Contrast-induced nephropathy
Encyclopedia
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 a radiographic examination using a contrast agent.
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.
. 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.
A clinical prediction rule
is available to estimate probability of nephropathy (increase ≥25% and/or ≥0.5 mg/dl in serum creatinine at 48 h):
Risk Factors:
Scoring:
5 or less points
6–10 points
11–16 points
>16 points
. 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.
A former study suggested that iso-osmolar, nonionic contrast media may be superior to others. randomized controlled trial
. 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.
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 per hour for 6–12 hours before and after the contrast.
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.
found higher doses of NAC ( IV bolus and 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 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.
In one study 15% of patients receiving NAC intravenously had allergic reactions.
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
, 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.
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 of 2010 in the sixty patient trial.
Radiocontrast
Radiocontrast agents are a type of medical contrast medium used to improve the visibility of internal bodily structures in an X-ray based imaging techniques such as computed tomography or radiography...
-induced nephropathy
Nephropathy
Nephropathy refers to damage to or disease of the kidney. An older term for this is nephrosis.-Causes:Causes of nephropathy include administration of analgesics, xanthine oxidase deficiency, and long-term exposure to lead or its salts...
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 a radiographic examination using a contrast agent.
A new definition of contrast nephropathy in patients undergoing percutaneous coronary intervention
Percutaneous coronary intervention
Percutaneous coronary intervention , commonly known as coronary angioplasty or simply angioplasty, is one therapeutic procedure used to treat the stenotic coronary arteries of the heart found in coronary heart disease. These stenotic segments are due to the build up of cholesterol-laden plaques...
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.
Risk factors
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-analysisMeta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
. A separate meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
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.
A clinical prediction rule
Clinical prediction rule
A clinical prediction rule is type of medical research study in which researchers try to identify the best combination of medical sign, symptoms, and other findings in predicting the probability of a specific disease or outcome....
is available to estimate probability of nephropathy (increase ≥25% and/or ≥0.5 mg/dl in serum creatinine at 48 h):
Risk Factors:
- 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
-
- or
- Estimated Glomerular filtration rate (online calculator)
- 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
- or
Scoring:
5 or less points
- Risk of CIN - 7.5
- Risk of Dialysis - 0.04%
6–10 points
- Risk of CIN - 14.0
- Risk of Dialysis - 0.12%
11–16 points
- Risk of CIN - 26.1*
- Risk of Dialysis - 1.09%
>16 points
- 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 viscosityViscosity
Viscosity is a measure of the resistance of a fluid which is being deformed by either shear or tensile stress. In everyday terms , viscosity is "thickness" or "internal friction". Thus, water is "thin", having a lower viscosity, while honey is "thick", having a higher 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.
A former study suggested that iso-osmolar, nonionic contrast media may be superior to others. randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
. 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 trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
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
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
, 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
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
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.
Methylxanthines
Adenosine antagonists such as the methylxanthines theophyllineTheophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
and aminophylline
Aminophylline
Aminophylline is a bronchodilator. It is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate-Properties:...
, 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
N-acetylcysteine (NAC) 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 trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
found higher doses of NAC ( IV bolus and orally twice daily for 2 days) benefited (relative risk reduction
Relative risk reduction
In epidemiology, the relative risk reduction is a measure calculated by dividing the absolute risk reduction by the control event rate.The relative risk reduction can be more useful than the absolute risk reduction in determining an appropriate treatment plan, because it accounts not only for the...
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 give four times around coronary angiography, found statistically insignificant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
trends towards benefit.
Some authors believe the benefit is not overwhelming. The strongest results were from an unblinded randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
that used NAC intravenously. A systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
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
Cystatin C
Cystatin C or cystatin 3 , a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease...
levels.
In one study 15% of patients receiving NAC intravenously had allergic reactions.
Prophylactic hemodialysis
Patients with chronic renal insufficiencyRenal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
and a creatinine over 309.4 µmol/L (3.5 mg.dl) who have elective coronary catheterization
Coronary catheterization
A coronary catheterization is a minimally invasive procedure to access the coronary circulation and blood filled chambers of the heart using a catheter. It is performed for both diagnostic and interventional purposes....
, a randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
found benefit from prophylactic hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...
Other interventions
Other pharmacological agents, such as furosemideFurosemide
Furosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...
, mannitol
Mannitol
Mannitol is a white, crystalline organic compound with the formula . This polyol is used as an osmotic diuretic agent and a weak renal vasodilator...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, and atrial natriuretic peptide
Atrial natriuretic peptide
Atrial natriuretic peptide , atrial natriuretic factor , atrial natriuretic hormone , or atriopeptin, is a powerful vasodilator, and a protein hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water, sodium, potassium and fat...
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.
Clinical Research
While there are currently no FDA-approved therapies for Contrast Induced Nephropathy, CorMedix, Inc. is currently in the latter part of Stage II clinical trials with approved Phase III Special Protocol AssessmentFDA Special Protocol Assessment
A Special Protocol Assessment is a declaration from the Food and Drug Administration that an uncompleted Phase III trial's design, clinical endpoints, and statistical analyses are acceptable for FDA approval....
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 of 2010 in the sixty patient trial.