Letter to the Editor: “What Is the Best Definition of Contrast-Induced Nephropathy?”

Abstract

Radiological procedures require the intravascular administration of iodinated contrast media, which are becoming a great source of an iatrogenic disease known as contrast-induced nephropathy. The development of contrast-induced nephropathy is associated with prolonged hospitalization, the potential need for renal replacement therapy, and increased mortality. Despite numerous clinical and experimental studies, several important issues regarding contrast-induced nephropathy remain controversial. One of the controversial points is its very definition: a universally accepted definition of contrast-induced nephropathy does not exist. This can be a major problem. Differing definitions of contrast-induced nephropathy and the clinical importance of these definitions were discussed in this letter.

Keywords:

• contrast media
• contrast-induced nephropathy
• cystatin-C
• definition
• serum creatinine

What Is the Best Definition of Contrast-Induced Nephropathy?

Dear Editor:

The definition of contrast-induced nephropathy (CIN) is a major problem in clinical practice. We did not have a unique accepted definition of CIN. According to the guidelines of European Society of Urogenital Radiology, the term “contrast-induced nephropathy” indicates an impairment of renal function (the elevation of serum creatinine by ≥0.5mg/dL or ≥25%) occurring within three days following the intravascular administration of contrast media and the absence of an alternative etiology.[1] The Iohexol Cooperative Study defined CIN as an increase in serum creatinine of ≥1 mg/dL 48 to 72 hours post-contrast.[2] The Nephric Trial has two separate primary endpoints, including 0.5 and 1.0 mg/dL rises in serum creatinine from day 0 to day 7.[3] The CIN Consensus Working Panel agreed that the RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage renal failure) classification, which defines renal failure in terms of glomerular filtration rate (GFR) or urine output, will be useful in the future to define CIN.[4]

Serum creatinine is the standard marker to detect CIN. However, serum creatinine demonstrates major limitations, especially in elderly patients. Minor changes of serum creatinine after contrast media infusions are frequent but usually without any clinical relevance. The incidence rates of CIN are sensitive to the definition used. The incidence of CIN is reported to be 0.6–2.3% in general population who do not have any risk factor for CIN, but the incidence can be increased to 90% in patients at high risk for CIN.[1],[4],[5] The incidence of CIN is considerably lower when the definitions of at least a 0.5 mg/dL or 1 mg/dL absolute increase in serum creatinine are used. The definition, which requires smaller increases in serum creatinine (≥25%), is more sensitive for the diagnosis of CIN associated with clinically important adverse short- and long-term outcomes.[6],[7] However, this definition should be restricted only in patients who have increased baseline serum creatinine levels or at least a baseline serum creatinine level of ≥1 mg/dL. For example, if a patient's serum creatinine level is 0.60 mg/dL at baseline, when it increases to 0.75 mg/dL after coronary angiography, is it a CIN? According to the above definition, the answer is yes; however, there is only a 0.15 mg/dL increase. Radionuclide techniques give the most accurate measurement of GFR but are labor-intensive and expensive. Using the Cockcroft-Gault and the Modification of Diet in Renal Disease equations are useful in estimating the GFR. Serum cystatin C has been proposed as an alternative endogenous marker of GFR, showing higher correlation to standard clearance methods such as inulin or iohexol clearance. Serum cystatin C may detect CIN one to two days earlier than creatinine.[8]

Cholesterol atheroemboli, volume depletion, and interstitial nephritis should be excluded when diagnosing CIN. Cholesterol embolism is usually accompanied by livedo reticularis, eosinophilia, decreased complement levels, and progressive deterioration in kidney function. The incidence of cholesterol embolism following coronary angiography was reported to be 0.09% to 1.4%.[9] In a recent study of 266 patients undergoing coronary angiography, there has been no reported case of cholesterol embolism.[10] Before contrast-using procedures, the volume status of high-risk patients can be assessed through the inferior vena cava index. In a recent CIN study, it was shown that 23 of the 421 patients (5.5%) who underwent coronary angiography have hypovolemia, which is defined an inferior vena cava index of ≤8 mm/m².[11] If the researchers don't examine the volume status, especially in the elderly patients, and if they gave the same rate and dose of the saline, the intravenous volume will not be same, and the results of the CIN incidences may be changed.

In conclusion, a universally accepted definition of CIN does not exist. The most commonly used definition for CIN in clinical trial is the elevation of serum creatinine by ≥0.5mg/dL or ≥25% occurring within 48 hours after administration of contrast media. Serum cystatin C may detect CIN one to two days earlier than creatinine. Cholesterol atheroemboli, volume depletion, and interstitial nephritis should be considered in the differential diagnosis of CIN.

Notes

*There is no conflict of interest or financial support to declare for this study.