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 after using iodine contrast agent without another clear cause for acute kidney injury, but other definitions have also been used.
Despite extensive speculation, the actual occurrence of contrast-induced nephropathy has not been demonstrated in the literature. 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.
Analysis of observational studies has shown that radiocontrast use in CT scanning is not causally related to changes in kidney function. Given the increasing doubts about the contribution of radiocontrast to acute kidney injury, the American College of Radiology has proposed the name Post-Contrast Acute Kidney Injury (PC-AKI) does not imply a causal role, with CIN or Contrast Induced Acute Kidney Injury (CI-AKI) 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 review in 2016 emphasized chronic kidney disease, diabetes mellitus, high blood pressure, reduced intravascular volume, and old age.
Decreased kidney function.
European guidelines classify a pre-existing decreased kidney function to be a risk factor of contrast-induced nephropathy in the following cases:
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.
Roxana Mehran score.
The Roxana Mehran score is a clinical prediction rule to estimate probability of nephropathy (increase ≥25% and/or ≥0.5 mg/dl in serum creatinine at 48 h):
Risk Factors:
Scoring:<br>
5 or less points
6–10 points
11–16 points
>16 points
Other factors.
European guidelines include the following procedure-related risk factors:
Swedish guidelines list the following additional risk factors:
Prevention.
The main alternatives in people with a risk of contrast-induced nephropathy are:
Dose adjustment.
According to European guidelines, the ratio of the contrast dose (in grams of iodine) divided by the absolute estimated glomerular filtration rate (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 or intravenous volume expander, either before or after contrast administration, decreases the risk of contrast-induced nephropathy. Evidence also supports the use of N-acetylcysteine with intravenous saline among those getting low molecular weight contrast. The use of statins with N-acetylcysteine and intravenous saline is also supported.
Diagnosis.
The American College of Radiology currently 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 exposure one of the following occurs:
1) Absolute serum creatinine increase of ≥0.3 mg/dl (>26.4 µmol/L)
2) Relative serum creatinine increase of ≥50 % (≥1.5-fold above baseline)
3) Urine output reduced to ≤0.5 mL/kg/hour for at least 6 hours
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.
Research directions.
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.
There is also a phase III clinical trial of RenalGuard Therapy to prevent contrast-induced nephropathy. 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.
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; REMEDIAL II, which found RenalGuard to be superior to sodium bicarbonate hydration; 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; and AKIGUARD, which showed significant improvement in long-term outcomes when using RenalGuard vs. standard therapy. Two meta-analysis of these results (Putzu and Mattathil) found RenalGuard consistently reduced kidney injury, dialysis, adverse events and mortality compared to standard therapy.
Clinical relevance.
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. 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.