Contrast induced nephropathy primary prevention

Jump to navigation Jump to search

Contrast Induced Nephropathy Microchapters

Home

Patient Information

Overview

Definition

Historical Perspective

Pathophysiology

Differentiating Contrast induced nephropathy from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Treatment

Medical Therapy

Primary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Contrast induced nephropathy primary prevention On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Contrast induced nephropathy primary prevention

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Contrast induced nephropathy primary prevention

CDC on Contrast induced nephropathy primary prevention

Contrast induced nephropathy primary prevention in the news

Blogs on Contrast induced nephropathy primary prevention

Directions to Hospitals Treating Contrast induced nephropathy

Risk calculators and risk factors for Contrast induced nephropathy primary prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]

Overview

General measures should be followed to minimize the incidence of CIN, include carefully considering whether the contrast examination is absolutely needed, especially in high-risk patients, using the minimal effective dose, and eliminating potentially nephrotoxic drugs at least 24 hr before the study. Encourage IV hydration and following protocols that allow clear liquids up to 2 hr before the procedure. Alternative diagnostic procedures should be considered in those at high-risk.

Prevention

Strategies proposed to prevent the occurrence of CIN have been extensively studied but compelling evidence regarding the implementation of most of these approaches is still lacking. Prophylactic measures were recently defined in the 2012 KDIGO Guidelines and divided broadly into pharmacologic and non-pharmacologic approaches.

Non-Pharmacologic Approaches

Dose of contrast media

It has been shown that larger doses of contrast media are associated with higher risks of CIN. Still, no specific dose recommendations have been made due to lack of robust evidence. The 2012 KDIGO guidelines recommended using the smallest possible dose in every procedure requiring IV contrast especially in patients at high risk for developing CIN.[1] Nyman et al suggested an alternative approach, using the ratio of dose of iodine (in grams) to estimated glomerular filtration rate (eGFR). The team found the ratio to be predictive of the risk of CIN. A ratio I(g)/eGFR < 1 was shown to be relatively safe even in patients with many possible risk factors. The estimated risk decreased eightfold when the ratio dropped below 1.[2]

Route of Administration

Most studies illustrating the pathophysiology, treatment and prophylaxis of CIN focus on intra-arterial (IA) injection of contrast media since it has been associated with the highest cases of CIN. A number of trials have also shown that intra-venous (IV) contrast has a significantly lower risk of CIN than IA contrast.[3][4] In fact, a review by Rao and Newhouse showed that in studies with proper controls, the risk of CIN after IV contrast administration did not differ between the study groups and the control groups.[5] This further emphasizes the importance of the route of contrast administration, and points to the fact that IV contrast has not been explicitly shown to be nephrotoxic.

Osmolarity of Contrast Agent

Pharmacologic Approaches

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 creatinne of at least 1.1 mg/dL (97.2 µmol/L) .[6] 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[7]. 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.[8].

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.[9]

Methylxanthines

Adenosine antagonists such as the methylxanthines theophylline and aminophylline, may help although studies have conflicting results.[10] The best studied dose is 200 mg of theophylline given IV 30 minutes before contrast administration.[11][12]

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.[13]. 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[14].

Since publication of the meta-analyses, two small and underpowered negative studies, one of IV NAC[15] and one of 600 mg give four times around coronary angiography[16], found statistically insignificant trends towards benefit.

Some authors believe the benefit is not overwhelming.[17] The strongest results were from an unblinded randomized controlled trial that used NAC intravenously.[18] A systematic review by Clinical Evidence concluded that NAC is "likely to beneficial" but did not recommend a specific dose.[19] One study found that the apparent benefits of NAC may be due to its interference with the creatinine laboratory test itself.[20] This is supported by a lack of correlation between creatinine levels and cystatin C levels.

ACT Trial which is a randomized, placebo controlled trial randomized 2308 patients undergoing angiography with at least one risk factor for contrast induced nephropathy. Patients were randomized to receive either high dose of NAC or placebo on the day before and after the procedure. No difference was noted in rates of developing nephropathy between the two groups[21]. Therefore short-term use of NAC for the prevention of contrast induced nephropathy should be avoided[22].

In a series, 15% of patients receiving NAC intravenously had allergic reactions[18].

Prophylactic hemodialysis

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[23]

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.[9][24]

REMEDIAL II Trial which is a randomized, multicenter, investigator-driven trial involving patients who are at high risk (GFR ≤30 mL · min−1 · 1.73 m−2 and/or a risk score ≥11) for contrast induced nephropathy tested the strategy of forced diuresis. These patients were randomized to receive either NAC + saline or NAC + saline + furosemide. Rates of developing nephropathy was lower among the group receiving diuretic as furosemide reduces the contrast exposure and renal reuptake while promoting accelerated elimination of contrast[25].

Choice of contrast agent

The osmolality of the contrast agent has traditionally been believed to be of great importance in contrast-induced nephropathy. Ideally, the contrast agent should be iso-osmolar to blood. Modern iodinated contrast agents are non-ionic.

  • Hypo-osmolar, non-ionic contrast agents are beneficial if iso-osmolar, nonionic contrast media is not available due to costs.[27]

2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury (DO NOT EDIT)[28]

Nonpharmacological prevention strategies of CI-AKI

Level 1
"1. We recommend using either iso-osmolar or low-osmolar iodinated contrast media, rather than high-osmolar iodinated contrast media in patients at increased risk of CI-AKI. (Level of Evidence: 1B)"
Not Graded
"1. Use the lowest possible dose of contrast medium in patients at risk for CI-AKI. (Level of Evidence: Not Graded)"
Level 2
"1. We suggest not using prophylactic intermittent hemodialysis (IHD) or hemofiltration (HF) for contrast-media removal in patients at increased risk for CI-AKI. (Level of Evidence: 2C)"

Pharmacological prevention strategies of CI-AKI

Level 1
"1. We recommend i.v. volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no i.v. volume expansion, in patients at increased risk for CI-AKI. (Level of Evidence: 1A)"
"2. We recommend not using oral fluids alone in patients at increased risk of CI-AKI. (Level of Evidence: 1C)"
"3. We recommend not using fenoldopam to prevent CI-AKI. (Level of Evidence: 1B)"
Level 2
"1. We suggest using oral NAC, together with i.v. iso-tonic crystalloids, in patients at increased risk of CI-AKI. (Level of Evidence: 2D)"
"2. We suggest not using theophylline to prevent CI-AKI. (Level of Evidence: 2C)"

2011 ACCF/AHA/SCAI Guideline Recommendations: Pre-procedural Considerations (DO NOT EDIT)[29]

Contrast-Induced Acute Kidney Injury

Class I
"1. Patients should be assessed for risk of contrast-induced acute kidney injury before PCI.[30][31] (Level of Evidence: C)"
"2. Patients undergoing cardiac catheterization with contrast media should receive adequate preparatory hydration.[32][8][9][33] (Level of Evidence: B)"
"3. In patients with chronic kidney disease (CKD) (creatinine clearance <60 mL/min), the volume of contrast media should be minimized.[34][35][36] (Level of Evidence: B)"
Class III: Harm
"'1. Administration of N-acetyl-L-cysteine is not useful for the prevention of contrast-induced acute kidney injury.[37][38][39][40][21] (Level of Evidence: B)"

References

  1. Kidney Disease Improving Global Outcomes Work Group (2012). "2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury". Kidey Int Supp. 2: 69–88. doi:10.1038/kisup.2011.34.
  2. Nyman U, Björk J, Aspelin P, Marenzi G (2008). "Contrast medium dose-to-GFR ratio: a measure of systemic exposure to predict contrast-induced nephropathy after percutaneous coronary intervention". Acta Radiol. 49 (6): 658–67. doi:10.1080/02841850802050762. PMID 18568558.
  3. Cramer BC, Parfrey PS, Hutchinson TA, Baran D, Melanson DM, Ethier RE; et al. (1985). "Renal function following infusion of radiologic contrast material. A prospective controlled study". Arch Intern Med. 145 (1): 87–9. PMID 3882071.
  4. Heller CA, Knapp J, Halliday J, O'Connell D, Heller RF (1991). "Failure to demonstrate contrast nephrotoxicity". Med J Aust. 155 (5): 329–32. PMID 1895978.
  5. Rao QA, Newhouse JH (2006). "Risk of nephropathy after intravenous administration of contrast material: a critical literature analysis". Radiology. 239 (2): 392–7. doi:10.1148/radiol.2392050413. PMID 16543592.
  6. 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.
  7. 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.
  8. 8.0 8.1 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.
  9. 9.0 9.1 9.2 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. Gleeson TG, Bulugahapitiya S (2004). "Contrast-induced nephropathy". AJR Am J Roentgenol. 183 (6): 1673–89. PMID 15547209.
  18. 18.0 18.1 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.
  19. Kellum J, Leblanc M, Venkataraman R (2006). "Renal failure (acute)". Clinical evidence (15): 1191–212. PMID 16973048.
  20. 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.
  21. 21.0 21.1 ACT Investigators (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. doi:10.1161/CIRCULATIONAHA.111.038943. PMID 21859972.
  22. http://circ.ahajournals.org/content/124/11/1210.full
  23. 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.
  24. 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.
  25. Briguori C, Visconti G, Focaccio A, Airoldi F, Valgimigli M, Sangiorgi GM; et al. (2011). "Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II): RenalGuard System in High-Risk Patients for Contrast-Induced Acute Kidney Injury". Circulation. doi:10.1161/CIRCULATIONAHA.111.030759. PMID 21844075.
  26. 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.
  27. 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.
  28. Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID doi:10.1038/kisup.2011.34 Check |pmid= value (help).
  29. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B; et al. (2011). "2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions". Circulation. 124 (23): e574–651. doi:10.1161/CIR.0b013e31823ba622. PMID 22064601.
  30. Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, Mintz GS, Lansky AJ, Moses JW, Stone GW, Leon MB, Dangas G (2004). "A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation". Journal of the American College of Cardiology. 44 (7): 1393–9. doi:10.1016/j.jacc.2004.06.068. PMID 15464318. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)
  31. Moscucci M, Rogers EK, Montoye C, Smith DE, Share D, O'Donnell M, Maxwell-Eward A, Meengs WL, De Franco AC, Patel K, McNamara R, McGinnity JG, Jani SM, Khanal S, Eagle KA (2006). "Association of a continuous quality improvement initiative with practice and outcome variations of contemporary percutaneous coronary interventions". Circulation. 113 (6): 814–22. doi:10.1161/CIRCULATIONAHA.105.541995. PMID 16461821. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)
  32. Bader BD, Berger ED, Heede MB, Silberbaur I, Duda S, Risler T, Erley CM (2004). "What is the best hydration regimen to prevent contrast media-induced nephrotoxicity?". Clinical Nephrology. 62 (1): 1–7. PMID 15267006. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  33. Trivedi HS, Moore H, Nasr S, Aggarwal K, Agrawal A, Goel P, Hewett J (2003). "A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity". Nephron. Clinical Practice. 93 (1): C29–34. PMID 12411756. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  34. Marenzi G, Assanelli E, Campodonico J, Lauri G, Marana I, De Metrio M, Moltrasio M, Grazi M, Rubino M, Veglia F, Fabbiocchi F, Bartorelli AL (2009). "Contrast volume during primary percutaneous coronary intervention and subsequent contrast-induced nephropathy and mortality". Annals of Internal Medicine. 150 (3): 170–7. PMID 19189906. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  35. 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". The American Journal of Medicine. 103 (5): 368–75. PMID 9375704. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)
  36. Russo D, Minutolo R, Cianciaruso B, Memoli B, Conte G, De Nicola L (1995). "Early effects of contrast media on renal hemodynamics and tubular function in chronic renal failure". Journal of the American Society of Nephrology : JASN. 6 (5): 1451–8. PMID 8589322. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)
  37. Gonzales DA, Norsworthy KJ, Kern SJ, Banks S, Sieving PC, Star RA, Natanson C, Danner RL (2007). "A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity". BMC Medicine. 5: 32. doi:10.1186/1741-7015-5-32. PMC 2200657. PMID 18001477. Retrieved 2011-12-06.
  38. Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O, Baris N, Aslan O, Badak O (2007). "Sodium bicarbonate, N-acetylcysteine, and saline for prevention of radiocontrast-induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures. A single-center prospective controlled trial". American Heart Journal. 154 (3): 539–44. doi:10.1016/j.ahj.2007.05.012. PMID 17719303. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)
  39. Thiele H, Hildebrand L, Schirdewahn C, Eitel I, Adams V, Fuernau G, Erbs S, Linke A, Diederich KW, Nowak M, Desch S, Gutberlet M, Schuler G (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". Journal of the American College of Cardiology. 55 (20): 2201–9. doi:10.1016/j.jacc.2009.08.091. PMID 20466200. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)
  40. Webb JG, Pate GE, Humphries KH, Buller CE, Shalansky S, Al Shamari A, Sutander A, Williams T, Fox RS, Levin A (2004). "A randomized controlled trial of intravenous N-acetylcysteine for the prevention of contrast-induced nephropathy after cardiac catheterization: lack of effect". American Heart Journal. 148 (3): 422–9. doi:10.1016/j.ahj.2004.03.041. PMID 15389228. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)

Template:WH Template:WS