Contrast-induced Nephropathy
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Contrast-induced nephropathy (CIN) is a purported form of kidney damage in which there has been recent exposure to medical imaging contrast material without another clear cause for the acute kidney injury. Despite extensive speculation, the actual occurrence of contrast-induced nephropathy has not been demonstrated in the literature. Analysis of observational studies has shown that radiocontrast use in CT scanning is not causally related to changes in kidney function.


Terminology

Given the increasing doubts about the contribution of radiocontrast to acute kidney injury, the
American College of Radiology The American College of Radiology (ACR), founded in 1923, is a professional medical society representing nearly 40,000 diagnostic radiologists, radiation oncologists, interventional radiologists, nuclear medicine physicians and medical physicists ...
has proposed the name contrast-associated acute kidney injury (CA-AKI) (formerly referred to as post-contrast acute kidney injury; PC-AKI) does not imply a causal role, with the name contrast-induced acute kidney injury (CI-AKI) (formerly referred to as contrast-induced nephropathy; CIN) reserved for the rare cases where radiocontrast is likely to be causally related.


Risk factors

There are multiple risk factors of contrast-induced nephropathy, whereof a 2016 review emphasized
chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, ...
,
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
,
high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...
, reduced intravascular volume, and old age.


Decreased kidney function

European guidelines classify a pre-existing decreased
kidney function Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's fluid ...
to be a risk factor of contrast-induced nephropathy in the following cases: * Estimated
glomerular filtration rate Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pre ...
(eGFR) < 45 ml/min/1.73 m2 of
body surface area In physiology and medicine, the body surface area (BSA) is the measured or calculated surface area of a human body. For many clinical purposes, BSA is a better indicator of metabolic mass than body weight because it is less affected by abnormal a ...
before intra-arterial administration with first-pass renal exposure (not passing lungs or peripheral circulation before kidneys), or in the
intensive care unit 220px, Intensive care unit An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensi ...
* eGFR < 30 ml/min/1.73 m2 before intravenous administration or intra-arterial administration with second-pass renal exposure * Known or suspected
acute kidney injury Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cl ...
To calculate estimated GFR from creatinine, European guidelines use the CKD-EPI formula in adults ≥ 18 years, and the revised Schwartz formula in children. Swedish guidelines recommends no specific formula in children because of lack of evidence, but on the other hand recommends GFR based on cystatin C rather than creatinine in those with abnormal muscle mass or liver failure or cirrhosis.


Mehran score

The Mehran score is a
clinical prediction rule A clinical prediction rule or clinical probability assessment specifies how to use medical signs, symptoms, and other findings to estimate the probability of a specific disease or clinical outcome. Physicians have difficulty in estimated risks of ...
to estimate probability of CIN which includes the following risk factors: systolic
blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressur ...
<80 mm Hg for at least one hour requiring inotropic support, intra-arterial balloon pump,
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
with NYHA class III or worse, history of
pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is du ...
, age >75 years, hematocrit level <39% for men and <35% for women, diabetes mellitus, contrast media volume, decreased kidney function (serum creatinine level >1.5 g/dL or decreased estimated
glomerular filtration rate Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pre ...
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Other factors

European guidelines include the following procedure-related risk factors: * Large doses of contrast given intra-arterially with first-pass renal exposure * Use of contrast agents with high osmolality (limited use today) * Multiple contrast injections within 48–72 h. Swedish guidelines also include gadolinium
MRI contrast agent MRI contrast agents are contrast agents used to improve the visibility of internal body structures in magnetic resonance imaging (MRI). The most commonly used compounds for contrast enhancement are gadolinium-based. Such MRI contrast agents shorte ...
s in this aspect. Swedish guidelines list the following additional risk factors: * Hypoxia *
Cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
*
NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
or nephrotoxic medication * Individuals on dialysis with residual renal function of at least 400 ml urine/24h * Individuals having undergone
kidney transplantation Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with chronic kidney disease, end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or li ...


Prevention

The main alternatives in people with a risk of contrast-induced nephropathy are: * Adjustment of the radiocontrast dose * Treating or mitigating risk factors * Using no intravenous contrast for the investigation. * Switching to another modality such as
ultrasonography Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies f ...
or MRI.


Dose adjustment

According to European guidelines, the ratio of the contrast dose (in grams of iodine) divided by the absolute estimated
glomerular filtration rate Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pre ...
(GFR) should be less than 1.1 g/(ml/min) for intra-arterial contrast medium administration with first-pass renal exposure (not passing lungs or peripheral tissue before reaching the kidneys). Swedish guidelines are more restrictive, recommending a ratio of less than 0.5 g/(ml/min) in patients with risk factors and irrespective of route of administration, and even more caution in first-pass renal exposure.


Treating or mitigating risk factors

Hydration by
drinking Drinking is the act of ingesting water or other liquids into the body through the mouth, proboscis, or elsewhere. Humans drink by swallowing, completed by peristalsis in the esophagus. The physiological processes of drinking vary widely among ...
or intravenous
volume expander A volume expander is a type of intravenous therapy that has the function of providing volume for the circulatory system. It may be used for fluid replacement or during surgery to prevent nausea and vomiting after surgery. Physiology When blood is ...
, either before or after contrast administration, decreases the risk of contrast-induced nephropathy. Evidence also supports the use of
N-acetylcysteine Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...
with intravenous saline among those getting low molecular weight contrast. The use of
statins Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Lo ...
with N-acetylcysteine and intravenous saline is also supported. * Oral hydration may be as effective as the intravenous route for volume expansion to prevent contrast-induced nephropathy, according to a review in 2013. *
Adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside buildin ...
antagonists such as the
methylxanthine Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine, ...
s
theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
and aminophylline, may help although studies have conflicting results. * N-acetylcysteine (NAC) by mouth twice a day, on the day before and of the procedure if creatinine clearance is estimated to be less than 60 mL/min .00 mL/s may reduce risk. Some authors believe the benefit is not overwhelming. A
systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...
concluded that NAC is "likely to be beneficial" but did not recommend a specific dose. *
Ascorbic acid Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) a ...
may be protective against CIN, according to a
systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...
of
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical ...
s. * Matched hydration, meaning infusion of a volume of normal saline equal to the urine output, has been found to reduce kidney injury, dialysis, adverse events and mortality compared to standard therapy.


Diagnosis

CIN is classically defined as a
serum creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...
increase of at least 25% and/or an absolute increase in serum creatinine of 0.5 mg/dL after using iodine
contrast agent A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radio ...
without another clear cause for acute kidney injury, but other definitions have also been used. The
American College of Radiology The American College of Radiology (ACR), founded in 1923, is a professional medical society representing nearly 40,000 diagnostic radiologists, radiation oncologists, interventional radiologists, nuclear medicine physicians and medical physicists ...
recommends the usage of the AKIN criteria for the diagnosis of CIN or PC-AKI. The AKIN criteria states that the diagnosis is made if within 48 hours from intravascular
contrast medium A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radi ...
exposure one of the following occurs: # Absolute
serum Serum may refer to: *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid * Truth serum, a drug that is likely to mak ...
creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...
increase of ≥0.3 mg/dl (>26.4 µmol/L) # Relative
serum Serum may refer to: *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid * Truth serum, a drug that is likely to mak ...
creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...
increase of ≥50 % (≥1.5-fold above baseline) # Urine output reduced to ≤0.5 mL/kg/hour for at least 6 hours


Mechanism

The mechanism of contrast-induced nephropathy is not entirely understood, but is thought to include direct damage from
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen ...
, contrast-induced increase in urine output, increased oxygen consumption, changes in dilation and narrowing of the blood vessels to the kidneys, and changes in urine viscosity.


Prognosis

It is unclear if CIN causes persisting decline in renal function since few studies has followed patients for more than 72 hours. In one meta-analysis the decline in renal function was shown to persist in 1.1 % of the patients with CIN.


Clinical relevance

Doubts regarding the significance of the phenomenon appeared in the scientific literature. Several studies have shown that intravenous contrast material administration was not associated with excess risk of
acute kidney injury Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cl ...
, dialysis, or death, even among patients with comorbidities reported to predispose them to nephrotoxicity. Moreover, hydration, the most established prevention measure to prevent contrast-induced nephropathy was shown to be ineffective in the POSEIDON trial, raising further doubts regarding the significance of this disease state. A meta-analysis of 28 studies of AKI after CT with radiocontrast showed no causal relationship between the use of radiocontrast and AKI.


References


External links

{{Urologic disease Radiology Kidney diseases