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Are Screening Serum Creatinine Levels Necessary prior to Outpatient CT Examinations?¹

¹ From the Radiology Section, Emory Clinic, 1364 Clifton Rd NE, Atlanta, GA 30322. From the 1996 RSNA scientific assembly. Received November 25, 1998; revision requested January 18, 1999; final revision received December 3; accepted December 17. Address correspondence to R.B.T. (e-mail: rtippin@emory.edu).

	ABSTRACT

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PURPOSE: To determine the percentage of outpatients with elevated serum creatinine levels (2.0 mg/dL [177 µmol/L]) and associated reported risk factors for contrast material–induced nephrotoxic reactions (eg, diabetes, renal disease, male, age 60 years, chemotherapy) who undergo computed tomography (CT) and to define a true high-risk population.

MATERIALS AND METHODS: The serum creatinine levels were obtained in a total of 2,034 consecutive outpatients (969 male, 1,065 female) who underwent contrast material–enhanced CT. In addition, selected patient charts were reviewed to determine the presence of risk factors for contrast material–induced nephrotoxic reactions.

RESULTS: Only 66 (3.2%) had an elevated serum creatinine level. Risk factors were identified in 64 of the 66 (97%) patients with an elevated serum creatinine level. Renal disease was present in 62 of the 66 (94%) patients. Two of the 66 patients with an elevated creatinine level had no identifiable risk factors, representing 0.1% of the total number of patients.

CONCLUSION: The data suggest that the majority of patients with a serum creatinine level of at least 2.0 mg/dL (177 µmol/L) will be identified by screening for risk factors. Careful patient screening, especially for renal disease, at the time of scheduling could result in considerable savings in terms of radiology man-hours expended and laboratory costs.

Index terms: Contrast media, complications, 81.12112 • Kidney, CT, 81.12112 • Kidney, failure

	INTRODUCTION

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Acute impairment of renal function from the use of intravascular radiographic contrast material is a well-documented complication (1–19). At many medical centers, serum creatinine levels are routinely obtained prior to contrast material–enhanced examinations as a method for predicting those susceptible to renal impairment. Contrast material–induced nephropathy has been investigated in many studies, but these studies were complicated by a number of factors, which included the lack of a clearly defined mechanism for nephrotoxic reactions, different parameters used to measure renal failure and renal insufficiency, a low prevalence of clinically important renal insufficiency, and a large number of associated risk factors (1,2,5,6,8–15,19).

The most commonly cited risk factors for contrast material–induced nephrotoxic reactions are preexistent renal insufficiency and diabetes mellitus (1–3,5,8–19). Other risk factors cited include advanced age, diuretic use, nephrotoxic medications (eg, aminoglycosides), dehydration, multiple myeloma, congestive heart failure, previous myocardial infarction, the presence of a single kidney, and a large volume of contrast material (1–19). Advanced age has been variably defined as age greater than 55 years (3), greater than 60 years (1,9), and greater than 70 years (14). A large volume of contrast material has been cited as ranging from 30 to 250–800 mL of low-osmolality contrast material (5,14,15).

In addition to the large number of risk factors previously associated with contrast-induced nephrotoxic reactions, studies are further complicated by the interrelationship between many of these risk factors. The purpose of this study was to determine the percentage of outpatients referred for contrast-enhanced computed tomography (CT) who have an elevated baseline serum creatinine level and to identify any associated risk factors in an attempt to define a true high-risk population and eliminate the need for routinely obtaining serum creatinine levels.

	MATERIALS AND METHODS

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Serum creatinine levels are routinely obtained in all patients scheduled to undergo contrast-enhanced CT at our institution. In this study, creatinine levels were obtained in 2,555 consecutive outpatients prior to CT with intravenous administration of contrast material over 9 months. Duplicate CT scans in the same patients were eliminated; thus, the total number of different patients was 2,034. Of these, 1,065 were female and 969 were male.

Different baseline serum creatinine values, ranging from 1.5 to 2.0 mg/dL (133 to 177 µmol/L), have been used in various studies to indicate preexistent renal insufficiency (1,3,8–15,17–19). The clinical laboratory at our institution reports a creatinine value of greater than 1.5 mg/dL (133 µmol/L) as abnormal, but historically at our institution, contrast material has been frequently administered to patients with a creatinine level of up to 1.9 mg/dL (168 µmol/L). For the purposes of this study, the following three categories of creatinine levels were defined: "normal" for creatinine levels less than 1.5 mg/dL (133 µmol/L), "borderline" for creatinine levels of 1.5–1.9 mg/dL (133–168 µmol/L), and "abnormal" for creatinine levels greater than or equal to 2.0 mg/dL (177 µmol/L).

The most recent creatinine level prior to scanning was determined for each of the 2,034 patients, and the creatinine level in each patient was then assigned to one of the three categories. Of these 2,034 patients, 66 had abnormal creatinine levels, 102 had borderline creatinine levels, and 1,866 patients had normal creatinine levels. A majority of the creatinine levels were obtained within a few days (mean ± SD = 12.7 days ± 1.2, with a median of 3 days and a mode of 0 days) prior to CT.

The medical record of each patient in the abnormal and borderline creatinine level categories was then reviewed (R.B.T.) to identify any risk factors that might be associated with nephrotoxic reactions. These risk factors were a history of renal insufficiency or renal disease, diabetes mellitus, advanced age, male sex, nephrotoxic-drug (furosemide) use, and chemotherapy (including amphotericin B, aminoglycosides, vancomycin, methotrexate, cyclosporine, nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, cisplatin, doxorubicin hydrochloride, tacrolimus, and fluorouracil), human immunodeficiency virus or acquired immunodeficiency syndrome, and the presence of a solitary kidney. A sample of 240 patients with normal creatinine levels were chosen randomly to give a total number in the normal creatinine level category that was approximately four times greater than the number of patients in the abnormal creatinine level category, and the medical records of the patients in this category were reviewed.

Comparison between groups was performed by using the ² test of homogeneity. Linear regression analysis was performed to compare age and creatinine level. A P value of less than .05 indicated a significant difference.

Our internal review board was consulted and determined that its approval and informed consent were not required for our study.

	RESULTS

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Charts were reviewed for all of the 66 patients with abnormal and the 102 patients with borderline creatinine levels, as well as for the 240 randomly selected patients with normal creatinine levels, for a total of 408 (182 female, 226 male) of the 2,034 patients. The ages ranged from 13 to 94 years, with a mean age of 57 years for female and 60 years for male patients. The most frequently occurring single creatinine level was 1.5 mg/dL (133 µmol/L) among the 2,034 patients; however, 70% of the levels were less than this. The maximum serum creatinine level obtained was 11.5 mg/dL (1,017 µmol/L). Of the 66 abnormal values, 39 (59%) were 2.0–2.9 mg/dL (177–256 µmol/L), six (9%) were 3.0–3.9 mg/dL (265–345 µmol/L), four (6%) were 4.0–4.9 mg/dL (354–433 µmol/L), two (3%) were 5.0–5.9 mg/dL (442–522 µmol/L), three (5%) were 6.0–6.9 mg/dL (530–610 µmol/L), four (6%) were 7.0–7.9 mg/dL (619–698 µmol/L), and two (3%) each were 8.0–8.9 mg/dL (707–787 µmol/L), 9.0–9.9 mg/dL (796–875 µmol/L), 10.0–10.9 mg/dL (884–964 µmol/L), or 11.0–11.9 mg/dL (972–1,052 µmol/L).

Within each creatinine level category, there was no significant difference between the mean ages or the mean creatinine levels of male and female patients. In the borderline category, there were 76 male and 26 female patients (P < .001), with mean creatinine levels of 1.6 mg/dL (141 µmol/L) for both groups. There were 44 male and 22 female patients (P < .001) in the abnormal creatinine level category with mean creatinine levels of 4.3 and 4.7 mg/dL (380 and 415 µmol/L), respectively. There was no significant difference in the number of male and female patients when the normal and borderline creatinine level categories were combined and were compared with the abnormal creatinine level category. The difference between the abnormal and normal categories was significant (P =.049).

There was no linear correlation between the patient age and the creatinine level (r² = 0.002). When age was considered as a discrete variable, with cutoff ages of 60–80 years in 5-year increments starting at 60 years (<60 vs 60 years, <65 vs 65 years, etc), there was no age cutoff associated with an increased risk of having an abnormal creatinine level by using normal and borderline groups combined and comparing the combined group with the abnormal group.

Only one patient with a normal creatinine level in the randomly selected subset had more than one risk factor present (Fig 1) when excluding patient age as a risk factor. Age was excluded in this consideration because it was not found to be a significant contributing factor for creatinine levels greater than or equal to 2.0 mg/dL (177 µmol/L). This male patient had insulin-dependent diabetes (IDDM) and was receiving furosemide therapy. He represented 0.4% of the patients in the normal creatinine level category. Of the remaining patients in the normal subset, 68% (163 of 240) had no risk factors, and 30% (73 of 240) had one risk factor. In the borderline category, with age excluded, 47% (48 of 102) of the patients had no risk factors, and 53% (54 of 102) had one or more risk factors. Of those patients in the abnormal category, with age excluded as a risk factor, 3% (two of 66) had no identifiable risk factor, and 97% (64 of 66) had one or more risk factors present.

View larger version (37K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Bar graph shows the number of risk factors present in categories of serum creatinine levels. Dotted bar = normal creatinine level, black bar = borderline creatinine level, and hatched bar = abnormal creatinine level.

View larger version (27K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Bar graph shows the percentage of patients with each category of creatinine values and with various risk factors. Dotted bar = normal creatinine level, black bar = borderline creatinine level, and hatched bar = abnormal creatinine level. CHEMO = chemotherapy at the time the creatinine level was obtained, RI = renal insufficiency, and SOL. KIDNEY = solitary kidney.

Of those patients with multiple risk factors present, none of the patients in the normal creatinine level category had both the risk factors of diabetes and preexistent renal insufficiency. Two of the seven patients with NIDDM (and none of the patients with IDDM) in the borderline creatinine level category had a history of renal insufficiency. All nine of the patients with IDDM and all three of the patients with NIDDM in the abnormal creatinine level category had a history of renal insufficiency. Therefore, in total, with inclusion of all categories, nine of 18 patients with IDDM and five of 21 patients with NIDDM had coexistent renal insufficiency.

	DISCUSSION

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A substantial amount of time and expense is spent in obtaining creatinine levels in all patients scheduled for contrast-enhanced radiologic procedures at our institution, as well as many others around the country. Through careful patient screening, the routine acquisition of serum creatinine levels could be limited to a high-risk subpopulation, which would lead to substantial cost savings.

In our study, a history of previous renal disease was the risk factor found to be most significantly associated with an elevated baseline serum creatinine level, with 94% of the patients in the abnormal category having this finding. IDDM or NIDDM was also significantly associated with an elevated creatinine level (18% of the patients with an abnormal serum creatinine level). Fifty percent of the patients with IDDM had coexistent renal insufficiency.

This is similar to findings in the report by Lautin et al (1), who found that baseline renal insufficiency and diabetes mellitus were statistically significant predisposing factors for contrast material–induced nephropathy. Also, patients with IDDM and renal insufficiency had a greater increase in serum creatinine levels after contrast material injection than did patients with IDDM and no renal insufficiency (1,4).

In our study, all of the patients with IDDM or NIDDM and an abnormal creatinine level had an identifiable history of renal insufficiency. Rudnick et al (19) found that "in patients undergoing cardiac angiography, only those with pre-existing renal insufficiency alone or combined with diabetes are at higher risk for acute contrast nephrotoxicity." Parfrey et al (13), in a prospective study, reported little risk of clinically important nephrotoxic reaction in patients with diabetes and normal renal function or with preexistent renal insufficiency (creatinine level 1.7 mg/dL [150 µmol/L]) without diabetes. It has been noted that patients with renal insufficiency secondary to diabetes mellitus may be at greater risk of contrast material–induced nephrotoxic reactions than patients with renal insufficiency from other causes (9).

Lautin et al (1) also found that the age and sex of the patients were not important contributing factors (1), although progressive reduction in renal mass and blood flow occurs with aging (9). In our study, no linear correlation was found between the patient age and the creatinine level. There was no significant difference between age and creatinine level when using age as a discrete variable, with the categories combined as normal and borderline versus the abnormal category. Bettman (2) has questioned the validity of using age as a binary variable rather than a continuous variable; however, he argues that this also applies to an arbitrary definition of azotemia, due to the relative inaccuracy of single isolated measurements. This again underscores the complexities encountered when investigating this topic.

Cochran et al (3) found that both age and male sex were risk factors for the development of renal angiography–induced acute renal impairment, with patients older than 55 years being 1.9 times more likely and male patients being 3.2 times more likely than female patients to have an increase in the serum creatinine level. In our study, male patients were significantly more likely to have an elevated baseline serum creatinine level when comparing the categories of normal, borderline, and abnormal. Male patients were only slightly more likely (not statistically significant) to have an elevated baseline serum creatinine level when comparing normal plus borderline versus abnormal categories. Cochran et al (3) suggested that, whereas age is an independent risk factor, sex is strongly related to other risk factors.

Only 66 of 2,034 (3.2%) different patients who underwent contrast-enhanced CT had an abnormal creatinine level (2.0 mg/dL [177 µmol/L]). Two of these patients had no identifiable risk factors, representing 0.1% (exclusive of age) of the total number of patients who would have been "missed" by using a selective screening process rather than routine screening of serum creatinine levels in all patients. The creatinine levels in these two patients were 2.0 mg/dL (177 µmol/L) and 2.2 mg/dL (194 µmol/L). Findings of prior studies (6,15) suggest that if these patients had received intravenous contrast material, they would have most likely experienced a transient increase in the serum creatinine level, which would have been clinically unimportant.

This project was undertaken in an effort to identify risk factors for contrast material–induced nephrotoxic reactions prior to contrast-enhanced CT, and it was not within the scope of this project to follow up patients (particularly those in the borderline creatinine level category) with subsequent acquisition of postcontrast creatinine levels. While there remains an ethical dilemma in the possibility of missing an elevated creatinine level, there are many institutions and clinical practices that do not routinely check creatinine levels. This project was performed in an attempt to elucidate those factors in the patient history that would signal a patient at risk and therefore identify the patient in whom determining a creatinine level would be mandatory prior to intravenous contrast material administration.

Our data show that identifying risk factors will result in the identification of the majority of patients with an elevated creatinine level and may decrease the need for routine screening of serum creatinine levels in outpatients scheduled for contrast-enhanced CT of intravenous urography. Identification of one or more risk factors at the time of scheduling, particularly previous renal disease or diabetes mellitus, would result in obtaining creatinine levels in only a minority of select patients.

The laboratory cost of obtaining a creatinine level at our institution is $15.00, and the cost is $65.00 for a sequential multichannel autoanalyzer 8 basic metabolic screening. The elimination of routine creatinine testing might have saved between $29,000 and $125,700 for the 2,034 patients in this study, depending on the laboratory test ordered. Many of these patients probably would have had laboratory studies available anyway, but selective screening of patients could still result in a substantial cost savings in both the direct laboratory costs and the indirect costs, such as radiology man-hours spent in obtaining the laboratory results and patient inconvenience for another laboratory test. Prescreening by asking the patient a few simple clinical questions could result in identification of those patients in whom a baseline serum creatinine level is needed as an additional predictor of their risk of contrast material–induced nephrotoxic reaction.

	ACKNOWLEDGMENTS

 
We thank Michelle Light, BS, for assistance in data collection for this manuscript.

	FOOTNOTES

 
Abbreviations: IDDM = insulin-dependent diabetes mellitus, NIDDM = non–insulin-dependent diabetes mellitus

Author contributions: Guarantors of integrity of entire study, R.B.T., W.E.T., B.R.B.; study concepts and design, R.B.T., W.E.T., B.R.B.; definition of intellectual content, all authors; literature research, R.B.T.; clinical studies, all authors; data acquisition, R.B.T.; data analysis, all authors; statistical analysis, R.B.T., D.A.B.; manuscript preparation, R.B.T.; manuscript editing, R.B.T., W.E.T., B.R.B.; manuscript review, W.E.T., B.R.B., D.A.B.

	REFERENCES

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