Contrast induced nephropathy overview

# Overview
Contrast media (CM) are widely used in diagnostic and interventional procedures with rising incidence of iatrogenic renal function impairment caused by the exposure to contrast media, a condition known as contrast-induced nephropathy (CIN).

# Definition
In 2012, a new definiton for contrast induced nephropathy was put forth by the KDIGO-AKI guidelines. CIN was to be considered a new form of acute kidney injury (AKI) caused by contrast media, and definition criteria for AKI would also apply for CIN now called contrast-induced acute kidney injury (CI-AKI).  However, the most commonly used definition in clinical trails  is acute renal insufficiency marked by an increase in baseline serum creatinine of >25% or an absolute increase in serum creatinine of 0.5 mg/dL that occurs 48-72 hours following the exposure to CM.  The new definition shifted the 0.5 mg/dL cut-off to 0.3 mg/dL and the 25% increase in baseline to 1.5 times the original serum creatinine.

# Historical Perspective
Most of data related to the contrast nephropathy come from animal models. Studies show evidence of acute tubular necrosis (ATN) but the mechanism by which ATN occurs is not well understood.

# Pathophysiology
The pathophysiology of CIN is not clearly understood; however, several attempts have been made to explain the underlying mechanism.  It is generally agreed that CIN is due to a combination of several influences brought on by contrast-media infusion rather than a single process.  The most important mechanism thought to be involved in CIN is a reduction in renal perfusion and subsequent hypoxia.  This has been attributed to several alterations in the renal microenvironment including activation of the tubuloglomerular feeback, local vasoactive metabolites including adenosine, prostaglandin, NO, and endothelin as well as increased interstitial pressure.  Although sometimes considered controversial, studies have also proposed injury to renal tubular cells as another contributor both via a direct cytotoxic effect and via reactive oxygen species production.

# Contrast induced nephropathy differential diagnosis
The differential diagnosis includes atheroembolic renal failure, acute renal failure, acute interstitial nephritis, and acute tubular necrosis.

# Epidemiology and Demographics
Incidence of CIN in the general population have been reported to be 0.62.3%.  Considered to be the third most common cause of renal failure with overall mortality rate 19.4%, which is similar for all causes of renal insufficiency.

# Risk Factors
Many factors have been associated with an increased risk of nephropathy in patients exposed to contrast media.  Pre-existing renal insufficiency, pre-existing diabetes, age, volume of CM, and reduced intravascular volume are examples for these risk factor.  The total risk rises as the number of risk factors increase, it has been recommended that every known risk factor should be analyzed, to properly evaluate a total cumulative risk of developing contrast-induced nephropathy.   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).

# Natural history, Complications and Prognosis
CIN is often characterized by a transient increase in serum creatinine that peaks at 3 to 6 days after exposure to radiocontrast. Rarely, CIN leads to ESRD in patients with baseline kidney disease. CIN is also associated with increased risk for adverse cardiovascular events and a higher all-cause mortality. Prognosis is especially poor in patients that require hemodialysis after CIN.

# History and Symptoms
Creatinine increase is the characteristic finding in CIN, kidney injury occur with in minutes of exposure to contrast agents, however clinical manifestations such as oliguria or elevation of serum creatinine are generally observed within 24 to 48 hours after contrast exposure.

# Physical Examination
Physical examination is helpful to differentiate other causes of acute nephropathy, examples for different presentations include rash in drug-induced interstitial nephritis, blue toe and livedo reticularis in case of embolism.
Some risk factors can be detected as evidence of volume depletion, and decompensated CHF, and correcting these factors help improving the outcome.

# Laboratory Findings
Increase in the serum creatinine are generally observed within 24 to 48 hours after contrast exposure in most of patients, hyperkalemia, acidosis and hyperphosphatemia may be present.

# Medical Therapy
Management of CIN routinely includes the avoidance of substances that are toxic to the kidneys.  Dialysis is rarely required for AKI following contrast administration, but occasionally patients will require dialysis in the acute setting, the indications for dialysis are the same as in other forms of AKI.

# Prevention
Many strategies have aimed at preventing CIN. Non-therapeutic measures include smaller doses of contrast and use of low-osmolar or iso-osmolar agents. Several therapeutic measures have also been investigated notably volume expansion, N-acetylcysteine (NAC) , theophylline, statins, and fenoldopam. Evidence regarding the efficacy and benefit of each of these medical therapies has been contradictory although some have shown more promise than others. Currently only 2 therapies are indicated as preventative measures for CIN. Volume expansion via isotonic crystalloid administration (normal saline or isotonic bicarbonate) is recommended with most studies suggesting initiation 1-2 hours before and maintenance for 36 hours after contrast exposure. NAC is also recommended at 600-1200 mg orally twice daily, one day before the procedure and on the day of the procedure.