Computerized Tomography Contrast Induced Nephropathy (CIN) among adult inpatients

Abstracts

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 1.57- 7.17; 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.

renal insufficiency; acute kidney injury; contrast media; hospital mortality; nephrology; inpatients; tomography

Introdução:

Nefropatia induzida por contraste (NIC) é consequência do uso de meios de contraste intravenoso, sendo definida como uma redução da taxa de filtração glomerular. A maioria dos dados de NIC são da literatura cardiovascular, que identificou como fatores de risco insuficiência renal crônica e diabetes. Entretanto, esses estudos limitam suas conclusões a uma população especifica de pacientes. Tomografia Computadorizada contrastada como causa de NIC foi menos estudada.

Objetivo:

Reportar incidência de NIC numa população de pacientes internados em hospital terciário submetidos à tomografia computadorizada com contraste, identificando possíveis fatores de risco evitáveis.

Métodos:

Realizamos um estudo de coorte prospectivo com pacientes internados em hospital terciário e que necessitaram de tomografia computadorizada com contraste. O desfecho primário foi desenvolvimento de NIC, verificado por meio da variação da creatinina sérica ou taxa de filtração glomerular em 48 ou 72 horas. Em entrevista clínica, verificamos possíveis fatores de risco, assim como medidas preventivas instituídas pela equipe médica e suas possíveis associações com desenvolvimento de NIC.

Resultados:

Do total de 410 pacientes, 35 (8,5%) desenvolveram NIC. Houve correlação positiva entre desenvolvimento de NIC e a presença de diabetes mellitus (OR = 2,15; 95%CI 1,35-4,06; p = 0,02), insuficiência cardíaca (OR = 2,23; 95%CI 1,18-8,8; p = 0,022), e insuficiência renal (OR = 3,36; 95%CI 1,57-7,17; p = 0,002).

Conclusão:

A incidência de NIC varia de acordo com a população. Diabetes, insuficiência cardíaca e insuficiência renal foram fatores de risco independentes para o desenvolvimento de NIC. Mais estudos são necessários para melhor entendimento e tratamento da NIC relacionada à tomografia computadorizada.

insuficiência renal; lesão renal aguda; meios de contraste; mortalidade hospitalar; nefropatias; pacientes internados; tomografia

Introduction

Contrast induced nephropathy (CIN) is one of the most serious consequences of the use of intravascular contrast agents, being defined as a reduction of the glomerular filtration rate caused by the iodinated contrast.^1-3 When not prevented, CIN may result in significant morbidity and mortality.^4-16 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.¹⁷ Most CIN data derive from the cardiovascular literature, which identified as the most consistent risk factors pre-existing chronic renal insufficiency and diabetes mellitus.¹⁸ However, 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 These few studies pointed out to diverse incidences and risk factors of CIN, possibly due to differences both in the definition of CIN and in patient characteristics.^19-22 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/H₂O) 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.²³ Age 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/1.73 m² by the Cockroft-Gault formula or a serum creatinine ≥ 1.5 mg/dL.^24,25 Ultimately, 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.²⁶ In 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 (c²) 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.

The indications for a CT in our study were: staging of neoplasms (62.2%), evaluation of pulmonary thromboembolism (12%), abdominal pain (5.6%), infectious diseases (4.4%), liver diseases (2.9%), thoracic and abdominal aortic aneurisms (3.6%), neurologic diseases (2%), or other (7.3%). Mean contrast volume during CT was 139.1 ± 31.2 mL. Correcting according to the body's surface area, we obtained a value of 81.0 ± 2.1 mL/m².

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.

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).

Table 1
Variables associated with the development of CIN (backward stepwise logistic regression)

Variable	Significance	Odds Ratio	95.0% C.I. for EXP(B)
DM	0.019	2.149	1.135	4.067
Heart failure	0.022	3.23	1.184	8.816
NSAIDs	0.053	5.21	0.978	27.79
Renal failure	0.002	3.36	1.574	7.174
Age ≥ 65 years	0.79	0.33	0.096	1.138

• Variable(s) entered on step 1: gender, race, hypertension, DM, heart failure, cancer, NSAIDs, betablockers, age 65 or older, BMI, hydration protocol, renal failure.

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 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.²¹ described 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.²⁸ Heart failure, however, is viewed a possible risk factor.^27,29 The 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.³⁰

The role of NSAIDs as risk factors for CIN has been recently debated.^23,31 Although 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.³⁰ We have recently reported a lack of association between the use of NSAIDs and CIN in a population submitted to cardiac catheterism.²³ Other potential risk factors for CIN, such as multiple myeloma, were not confirmed by clinical studies.³² According 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 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.

References

• ¹
  El-Hajjar M, Bashir I, Khan M, Min J, Torosoff M, DeLago A. Incidence of contrast-induced nephropathy in patients with chronic renal insufficiency undergoing multidetector computed tomographic angiography treated with preventive measures. Am J Cardiol 2008;102:353-6. PMID: 18638601 DOI: http://dx.doi.org/10.1016/j.amjcard.2008.03.067
  » http://dx.doi.org/10.1016/j.amjcard.2008.03.067
• ²
  Thomsen HS. Current evidence on prevention and management of contrast-induced nephropathy. Eur Radiol 2007;17:F33-7. DOI: http://dx.doi.org/10.1007/s10406-007-0226-5
  » http://dx.doi.org/10.1007/s10406-007-0226-5
• ³
  Ultramari FT, Bueno Rda R, da Cunha CL, de Andrade PM, Nercolini DC, Tarastchuk JC, et al. Contrast media-induced nephropathy following diagnostic and therapeutic cardiac catheterization. Arq Bras Cardiol 2006;87:378-90. PMID: 17057941 DOI: http://dx.doi.org/10.1590/S0066-782X2006001600023
  » http://dx.doi.org/10.1590/S0066-782X2006001600023
• ⁴
  Alonso A, Lau J, Jaber BL, Weintraub A, Sarnak MJ. Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomized, controlled trials. Am J Kidney Dis 2004;43:1-9. DOI: http://dx.doi.org/10.1053/j.ajkd.2003.09.009
  » http://dx.doi.org/10.1053/j.ajkd.2003.09.009
• ⁵
  Bagshaw SM, Ghali WA. Acetylcysteine for prevention of contrast-induced nephropathy after intravascular angiography: a systematic review and meta-analysis. BMC Med 2004;2:38. DOI: http://dx.doi.org/10.1186/1741-7015-2-38
  » http://dx.doi.org/10.1186/1741-7015-2-38
• ⁶
  Birck R, Krzossok S, Markowetz F, Schnülle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598-603. PMID: 12944058 DOI: http://dx.doi.org/10.1016/S0140-6736(03)14189-X
  » http://dx.doi.org/10.1016/S0140-6736(03)14189-X
• ⁷
  Eisenberg RL, Bank WO, Hedgock MW. Renal failure after major angiography can be avoided with hydration. AJR Am J Roentgenol 1981;136:859-61. PMID: 6784516 DOI: http://dx.doi.org/10.2214/ajr.136.5.859
  » http://dx.doi.org/10.2214/ajr.136.5.859
• ⁸
  Guru V, Fremes SE. The role of N-acetylcysteine in preventing radiographic contrast-induced nephropathy. Clin Nephrol 2004;62:77-83. PMID: 15356963 DOI: http://dx.doi.org/10.5414/CNP62077
  » http://dx.doi.org/10.5414/CNP62077
• ⁹
  Isenbarger DW, Kent SM, O'Malley PG. Meta-analysis of randomized clinical trials on the usefulness of acetylcysteine for prevention of contrast nephropathy Am J Cardiol 2003;92:1454-8. PMID: 14675586
• ¹⁰
  Kshirsagar AV, Poole C, Mottl A, Shoham D, Franceschini N, Tudor G, et al. N-acetylcysteine for the prevention of radiocontrast induced nephropathy: a meta-analysis of prospective controlled trials. J Am Soc Nephrol 2004;15:761-9. DOI: http://dx.doi.org/10.1097/01.ASN.0000116241.47678.49
  » http://dx.doi.org/10.1097/01.ASN.0000116241.47678.49
• ¹¹
  McCullough PA, Wolyn R, Rocher LL, Levin RN, O'Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997;103:368-75. PMID: 9375704 DOI: http://dx.doi.org/10.1016/S0002-9343(97)00150-2
  » http://dx.doi.org/10.1016/S0002-9343(97)00150-2
• ¹²
  Misra D, Leibowitz K, Gowda RM, Shapiro M, Khan IA. Role of N-acetylcysteine in prevention of contrast-induced nephropathy after cardiovascular procedures: a meta-analysis. Clin Cardiol 2004;27:607-10. DOI: http://dx.doi.org/10.1002/clc.4960271106
  » http://dx.doi.org/10.1002/clc.4960271106
• ¹³
  Mueller C, Buerkle G, Buettner HJ, Petersen J, Perruchoud AP, Eriksson U, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-36. PMID: 11822926 DOI: http://dx.doi.org/10.1001/archinte.162.3.329
  » http://dx.doi.org/10.1001/archinte.162.3.329
• ¹⁴
  Nallamothu BK, Shojania KG, Saint S, Hofer TP, Humes HD, Moscucci M, et al. Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis. Am J Med 2004;117:938-47. PMID: 15629733 DOI: http://dx.doi.org/10.1016/j.amjmed.2004.06.046
  » http://dx.doi.org/10.1016/j.amjmed.2004.06.046
• ¹⁵
  Pannu N, Manns B, Lee H, Tonelli M. Systematic review of the impact of N-acetylcysteine on contrast nephropathy. Kidney Int 2004;65:1366-74. DOI: http://dx.doi.org/10.1111/j.1523-1755.2004.00516.x
  » http://dx.doi.org/10.1111/j.1523-1755.2004.00516.x
• ¹⁶
  Teruel JL, Marcen R, Herrero JA, Felipe C, Ortuño J. An easy and effective procedure to prevent radiocontrast agent nephrotoxicity in high-risk patients. Nephron 1989;51:282. PMID: 2915771 DOI: http://dx.doi.org/10.1159/000185304
  » http://dx.doi.org/10.1159/000185304
• ¹⁷
  Ellis JH, Cohan RH. Reducing the risk of contrast-induced nephropathy: a perspective on the controversies. AJR Am J Roentgenol 2009;192:1544-9. PMID: 19457817 DOI: http://dx.doi.org/10.2214/AJR.09.2368
  » http://dx.doi.org/10.2214/AJR.09.2368
• ¹⁸
  Vercellino M, Bezante GP, Balbi M. Contrast medium induced nephropathy: new insights into prevention and risk management. Cardiovasc Hematol Agents Med Chem 2009;7:166-80. DOI: http://dx.doi.org/10.2174/187152509787847083
  » http://dx.doi.org/10.2174/187152509787847083
• ¹⁹
  Arana E, Catalá-López F. Contrast-induced nephropathy in patients at risk of renal failure undergoing computed tomography: systematic review and meta-analysis of randomized controlled trials. Med Clin (Barc) 2010;135:343-50. DOI: http://dx.doi.org/10.1016/j.medcli.2010.01.035
  » http://dx.doi.org/10.1016/j.medcli.2010.01.035
• ²⁰
  Lencioni R, Fattori R, Morana G, Stacul F. Contrast-induced nephropathy in patients undergoing computed tomography (CONNECT) - a clinical problem in daily practice? A multicenter observational study. Acta Radiol 2010;51:741-50. DOI: http://dx.doi.org/10.3109/02841851.2010.495350
  » http://dx.doi.org/10.3109/02841851.2010.495350
• ²¹
  Mitchell AM, Jones AE, Tumlin JA, Kline JA. Incidence of contrast-induced nephropathy after contrast-enhanced computed tomography in the outpatient setting. Clin J Am Soc Nephrol 2010;5:4-9. DOI: http://dx.doi.org/10.2215/CJN.05200709
  » http://dx.doi.org/10.2215/CJN.05200709
• ²²
  Rashid AH, Brieva JL, Stokes B. Incidence of contrast-induced nephropathy in intensive care patients undergoing computerised tomography and prevalence of risk factors. Anaesth Intensive Care 2009;37:968-75. PMID: 20014604
• ²³
  Diogo LP, Saitovitch D, Biehl M, Bahlis LF, Guterres MC, O'Keeffe CF, et al. Is there an association between non-steroidal anti-inflammatory drugs and contrast nephropathy? Arq Bras Cardiol 2010;95:726-31. PMID: 21109911
• ²⁴
  Chang CF, Lin CC. Current concepts of contrast-induced nephropathy: a brief review. J Chin Med Assoc 2013;76:673-81. PMID: 24090599 DOI: http://dx.doi.org/10.1016/j.jcma.2013.08.011
  » http://dx.doi.org/10.1016/j.jcma.2013.08.011
• ²⁵
  Deek H, Newton P, Sheerin N, Noureddine S, Davidson PM. Contrast media induced nephropathy: A literature review of the available evidence and recommendations for practice. Aust Crit Care 2014: pii:S1036-7314(13)00266-X. [Epub ahead of print] DOI: http://dx.doi.org/10.1016/j.aucc.2013.12.002
  » http://dx.doi.org/10.1016/j.aucc.2013.12.002
• ²⁶
  Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-12. PMID: 19414839 DOI: http://dx.doi.org/10.7326/0003-4819-150-9-200905050-00006
  » http://dx.doi.org/10.7326/0003-4819-150-9-200905050-00006
• ²⁷
  Ahuja TS, Niaz N, Agraharkar M. Contrast-induced nephrotoxicity in renal allograft recipients. Clin Nephrol 2000;54:11-4. PMID: 10939751
• ²⁸
  Tepel M, Aspelin P, Lameire N. Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation 2006;113:1799-806. DOI: http://dx.doi.org/10.1161/CIRCULATIONAHA.105.595090
  » http://dx.doi.org/10.1161/CIRCULATIONAHA.105.595090
• ²⁹
  Solomon R. Radiocontrast-induced nephropathy. Semin Nephrol 1998;18:551-7. PMID: 9754608
• ³⁰
  Tumlin J, Stacul F, Adam A, Becker CR, Davidson C, Lameire N, et al.; CIN Consensus Working Panel. Pathophysiology of contrast-induced nephropathy. Am J Cardiol 2006;98:14K-20K. PMID: 16949376 DOI: http://dx.doi.org/10.1016/j.amjcard.2006.01.020
  » http://dx.doi.org/10.1016/j.amjcard.2006.01.020
• ³¹
  Diogo LP, Saitovitch D, Biehl M, Bahlis LF, Guterres MC, O'Keeffe CF, et al. Is there an association between non-steroidal anti-inflammatory drugs and contrast nephropathy? Arq Bras Cardiol 2010;95:726-31. PMID: 21109911
• ³²
  McCarthy CS, Becker JA. Multiple myeloma and contrast media. Radiology 1992;183:519-21. PMID: 1561361 DOI: http://dx.doi.org/10.1148/radiology.183.2.1561361
  » http://dx.doi.org/10.1148/radiology.183.2.1561361
• ³³
  Goldenberg I, Matetzky S. Nephropathy induced by contrast media: pathogenesis, risk factors and preventive strategies. CMAJ 2005;172:1461-71. PMID: 15911862 DOI: http://dx.doi.org/10.1503/cmaj.1040847
  » http://dx.doi.org/10.1503/cmaj.1040847

Publication Dates

• Publication in this collection
  Oct-Dec 2014

History

• Received
  19 Feb 2014
• Accepted
  28 Aug 2014