Contrast-induced nephropathy

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In medicine, contrast-induced nephropathy is acute kidney injury from radiocontrast. It is defined as either a greater than 25% increase of serum creatinine or an absolute increase in serum creatinine of 0.5 mg/dL.[1]

Who is at risk?

Factors associated with an increased risk of contrast-induced nephropathy are:[2][3]

A clinical prediction rule is available to estimate probability of nephropathy (increase =25% and/or =0.5 mg/dl in serum creatinine at 48 h)[5]:

Risk Factors:

  • Systolic blood pressure <80 mm Hg - 5 points
  • Intraarterial balloon pump - 5 points
  • Congestive heart failure (Class III-IV or history of pulmonary edema) - 5 points
  • Age >75 y - 4 points
  • Hematocrit level <39% for men and <35% for women - 3 points
  • Diabetes - 3 points
  • Radiocontrast media volume - 1 point for each 100 mL
  • Renal insufficiency:
    • Serum creatinine level >1.5 g/dL - 4 points
or
  • 2 for 40–60 mL/min/1.73 m2
  • 4 for 20–40 mL/min/1.73 m2
  • 6 for < 20 mL/min/1.73 m2

Scoring:
5 or less points

  • Risk of CIN - 7.5
  • Risk of Dialysis - 0.04%

6–10 points

  • Risk of CIN - 14.0
  • Risk of Dialysis - 0.12%

11–16 points

  • Risk of CIN - 26.1*
  • Risk of Dialysis - 1.09%

>16 points

  • Risk of CIN - 57.3
  • Risk of Dialysis - 12.8%

Prevention

To minimize the risk for contrast-induced nephropathy, various actions can be taken if the patient has predisposing conditions. A meta-analysis suggests "High-dose statins plus hydration with or without NAC might be the preferred treatment strategy to prevent contrast-induced". [6] A separate meta-analysis addresses interventions in for emergent patients with baseline renal insufficiency.[7]

Choice of radiocontrast agent

Iso-osmolar, nonionic radiocontrast media may be the best according to a randomized controlled trial.[8]

Hypo-osmolar, non-ionic radiocontrast agents are beneficial if iso-osmolar, nonionic contrast media is not available due to costs.[9]

Hydration with or without bicarbonate

The roles of sodium bicarbonate administration to prevent acute kidney injury is not clear according to a systematic reviews of randomized controlled trials.[10][11] Heterogeneous, conflicting trial results may be due to publication bias with the smaller, less rigorous trials showing benefit.[10][11]

A common regimen is three 50 ml ampules of bicarbonate in 850 ml of water with 5% dextrose. The renoprotective effects of bicarbonate are thought to be due to urinary alkalinization, which creates an environment less amenable to the formation of harmful free radicals.[12].

A meta-analysis is available, but does not include all the studies in the evidence table below.[13]

Randomized controlled trials of sodium bicarbonate[14][15][16][17][18][19]
Study name or
first author		 Patients Intervention Primary outcomes Conclusion
Definition Rate in intervention group Rate in controlgroup
Merten (2004)[14] 119 patients with kidney disease (serum creatinine at least 1.1 mg/dL). Mean GFR was 41 mL/min per 1.73 m2 • 3 mL/kg per hour for 1 hour before contrast
• 1 mL/kg per hour for 6 hours during and after contrast		 > 25% rise in serum creatinine within 2 days 1.7% 13.6% Bicarb is beneficial
Masuda (2007)[16] 59 patients undergoing emergent coronary angiography • 3 mL/kg per hour for 1 hour before contrast
• 1 mL/kg per hour for 6 hours during and after contrast
Controls received isotonic saline:
• 3 mL/kg per hour for 1 hour before contrast
• 1 mL/kg per hour for 6 hours during and after contrast		 >0.5 mg/dl or > 25% rise in serum creatinine within 2 days 7% 35% Bicarb is beneficial
REMEDIAL (2007)[15] 219 patients with kidney disease (serum creatinine at least 2.0 mg/dL or GFR 40 mL/min per 1.73 m2 or less) undergoing coronary and/or peripheral procedures.
All patients received NAC		 • 3 mL/kg per hour for 1 hour before contrast
• 1 mL/kg per hour for 6 hours during and after contrast
Controls received isotonic saline:
• 3 mL/kg per hour for 1 hour before contrast
• 1 mL/kg per hour for 6 hours during and after contrast		 > 25% rise in serum creatinine within 2 days 1.9% 9.9% Bicarb is beneficial
Maioli (2008)[17] 502 patients with kidney disease (creatinine clearance 60 mL/min per 1.73 m2 or less; mean GFR was 48 mL/min per 1.73 m2) undergoing coronary angiography
All patients received NAC		 • 3 mL/kg per hour for 1 hour before contrast
• 1 mL/kg per hour for 6 hours after contrast
Controls received:
• isotonic saline 1 ml/kg/hr for 12 hours pre/post contrast		 0.5 mg/dl rise in creatinine within 5 days 10% 11.5% Bicarb is not beneficial
Brar (2008)[18] 353 patients with kidney disease (GFR 60 mL/min per 1.73 m2 or less; mean creatinine clearance was 36 - 39 mL/min) undergoing coronary angiography or intervention • 3 mL/kg per hour for 1 hour before contrast
• 1.5 mL/kg per hour for 4 hours during and after contrast
Controls received isotonic saline:
• 3 mL/kg per hour for 1 hour before contrast
• 1.5 mL/kg per hour for 4 hours during and after contrast		 > > 25% fall in GFR within 4 days 13.3% 14.6% Bicarb is not beneficial
Ueda (2011)[19] 59 patients with kidney disease (GFR 60 mL/min per 1.73 m2 or less or creat > >1.1 mg/dl ; undergoing coronary angiography or intervention • 3 mL/kg per hour for 1 hour before contrast
• 154 mEq/L of sodium bicarbonate 0.5 ml/kg before contrast
• 3 mL/kg per hour for 1 hour before contrast
• 154 mEq/L sodium bicarbonate at 1 ml/kg/hour for 6 hours after contrast to both groups		 > > 25% fall in GFR or >0.5 mg/dl rise serum creatinine level within 2 days 3.3% 27.6% Bicarb bolus is beneficial

Alternatively, one randomized controlled trial of patients with a creatinine over 1.6 mg per deciliter (140 µmol per liter) or creatinine clearance below 60 ml per minute used 1 ml/kg of 0.45 percent saline per per hour for 6-12 hours before and after the contrast.[20]

Methylxanthines

Adenosine antagonists such as the methylxanthines theophylline and aminophylline, may help[7] although studies have conflicting results.[21] The best studied dose is 200 mg of theophylline given IV 30 minutes before contrast administration.[22][23]

N-acetylcysteine

N-acetylcysteine (NAC) 600 mg orally twice a day, on the day before and of the procedure if creatinine clearance is estimated to be less than 60 mL/min [1.00 mL/s]) may reduce nephropathy.[24][25]. A randomized controlled trial found higher doses of NAC (1200-mg IV bolus and 1200 mg orally twice daily for 2 days) benefited (relative risk reduction of 74%) patients receiving coronary angioplasty with higher volumes of contrast[26]. However, a more recent trial found no benefit.[27]


Some authors believe the benefit is not overwhelming.[28] The strongest results were from an unblinded randomized controlled trial that used NAC intravenously.[29] A systematic review by Clinical Evidence concluded that NAC is "likely to beneficial" but did not recommend a specific dose.[30] One study found that the apparent benefits of NAC may be due to its interference with the creatinine laboratory test itself.[31] This is supported by a lack of correlation between creatinine levels and cystatin C levels.

In one study 15% of patients receiving NAC intravenously had allergic reactions.[29]

Prophylactic hemodialysis

Randomized controlled trials found benefit from prophylactic hemodialysis for patients with chronic kidney disease and a creatinine over 309.4 µmol/L (3.5 mg.dl) who have elective coronary catheterization.[32][33]


Ascorbic acid

Ascorbic acid may help according to a systematic review of randomized controlled trials.[34]

Other interventions

Other pharmacological agents, such as furosemide, mannitol, dopamine, and atrial natriuretic peptide have been tried, but have either not had beneficial effects, or had detrimental effects.[20][35]

References

  1. ↑ Barrett BJ, Parfrey PS (2006). "Clinical practice. Preventing nephropathy induced by contrast medium". N. Engl. J. Med. 354 (4): 379–86. DOI:10.1056/NEJMcp050801. PMID 16436769. Research Blogging.
  2. ↑ McCullough PA, Wolyn R, Rocher LL, Levin RN, O'Neill WW (1997). "Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality". Am J Med 103 (5): 368-75. PMID 9375704.
  3. ↑ Scanlon PJ, Faxon DP, Audet AM, Carabello B, Dehmer GJ, Eagle KA, Legako RD, Leon DF, Murray JA, Nissen SE, Pepine CJ, Watson RM, Ritchie JL, Gibbons RJ, Cheitlin MD, Gardner TJ, Garson A Jr, Russell RO Jr, Ryan TJ, Smith SC Jr (1999). "ACC/AHA guidelines for coronary angiography. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Coronary Angiography). Developed in collaboration with the Society for Cardiac Angiography and Interventions". J Am Coll Cardiol 33 (6): 1756-824. PMID 10334456.
  4. ↑ Marenzi, Giancarlo; Emilio Assanelli, Jeness Campodonico, Gianfranco Lauri, Ivana Marana, Monica De Metrio, Marco Moltrasio, Marco Grazi, Mara Rubino, Fabrizio Veglia, Franco Fabbiocchi, Antonio L. Bartorelli (2009-02-03). "Contrast Volume During Primary Percutaneous Coronary Intervention and Subsequent Contrast-Induced Nephropathy and Mortality". Ann Intern Med 150 (3): 170-177. Retrieved on 2009-02-03.
  5. ↑ Mehran R, Aymong ED, Nikolsky E, et al (2004). "A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation". J. Am. Coll. Cardiol. 44 (7): 1393–9. DOI:10.1016/j.jacc.2004.06.068. PMID 15464318. Research Blogging.
  6. ↑ Su X, Xie X, Liu L, Lv J, Song F, Perkovic V et al. (2016). "Comparative Effectiveness of 12 Treatment Strategies for Preventing Contrast-Induced Acute Kidney Injury: A Systematic Review and Bayesian Network Meta-analysis.". Am J Kidney Dis. DOI:10.1053/j.ajkd.2016.07.033. PMID 27707552. Research Blogging.
  7. ↑ 7.0 7.1 Sinert R, Doty CI (2007). "Evidence-based emergency medicine review. Prevention of contrast-induced nephropathy in the emergency department". Annals of emergency medicine 50 (3): 335-45, 345.e1-2. DOI:10.1016/j.annemergmed.2007.01.023. PMID 17512638. Research Blogging.
  8. ↑ Aspelin P, Aubry P, Fransson S, Strasser R, Willenbrock R, Berg K (2003). "Nephrotoxic effects in high-risk patients undergoing angiography". N Engl J Med 348 (6): 491-9. PMID 12571256.
  9. ↑ Schwab S, Hlatky M, Pieper K, Davidson C, Morris K, Skelton T, Bashore T (1989). "Contrast nephrotoxicity: a randomized controlled trial of a nonionic and an ionic radiographic contrast agent". N Engl J Med 320 (3): 149-53. PMID 2643042.
  10. ↑ 10.0 10.1 Zoungas S, Ninomiya T, Huxley R, Cass A, Jardine M, Gallagher M et al. (2009). "Systematic review: sodium bicarbonate treatment regimens for the prevention of contrast-induced nephropathy.". Ann Intern Med 151 (9): 631-8. DOI:10.1059/0003-4819-151-9-200911030-00008. PMID 19884624. Research Blogging.
  11. ↑ 11.0 11.1 Brar SS, Hiremath S, Dangas G, Mehran R, Brar SK, Leon MB (2009). "Sodium bicarbonate for the prevention of contrast induced-acute kidney injury: a systematic review and meta-analysis.". Clin J Am Soc Nephrol 4 (10): 1584-92. DOI:10.2215/CJN.03120509. PMID 19713291. PMC PMC2758263. Research Blogging.
  12. ↑ Mueller C, Buerkle G, Buettner H, Petersen J, Perruchoud A, Eriksson U, Marsch S, Roskamm H (2002). "Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty". Arch Intern Med 162 (3): 329-36. PMID 11822926.
  13. ↑ Sinert R, Doty CI (July 2009). "Update: Prevention of contrast-induced nephropathy in the emergency department". Ann Emerg Med 54 (1): e1–5. DOI:10.1016/j.annemergmed.2008.08.014. PMID 18926598. Research Blogging.
  14. ↑ 14.0 14.1 Merten G, Burgess W, Gray L, Holleman J, Roush T, Kowalchuk G, Bersin R, Van Moore A, Simonton C, Rittase R, Norton H, Kennedy T (2004). "Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial". JAMA 291 (19): 2328-34. PMID 15150204.
  15. ↑ 15.0 15.1 Briguori C, Airoldi F, D'Andrea D, Bonizzoni E, Morici N, Focaccio A, Michev I, Montorfano M, Carlino M, Cosgrave J, Ricciardelli B, Colombo A (2007). "Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies". Circulation 115 (10): 1211-7. PMID 17309916.
  16. ↑ 16.0 16.1 Masuda M, Yamada T, Mine T, et al. (September 2007). "Comparison of usefulness of sodium bicarbonate versus sodium chloride to prevent contrast-induced nephropathy in patients undergoing an emergent coronary procedure". Am. J. Cardiol. 100 (5): 781–6. DOI:10.1016/j.amjcard.2007.03.098. PMID 17719320. Research Blogging.
  17. ↑ 17.0 17.1 Maioli M, Toso A, Leoncini M, et al (August 2008). "Sodium bicarbonate versus saline for the prevention of contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention". Journal of the American College of Cardiology 52 (8): 599–604. DOI:10.1016/j.jacc.2008.05.026. PMID 18702961. Research Blogging.
  18. ↑ 18.0 18.1 Brar SS, Shen AY, Jorgensen MB, et al (September 2008). "Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial". JAMA : the journal of the American Medical Association 300 (9): 1038–46. DOI:10.1001/jama.300.9.1038. PMID 18768415. Research Blogging.
  19. ↑ 19.0 19.1 Ueda H, Yamada T, Masuda M, Okuyama Y, Morita T, Furukawa Y et al. (2011). "Prevention of contrast-induced nephropathy by bolus injection of sodium bicarbonate in patients with chronic kidney disease undergoing emergent coronary procedures.". Am J Cardiol 107 (8): 1163-7. DOI:10.1016/j.amjcard.2010.12.012. PMID 21349483. Research Blogging.
  20. ↑ 20.0 20.1 Solomon R, Werner C, Mann D, D'Elia J, Silva P (1994). "Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents". N. Engl. J. Med. 331 (21): 1416–20. PMID 7969280. [e]
  21. ↑ Bagshaw SM, Ghali WA (2005). "Theophylline for prevention of contrast-induced nephropathy: a systematic review and meta-analysis". Arch. Intern. Med. 165 (10): 1087-93. DOI:10.1001/archinte.165.10.1087. PMID 15911721. Research Blogging.
  22. ↑ Huber W, Schipek C, Ilgmann K, et al (2003). "Effectiveness of theophylline prophylaxis of renal impairment after coronary angiography in patients with chronic renal insufficiency". Am. J. Cardiol. 91 (10): 1157–62. DOI:10.1016/S0002-9149(03)00259-5. PMID 12745095. Research Blogging.
  23. ↑ Huber W, Ilgmann K, Page M, et al (2002). "Effect of theophylline on contrast material-nephropathy in patients with chronic renal insufficiency: controlled, randomized, double-blinded study". Radiology 223 (3): 772–9. PMID 12034949. [e]
  24. ↑ Trivedi H, Daram S, Szabo A, Bartorelli AL, Marenzi G (2009). "High-dose N-acetylcysteine for the prevention of contrast-induced nephropathy.". Am J Med 122 (9): 874.e9-15. DOI:10.1016/j.amjmed.2009.01.035. PMID 19699385. Research Blogging.
  25. ↑ Kay J, Chow W, Chan T, Lo S, Kwok O, Yip A, Fan K, Lee C, Lam W (2003). "Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial". JAMA 289 (5): 553-8. PMID 12578487.
  26. ↑ Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli A (2006). "N-acetylcysteine and contrast-induced nephropathy in primary angioplasty". N Engl J Med 354 (26): 2773-82. PMID 16807414.
  27. ↑ Thiele H, Hildebrand L, Schirdewahn C, Eitel I, Adams V, Fuernau G et al. (2010). "Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial.". J Am Coll Cardiol 55 (20): 2201-9. DOI:10.1016/j.jacc.2009.08.091. PMID 20466200. Research Blogging.
  28. ↑ Gleeson TG, Bulugahapitiya S (2004). "Contrast-induced nephropathy". AJR Am J Roentgenol 183 (6): 1673-89. PMID 15547209.
  29. ↑ 29.0 29.1 Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ (2003). "A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study". J. Am. Coll. Cardiol. 41 (12): 2114–8. PMID 12821233. [e]
  30. ↑ Kellum J, Leblanc M, Venkataraman R (2006). "Renal failure (acute)". Clinical evidence (15): 1191–212. PMID 16973048. [e]
  31. ↑ Hoffmann U, Fischereder M, Kruger B, Drobnik W, Kramer BK (2004). "The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable". J Am Soc Nephrol 15 (2): 407-10. PMID 14747387.
  32. ↑ Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW (1999). "Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators". Stroke 30 (6): 1223–9. PMID 10356104. [e]
  33. ↑ Lee PT, Chou KJ, Liu CP, et al (2007). "Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis. A randomized controlled trial". J. Am. Coll. Cardiol. 50 (11): 1015–20. DOI:10.1016/j.jacc.2007.05.033. PMID 17825709. Research Blogging.
  34. ↑ Sadat U, Usman A, Gillard JH, Boyle JR (2013). "Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: a systematic review with meta-analysis of randomized, controlled trials.". J Am Coll Cardiol 62 (23): 2167-75. DOI:10.1016/j.jacc.2013.07.065. PMID 23994417. Research Blogging.
  35. ↑ Abizaid AS, Clark CE, Mintz GS, Dosa S, Popma JJ, Pichard AD, Satler LF, Harvey M, Kent KM, Leon MB (1999). "Effects of dopamine and aminophylline on contrast-induced acute renal failure after coronary angioplasty in patients with preexisting renal insufficiency". Am J Cardiol 83 (2): 260-3, A5. PMID 10073832.
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