-normal renal function are at low risk
• Risks of CIN are beyond renal function worsening.
• For at-risk patients intravenous normal saline hydration is recommended
• Correct modifiable risk factors like anemia, hypoalbuminemia and
hypotension before elective procedures.
• Consider non contrast modalities or methods to minimize contrast volume
in those with advanced CKD.

27. Questions to be answered
1. What is contrast induced nephropathy?
2. How significant is the problem in routine clinical practice?
3. Can it be prevented ?
4. Is it difficult treat once occurred?