01 September 2011: Review Article
Contrast-induced nephropathy – a review of current literature and guidelines
Artur Maliborski , Paweł Żukowski , Grzegorz Nowicki , Romana Bogusławska
DOI: 10.12659/MSM.881923
Med Sci Monit 2011; 17(9): RA199-204
Abstract
ABSTRACT: The use of iodine-based contrast agents always entails the risk of contrast-induced nephropathy (CIN). The recently observed dramatic increase in the number of examinations and therapeutic procedures using iodine-based contrast media led us to conduct a thorough analysis of the growing number of scientific reports and collective works devoted to contrast-induced nephropathy, based on current definitions, epidemiology, pathophysiology, risk factors, successful prophylaxis and guidelines of the European Society of Urogenital Radiology (ESUR). Radiological contrast agents are the third most common cause of nephropathy among in-patients, accounting for 11–12% of cases. CIN is connected with some clinically significant consequences, including increased morbidity, prolonged hospitalisation, increased risk of complications, potential need for dialysis and increased mortality rate. A significant increase in the number of examinations applying iodine-based contrast media in the course of inpatient procedures requires close cooperation of the clinician and radiologist, supported by knowledge of all CIN issues. In order to protect patients from contrast-induced nephropathy, it is necessary to monitor their renal function, indentify patients with risk factors, refer patients for examinations in a responsible manner, and undertake successful preventive measures.
Keywords: Questionnaires, Kidney Diseases - prevention & control, Guidelines as Topic, Contrast Media - adverse effects, Risk Factors
Background
A substantial increase in the number of multi-detector CT scanners in Poland, and a significant improvement in the quality of contrast media, has led in recent years to a marked rise in the number of examinations applying iodine-based contrast media. Despite a significant increase in the number of performed procedures [1,2], both in Poland and in other countries, the incidence of contrast-induced nephropathy fell in the last decade from 15% to 7% [3]. The currently applied non-iodine contrast agents cause a lower number of adverse effects; however, CIN still remains a significant problem, requiring the radiologist and the referring clinician to remain alert to threats and risk factors of nephropathy.
Definition of Contrast-Induced Nephropathy
EPIDEMIOLOGY:
Use of radiological contrast media is the third most common cause of inpatient renal insufficiency, accounting for 11–12% of all cases [6,7]. CIN is connected with significant clinical outcomes, such as prolonged hospitalization, increased risk of nosocomial complications, potential need for dialysis and increased risk of death [5,8,9]. The incidence of CIN in the general population is estimated at 1–2%. However, in older patients with diabetes, in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, congestive heart failure, or previous renal failure, the risk of nephropathy may increase to 25–30% [10–14]. The population at particular risk includes patients with diabetes accompanied by renal failure, with a risk of 50% [15,16]. The mean intrahospital case mortality rate among patients who underwent contrast-enhanced examinations and did not develop CIN is 1–2%. In patients with CIN, the rate is significantly higher and reaches 7–22%, and 36% in CIN patients requiring dialysis [8,17–19]. The long-term mortality rate (within 1–5 years) among inpatients undergoing contrast-enhanced examinations is 6–12% in individuals not developing acute renal failure, and is as high as 44% in patients developing CIN after percutaneous coronary interventions (PCI), and 55% in patients after PCI with CIN and requiring dialysis [19,20].
SCREENING OF THE BASIC RENAL FUNCTION:
Glomerular filtration rate (GFR) is an expression of the quantity of glomerular filtrate formed per unit time (usually each minute) in the nephrons of both kidneys. It indicates the volume of blood plasma filtrated per unit time by the glomeruli. GFR is usually given in ml/min or better, in ml/min * 1.72 m2 (converted to a standard body surface area) [21].
The gold standard for measuring the GFR is inulin clearance. Inulin is uniquely treated by nephrons in that it is completely filtered at the glomerulus but is neither secreted not reabsorbed by the tubules. This property of inulin allows the clearance of inulin to be used clinically as a highly accurate measure of GFR. This is clearly more accurate than the method of estimating GFR based on creatinine clearance, but is methodologically inconvenient. Unlike creatinine, inulin is not naturally present in the body. This is an advantage of inulin, because the amount infused will be known, but it is also a disadvantage because an infusion is necessary.
Inulin clearance is used more often in research than in clinical practice. Some studies have compared the determination of the inulin plasma clearance by 2 methods: the single injection and the continuous infusion method [22].
At present, the serum creatinine level remains the basic indicator of renal function. However, only the reduction of the glomerular filtration rate (GFR) by 50% leads to an increase in serum creatinine concentration, which is why its normal concentration does not exclude renal failure. In practice, this is a not a reliable indicator of the glomerular filtration rate due to (inter alia) a high dependence on other factors such as diet, muscle mass, tubular secretion of creatinine, age and sex. A better indicator is the 12- or 24-hour creatinine clearance.
CCr – Creatinine clearance,
UCr – Urine creatinine,
V – Volume of the collected urine,
SCr – Serum creatinine,
T – Time of urine collection.
Normal CCr values range from 97 to 137 ml/min for men and from 88 to 128 ml/min for women. The clearance method is a reliable indication of the glomerular filtration if the difference between the first and the second measurement does not exceed 10% [21,23]. In case of CIN development, this condition is never met. Another marker used for evaluation of the renal function (in clinical trials rather than in everyday clinical practice) is cystatin C, produced by all cells with a nucleus (cell core containing the DNA), which is freely filtered at the glomerulus and not reabsorbed. This protein seems to be a slightly more sensitive indicator of mild GFR decreases than is creatinine, especially in diabetic patients. Correlation coefficients (r) with the GFR is in favor of cystatin C over creatinine and even more in favor of the Cockcroft-Gault formula (r=74) vs. (r=67) vs. (r=88). Moreover, the Cockcroft formula is more sensitive – 96% (in comparison to 87% for cystatin C and 77% for creatinine) [24,25]. Many studies have demonstrated that cystatin-C is a better marker of renal function, particularly in diabetic patients. As the Cockcroft-Gault equation calculates GFR proportional to body weight, it considerably overestimates GFR in obese subjects. This tendency is likely to increase because the mean BMI of subjects entering dialysis is increasing twice as fast as the BMI of the U.S. general population [24]. Cystatin C clearance is an alternative method for determination of GFR [24–26].
The National Kidney Foundation Kidney Disease Outcome Quality Initiative also recommends use of GFR based on Cockcroft’s formula for clinical evaluation of renal function. The GFR should, as far as possible (emergency examinations), be established in each patient before testing using iodine contrast media [23,24,27].
The Cockcroft-Gault formula should not be used for evaluation of renal function in children under the age of 13 years. In this group of patients, its concordance with GFR is the lowest and these are cases where serum cystatin C level or Schwartz formula for pediatrics should be established, being the most reliable indicators [28,29,30].
The Schwartz formula, creatinine-based prediction of GFR, depends on age, sex, body weight and serum creatinine [29].
K=0.33 in premature infants,
K=0.45 in term infants to 1 year old,
K=0.55 in children to 13 years and adolescent females,
K=0.65 in adolescent males.
Pathophysiology
RISK FACTORS FOR CIN:
In spring 2008, on the basis of research results, the Contrast Media Safety Committee of the ESUR established risk factors for CIN development, dividing them into 2 groups: those connected with the patient and those connected with the contrast agents [4,36,37].
CIN prophylaxis
PREVENTION MEASURES AFTER THE EXAMINATION:
In recent years there have been many attempts at evaluation of the effects of different factors on prevention of contrast-induced nephropathy [40–43]. Most studies examined normal saline, sodium bicarbonate, n-acetylcysteine, theophylline, dopamine, nitrendipine, furosemide, mannitol and ascorbic acid. The effectiveness of patient hydration with the use of different methods is still ambiguous. Finally, in 2008, there appeared results of a meta-analysis including 40 randomised controlled trials in which the following substances were administered: sodium bicarbonate, n-acetylcysteine, theophylline, dopamine, nitrendipine, statins, furosemide, mannitol, and ascorbic acid [44–49]. According to the results, only the administration of n-acetylcysteine or theophylline was more advantageous to patients than hydration with normal saline, while the use of furosemide significantly increased the risk of CIN [50–55]. Taking into consideration the large number of trials and their variable results, the ESUR took a definite stand on this matter and stated that no pharmacological manipulations cold achieve comprehensive prevention of CIN. In most of the studies, hydration with 0.9% NaCl resulted in a significant reduction in the risk of contrast-induced nephropathy.
Conclusions
In everyday clinical practice, the key role in patient protection from contrast-induced nephropathy is the proper monitoring of renal function, identification of patients with risk factors, and introduction of effective preventive measures. One of the most important components of comprehensive prophylaxis is close cooperation between the radiologist and the clinician referring the patient for contrast-enhanced procedures. The result of such cooperation is unquestionably a responsible referral of the patients for examinations and proper preparation of these patients, for example by development of a proper medical history questionnaire (Figure 1), filled out before the examination, with involvement of the clinician, and allowing the radiologist to make conscious decisions and to plan the entire process before and after the examination.
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