Prophylaxis Strategies for Contrast-Induced Nephropathy

							     Prophylaxis Strategies for
   Contrast-Induced Nephropathy

            JAMA. 2006;295:2765-2779

   Neesh Pannu, MD; Natasha Wiebe, MMath,
   Pstat; Marcello Tonelli, MD, SM
   for the Alberta Kidney Disease Network
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       Contrast-Induced Nephropathy
 3rdleading cause of hospital-acquired ARF (12%)
 Significant consequences
   Prolonged  hospitalization
   Requirement for dialysis
   Increased risk of death




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      Contrast-Induced Nephropathy
 ARF         in cardiac catheterization
   In-hospitalmortality: 20% in unselected patients
   1-year mortality: 66% in AMI & preexisting renal
    dysfunction
 Review
   Strategiesto prevent (evidence-based)
   Key areas of future research


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               METHODS
 English language
 MEDLINE & EMBASE
 1966 to January 2006




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                Risk Factors
 Radio   contrast nephropathy, contrastmedia,
  risk, diabetes, nephrotoxicity, creatinine,
  coronary disease, coronary procedures,
  dehydration, and hypovolemia
 59 studies




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                Clinical Trial
 Radio  contrast nephropathy, phropathy, contrast
  media, acetylcysteine, theophylline, sodium
  bicarbonate, HMG Co-A reductase inhibitors,
  ascorbic acid, kidney diseases, renal
  insufficiency, kidney failure, nephropathy,
  fenoldopam, saline, and diuretics
 331 studies, 63 randomized controlled trials
  (RCT)
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DEFINITIONS AND EPIDEMIOLOGY
 No   universally accepted definition
   Absence of other identifiable causes
   25% elevation in serum creatinine
   Absolute increase of 0.5 mg/dl (44 μmol/L), 2 to 7 days
    later
 Adverse     short- and long-term outcomes
   Unclearcausal pathway to adverse cardiovascular
    outcome
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 DEFINITIONS AND EPIDEMIOLOGY
 Incidence:   1.6% ~ 2.3%
                > intra-venous adminstration
   Intra-arterial
   Lower as defined with absolute increase
   Lower as earlier SCr measurement




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               Contrast Nephropathy
 Nonoliguric  & reversible
 SCr peaks between 2 and 5 days
 SCr returns to normal within 14 days
 Requiring dialysis: 0.4%




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               RISK FACTORS
 Retrospective,   coronary angiography
   Periprocedural hydration ?
   Accurate assessment of comorbidity ?




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               Patient-Related Factors
 Diabetes& chronic renal disease: 4 fold
 Hypovolemia, decreased effective volume
   Never assessed in clinical trials
   Benefit in hydration
   Deleterious effect of diuretics
   Cardiogenic shock, IABP, hypotension, CHF, EF <
    40%
 Female:      not increase risk independently
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        Non-Patient-Related Factors




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           Non-Patient-Related Factors
 Osmolality> 780 mOsm/kg: nephrotoxicity
 1992 meta-analysis in 25 randomized trials
   >1400    mOsm/kg in prezxisting renal disease:
     significantly increase
 Iohexol       v.s. iopamidol v.s. Iodixanol
   25%        v.s. 13.5% v.s. 11%


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           Non-Patient-Related Factors
 Nonionic     contrast
   Controversial
   Confounded    by differences in osmolality
 Severalrandomized studies: no difference
 One post-hoc analysis
   Inpreexisting renal dysfunction
   Nonionic is better

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              RISK STRATIFICATION
 None
   Validatedprospectively or in other database
   Comorbidity
   Prophylactic interventions

 Coronary     angiography



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                 RISK STRATIFICATION
   Bartholomew (n=20,479), Cr greater than 1 mg/dl
     Creatinine clearance < 60 mL/min
     IABP
     Urgent coronary procedure
     Diabetes
     CHF
     Hypertension
     Peripheral vascular disease
     Contrast volume

   2% v.s 28% in nephropathy; 17% risk of death
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              RISK STRATIFICATION
 Mehran
   Older age
   Presence of hypotension
   Anemia

 Change       in SCr ≧25% or ≧0.5 mg/dl
   Incidence:    13.1%


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  PROPHYLACTIC STRATEGIES
 Mechanism:       poorly understood
   Reduction  in renal perfusion
   Direct tubular toxicity

 Limited      success in treatment
   Renalvasoconstriction
   Hypoxia-induced oxidative stress



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   PROPHYLACTIC STRATEGIES
 Small
 Unpowered    to detect a significant benefit
 Not double-blinded
 Loss to follow up




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                              Hydration
 No  RCT studied hydration alone
 10 studies: hydration protocol & diuretics
  4     forced diuretics with hydration
       3      significant increase in nephropathy
  2   bolus infusions of N/S 250-300 ml immediately
     before or during v.s. slowly infusion for 12 hours
        No     significant difference


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                             Hydration
2    Oral hydration v.s prolonged infusion (12 hrs)
   Contradictory         result
 Time,          route, fluid tonicity & composition
           better than hypotonic
   Isotonic
   Sodium bicarbonate
          Alkalinizing   tubular fluid and minimizing damage



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                     Hydration
 Suggestive,   but incomplete evidence
 Question
   Allpatients
   Route, type, volume, timing
   Outpatient ?




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                         Vasodilators
4    RCTs “renal dose” dopamine
   None         showed a benefit
 Fenoldopam
   Dopamine-1         receptor
   Vasodilatory
  3       RCTs, 1 favored but not significant
 Insufficient       vasodilation ??
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                             Theophylline
9    trials
  RR:           0.07 ~ 1.7 (median: 0.25)
         3      of 5 favored, 1 significant
  Change            in SCr: -0.29 to 0 mg/dl (median: -0.14)
          6/8     favored, 2 significant




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                  Antioxidants
 N-Acetylcysteine
   Scavenging oxygen free radicals
   Enhancing vasodilatory effect of NO

 22   trials
   RR: 0.11 to 1.5 (median, 0.72)
   11/20 nephropathy, 13/20 change in SCr: favored



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               Ascorbic Acid
A   double-blinded RCT
  231underwent coronary catheterization
  Odd ratio: 0.38; 95% CI: 0.17 ~ 0.85




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 Extracorporeal Removal of Contrast
4    small trials with impaired renal function
  2       no benefit, 1 harmful
 Compared  with hydration alone in renal
  dysfunction
       2 trails: benefit
 Cost-effective:       SCr> 265 umol/L


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SUGGESTED MANAGEMENT STRATEGY




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               FUTURE DIRECTIONS
 Variation  in the definition of contrast-induced
  nephropathy
 Inability to accurately identify high-risk patient
 Inconsistency in the administration of cotherapies
  like hydration
 Small sample size with suboptimal study design


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                    Conclusion

While several risk factors for contrast-induced
 nephropathy have been identified, the development
 of an effective prophylaxis strategy for contrast-
 induced nephropathy has been limited by our poor
 understanding of the pathophysiology and the
 clinical significance of this condition. Future research
 should focus on correctly identifying higher-risk
 patients and testing therapies in the setting of large
 well-powered clinical trials.
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