Oral Contraceptives and the Diabetic Kidney

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Stop the Posttransplant Corticosteroids Sooner?

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Angiotensin-receptor blockers: Benefits beyond lowering blood pressure

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Hypertensive disorders of pregnancy: Overdiagnosis is appropriate

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What interventions reduce the risk of contrast nephropathy for high-risk patients?

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EVIDENCE-BASED ANSWER

Several interventions may reduce the risk of contrast nephropathy for high-risk patients; however, most evidence uses surrogate markers for clinically relevant outcomes. Because dehydration is a risk factor for developing contrast nephropathy, periprocedural hydration is routinely recommended (strength of recommendation [SOR]: C, expert opinion). Single studies have suggested that isotonic saline is associated with less risk than half-normal saline, and hydration with fluids containing sodium bicarbonate is more efficacious than those containing isotonic saline (SOR: B, single randomized controlled trial [RCT]).

Oral acetylcysteine lowers the risk of post-contrast elevations in creatinine if taken more than 24 hours before contrast administration (SOR: A, RCTs). Acetylcysteine’s low cost and favorable side effect profile make it an appealing option. Hypoosmolar contrast media are less likely to induce contrast nephropathy than hyper-osmolar media (SOR: A, RCTs). Finally, hemofiltration might be considered for patients with extremely high risk of developing contrast nephropathy (SOR: B, single RCT).

 

Evidence summary

Intravascular administration of radiocontrast is frequently associated with acute reductions in renal function, particularly for patients with risk factors (TABLE 1). Most studies have used operational definitions of contrast nephropathy based on predefined elevations in serum creatinine from baseline, the great majority of which are transient and clinically insignificant. It is unclear if interventions that reduce the rate of mild creatinine elevations (TABLE 2) also reduce the risk of clinically relevant adverse outcomes.

A single RCT showed decreased risk of contrast nephropathy for patients pretreated with intravenous fluids containing sodium bicarbonate compared with those pretreated with a sodium chloride solution (number needed to treat [NNT]=8.4).2 Another RCT showed that periprocedural hydration with isotonic saline is superior to half-normal saline in preventing contrast nephropathy (NNT=77).3 Several studies have demonstrated decreased risk of contrast nephropathy for high-risk patients when low-osmolality contrast media are used rather than high-osmolality contrast media (NNT=27).4 A single study suggested that iso-osmolar contrast media generate less contrast induced nephropathy than low-osmolar contrast media.5 Because the primary outcome in these studies was a change in serum creatinine, the NNTs listed above may not predict clinical outcomes.

Periprocedural administration of acetylcysteine reduces the risk of contrast nephropathy in high-risk patients (odds ratio=0.56; 95% confidence interval, 0.37–0.84). Oral acetylcysteine is effective if intervention is begun 24 hours before contrast administration.6 Preliminary evidence shows that intravenous administration of acetylcysteine immediately before contrast administration lowers the risk of contrast nephropathy.7 Oral acetylcysteine is low in cost and has no known side effects.

A single RCT suggests that hemofiltration initiated 4 to 6 hours before contrast administration reduces the incidence of contrast nephropathy among high-risk patients.8 The study was unusual in that patients in the intervention group experienced statistically significant reductions in several clinically relevant outcomes, including in-hospital mortality and cumulative 1-year mortality (in-hospital mortality, NNT=8.3; cumulative 1-year mortality, NNT=5). Hemofiltration is expensive and is not available in many institutions.

TABLE 1
Risk factors for the development of contrast nephropathy

Advanced age
Diabetes mellitus
Chronic renal insufficiency
Congestive heart failure
Acute myocardial infarction
Cardiogenic shock
Renal transplant
Hemodynamic instability
Dehydration
Low serum albumin
Angiotensin-converting enzyme use
Nonsteroidal anti-inflammatory drug use
Furosemide use
Higher volume of contrast media
Source: Nikolsky et al, Rev Cardiovasc Med 2003.1

TABLE 2
Interventions to reduce risk of contrast nephropathy

INTERVENTIONSORPROTOCOLS
Acetylcysteine (oral)AAcetylcysteine 600 mg PO twice daily is generally given for 2 days beginning on the day prior to the procedure.6
Hypo-osmolar contrast mediaAA variety of protocols have been demonstrated to be effective.4
Acetylcysteine (IV)B150 mg/kg of acetylcysteine was given in 500 mL of normal saline over 30 min immediately before contrast followed by 50 mg/kg of acetylcysteine in 500 mL of normal saline over 4 h. 7
Iso-osmolar contast mediaBVarying volumes of iodixanol, an iso-osmolar contrast medium, were used rather than iohexol, a low osmolar contrast medium.5
Sodium bicarbonateBPatients were given 4.23% dextrose in H20 with 154 mEq of sodium bicarbonate added per liter. Fluids were begun 1 hour prior to contrast administration running at 3 mL/kg/hr for 1 hour and then at 1 mL/kg/hr until 6 hours after contrast administration.2
Isotonic salineB0.9% sodium chloride was run at 1 mL/kg/hr beginning at 8 a.m. on the morning of the procedure or as early as possible prior to emergency procedures. The infusion was discontinued at 8 a.m. on the morning following the procedure.3
HemofiltrationBHemofiltration was started 4 to 6 hours before the procedure. It was resumed after the procedure was completed and continued for 18 to 24 hours.8
SOR, strength of recommendation. (For more on evidence ratings, see “Evidence-based medicine terms” on page 381.
 

 

 

Recommendations from others

The American College of Radiology recommends using low-osmolality contrast media for patients with renal insufficiency, particularly those with diabetes.9 Clinical Evidence found support for the use of low-osmolality contrast media, periprocedural hydration, and acetylcysteine as interventions to reduce the risk of contrast nephropathy.10

Clinical Commentary

Avoid radiocontrast agents when possible; consider hydration and acetylcysteine
Richard A. Guthmann, MD
Illinois Masonic Family Practice Residency, University of Illinois at Chicago

The best prevention of contrast nephropathy is to avoid radiocontrast agents whenever possible. Ultrasound, MRI, or CT scanning without radiocontrast can often provide adequate information. However, when contrast agents must be used for high-risk patients, lower doses and iso-osmolal nonionic agents should be considered, and serial studies should be spaced out.

Adequate hydration and avoidance of drugs with renal effects, including nonsteroidal anti-inflammatory drugs, diuretics, and angiotensin-converting enzyme inhibitors, can decrease the risk of contrast nephropathy for patients requiring a contrast study. Patients can be hydrated and their medicines held starting the day before the procedure. For patients with any risk factors for contrast nephropathy, acetylcysteine should also be administered. Sodium bicarbonate can also lower the risk of nephropathy by administering it at the time of the procedure.

Contrast nephropathy has often been defined as an immediate increase in creatinine greater than 25%. The clinical significance of small transient elevations in creatinine is unclear. Furthermore, the wide variability reported in the incidence of contrast nephropathy results from differences in the presence of risk factors. Therefore, it is important to assess each patient’s risk individually and undertake additional preventive measures accordingly.

References

1. Nikolsky E, Aymong ED, Dangas G, Mehran R. Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function. Rev Cardiovasc Med 2003;4 Suppl 1:S7-S14.

2. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328-2334.

3. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336.

4. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993;188:171-178.

5. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-499.

6. Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598-603.

7. Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol 2003;41:2114-2118.

8. Marenzi G, Marana I, Lauri G, et al. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med 2003;349:1333-1340.

9. Hauser JB, Segal A, et al. ACR Practice Guideline for the Use of Intravascular Contrast Media. American College of Radiology Practice Guidelines. 2001 (effective 1/1/2002).

10. Kellum JA, Leblanc M, Venkataraman R. Acute renal failure. Clinical Evidence. Available at: www.clinicalevidence.org. Accessed April 2004.

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EVIDENCE-BASED ANSWER

Several interventions may reduce the risk of contrast nephropathy for high-risk patients; however, most evidence uses surrogate markers for clinically relevant outcomes. Because dehydration is a risk factor for developing contrast nephropathy, periprocedural hydration is routinely recommended (strength of recommendation [SOR]: C, expert opinion). Single studies have suggested that isotonic saline is associated with less risk than half-normal saline, and hydration with fluids containing sodium bicarbonate is more efficacious than those containing isotonic saline (SOR: B, single randomized controlled trial [RCT]).

Oral acetylcysteine lowers the risk of post-contrast elevations in creatinine if taken more than 24 hours before contrast administration (SOR: A, RCTs). Acetylcysteine’s low cost and favorable side effect profile make it an appealing option. Hypoosmolar contrast media are less likely to induce contrast nephropathy than hyper-osmolar media (SOR: A, RCTs). Finally, hemofiltration might be considered for patients with extremely high risk of developing contrast nephropathy (SOR: B, single RCT).

 

Evidence summary

Intravascular administration of radiocontrast is frequently associated with acute reductions in renal function, particularly for patients with risk factors (TABLE 1). Most studies have used operational definitions of contrast nephropathy based on predefined elevations in serum creatinine from baseline, the great majority of which are transient and clinically insignificant. It is unclear if interventions that reduce the rate of mild creatinine elevations (TABLE 2) also reduce the risk of clinically relevant adverse outcomes.

A single RCT showed decreased risk of contrast nephropathy for patients pretreated with intravenous fluids containing sodium bicarbonate compared with those pretreated with a sodium chloride solution (number needed to treat [NNT]=8.4).2 Another RCT showed that periprocedural hydration with isotonic saline is superior to half-normal saline in preventing contrast nephropathy (NNT=77).3 Several studies have demonstrated decreased risk of contrast nephropathy for high-risk patients when low-osmolality contrast media are used rather than high-osmolality contrast media (NNT=27).4 A single study suggested that iso-osmolar contrast media generate less contrast induced nephropathy than low-osmolar contrast media.5 Because the primary outcome in these studies was a change in serum creatinine, the NNTs listed above may not predict clinical outcomes.

Periprocedural administration of acetylcysteine reduces the risk of contrast nephropathy in high-risk patients (odds ratio=0.56; 95% confidence interval, 0.37–0.84). Oral acetylcysteine is effective if intervention is begun 24 hours before contrast administration.6 Preliminary evidence shows that intravenous administration of acetylcysteine immediately before contrast administration lowers the risk of contrast nephropathy.7 Oral acetylcysteine is low in cost and has no known side effects.

A single RCT suggests that hemofiltration initiated 4 to 6 hours before contrast administration reduces the incidence of contrast nephropathy among high-risk patients.8 The study was unusual in that patients in the intervention group experienced statistically significant reductions in several clinically relevant outcomes, including in-hospital mortality and cumulative 1-year mortality (in-hospital mortality, NNT=8.3; cumulative 1-year mortality, NNT=5). Hemofiltration is expensive and is not available in many institutions.

TABLE 1
Risk factors for the development of contrast nephropathy

Advanced age
Diabetes mellitus
Chronic renal insufficiency
Congestive heart failure
Acute myocardial infarction
Cardiogenic shock
Renal transplant
Hemodynamic instability
Dehydration
Low serum albumin
Angiotensin-converting enzyme use
Nonsteroidal anti-inflammatory drug use
Furosemide use
Higher volume of contrast media
Source: Nikolsky et al, Rev Cardiovasc Med 2003.1

TABLE 2
Interventions to reduce risk of contrast nephropathy

INTERVENTIONSORPROTOCOLS
Acetylcysteine (oral)AAcetylcysteine 600 mg PO twice daily is generally given for 2 days beginning on the day prior to the procedure.6
Hypo-osmolar contrast mediaAA variety of protocols have been demonstrated to be effective.4
Acetylcysteine (IV)B150 mg/kg of acetylcysteine was given in 500 mL of normal saline over 30 min immediately before contrast followed by 50 mg/kg of acetylcysteine in 500 mL of normal saline over 4 h. 7
Iso-osmolar contast mediaBVarying volumes of iodixanol, an iso-osmolar contrast medium, were used rather than iohexol, a low osmolar contrast medium.5
Sodium bicarbonateBPatients were given 4.23% dextrose in H20 with 154 mEq of sodium bicarbonate added per liter. Fluids were begun 1 hour prior to contrast administration running at 3 mL/kg/hr for 1 hour and then at 1 mL/kg/hr until 6 hours after contrast administration.2
Isotonic salineB0.9% sodium chloride was run at 1 mL/kg/hr beginning at 8 a.m. on the morning of the procedure or as early as possible prior to emergency procedures. The infusion was discontinued at 8 a.m. on the morning following the procedure.3
HemofiltrationBHemofiltration was started 4 to 6 hours before the procedure. It was resumed after the procedure was completed and continued for 18 to 24 hours.8
SOR, strength of recommendation. (For more on evidence ratings, see “Evidence-based medicine terms” on page 381.
 

 

 

Recommendations from others

The American College of Radiology recommends using low-osmolality contrast media for patients with renal insufficiency, particularly those with diabetes.9 Clinical Evidence found support for the use of low-osmolality contrast media, periprocedural hydration, and acetylcysteine as interventions to reduce the risk of contrast nephropathy.10

Clinical Commentary

Avoid radiocontrast agents when possible; consider hydration and acetylcysteine
Richard A. Guthmann, MD
Illinois Masonic Family Practice Residency, University of Illinois at Chicago

The best prevention of contrast nephropathy is to avoid radiocontrast agents whenever possible. Ultrasound, MRI, or CT scanning without radiocontrast can often provide adequate information. However, when contrast agents must be used for high-risk patients, lower doses and iso-osmolal nonionic agents should be considered, and serial studies should be spaced out.

Adequate hydration and avoidance of drugs with renal effects, including nonsteroidal anti-inflammatory drugs, diuretics, and angiotensin-converting enzyme inhibitors, can decrease the risk of contrast nephropathy for patients requiring a contrast study. Patients can be hydrated and their medicines held starting the day before the procedure. For patients with any risk factors for contrast nephropathy, acetylcysteine should also be administered. Sodium bicarbonate can also lower the risk of nephropathy by administering it at the time of the procedure.

Contrast nephropathy has often been defined as an immediate increase in creatinine greater than 25%. The clinical significance of small transient elevations in creatinine is unclear. Furthermore, the wide variability reported in the incidence of contrast nephropathy results from differences in the presence of risk factors. Therefore, it is important to assess each patient’s risk individually and undertake additional preventive measures accordingly.

EVIDENCE-BASED ANSWER

Several interventions may reduce the risk of contrast nephropathy for high-risk patients; however, most evidence uses surrogate markers for clinically relevant outcomes. Because dehydration is a risk factor for developing contrast nephropathy, periprocedural hydration is routinely recommended (strength of recommendation [SOR]: C, expert opinion). Single studies have suggested that isotonic saline is associated with less risk than half-normal saline, and hydration with fluids containing sodium bicarbonate is more efficacious than those containing isotonic saline (SOR: B, single randomized controlled trial [RCT]).

Oral acetylcysteine lowers the risk of post-contrast elevations in creatinine if taken more than 24 hours before contrast administration (SOR: A, RCTs). Acetylcysteine’s low cost and favorable side effect profile make it an appealing option. Hypoosmolar contrast media are less likely to induce contrast nephropathy than hyper-osmolar media (SOR: A, RCTs). Finally, hemofiltration might be considered for patients with extremely high risk of developing contrast nephropathy (SOR: B, single RCT).

 

Evidence summary

Intravascular administration of radiocontrast is frequently associated with acute reductions in renal function, particularly for patients with risk factors (TABLE 1). Most studies have used operational definitions of contrast nephropathy based on predefined elevations in serum creatinine from baseline, the great majority of which are transient and clinically insignificant. It is unclear if interventions that reduce the rate of mild creatinine elevations (TABLE 2) also reduce the risk of clinically relevant adverse outcomes.

A single RCT showed decreased risk of contrast nephropathy for patients pretreated with intravenous fluids containing sodium bicarbonate compared with those pretreated with a sodium chloride solution (number needed to treat [NNT]=8.4).2 Another RCT showed that periprocedural hydration with isotonic saline is superior to half-normal saline in preventing contrast nephropathy (NNT=77).3 Several studies have demonstrated decreased risk of contrast nephropathy for high-risk patients when low-osmolality contrast media are used rather than high-osmolality contrast media (NNT=27).4 A single study suggested that iso-osmolar contrast media generate less contrast induced nephropathy than low-osmolar contrast media.5 Because the primary outcome in these studies was a change in serum creatinine, the NNTs listed above may not predict clinical outcomes.

Periprocedural administration of acetylcysteine reduces the risk of contrast nephropathy in high-risk patients (odds ratio=0.56; 95% confidence interval, 0.37–0.84). Oral acetylcysteine is effective if intervention is begun 24 hours before contrast administration.6 Preliminary evidence shows that intravenous administration of acetylcysteine immediately before contrast administration lowers the risk of contrast nephropathy.7 Oral acetylcysteine is low in cost and has no known side effects.

A single RCT suggests that hemofiltration initiated 4 to 6 hours before contrast administration reduces the incidence of contrast nephropathy among high-risk patients.8 The study was unusual in that patients in the intervention group experienced statistically significant reductions in several clinically relevant outcomes, including in-hospital mortality and cumulative 1-year mortality (in-hospital mortality, NNT=8.3; cumulative 1-year mortality, NNT=5). Hemofiltration is expensive and is not available in many institutions.

TABLE 1
Risk factors for the development of contrast nephropathy

Advanced age
Diabetes mellitus
Chronic renal insufficiency
Congestive heart failure
Acute myocardial infarction
Cardiogenic shock
Renal transplant
Hemodynamic instability
Dehydration
Low serum albumin
Angiotensin-converting enzyme use
Nonsteroidal anti-inflammatory drug use
Furosemide use
Higher volume of contrast media
Source: Nikolsky et al, Rev Cardiovasc Med 2003.1

TABLE 2
Interventions to reduce risk of contrast nephropathy

INTERVENTIONSORPROTOCOLS
Acetylcysteine (oral)AAcetylcysteine 600 mg PO twice daily is generally given for 2 days beginning on the day prior to the procedure.6
Hypo-osmolar contrast mediaAA variety of protocols have been demonstrated to be effective.4
Acetylcysteine (IV)B150 mg/kg of acetylcysteine was given in 500 mL of normal saline over 30 min immediately before contrast followed by 50 mg/kg of acetylcysteine in 500 mL of normal saline over 4 h. 7
Iso-osmolar contast mediaBVarying volumes of iodixanol, an iso-osmolar contrast medium, were used rather than iohexol, a low osmolar contrast medium.5
Sodium bicarbonateBPatients were given 4.23% dextrose in H20 with 154 mEq of sodium bicarbonate added per liter. Fluids were begun 1 hour prior to contrast administration running at 3 mL/kg/hr for 1 hour and then at 1 mL/kg/hr until 6 hours after contrast administration.2
Isotonic salineB0.9% sodium chloride was run at 1 mL/kg/hr beginning at 8 a.m. on the morning of the procedure or as early as possible prior to emergency procedures. The infusion was discontinued at 8 a.m. on the morning following the procedure.3
HemofiltrationBHemofiltration was started 4 to 6 hours before the procedure. It was resumed after the procedure was completed and continued for 18 to 24 hours.8
SOR, strength of recommendation. (For more on evidence ratings, see “Evidence-based medicine terms” on page 381.
 

 

 

Recommendations from others

The American College of Radiology recommends using low-osmolality contrast media for patients with renal insufficiency, particularly those with diabetes.9 Clinical Evidence found support for the use of low-osmolality contrast media, periprocedural hydration, and acetylcysteine as interventions to reduce the risk of contrast nephropathy.10

Clinical Commentary

Avoid radiocontrast agents when possible; consider hydration and acetylcysteine
Richard A. Guthmann, MD
Illinois Masonic Family Practice Residency, University of Illinois at Chicago

The best prevention of contrast nephropathy is to avoid radiocontrast agents whenever possible. Ultrasound, MRI, or CT scanning without radiocontrast can often provide adequate information. However, when contrast agents must be used for high-risk patients, lower doses and iso-osmolal nonionic agents should be considered, and serial studies should be spaced out.

Adequate hydration and avoidance of drugs with renal effects, including nonsteroidal anti-inflammatory drugs, diuretics, and angiotensin-converting enzyme inhibitors, can decrease the risk of contrast nephropathy for patients requiring a contrast study. Patients can be hydrated and their medicines held starting the day before the procedure. For patients with any risk factors for contrast nephropathy, acetylcysteine should also be administered. Sodium bicarbonate can also lower the risk of nephropathy by administering it at the time of the procedure.

Contrast nephropathy has often been defined as an immediate increase in creatinine greater than 25%. The clinical significance of small transient elevations in creatinine is unclear. Furthermore, the wide variability reported in the incidence of contrast nephropathy results from differences in the presence of risk factors. Therefore, it is important to assess each patient’s risk individually and undertake additional preventive measures accordingly.

References

1. Nikolsky E, Aymong ED, Dangas G, Mehran R. Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function. Rev Cardiovasc Med 2003;4 Suppl 1:S7-S14.

2. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328-2334.

3. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336.

4. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993;188:171-178.

5. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-499.

6. Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598-603.

7. Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol 2003;41:2114-2118.

8. Marenzi G, Marana I, Lauri G, et al. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med 2003;349:1333-1340.

9. Hauser JB, Segal A, et al. ACR Practice Guideline for the Use of Intravascular Contrast Media. American College of Radiology Practice Guidelines. 2001 (effective 1/1/2002).

10. Kellum JA, Leblanc M, Venkataraman R. Acute renal failure. Clinical Evidence. Available at: www.clinicalevidence.org. Accessed April 2004.

References

1. Nikolsky E, Aymong ED, Dangas G, Mehran R. Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function. Rev Cardiovasc Med 2003;4 Suppl 1:S7-S14.

2. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328-2334.

3. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336.

4. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993;188:171-178.

5. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-499.

6. Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598-603.

7. Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol 2003;41:2114-2118.

8. Marenzi G, Marana I, Lauri G, et al. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med 2003;349:1333-1340.

9. Hauser JB, Segal A, et al. ACR Practice Guideline for the Use of Intravascular Contrast Media. American College of Radiology Practice Guidelines. 2001 (effective 1/1/2002).

10. Kellum JA, Leblanc M, Venkataraman R. Acute renal failure. Clinical Evidence. Available at: www.clinicalevidence.org. Accessed April 2004.

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