|Classification and external resources|
Contrast-induced nephropathy is defined as either a greater than 25% increase of serum creatinine or an absolute increase in serum creatinine of 0.5 mg/dL after percutaneous coronary intervention (PCI) using a contrast agent. Despite extensive speculation, the actual occurrence of contrast-induced nephropathy in other patient populations has not been demonstrated in the literature.
A new definition of contrast nephropathy in patients undergoing percutaneous coronary intervention was recently proposed by Harjai, et al. This tripartite definition classifies contrast nephropathy as grade 0 (serum creatinine increase <25% above baseline and <0.5 mg/dL above baseline), grade 1 (serum creatinine increase >/=25% above baseline and <0.5 mg/dL above baseline), or grade 2 (serum creatinine increase >/=0.5 mg/dL above baseline). This classification is prognostic of long-term outcomes of patients after percutaneous coronary intervention. Patients with grade 2 nephropathy had the worst outcome while those with grade 0 nephropathy had the best outcome on long-term follow-up.
To minimize the risk for contrast-induced nephropathy, various actions can be taken if the patient has predisposing conditions. These have been reviewed in a meta-analysis. A separate meta-analysis addresses interventions in for emergent patients with baseline renal insufficiency.
Three factors have been associated with an increased risk of contrast-induced nephropathy: preexisting renal insufficiency (such as Creatinine clearance < 60 mL/min [1.00 mL/s] - online calculator), preexisting diabetes, and reduced intravascular volume.
- 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
- Contrast media volume - 1 point for each 100 mL
- Renal insufficiency:
- Serum creatinine level >1.5 g/dL - 4 points
- 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
5 or less points
- Risk of CIN - 7.5
- Risk of Dialysis - 0.04%
- Risk of CIN - 14.0
- Risk of Dialysis - 0.12%
- Risk of CIN - 26.1*
- Risk of Dialysis - 1.09%
- Risk of CIN - 57.3
- Risk of Dialysis - 12.8%
Choice of contrast agent
The osmolality of the contrast agent was previously believed to be of paramount importance in contrast-induced nephropathy. Today it has become increasingly clear that other physicochemical properties play a greater role, such as viscosity. Attention should be paid to use contrast agents of low viscosity. Moreover, sufficient fluids should be supplied to limit fluid viscosity of urine. Modern iodinated contrast agents are non-ionic, the older ionic types caused more adverse effects and are not used much anymore.
One study has suggested that iso-osmolar, nonionic contrast media may be superior to others. However, several subsequent studies failed to confirm this. A large scale study strongly suggested that an iso-osmolar contrast media more often cause clinically relevant kidney failure than a low-osmolar contrast agent.
Hydration with or without bicarbonate
Administration of sodium bicarbonate 3 mL/kg per hour for 1 hour before, followed by 1 mL/kg per hour for 6 hours after contrast was found superior to plain saline on one randomized controlled trial of patients with a creatinine of at least 1.1 mg/dL (97.2 µmol/L) . To make the solution, the study used 154 mL of 1000 mEq/L sodium bicarbonate to 846 mL of 5% dextrose. This is approximately three 50 ml ampules of bicarbonate in 850 ml of water with 5% dextrose. This was subsequently corroborated by a multi-center randomized controlled trial, which also demonstrated that IV hydration with sodium bicarbonate was superior to 0.9% normal saline. However, additional confirmatory trials with sodium bicarbonate are needed because the largest trial to date showed no benefit of sodium bicarbonate over normal saline . 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.
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 hour for 6–12 hours before and after the contrast.
Adenosine antagonists such as the methylxanthines theophylline and aminophylline, may help although studies have conflicting results. The best studied dose is 200 mg of theophylline given IV 30 minutes before contrast administration.
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. A randomized controlled trial in 2006 found that 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.
Since publication of the meta-analyses, two small and underpowered negative studies, one of IV NAC and one of 600 mg give four times around coronary angiography, found statistically insignificant trends towards benefit.
Some authors believe the benefit is not overwhelming. The strongest results were from an unblinded randomized controlled trial that used NAC intravenously. A systematic review by Clinical Evidence concluded that NAC is "likely to be beneficial" but did not recommend a specific dose. One study found that the apparent benefits of NAC may be due to its interference with the creatinine laboratory test itself. This is supported by a lack of correlation between creatinine levels and cystatin C levels.
A clinical trial from 2010, however, found that acetylcysteine is ineffective for the prevention of contrast-induced nephropathy. This trial, involving 2,308 patients, found that acetylcysteine was no better than placebo; whether acetylcysteine or placebo was used, the incidence of nephropathy was the same — 13%.
Patients with chronic renal insufficiency and a creatinine over 309.4 µmol/L (3.5 mg.dl) who have elective coronary catheterization, a randomized controlled trial found benefit from prophylactic hemodialysis
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. Of course, limiting the total contrast volume also aids greatly in reducing the incidence of contrast nephropathy.
While there are currently no FDA-approved therapies for Contrast Induced Nephropathy, two therapies are currently being investigated. CorMedix, Inc. is currently in the latter part of Stage II clinical trials with approved Phase III Special Protocol Assessment for CRMD001 (unique formulation Deferiprone) to prevent Contrast-Induced Acute Kidney Injury (AKI) and to slow progression of Chronic Kidney Disease (CKD). Dosing trials began in June 2010 in the sixty patient trial.
PLC Medical Systems, Inc. has begun a Stage III clinical trial of RenalGuard Therapy to prevent Contrast-induced nephropathy. The therapy utilizes the RenalGuard System, which measures the patient's urine output and infuses an equal volume of normal saline in real-time. The therapy involves connecting the patient to the RenalGuard System, then injecting a small dosage of furosemide to induce high urine rates. RenalGuard Therapy has already been studied in two Italian studies, both of which found the therapy to be superior to the current standard of care.
- 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.
- Harjai KJ, et al. A comparison of contemporary definitions of contrast nephropathy in patients undergoing percutaneous coronary intervention and a proposal for a novel nephropathy grading system. Am J Cardiol 2008;101(6):812-9.
- Pannu N, Wiebe N, Tonelli M (2006). "Prophylaxis strategies for contrast-induced nephropathy". JAMA 295 (23): 2765–79. doi:10.1001/jama.295.23.2765. PMID 16788132.
- 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.
- 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. doi:10.1016/S0002-9343(97)00150-2. PMID 9375704.
- 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. doi:10.1016/S0735-1097(99)00126-6. PMID 10334456.
- 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.
- 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. doi:10.1056/NEJMoa021833. PMID 12571256.
- Liss P, Persson PB, Hansell P, Lagerqvist B (2006). "Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media". Kidney Int. 70 (10): 1811–7. doi:10.1038/sj.ki.5001887. PMID 17003814.
- 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. doi:10.1001/jama.291.19.2328. PMID 15150204.
- 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. doi:10.1161/CIRCULATIONAHA.106.687152. PMID 17309916.
- Brar SS, Shen AY, Jorgensen MB, Kotlewski A, Aharonian VJ, Desai N, Ree M, Shah AI, Burchette RJ (2008). "Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial". JAMA 300 (9): 1038–46. doi:10.1001/jama.300.9.1038. PMID 18768415.
- 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. doi:10.1001/archinte.162.3.329. PMID 11822926.
- 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. doi:10.1056/NEJM199411243312104. PMID 7969280.
- 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.
- 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.
- 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. doi:10.1148/radiol.2233010609. PMID 12034949.
- 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. doi:10.1001/jama.289.5.553. PMID 12578487.
- 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. doi:10.1056/NEJMoa054209. PMID 16807414.
- Haase M, Haase-Fielitz A, Bagshaw SM, et al. (2007). "Phase II, randomized, controlled trial of high-dose N-acetylcysteine in high-risk cardiac surgery patients". Crit. Care Med. 35 (5): 1324–31. doi:10.1097/01.CCM.0000261887.69976.12. PMID 17414730.
- Seyon RA, Jensen LA, Ferguson IA, Williams RG (2007). "Efficacy of N-acetylcysteine and hydration versus placebo and hydration in decreasing contrast-induced renal dysfunction in patients undergoing coronary angiography with or without concomitant percutaneous coronary intervention". Heart & lung : the journal of critical care 36 (3): 195–204. doi:10.1016/j.hrtlng.2006.08.004. PMID 17509426.
- Gleeson TG, Bulugahapitiya S (2004). "Contrast-induced nephropathy". AJR Am J Roentgenol 183 (6): 1673–89. doi:10.2214/ajr.183.6.01831673. PMID 15547209.
- 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. doi:10.1016/S0735-1097(03)00487-X. PMID 12821233.
- Kellum J, Leblanc M, Venkataraman R (2006). "Renal failure (acute)". Clinical evidence (15): 1191–212. PMID 16973048.
- 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. doi:10.1097/01.ASN.0000106780.14856.55. PMID 14747387.
- Act, Investigators (September 2011). "Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT)". Circulation 124 (11): 1250–9. doi:10.1161/CIRCULATIONAHA.111.038943. PMID 21859972.
- 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.
- 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. doi:10.1161/01.STR.30.6.1223. PMID 10356104.
- 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. doi:10.1016/S0002-9149(98)00833-9. PMID 10073832.
- , CorMedix June 25, 2010 Press Release, "CorMedix Doses First Patient in Phase II Clinical Trial of CRMD-001"
- , ClinicalTrials.gov, "Deferiprone for the Prevention of Contrast-Induced Acute Kidney Injury"
- , ClinicalTrials.gov,"Evaluation of RenalGuard® System to Reduce the Incidence of Contrast Induced Nephropathy in At-Risk Patients (CIN-RG)"
- Marenzi, Giancarlo; Bartorelli,A (2012). "Prevention of Contrast Nephropathy by Furosemide With Matched Hydration". J Am Coll Cardiol Intv 5 (1): 90–97. doi:10.1016/j.jcin.2011.08.017. PMID 22230154.
- Briguori, Carlo (September 2011). "Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II): RenalGuard System in high-risk patients for contrast-induced acute kidney injury.". Circulation 124 (11): 1260–9. doi:10.1161/CIRCULATIONAHA.111.030759. PMID 21844075.