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Contrast-induced nephropathy

Contrast-induced nephropathy (CIN) is a 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. CIN is classically defined as a serum creatinine increase of at least 25% and/or an absolute increase in serum creatinine of 0.5 mg/dL[1] after using iodine contrast agent without another clear cause for acute kidney injury,[2] but other definitions have also been used.[3]

Contrast-induced nephropathy
Specialty Nephrology Edit this on Wikidata

Despite extensive speculation, the actual occurrence of contrast-induced nephropathy has not been demonstrated in the literature.[4] The mechanism of contrast-induced nephropathy is not entirely understood, but is thought to include direct damage from reactive oxygen species, 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.[citation needed]

Analysis of observational studies has shown that radiocontrast use in CT scanning is not causally related to changes in kidney function.[3] Given the increasing doubts about the contribution of radiocontrast to acute kidney injury, the American College of Radiology has proposed the name postcontrast acute kidney injury which does not imply a causal role, with CIN reserved for the rare cases where radiocontrast is likely to be causally related.[3][5]


Risk factorsEdit

Individuals with chronic kidney disease, diabetes mellitus, high blood pressure, reduced intravascular volume, or who are elderly are at increased risk of developing CIN after exposure to iodinated contrast.[2]

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):[6]

Risk Factors:

  • Systolic blood pressure <80 mm Hg - 5 points
  • Intra-arterial 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 mellitus- 3 points
  • Contrast media volume - 1 point for each 100 mL
  • Decreased kidney function:
    • Serum creatinine level >1.5 g/dL - 4 points
    • 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

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%

Contrast agentEdit

The osmolality of the contrast agent was previously believed to be an important factor in contrast-induced nephropathy. Today it has become increasingly clear that other physicochemical properties play a greater role, such as viscosity. Attention should be paid to using 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 their use has diminished.[citation needed]


Hydration by drinking or intravenous volume expander, either before or after contract administration, decreases the risk of contrast-induced nephropathy.[7] Evidence also supports the use of N-acetylcysteine with intravenous saline among those getting low molecular weight contrast.[dubious ] The use of statins with N-acetylcysteine and intravenous saline is also supported.[8]


A review in 2013 came to the conclusion that the oral route of hydration may be as effective as the intravenous route for volume expansion to prevent contrast-induced nephropathy.[7]


Adenosine antagonists such as the methylxanthines theophylline and aminophylline, may help[9] although studies have conflicting results.[10]


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 [1.00 mL/s]) may reduce risk.[medical citation needed] Some authors believe the benefit is not overwhelming.[11] A systematic review concluded that NAC is "likely to be beneficial" but did not recommend a specific dose.[12][needs update]

Ascorbic acidEdit

Ascorbic acid may be protective against CIN, according to a systematic review of randomized controlled trials.[13]

Research directionsEdit

While there are currently no FDA-approved therapies for contrast-induced nephropathy, two therapies are currently being investigated. CorMedix is currently in the latter part of phase II clinical trials with approved phase III Special Protocol Assessment for CRMD001 (unique formulation Deferiprone) to prevent contrast-induced acute kidney injury and to slow progression of chronic kidney disease. Dosing trials began in June 2010 in the sixty patient trial.[14][15]

There is also a phase III clinical trial of RenalGuard Therapy to prevent contrast-induced nephropathy.[16] The therapy utilizes the RenalGuard System, which measures a person's urine output and infuses an equal volume of normal saline in real-time. The therapy involves connecting the person to the RenalGuard System, then injecting a low dose of the loop diuretic furosemide to induce high urine output rates.[17]

A number of studies have reported the ability of RenalGuard to protect patients from CIN following catheterization procedures when compared to the standard of care, including: MYTHOS, which found RenalGuard to be superior to overnight hydration;[18] REMEDIAL II, which found RenalGuard to be superior to sodium bicarbonate hydration;[19] Protect-TAVI, which reported a significant reduction in post-procedural acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) when using RenalGuard during the procedure, compared to standard therapy;[20] and AKIGUARD, which showed significant improvement in long-term outcomes when using RenalGuard vs. standard therapy.[21] Two meta-analysis of these results (Putzu[22] and Mattathil[23]) found RenalGuard consistently reduced kidney injury, dialysis, adverse events and mortality compared to standard therapy.

Clinical relevanceEdit

Recently, 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 (AKI), dialysis, or death, even among patients with comorbidities reported to predispose them to nephrotoxicity.[4] Moreover, hydration, the most established prevention measure to prevent contrast induced nephropathy was shown to be ineffective in the POSEIDON trial,[24] raising further doubts regarding the significance of this disease state.[25] A meta-analysis of 28 studies of AKI after CT with radiocontrast showed no causal relationship between the use of radiocontrast and AKI.[3]


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