Computerized Tomography Contrast Induced Nephropathy ( CIN ) among adult inpatients

Introduction: Contrast induced nephropathy (CIN) is one of the complications of the use of intravascular contrast agents, being defined as a reduction of the glomerular filtration rate caused by the iodinated contrast. Most CIN data derive from the cardiovascular literature, which identified as the most consistent risk factors pre-existing chronic renal insufficiency and diabetes mellitus. However, these studies limit their conclusions to a more specific patient population. Computerized tomography as a cause of CIN has been studied less often. Objective: To report on the incidence of computerized tomography contrast induced nephropathy (CIN) in an inpatient population of a tertiary general hospital, identifying potentially avoidable risk factors. Methods: We performed a prospective cohort study with inpatients admitted at a tertiary hospital requiring contrast-induced CT. The primary outcome was the development of CIN, measure by the alteration of serum creatinine or glomerular filtration rate in 48 or 72 hours. Through clinical interview, we verified possible risk factors and preventive measures instituted by the medical team and their association with development of CIN. Results: Of a total of 410 patients, 35 (8.5%) developed CIN. There was a positive correlation between CIN and the presence of diabetes mellitus (OR = 2.15; 95%CI 1.35-4.06; p = 0.02), heart failure (OR = 2.23; 95%CI 1.18-8.8; p = 0.022), and renal failure (OR = 3.36; 95%CI 1.577.17; p = 0.002) Conclusion: Incidence of CIN varies according to the population. Diabetes mellitus, heart failure and renal failure were independent risk factors for the development of CT-associated CIN. Further studies are needed to better understand and treat CT-associated CIN. Resumo


IntRoductIon
][6][7][8][9][10][11][12][13][14][15][16] Although low osmolarity and iso-osmolarity contrast media have been used for more than half a century, its physiopathologic effects on the kidneys remain largely unknown. 17Most CIN data derive from the cardiovascular literature, which identified as the most consistent risk factors pre-existing chronic renal insufficiency and diabetes mellitus. 18However, these studies limit their conclusions to a more specific patient population.
Contrast induced nephropathy in computerized tomography (CT) has been studied less often.A recent meta-analysis on the subject found only five clinical trials correlating CIN and computerized tomography, none of them in an inpatient population. 19][21][22] The objective of our study is to report on the incidence of computerized tomography CIN in an inpatient population of a tertiary general hospital, identifying potentially avoidable risk factors.

methods
We performed a cohort study with inpatients of a tertiary hospital submitted to various regimens of CT with intravenous contrast media.All subjects were at least 18 years old, remained in the hospital for at least 48 hours after the CT, and signed an informed consent.We excluded from the study patients who had been exposed to contrast media in the previous 30 days prior to enrollment, patients who died or were discharged less than 48 hours after the CT, and those who did not sign the informed consent form.
Data were collected from patient interviews, chart reviews, and laboratory exams.The variables accessed were: age, gender, diabetes mellitus, hypertension, heart failure, stroke, body mass index (BMI), serum creatinine, glomerular filtration rate (GFR), drug use, more specifically metformin, acetyl salicylic acid (ASA), angiotensin conversion enzyme (ACE) inhibitors, beta blockers, non-steroidal anti-inflammatory drugs (NSAIDs), and antibiotics, and the adoption of specific CIN preventive measures instituted by the medical team (so far, there are no standard protocols for the prevention of CIN at our institution).
Serum creatinine was obtained before contrast injection and 48hs after the exam.The same contrast media (intravenous Telebrix 30 ® , Guebert Laboratories, 1650 mOsm/Kg/H 2 O) was employed in all studies.We defined CIN as an absolute rise in serum creatinine of at least 0.5 mg/dL or as a relative increase in serum creatinine of at least 25% of the base value, 48hs after the administration of the intravenous contrast. 23Age was dichotomized in less than 65 years or 65 years of more.The loss of renal function was defined by different methodologies; initially, we considered the classic, most common definition of renal function loss as a glomerular filtration rate (GFR) of less than 60 mL/min/1.73m 2 by the Cockroft-Gault formula or a serum creatinine ≥ 1.5 mg/dL. 24,25ltimately, we have adopted the recommendation from the Kidney Disease Improving Global Outcomes (KDIGO), which defines the loss of renal function using the 2009 Chronic Kidney Disease Epidemiology Collaboration's (CKD-EPI) formula. 26In doing so, additional data were obtained from patients, from family members, and from chart reviews.
Data were entered twice into a Microsoft Excel ® , (version 7 for Windows) database by two different data managers, and were ultimately compared, to control for typing errors.Continuous variables were described as means and standard deviation (SD); categorical variables were described as frequencies and percentages.Student's t test was used to compare continuous variables, whereas Chi-square (c 2 ) and Fisher's exact tests were used for categorical variables and Kappa test.Stepwise Backward logistic regression was used to evaluate the correlation of the variables with the development of CIN.Statistical analysis was performed with the software SPSS ® (Statistical Package for the Social Sciences v. 17.0 for Windows).We considered as statistically significant a p value of less than 5% (p ≤ 0.05).

Results
From May 2007 to February 2008, we have studied 410 patients, of whom 52% were male, 12.7% were older than 65 years, 80% were caucasian and 19.2% were black.Hypertension was present in 39.5%, whereas renal failure was seen in 31% (Cockroft-Gault) and 30.2% (CKD-EPI 2009) of patients.Cancer was present in 30.5%, diabetes in 14.1%, and heart failure in 7.1%.Regarding medications used when CT was performed, 23.3% of the patients were using ACE inhibitors, 17.8% beta-blockers, 15.1% ASA, and 2.2% NSAIDs.
In our study, 23% of the patients were treated with intravenous saline before and after the procedure, whereas only 2.5% received bicarbonate.However, there was no significant association between these measures and a reduction in CIN.
Overall, 35 patients (8.5%) developed CIN.There was a positive correlation between CIN and the presence of diabetes mellitus, heart failure and renal failure, as shown in Table 1.
diagnostic CT for peripheral arterial disease in an ambulatory population, El-Hajjar et al. 1 described a 1.75% incidence of CIN.Mitchell et al. 21described an 11% incidence of CT-associated CIN (with a 2% mortality rate) in emergency room patients.In a cohort of kidney transplant receptors, Ahuja et al. 27 have reported on a 21.0% incidence of CIN.Lencione et al. 20 describe an incidence of 2.5% of CIN with inpatients but it was a retrospective study.Our incidence of computerized tomography CIN (8.5%) refers to an inpatient population from a tertiary hospital, which treats a wide range of medical conditions.We did not study ambulatory or emergency care patients, and this has to be taken into account when analyzing our results.We believe that the differences in the incidence of CIN verified across the studies are mainly due to the variability of the patients' clinical conditions, rather than to disparities in the definition criteria of CIN.
The significant risk factors for CT-associated CIN in our study were renal failure, DM, and heart failure.Both renal failure and DM are established as risk factors for CIN in the literature. 28Heart failure, however, is viewed a possible risk factor. 27,29The association of heart failure and CIN could be due to aspects peculiar to these patients: low cardiac output and high levels of cathecolamines which eventually impair renal perfusion. 30he role of NSAIDs as risk factors for CIN has been recently debated. 23,31Although NSAIDs have been listed as possible risk factors for CIN, it is mostly based on physiopathologic assumptions, and there are no consistent evidences to support this association. 30We have recently reported a lack of association between the use of NSAIDs and CIN in a population submitted to cardiac catheterism. 23Other potential risk factors for CIN, such as multiple myeloma, were not confirmed by clinical studies. 32According to Goldemberg & Matetzky, 33 many of the conditions pointed in the literature as risk factors for CIN were determined by studies that were either controversial or experimental.Although the alpha have been borderline, due to the very low frequency of NSAIDs use in our sample (2.2%), it was not possible to ascertain the actual interaction between these drugs and CIN in this study.
Our study has some limitations that cannot be underestimated.Firstly, most CTs performed in our study were required for the diagnosis or staging of patients with cancer, and this should be taken into  In comparing the diagnosis of renal failure using the Cockroft-Gault formula and the 2009 CKD-EPI test, we obtained a value of 0.954 (pα 0,016; kappa statistics).

dIscussIon And conclusIons
Current knowledge about the actual magnitude of CIN in CT derives from studies performed in diverse populations, none of them inpatients.In a study of account when generalizing our results.Secondly, we have evaluated exams performed with only one type of contrast media, and we did not access the impact of agents that are supposedly less nephrotoxic (non-ionic, low-osmolarity agents).Thirdly, although we could not find a significant association between the use of NSAIDs and CIN, few patients were using NSAIDs at the time of the study.Finally, we have excluded from analysis patients with multiple exposures to contrast media previously to enrollment, which could be a risk factor for the development of CIN by itself.
To our knowledge, this is the first prospective study of CT-associated CIN in patients admitted to a tertiary hospital.Further studies are necessary to evaluate risk factors for CT-associated CIN in different patient populations.