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Prevention of Contrast-Induced
Nephropathy (CIN)
Sepehr Khashaei, MD
Assistant professor
Department of Internal Medicine
What will be covered today?
• Definition of CIN
• Why is prevention of CIN important?
• Some other information/statistics about CIN
• Who is at high risk for CIN?
• Information and conclusions based on
outcomes from clinical trials
• Simple measures for prevention
• Cost to patients.
• References.
• Questions and discussion.
Please save all your
questions and
discussions for the end.
Definition of CIN
• CIN is defined as an increase in baseline serum
creatinine level of 25% or an absolute increase
of 0.5 mg/dL, 2 to 5 days after radiocontrast
administration.
Why is prevention of CIN important?
• Radiocontrast administration is a common cause of
hospital-acquired acute renal failure (10% of cases).
• In its severe form, CIN is associated with clinically
significant morbidity and mortality, including
prolonged hospitalization, requirement for dialysis, and
an increased risk for death.
• CIN increases the costs of medical care by at least
extending the hospital stay.
• There is no specific treatment once CIN develops, and
management must be as for any cause of ATN, with
focus on maintaining fluid and electrolyte balance. The
best treatment of CIN is prevention.
Some other information/statistics
about CIN
• Individuals with pre-existing renal
insufficiency and diabetes are much more
likely to experience contrast-induced
nephropathy.
• Typically, serum creatinine levels begin to
increase at 48-72 hours, peak at 3 to 5 days,
and return to baseline within another 3-5
days.
• In most cases there is no permanent sequelae.
Some data from 2004
• More than a million radiocontrast procedures
were performed annually.
• Incidence of CIN was 150,000/yr.
• 1% of CIN required dialysis and caused
prolongation of hospital stay to an average of
17 days.
• For episodes that did not require dialysis,
there was prolongation of hospital stay by 2
days on an average.
Total CT scans with contrast
done in 2009 at all UNM
facilities where 18,350.
Who is at high risk?
• Patients with GFR <60 ml/min particularly if
diabetic.
• UNM radiology department uses a creatinine
of >1.0 for a female and >1.3 for a male as
definition of a high risk patient.
Proposed interventions studied in
literature
• Saline hydration
• Diuretics
• Mannitol
• Intravenous bicarbonate
• Saline plus Mannitol
• Saline plus diuretics
• Oral hydration
• Calcium channel antagonists (i.e. nifedipine)
• Theophylline
• Endothelin receptor antagonists
• Dopamine
• Fenoldopam (dopamine-1 receptor)
• Antioxidant N-acetylcysteine
• Iso-osmolar or low-osmolal contrast agents
• Hemodialysis
• Hemofiltration
• Use of MRI in place of CT
• Atrial natriuretic peptide
• Statins
• Ascorbic acid
Simple measures for prevention
• The use of lower doses of contrast.
• Avoidance of repetitive contrast studies that
are closely spaced (within 48-72 hours).
• Avoidance of volume depletion
• Avoidance of NSAIDS
• Avoidance of nephrotoxic drugs
Information and
conclusions based on
outcomes from
clinical trials
• Patients with near-normal kidney function are
at little risk for CIN (about 3%) and few
precautions are necessary other than
avoidance of volume depletion.
• The patients at increased risk for contrast-
induced nephropathy are diabetics (especially
insulin-dependent diabetics) and patients with
underlying renal insufficiency (12-50%
incidence).
• The effects of poor hydration and the volume
of contrast medium administered are less
clear but are possible risk factors.
• Risk factors may be additive.
• The risk for CIN does not appear to be
influenced by the patient’s age or sex.
• Absence of risk factors does not preclude the
development of CIN.
• Although theoretically beneficial, there is little
evidence in support of vasodilators (such as
nifedipine, captopril, prostglandin E, low-dose
dopamine, fenoldopam, endothelin receptor
antagonists, and theophylline) in reducing risk
of CIN.
• Infuse NS (Grade 1B) at a rate of 1ml/Kg per
hour starting at least two and preferably 6-12
hours prior to the procedure, and continuing
for 6 to 12 hours after contrast administration.
The duration of administration of fluid should
be directly proportional to the degree of renal
impairment (e.g., should be longer for
individuals with more severe renal
impairment). Dose should be adjusted
depending on patient’s underlying medical
condition and their level of hydration.
Hydration with NS was superior to 1/2NS at
least in one clinical trial.
• Intravenous hydration is superior to oral
hydration. Oral hydration with water alone
should not be used.
• Use, if possible, ultrasonography, MRI without
gadolinium contrast, or CT scanning without
radiocontrast agents.
• Based on limited literature, it is difficult to be
certain that gadolinium used in MRI scanning
is completely free of nephroxicity in high-risk
patients. Also, gadolinium-based imaging
should not be performed, if at all possible, in
patients with GFR <30 ml/min because of risk
of nephrogenic systemic fibrosis. In such
patients, if a contrast study is necessary, use
of low-osmolar or isoosmolar iodinated
contrast media, using all the preventive
measures that are available, is preferred.
• Oral acetylcysteine administed as 1200mg
twice daily the day before and the day after
the procedure (Grade 2B). Do not use iv
acetylcysteine for prevention of CIN (Grade
2B).
• Do not use mannitol or other diuretics
prophylactically (Grade 1B).
• However, diuretics may be required to treat
volume overload.
• Do not use high osmolal agents (1400 to 1800
mosmol/KG) (Grade 1A).
• Use nonionic isoosmolar agents such as
iodixanol (Visipaque) or nonionic low-osmolal
agents such as iopamidol (Isoview) (Grade 1B)
if a contrast study is necessary.
Low or iso-osmolar nonionic contrast
• Decreased incidence of CIN.
• Cost reductions
• Increased patient tolerability
• Decreased hypersensitivity reactions
• The benefit is higher in diabetics with renal insufficiency
• Now administered for the majority of radiologic procedures
that use iv contrast media.
• There appears to be little or no advantage in the prevention
of CIN when compared to ionic hyperosmolar agents in
patients with normal renal function.
• At UNM we use iopamidol (a low-osmolar non-ionic agent)
on all adults who have contrast studies regardless of their
GFR.
• Among patients with stage 3 and 4 CKD do not
perform prophylactic hemofiltration (see
below) or hemodialysis (Grade 1B).
• Hemofiltration is expensive, logically
cumbersome and associated with significant
risks, its effectiveness compared to other less
expensive strategies is not well established,
and the reported benefits are implausible.
Therefore currently prophylactic
hemofiltration is not recommended.
• Among patients with stage 5 CKD, most
suggest hemodialysis after contrast exposure
if there is already a functioning access (Grade
2C) (although there is lack of sufficient data).
Do not place a temporary access for
prophylactic hemodialysis in these patients.
• The effectiveness of sodium bicarbonate
treatment to prevent CIN remains uncertain.
Earlier reports probably overestimated the
magnitude of any benefit, whereas larger,
more recent trials have had neutral results.
Large multicenter trials are required to clarify
whether sodium bicarbonate has value for
prevention of CIN before routine use can be
recommended.
Cost to patients
• One bag of NS (1000cc) = $40.00
• 1200mg of acetylcysteine = $5.00
• One day on 4-W = $5,489 (Medicine Subacute)
• One day on 4-E = $7,129 (Med/surg Subacute)
• One day on 4-S = $6, 863 (Orthopedics)
• One day on 5-W = $ 4,049 (General Medicine)
• One day on 5-S = $6,152 (NeuroScience)
• One day on 6-S = $7,580 (General Surgery)
• One day on 7-S = $8,517 (Cardiothoracic)
• One day on Medical ICU = $7,747
References
1. Asif, A, Epstein, M. Prevention of Radiocontrast-Induced
Nephropathy. AM J Kidney Dis 2004; 44:12-24
2. Rudnick, M, Feldman, H. Contrast-Induced Nephropathy: what
are the true clinical consequences?. Clin J Am Soc Nephrol 2008;
3:263.
3. Rudnick, MR, Goldfarb, S, Wexler, L, et al. Nephrotoxicity of ionic
and nonionic contrast media in 1196 patients: A randomized trial.
Kidney Int 1995; 47:254.
4. Barrett, BJ. Contrast nephrotoxicity. J Am Soc Nephrol 1994; 5:125
5. Shwab, SJ, Hlatky, MA, Pieper, KS, et al. Contrast nephrotoxicity: a
randomized controlled trial of a nonionic and an ionic radiographic
contrast agent. N Engl J Med 1989; 320:149.
6. Solomon, R, Werner, C, Mann, D, et al. Effects of saline, mannitol,
and furosemide on acute decreases in renal function induced by
radiocontrast agents. N Engl J Med 1994; 331: 1416.
7. Weisbord, SD, Palevsky, PM. Prevention of contrast-induced
nephropathy with volume expansion. Clin J Am Soc Nephrol 2008;
3:273.
8. Taylor, AJ, Hotchkiss, D, Morse, RW, McCabe, J. PREPARED:
Preparation for Angiography in Renal Dysfunction: a randomized
trial of inpatient vs outpatient hydration protocols for cardiac
catheterization in mild-to-moderate renal dysfunction. Chest
1998; 114:1570.
9. Kshirsagar, AV, Poole, C, Mottl, A et al. N-acetylcysteine for
prevention of radiocontrast induced nephropathy: a meta-analysis
of prospective controlled trials. J Am Soc Nephrol 2004; 15:761.
10. Alonso, a, Lau, J, Jaber, BL, Weintraub, A. Prevention of
radiocontrast nephropathy with N-acetylcysteine in patients with
chronic kidney disease: a meta-analysis of randomized controlled
trials. Am J Kidney Dis 2004; 43:1.
11. Gonzales, DA, Norsworthy, KJ, Kern, SJ, et al. A meta-analysis of N-
acetylcysteine in contrast-induced nephrotoxicity: unsupervised
clustering to resolve heterogeneity. BMC Med 2007; 5:32.
12. Trivedi, H, Daram, S, Szabo, A, et al. High-dose N-acetylcysteine
for the prevention of contrast-induced nephropathy. Am J Med
2009; 122:874.
13. Klarenbach, SW, Pannu, N, Tonelli, MA, Manns, BJ. Cost-
effectiveness of hemofiltration to prevent contrast nephropathy in
patients with chronic kidney disease. Crit Care Med 2006;
34:1044.
14. Lee, PT, Chou, KJ, Liu, CP, et al. Renal protection for coronary
angiography in advanced renal failure patients by prophylactic
hemodialysis. A randomized controlled trial. J Am Coll Cardiol
2007; 50:1015.
15. Ledneva, E, Karie, S, Launay-Vacher, V, et al. Renal safety of
gadollinium-based contrast media in patients with chronic renal
insufficiency. Radiology 2009; 250:618.
16. Kurnik, BR, Allgren, RL Genter, FC, et al. Prospective study of atrial
natriuretic peptide for the prevention of radiocontrast-induced
nephropathy. Am J Kidney Dis 1998; 31:674.
17. Patti, G, Nusca, A, Chello, M, et al. Usefulness of statin
pretreatment to prevent contrast-induced nephropathy and to
improve long-term outcome in patients undergoing percutaneous
coronary intervention. Am J Cardiol 2008; 101:279.
18. Briguori, C, Airoldi, F, D’Andrea, D, et al. Renal Insufficency
Following Contrast Media Administration Trial (REMEDIAL): a
randomized comparison of 3 preventive strategies. Circulation
2007; 115:1211.
19. Zoungas, S, Ninomiya, T, Huxley R, et al. Systemic review:
sodium bicarbonate treatment regimens for the prevention of
contrast-induced nephropathy. Ann Inern Med. 2009 Nov 3;
151 (9): 631-8
20. Stone GW, McCullough PA, Tumlin JA, et al: Fenoldopam
mesylate for prevention of contrast-induced nephropathy: a
randomized controlled trial. CONTRAST Investigators. JAMA
290:2284-2291,2003.
21. Kuhn, K, Chen, N, Dushyant, VS, et al: The PREDICT study: A
randomized double-blind comparison of contrast-induced
nephropathy after low- or isoosmolar contrast agent
exposure. AJR 191: 151-157, July 2008.
22. Lautin, EM, Freeman, NJ, et al: Radiocontrast-associated
renal dysfunction: incidence and risk factors. AJR 157: 49-58,
July 1991.
Questions and
discussion

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Prevention-of-contrast-induced-nephropathy-_1_.ppt

  • 1. Prevention of Contrast-Induced Nephropathy (CIN) Sepehr Khashaei, MD Assistant professor Department of Internal Medicine
  • 2. What will be covered today? • Definition of CIN • Why is prevention of CIN important? • Some other information/statistics about CIN • Who is at high risk for CIN? • Information and conclusions based on outcomes from clinical trials • Simple measures for prevention • Cost to patients. • References. • Questions and discussion.
  • 3. Please save all your questions and discussions for the end.
  • 4. Definition of CIN • CIN is defined as an increase in baseline serum creatinine level of 25% or an absolute increase of 0.5 mg/dL, 2 to 5 days after radiocontrast administration.
  • 5. Why is prevention of CIN important? • Radiocontrast administration is a common cause of hospital-acquired acute renal failure (10% of cases). • In its severe form, CIN is associated with clinically significant morbidity and mortality, including prolonged hospitalization, requirement for dialysis, and an increased risk for death. • CIN increases the costs of medical care by at least extending the hospital stay. • There is no specific treatment once CIN develops, and management must be as for any cause of ATN, with focus on maintaining fluid and electrolyte balance. The best treatment of CIN is prevention.
  • 6. Some other information/statistics about CIN • Individuals with pre-existing renal insufficiency and diabetes are much more likely to experience contrast-induced nephropathy. • Typically, serum creatinine levels begin to increase at 48-72 hours, peak at 3 to 5 days, and return to baseline within another 3-5 days. • In most cases there is no permanent sequelae.
  • 7. Some data from 2004 • More than a million radiocontrast procedures were performed annually. • Incidence of CIN was 150,000/yr. • 1% of CIN required dialysis and caused prolongation of hospital stay to an average of 17 days. • For episodes that did not require dialysis, there was prolongation of hospital stay by 2 days on an average.
  • 8. Total CT scans with contrast done in 2009 at all UNM facilities where 18,350.
  • 9. Who is at high risk? • Patients with GFR <60 ml/min particularly if diabetic. • UNM radiology department uses a creatinine of >1.0 for a female and >1.3 for a male as definition of a high risk patient.
  • 10. Proposed interventions studied in literature • Saline hydration • Diuretics • Mannitol • Intravenous bicarbonate • Saline plus Mannitol • Saline plus diuretics • Oral hydration • Calcium channel antagonists (i.e. nifedipine) • Theophylline • Endothelin receptor antagonists • Dopamine • Fenoldopam (dopamine-1 receptor) • Antioxidant N-acetylcysteine • Iso-osmolar or low-osmolal contrast agents • Hemodialysis • Hemofiltration • Use of MRI in place of CT • Atrial natriuretic peptide • Statins • Ascorbic acid
  • 11. Simple measures for prevention • The use of lower doses of contrast. • Avoidance of repetitive contrast studies that are closely spaced (within 48-72 hours). • Avoidance of volume depletion • Avoidance of NSAIDS • Avoidance of nephrotoxic drugs
  • 12. Information and conclusions based on outcomes from clinical trials
  • 13. • Patients with near-normal kidney function are at little risk for CIN (about 3%) and few precautions are necessary other than avoidance of volume depletion.
  • 14. • The patients at increased risk for contrast- induced nephropathy are diabetics (especially insulin-dependent diabetics) and patients with underlying renal insufficiency (12-50% incidence).
  • 15. • The effects of poor hydration and the volume of contrast medium administered are less clear but are possible risk factors.
  • 16. • Risk factors may be additive.
  • 17. • The risk for CIN does not appear to be influenced by the patient’s age or sex.
  • 18. • Absence of risk factors does not preclude the development of CIN.
  • 19. • Although theoretically beneficial, there is little evidence in support of vasodilators (such as nifedipine, captopril, prostglandin E, low-dose dopamine, fenoldopam, endothelin receptor antagonists, and theophylline) in reducing risk of CIN.
  • 20. • Infuse NS (Grade 1B) at a rate of 1ml/Kg per hour starting at least two and preferably 6-12 hours prior to the procedure, and continuing for 6 to 12 hours after contrast administration. The duration of administration of fluid should be directly proportional to the degree of renal impairment (e.g., should be longer for individuals with more severe renal impairment). Dose should be adjusted depending on patient’s underlying medical condition and their level of hydration. Hydration with NS was superior to 1/2NS at least in one clinical trial.
  • 21. • Intravenous hydration is superior to oral hydration. Oral hydration with water alone should not be used.
  • 22. • Use, if possible, ultrasonography, MRI without gadolinium contrast, or CT scanning without radiocontrast agents.
  • 23. • Based on limited literature, it is difficult to be certain that gadolinium used in MRI scanning is completely free of nephroxicity in high-risk patients. Also, gadolinium-based imaging should not be performed, if at all possible, in patients with GFR <30 ml/min because of risk of nephrogenic systemic fibrosis. In such patients, if a contrast study is necessary, use of low-osmolar or isoosmolar iodinated contrast media, using all the preventive measures that are available, is preferred.
  • 24. • Oral acetylcysteine administed as 1200mg twice daily the day before and the day after the procedure (Grade 2B). Do not use iv acetylcysteine for prevention of CIN (Grade 2B).
  • 25. • Do not use mannitol or other diuretics prophylactically (Grade 1B). • However, diuretics may be required to treat volume overload.
  • 26. • Do not use high osmolal agents (1400 to 1800 mosmol/KG) (Grade 1A).
  • 27. • Use nonionic isoosmolar agents such as iodixanol (Visipaque) or nonionic low-osmolal agents such as iopamidol (Isoview) (Grade 1B) if a contrast study is necessary.
  • 28. Low or iso-osmolar nonionic contrast • Decreased incidence of CIN. • Cost reductions • Increased patient tolerability • Decreased hypersensitivity reactions • The benefit is higher in diabetics with renal insufficiency • Now administered for the majority of radiologic procedures that use iv contrast media. • There appears to be little or no advantage in the prevention of CIN when compared to ionic hyperosmolar agents in patients with normal renal function. • At UNM we use iopamidol (a low-osmolar non-ionic agent) on all adults who have contrast studies regardless of their GFR.
  • 29. • Among patients with stage 3 and 4 CKD do not perform prophylactic hemofiltration (see below) or hemodialysis (Grade 1B). • Hemofiltration is expensive, logically cumbersome and associated with significant risks, its effectiveness compared to other less expensive strategies is not well established, and the reported benefits are implausible. Therefore currently prophylactic hemofiltration is not recommended.
  • 30. • Among patients with stage 5 CKD, most suggest hemodialysis after contrast exposure if there is already a functioning access (Grade 2C) (although there is lack of sufficient data). Do not place a temporary access for prophylactic hemodialysis in these patients.
  • 31. • The effectiveness of sodium bicarbonate treatment to prevent CIN remains uncertain. Earlier reports probably overestimated the magnitude of any benefit, whereas larger, more recent trials have had neutral results. Large multicenter trials are required to clarify whether sodium bicarbonate has value for prevention of CIN before routine use can be recommended.
  • 32. Cost to patients • One bag of NS (1000cc) = $40.00 • 1200mg of acetylcysteine = $5.00 • One day on 4-W = $5,489 (Medicine Subacute) • One day on 4-E = $7,129 (Med/surg Subacute) • One day on 4-S = $6, 863 (Orthopedics) • One day on 5-W = $ 4,049 (General Medicine) • One day on 5-S = $6,152 (NeuroScience) • One day on 6-S = $7,580 (General Surgery) • One day on 7-S = $8,517 (Cardiothoracic) • One day on Medical ICU = $7,747
  • 33. References 1. Asif, A, Epstein, M. Prevention of Radiocontrast-Induced Nephropathy. AM J Kidney Dis 2004; 44:12-24 2. Rudnick, M, Feldman, H. Contrast-Induced Nephropathy: what are the true clinical consequences?. Clin J Am Soc Nephrol 2008; 3:263. 3. Rudnick, MR, Goldfarb, S, Wexler, L, et al. Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: A randomized trial. Kidney Int 1995; 47:254. 4. Barrett, BJ. Contrast nephrotoxicity. J Am Soc Nephrol 1994; 5:125 5. Shwab, SJ, Hlatky, MA, Pieper, KS, et al. Contrast nephrotoxicity: a randomized controlled trial of a nonionic and an ionic radiographic contrast agent. N Engl J Med 1989; 320:149. 6. Solomon, R, Werner, C, Mann, D, et al. Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med 1994; 331: 1416.
  • 34. 7. Weisbord, SD, Palevsky, PM. Prevention of contrast-induced nephropathy with volume expansion. Clin J Am Soc Nephrol 2008; 3:273. 8. Taylor, AJ, Hotchkiss, D, Morse, RW, McCabe, J. PREPARED: Preparation for Angiography in Renal Dysfunction: a randomized trial of inpatient vs outpatient hydration protocols for cardiac catheterization in mild-to-moderate renal dysfunction. Chest 1998; 114:1570. 9. Kshirsagar, AV, Poole, C, Mottl, A et al. N-acetylcysteine for prevention of radiocontrast induced nephropathy: a meta-analysis of prospective controlled trials. J Am Soc Nephrol 2004; 15:761. 10. Alonso, a, Lau, J, Jaber, BL, Weintraub, A. Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomized controlled trials. Am J Kidney Dis 2004; 43:1. 11. Gonzales, DA, Norsworthy, KJ, Kern, SJ, et al. A meta-analysis of N- acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity. BMC Med 2007; 5:32. 12. Trivedi, H, Daram, S, Szabo, A, et al. High-dose N-acetylcysteine for the prevention of contrast-induced nephropathy. Am J Med 2009; 122:874.
  • 35. 13. Klarenbach, SW, Pannu, N, Tonelli, MA, Manns, BJ. Cost- effectiveness of hemofiltration to prevent contrast nephropathy in patients with chronic kidney disease. Crit Care Med 2006; 34:1044. 14. Lee, PT, Chou, KJ, Liu, CP, et al. Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis. A randomized controlled trial. J Am Coll Cardiol 2007; 50:1015. 15. Ledneva, E, Karie, S, Launay-Vacher, V, et al. Renal safety of gadollinium-based contrast media in patients with chronic renal insufficiency. Radiology 2009; 250:618. 16. Kurnik, BR, Allgren, RL Genter, FC, et al. Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy. Am J Kidney Dis 1998; 31:674. 17. Patti, G, Nusca, A, Chello, M, et al. Usefulness of statin pretreatment to prevent contrast-induced nephropathy and to improve long-term outcome in patients undergoing percutaneous coronary intervention. Am J Cardiol 2008; 101:279. 18. Briguori, C, Airoldi, F, D’Andrea, D, et al. Renal Insufficency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation 2007; 115:1211.
  • 36. 19. Zoungas, S, Ninomiya, T, Huxley R, et al. Systemic review: sodium bicarbonate treatment regimens for the prevention of contrast-induced nephropathy. Ann Inern Med. 2009 Nov 3; 151 (9): 631-8 20. Stone GW, McCullough PA, Tumlin JA, et al: Fenoldopam mesylate for prevention of contrast-induced nephropathy: a randomized controlled trial. CONTRAST Investigators. JAMA 290:2284-2291,2003. 21. Kuhn, K, Chen, N, Dushyant, VS, et al: The PREDICT study: A randomized double-blind comparison of contrast-induced nephropathy after low- or isoosmolar contrast agent exposure. AJR 191: 151-157, July 2008. 22. Lautin, EM, Freeman, NJ, et al: Radiocontrast-associated renal dysfunction: incidence and risk factors. AJR 157: 49-58, July 1991.