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A. Pathophysiology navigator

  1. Not entirely clear
  2. Altered renal blood flow (vasoconstriction)
    1. Contrast may induce renal vasoconstriction
    2. Renal medulla is relatively hypoxic and sensitive to ischemic injury
    3. Reduced blood flow in medulla predisposes to damage
    4. Other drugs which increase renal vasoconstriction (such as NSAIDs) increase risk
  3. Direct Tubular Injury
    1. Production of reactice oxygen species has been found
    2. Increased superoxide, peroxides and lipid peroxidation
    3. Induction of superoxide dismutase (SOD, an oxygen scavenger enzyme)
    4. Oxidation effects of radiocontrast material suggests use of anti-oxidants
    5. N-Acetylcysteine, an antioxidant, may reduce risk of radiocontrast nephropathy [2]
  4. Intraluminal obstruction by tubular cells
    1. This causes secondary acute tubular necrosis (ATN)
    2. Leads to oliguria in many cases
  5. Vasoconstriction and tubular injury occur immediately with dye exposure
  6. Clinical signs (exept oliguria) not usually seen until 24-48 hours

B. Risk Factors [14]navigator

  1. Baseline Renal Insufficiency
    1. Risk of creatinine increase >0.5mg/dL is about 20% in patients with baseline Cr>2.0mg/dL
    2. In diabetic patients with creatinine >3.0mg/dL, risk of severe renal failure >50%
    3. Iso-osmolar nonionic (iodixanol) has much reduced risk compared with low-osmolar nonionic (iohexol) contrast medias [3]
    4. N-acetylcysteine given with radiocontrast reduces renal damage (see below) [2,4]
    5. Older age increases risk, likely due to effect on baseline renal function
  2. Prerenal Failure
    1. Congestive Heart Failure (CHF) / left ventricular systolic dysfunction
    2. Cirrhosis, especially with ascites
    3. Dehydration
  3. Dye Load
    1. Load >125mL has ~20% risk of significant nephropathy (versus 2% for <125mL)
    2. Second dye load within 72 hours of first increases risk significantly
  4. Diabetes Mellitus [3,6]
    1. Appears to be greatest risk factor for dye-induced renal failure
    2. For a given creatinine, diabetics have lower renal blood flow than non-diabetics
    3. In diabetics with creatinine >2.5mg/dL, risk of renal failure is >50%
  5. Probable Contributing Factors
    1. Renal and Peripheral Vascular Disease
    2. Multiple Myeloma
    3. Dehydration
    4. ACE Inhibitors
    5. Nephrotoxic drugs - NSAIDs, cyclosporine, aminoglycosides
    6. Low osmolar contrast medias are more toxic than iso-osmolar medias [3]
  6. Possible Contributing Factors
    1. Hypertension
    2. Hyperuricemia / gout
    3. Liver dysfunction (increased renal dye clearance)
  7. No decrease in incidence of radiocontrast nephropathy with non-ionic contrast [4]

C. Predicting Renal Decline After Percutaneous Coronary Intervention (Table 1, Ref [1])navigator

  1. Risk of Increase in Serum Creatinine >0.5mg/dL or >25% / Dialysis Risk
    1. Total risk score <6: 7.5% / 1 in 2500 (0.04%)
    2. Risk score 6-10: 14% / 1 in 850 (0.12%)
    3. Risk score 11-15: 26%; 1 in 90 (1.09%)
    4. Risk score >15: 57% / 1 in 8 (12.6%)
  2. Risk Factors and Points
    1. Systolic pressure <800mm Hg for >1 hour and patient requires inotropic support or intraaortic balloon pump within 24 hours after the procedure: 5 points
    2. CHF (NYHA Class III or IV) and/or history of pulmonary edema: 5 points
    3. Age >75 years: 4 points
    4. Hematocrit <39% in men, <36% in women: 3 points
    5. Diabetes Mellitus: 3 points
    6. Volume of contrast media: 1 point for each 100 mL
    7. Baseline Renal Function:
    8. Serum creatinine level >1.5mg/dL: 4 points OR
      1. Glomerular filtration rate (GFR) 40-59mL/min/1.73m2: 2 points OR
      2. GFR 20-39mL/min/1.73m2: 4 points OR
      3. GFR <20mL/min/1.73m2: 6 points

D. Diagnosisnavigator

  1. Oliguria
    1. However, initially, osmotic diuresis may occur
    2. Oliguria often follows; anuria is very unusual
  2. Serum creatinine elevation >0.5mg/dL 24-48 hours after dye load
  3. Low urinary sodium (Na) and Low Fractional Excretion of Na
    1. Renal arteriolar vasoconstriction appears to be major effect of dye
    2. Result is mainly a "prerenal" response by tubular cells with increased Na resorption
    3. Compare with acute tubular necrosis, which has high urinary Na
  4. Urinary Microscopic Exam
    1. Renal Tubular Cells
    2. Muddy Brown Casts are not common
    3. Coarse Granular Casts are more common

E. Prevention and Treatment [1] navigator

  1. High Risk Patients [14]
    1. Good hydration ± bicarbonate is critical
    2. Strongly consider iso-osmolar nonionic contrast media such as iodixanol [3]
    3. N-acetylcysteine (NAC) is clearly superior to hydration alone for prevention [5,17]
    4. NAC provides dose-dependent protection from contrast nephropathy after angioplasty [15]
    5. Strongly consider prophylactic administration of NAC [16,17]
    6. Ascorbic acid (Vitamin C) also of some benefit in very high risk patients
    7. Avoid use of mannitol or diuretics
  2. Maintain slightly hypervolemic fluid status with isotonic saline [6]
    1. Good hydration beginning 6-12 hours prior to dye exposure
    2. Hydration with isotonic saline superior to that with half-isotonic
    3. Starting dose 1mL/kg/hour at 8:00 AM on day of angioplasty until 8:00 AM day after
    4. Maintain good urine output
  3. Close monitoring and correction of electrolytes
    1. Especially sodium, potassium and magnesium
    2. Calcium and phosphate in renal failure
  4. N-Acetylcysteine (NAC) [2,4,5,15]
    1. Antioxidant agent with vasodilating and other properties
    2. Oral dosing 600mg bid on day before and day of contrast administration
    3. May also use 600mg IV dosing prior to and then oral 600mg bid x 48 hours after contrast
    4. IV dosing 150mg/kg 30 minutes before and 50mg/kg over 4 hours after radiocontrast [7]
    5. NAC oral or IV reduced incidence of creatinine rise >0.5mg/dL by 65-90%
    6. NAC showed trends to reducing hospital utilization after primary angioplasty [15]
    7. NAC was well tolerated with side effects similar to placebo
    8. Strongly recommend use of NAC in patients with any pre-existing renal dysfunction [16,17]
  5. Sodium Bicarbonate (NaHCO3) [8,14]
    1. 119 patients with creatinine >1.0mg/dL who are to recieve iopamidol contrast
    2. Receive either 154 mEq/L infusion with either normal saline (NaCl) or NaHCO3
    3. Solution given as 3mL/kg/hr x 1 hour before contrast, 1mL/kg/hr x 6 hours after
    4. Contast induced nephropathy in 13.6% with NaCl versus 1.7% with NaHCO3 (P=0.02)
    5. In additional 191 consecutive patients receiving NaHCO3, nephropathy occured in 1.6%
    6. Consider NaHCO3 for moderate to high risk patients
  6. Fenoldapam (Corlopam®) [9,10]
    1. Intravenous selective DA1 receptor agonist
    2. Vasodilatory and natriuretic effects approved for treatment of hypertensive crisis
    3. Starting dose is 0.1-0.3µg/kg/minute IV infusion; maximum 1.6µg/kg/minute IV
    4. Onset 4-5 minutes, duration 10-30 minutes
    5. Did not prevent radiocontrast nephropathy in patients with chronic renal failure [11]
    6. Side effects typical of vasodilation (hypotension, flushing, headache, dizziness)
  7. Forced diuresis is no longer recommended [1]
    1. Intravenous furosemide and/or mannitol recommended in past
    2. Saline 0.45% alone more effective in preventing renal failure than forced diuresis
    3. Furosemide and/or mannitol in diabetics receiving contrast is contraindicated
  8. Dopamine
    1. "Renal Range" ~1-3.5µg/kg/min IV
    2. Excellent for increasing diuresis in patients with underlying CHF but overall no ability to alter course of progression or prevent acute renal failure (ARF)
    3. Monitor heart rate (may increase with dopamine)
  9. Hemofiltration [12]
    1. Investigated in 114 patients at risk for ARF with serum creatinine >2mg/dL (>176.8mM)
    2. Definition of ARF in study is 25% increase in baseline creatinine
    3. Hemofiltration group had 5% incidence of ARF versus 50% with control patients
    4. Hemofiltration group had 9% in hospital events versus 52% with placebo
    5. Hemofiltration group had 10% 1-year mortality versus 30% with control
  10. Hemodialysis
    1. Short term dialysis may be needed
    2. Dialysis should only be instituted if needed
    3. Prophylactic hemodialysis is potentially harmful after nonionic contrast [13]

References navigator

  1. Barrett BJ and Parfrey PS. 2006.
  2. Kay J, Chow WH, Chan TM, et al. 2003. JAMA. 289(5):553 abstract
  3. Aspelin P, Aubry P, Fransson SG, et al. 2003. NEJM. 348(6):491 abstract
  4. Tepel M, van der Giet M, Schwarzfeld C, et al. 2000. NEJM. 343(3):180 abstract
  5. Birck R, Krzossok S, Markowetz F, et al. 2003. Lancet. 362(9382):598
  6. Mueller C, Buerlke G, Buettner HJ, et al. 2002. Arch Intern Med. 162:329 abstract
  7. Baker CS, Wragg A, Kumar S, et al. 2003. J Am Coll Cardiol. 41:2114 abstract
  8. Merten GJ, Burgess WP, Gray LV, et al. 2004. JAMA. 291(19):2328 abstract
  9. Murphy MB, Murray C, Shorten GD. 2001. NEJM. 345(21):1548 abstract
  10. Kini AS, Miltre CA, Kamran M, et al. 2002. Am J Cardiol. 89:999 abstract
  11. Stone GW, McCullough PA, Tumlin JA, et al. 2003. JAMA. 290(17):2284 abstract
  12. Marenzi G, Marana I, Lauri G, et al. 2003. NEJM. 349(14):1333 abstract
  13. Vogt B, Ferrari P, Schonholzer C, et al. 2001. Am J Med. 111(9):692 abstract
  14. Pannu N, Wiebe N, Tonelli M. 2006. JAMA. 295(23):2765 abstract
  15. Marenzi G, Assanelli E, Maranta I, et al. 2006. NEJM. 354(26):2773 abstract
  16. Goldfarb S. 2008. Ann Intern Med. 148(1):49 abstract
  17. Kelly AM, Dwamena B, Cronin P, et al. 2008. Ann Intern Med. 148(4):284 abstract