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Erschienen in: Cancer Imaging 1/2018

Open Access 01.12.2018 | Research article

Risk of renal events following intravenous iodinated contrast material administration among inpatients admitted with cancer a retrospective hospital claims analysis

verfasst von: Chaan S. Ng, Sanjeeva P. Kalva, Candace Gunnarsson, Michael P. Ryan, Erin R. Baker, Ravindra L. Mehta

Erschienen in: Cancer Imaging | Ausgabe 1/2018

Abstract

Background

There is little published evidence examining the use of contrast material (CM) and the risk of acute renal adverse events (AEs) in individuals with increasingly common risk factors including cancer and chronic kidney disease (CKD). The objective of this study was to use real world hospital data to test the hypothesis that inpatients with cancer having CT procedures with iodinated CM would have higher rates of acute renal AEs in comparison to inpatients without cancer.

Methods

Inpatient hospital visits in the Premier Hospital Database from January 1, 2010 through September 30, 2015 were eligible for inclusion. The outcome of interest was a composite of acute renal AEs including: acute kidney injury, acute renal failure requiring dialysis, contrast induced-acute kidney injury and renal failure. Multivariable models, adjusted for differences in patient demographics and comorbid conditions, were used to estimate the incremental risk of acute renal AEs by CT (with or without iodinated CM), CKD stage and type of cancer.

Results

Among 29,850,475 inpatient visits across 611 hospitals, 7.4% had record of a CT scan, 5.9% had CKD, and 3.4% had the primary diagnosis of cancer. The baseline risk for an acute renal AE in patients without cancer or CKD and no CT or CM was 0.5%. The absolute risk increases from baseline by 0.2% with a CT and by 0.8% with iodinated CM. Patients with CKD having a CT scan with iodinated CM have an absolute risk of 4.1 to 9.7% depending on the stage of CKD. For patients with cancer, the absolute risk increases, varying from 0.3 to 2.3% depending on the type of cancer.

Conclusions

Inpatients with cancer are at higher likelihood of developing acute renal AEs following CT with iodinated CM compared to those without a cancer. Understanding the underlying risks of acute renal AEs among complex inpatient admissions is an important consideration in treatment choices for oncology patients.
Abkürzungen
AE
Adverse event(s)
AKI
Acute kidney injury
ASN
American Society of Nephrology
CI-AKI
Contrast-induced acute kidney injury
CIN
Contrast-induced nephropathy
CKD
Chronic kidney disease
CM
Contrast material
CT
Computed tomography
ECI
Elixhauser comorbidity index
ESRD
End stage renal disease
ICD-9
International classification of diseases, ninth revision
NHDS
National Hospital Discharge Survey
PC-AKI
Post-contrast acute kidney injury
SCr
Serum creatinine
US
United States

Background

Adverse events (AEs) following intravascular administration of iodinated contrast material (CM) occur in 0.02 to 0.04% of patients. These include kidney injury, respiratory or cardiac arrest, convulsions, and loss of consciousness [13]. Renal insufficiency has been noted as both contributing to the risk of a post-CM AEs and as a result thereof [46]. However, the incidence of nephropathy specifically caused by iodinated CM is not well understood. As noted by the American College of Radiology, most published studies focus on the diagnosis of post-contrast acute kidney injury (PC-AKI), which is defined as sudden deterioration in renal function within 48 h following the intravascular administration of iodinated CM. PC-AKI is a correlative diagnosis, a subset of PC-AKI cases are contrast-induced nephropathy (CIN or CI-AKI), which is a causative diagnosis [7]. CI-AKI is commonly defined as an increase in serum creatinine (SCr) greater than 25% or 44.2umol/L (0.5 mg/dL) from baseline within 2 or 3 days of intravascular CM administration in the absence of an alternative cause [5, 8]. CI-AKI has an estimated incidence of 8 to 20% of cancer patients who undergo contrast-enhanced CT [6, 911]. However, most studies do not include a control group for analysis, which is problematic due to the variation in SCr observed in hospitalized patients regardless of CM administration [5]. Depending on the definition utilized, AKI has been reported in 6 to 35% of inpatients without CM exposure [5, 12].
Cancer treatments as well as the timing of treatment and CT imaging have been investigated as risk factors for acute reactions to iodinated CM [13, 14]. Other than chronic kidney disease (CKD), risk factors for CI-AKI include diabetes, hypertension, malignancy, age > 65 years, use of non-steroidal anti-inflammatory drugs, and timing of CT within 45 days after last chemotherapy [9, 15]. Regardless of the cause, cancer patients who develop renal failure may have worse prognosis and survival [1619].
While the biomedical literature indicates that the rate of AEs associated CM use is low, there is little evidence examining the use of CM and the risk of renal AEs in individuals with increasingly common risk factors including cancer and CKD. The objective of this study was to use real world hospital data to test the hypothesis that patients with cancer having CT with iodinated CM would have higher rates of acute renal AEs than those without cancer.

Methods

Data source

Data for the study were derived from the Premier Hospital Database, which currently contains data from more than 350 million patient encounters, or one in every five discharges in the United States (US) [20]. The database contains data from standard hospital discharge files, including a patient’s demographic and disease state, and information on billed services, including medications, laboratory, diagnostics and therapeutic services in de-identified patient daily service records. In addition, information on hospital characteristics, including geographic location, bed size and teaching status are also available. Preliminary comparisons between patient and hospital characteristics for the hospitals included in the database and those of the probability sample of hospitals and patients selected for the National Hospital Discharge Survey (NHDS) suggest that the patient populations are similar with regard to patient age, gender, length of stay, mortality, primary discharge diagnosis, and primary procedure groups [21]. All data used to perform this analysis were de-identified and accessed in compliance with the Health Insurance Portability and Accountability Act. As a retrospective analysis of a de-identified database, the research was exempt from IRB review under 45 CFR 46.101(b)(4).

Inclusion/exclusion criteria

Any inpatient hospital visit in the Premier Hospital Database from January 1, 2010 through September 30, 2015 was eligible for inclusion. Inpatient was defined as a visit which included an overnight stay. Patient visits were excluded if a patient had a record of end stage renal disease requiring dialysis (ESRD ICD-9 code: 585.6), kidney transplantation (ICD-9 code: V42.0, 996.81, or 55.6×) or AKI (ICD-9 code: 584.9) upon admission (determined by a variable that indicated the patient had the condition upon admission). To isolate the risk of renal events among oncology patients hospitalized for diagnosis or treatment of cancer, visits with a secondary or historical diagnosis of cancer were excluded. Visits where the primary diagnosis or reason for the inpatient stay was cancer were included (Table 5 in Appendix).

Variables of interest

Patient visits with a record of primary cancer were further categorized by the following types of cancer: Bone, Breast, Colorectal, Endocrine, Gastrointestinal, Gynecological, Hemolymph, Leukemia, Liver, Lung, Neurological, Respiratory, Skin, Urinary and Miscellaneous (rare cancers).
The primary outcome of interest was a composite of adverse renal events, defined as one or more of the following: AKI, acute renal failure requiring dialysis, CI-AKI or renal failure (ICD-9 codes Table 6 in Appendix). Acute renal events were identified as being outcomes if there was a record of the event during the hospitalization and the event of interest was not recorded as present on admission.
To identify usage of CM, keyword text mining was performed on patients’ charge master billing files. Using product brand names and generic keywords for CM use, the following categories were created: iodinated, non-iodinated, or unknown type. If no evidence of CM usage was found on the visit, the visit was assumed to have no CM usage. CM usage could have occured during a CT or CTA scan, see Table 7 of Appendix for codes used to define CT and CTA scans.
In order to quantify the effect of CKD, a dichotomous variable was made for CKD status based on the presence of CKD stage recorded in the visit. Additionally, an ordinal variable was created for CKD stage (0 = no disease, stage 1, stage 2, stage 3, stages 4 &5) (Table 8 in Appendix). It is important to note, that patients with unspecified CKD were only included in the dichotomous variable and excluded in the staging variable due to the non-specificity of their renal disease status.
The following variables were summarized prior to statistical modeling: patient demographics (age, race, gender, insurance type, and admission type), visit characteristics (whether or not the patient underwent a CT, CM usage and type), patient conditions (primary cancer, type of cancer, CKD severity, and overall disease severity as measured by the Elixhauser Comorbidity Index (ECI Table 9 in Appendix)) [22]. All components of the composite of renal AEs were described prior to multivariable modeling by the following key model inputs: CKD by severity, CT (with or without iodinated CM) and cancer type.

Statistical analyses

All multivariable renal AE models adjusted for differences in both patient demographics and comorbid conditions. The hospital fixed-effects specification was used to account for time-invariant variation across a hospital that was otherwise unobservable. This methodological choice was made to compensate for the non-random relationship between patients and hospital choice which may result in variation across hospitals in both patient mix (e.g. the share and severity of oncology patients) and in the rate of renal events which may lead to a spurious correlation. By limiting the analysis to variation within hospitals, we study patients treated in a similar environment using similar standards of care and hospital protocols. The decision to utilize a particular product or drug during a hospital visit may depend on formal hospital guidelines, physician practice patterns or preferences, negotiated reimbursement schedules with insurance companies, and other local (geographic and/or hospital) characteristics.
All analysis was performed in SAS version 9.4 (Cary, NC).

Results

A total of 29,850,475 inpatient visits across 611 hospitals met the study inclusion criteria (Fig. 1). The average age of patients at the time of the inpatient visit was 45 years (standard deviation (sd) 27.5). The majority of patients were female (60%), Caucasian (65%), and the most frequent insurer was Medicare (34%). Emergency and urgent hospitalizations made up 61% of all visits. Overall, 7% of inpatient visits had a record of a CT and 80% of visits had no record of CM (Table 1).
Table 1
Patient Visit Characteristics
 
Total
N
Percent
Total Visits
29,850,475
100%
Age
 Median
48
 
 Mean
45.0
 
 Standard deviation
27.50
 
Race
 Caucasian
19,314,454
64.7%
 African-American
4,052,601
13.6%
 Other
6,483,420
21.7%
Gender
 Female
17,831,769
59.7%
 Male
12,015,263
40.3%
 Unknown
3443
0.0%
Insurance
 Commercial
1,681,308
5.6%
 Medicare
10,010,108
33.5%
 Medicaid
6,968,569
23.3%
 Managed Care
8,043,140
26.9%
 Other
3,147,350
10.5%
Admission Type
 Emergency
13,780,883
46.2%
 Urgent
4,466,926
15.0%
 Elective
7,507,444
25.2%
 Other/Unknown
4,095,222
13.7%
CT Scan
2,195,374
7.4%
Contrast Used
 Iodinated
2,290,183
7.7%
 Non-Iodinated
463,956
1.6%
 Both
73,839
0.2%
 Unknown
3,258,046
10.9%
 None
23,764,451
79.6%
The population had a mean ECI score of 2.1 (sd 2.17), comorbid conditions and frequencies are shown in Table 2. Among the 6% of visits with CKD, the CKD stage was: stage 1 (0.7%), stage 2 (5.6%), stage 3 (36.5%), stage 4/5 (12.4%) and stage unspecified (44.8%). Cancer was the primary diagnosis in 3.4% of visits. The highest percentage of primary cancer visits reported were: gastrointestinal (16.1%), urinary (14.6%) and lung (13.1%).
Table 2
Patient Comorbidities
 
Total
 
N
Percent
Total Visits
29,850,475
100%
 
Elixhauser Comorbidities
 Congestive Heart Failure
2,956,976
9.9%
 
 Cardiac Arrhythmia
4,708,604
15.8%
 
 Valvular Disease
1,269,470
4.3%
 
 Pulmonary Circulation Disorders
896,999
3.0%
 
 Peripheral Vascular Disorders
1,392,847
4.7%
 
 Hypertension (Uncomplicated)
10,030,305
33.6%
 
 Hypertension (Complicated)
1,768,162
5.9%
 
 Paralysis
470,505
1.6%
 
 Other Neurological Disorders
2,076,621
7.0%
 
 Chronic Pulmonary Disease
5,651,859
18.9%
 
 Diabetes (Uncomplicated)
4,479,120
15.0%
 
 Diabetes (Complicated)
962,632
3.2%
 
 Hypothyroidism
2,680,999
9.0%
 
 Renal Failure
1,781,578
6.0%
 
 Liver Disease
1,017,975
3.4%
 
 Peptic Ulcer Disease (excluding bleeding)
219,464
0.7%
 
 AIDS/HIV
77,709
0.3%
 
 Lymphoma
50,977
0.2%
 
 Metastatic Cancer
375,880
1.3%
 
 Solid Tumor without Metastasis
816,723
2.7%
 
 Rheumatoid Arthritis Collagen
582,016
1.9%
 
 Coagulopathy
988,278
3.3%
 
 Obesity
3,335,095
11.2%
 
 Weight Loss
985,799
3.3%
 
 Fluid and Electrolyte Disorders
5,086,695
17.0%
 
 Blood Loss Anemia
260,342
0.9%
 
 Deficiency Anemia
711,987
2.4%
 
 Alcohol Abuse
1,672,862
5.6%
 
 Drug Abuse
1,684,008
5.6%
 
 Psychoses
920,047
3.1%
 
 Depression
4,026,007
13.5%
 
Elixhauser Comorbidity Index
 Median
2
  
 Mean
2.1
  
 Std Dev
2.17
  
Chronic Kidney Disease
 No CKD
28,085,084
94.0%
 
 CKD
1,765,391
5.9%
 
Stage of Chronic Kidney Disease
N
% Overall
% of CKD
 Stage 1
11,958
0.0%
0.7%
 Stage 2
99,004
0.3%
5.6%
 Stage 3
644,398
2.2%
36.5%
 Stage 4 & 5
219,255
0.7%
12.4%
 Unspecified
790,776
2.6%
44.8%
Diagnosis of Cancer
 No Cancer
28,828,219
97.0%
 
 Primary Cancer
1,022,256
3.4%
 
Type of Primary Cancer
N
% Overall
% of Cancer
 Bone
2991
0.0%
0.3%
 Breast
77,428
0.3%
7.6%
 Colorectal
127,275
0.4%
12.5%
 Endocrine
37,769
0.1%
3.7%
 Gastrointestinal
164,323
0.6%
16.1%
 Gynecological
64,034
0.2%
6.3%
 Hemolymph
42,572
0.1%
4.2%
 Leukemia
37,869
0.1%
3.7%
 Liver
18,022
0.1%
1.8%
 Lung
133,837
0.4%
13.1%
 Miscellaneous
120,556
0.4%
11.8%
 Neurological
29,724
0.1%
2.9%
 Respiratory
9034
0.0%
0.9%
 Skin
7073
0.0%
0.7%
 Urinary
149,749
0.5%
14.6%
CKD Chronic Kidney Disease
The unadjusted rates of the renal AE outcome and its components are reported in Table 3 by the following key variables: CKD stage, CT (with or without iodinated CM) and cancer type. The unadjusted baseline rate of the renal AEs was 0.5% for inpatient visits without cancer, CKD or CT and CM. The frequency of renal events increased with CKD severity (0.9% for patients with no record of CKD; 6.1% for a patient with CKD stage 1 to 12.7% among CKD patients stage 4 & 5). Among visits with primary cancer, the unadjusted rate of renal events was 3.0%, an increase from 1.4% in visits with no cancer diagnosis. The unadjusted rate of renal events varied by cancer type: leukemia (5.3%), liver (4.3%), urinary (4.1%), and colorectal (4.1%). When considering all AEs which make up the renal AE composite, AKI without dialysis contributed to the composite more than other components.
Table 3
Renal Adverse Events: Prior to Multivariable Modeling (Unadjusted)
 
Renal Adverse Event Outcome
Components of the Renal Adverse Events Outcome
Acute Kidney Injury without dialysis
Acute Kidney Injury with dialysis
CI-AKI
Renal Failure
Baseline
0.5%
0.5%
0.0%
0.0%
0.0%
No CKD
0.9%
0.8%
0.0%
0.0%
0.0%
CKD Stage 1
6.1%
6.0%
0.1%
0.2%
0.0%
CKD Stage 2
8.4%
8.3%
0.1%
0.2%
0.0%
CKD Stage 3
11.4%
11.1%
0.3%
0.3%
0.1%
CKD Stage 4&5
12.7%
11.6%
0.8%
0.3%
0.2%
CT
2.8%
2.6%
0.1%
0.1%
0.0%
No CT
1.3%
1.3%
0.0%
0.0%
0.0%
CT with Iodinated Contrast
2.9%
2.8%
0.1%
0.1%
0.0%
CT without Iodinated Contrast
2.7%
2.6%
0.1%
0.1%
0.0%
No-Cancer
1.4%
1.3%
0.0%
0.0%
0.0%
Cancer
3.0%
2.9%
0.1%
0.0%
0.0%
 Bone
1.4%
1.3%
0.1%
0.0%
0.0%
 Breast
0.6%
0.6%
0.0%
0.0%
0.0%
 Colorectal
4.1%
4.0%
0.1%
0.0%
0.0%
 Endocrine
1.5%
1.5%
0.1%
0.0%
0.0%
 Gastrointestinal
3.3%
3.2%
0.1%
0.1%
0.0%
 Gynecological
2.5%
2.4%
0.1%
0.0%
0.0%
 Hemolymph
3.9%
3.5%
0.3%
0.1%
0.1%
 Leukemia
5.3%
4.9%
0.3%
0.1%
0.1%
 Liver
4.3%
4.0%
0.2%
0.1%
0.1%
 Lung
2.8%
2.7%
0.1%
0.1%
0.0%
 Miscellaneous
1.9%
1.9%
0.0%
0.0%
0.0%
 Neurological
1.0%
0.9%
0.0%
0.0%
0.0%
 Respiratory
2.2%
2.2%
0.0%
0.0%
0.0%
 Skin
1.6%
1.6%
0.0%
0.0%
0.0%
 Urinary
4.1%
4.0%
0.1%
0.0%
0.0%
AKI Acute Kidney Injury, CKD Chronic Kidney Disease, CI-AKI Contrast induced acute kidney injury
The fixed effects multivariable models controlled for differences in patient demographics and comorbid conditions and decomposed the risk by the following variables: CT, iodinated CM, CKD stage and cancer type (Table 4 and Fig. 2). Estimates of absolute risk of the renal AEs are reported with confidence intervals for CT, iodinated CM, CKD stage and cancer (Table 4). Absolute risk of an acute renal event increased with non-contrast CT by 0.2%, iodinated CM increased the risk by an additional 0.8%. The increased risk varied by cancer type, overall, the risk of a renal event increased by 0.9%. The risk by individual cancer types range from 0.3% for endocrine cancer to 2.3% for urinary cancers. Absolute risk increased with CKD severity: stage 1 (2.5%), stage 2 (4.6%), stage 3 (7.2%), stage 4 & 5 (8.1%).
Table 4
Multivariable Estimates of Absolute risk of an Acute Renal Adverse Event
Variable
Absolute Risk Estimate (95% confidence interval)
P-Value
CT
0.19% (0.17, 0.21%)
< 0.0001
Iodinated CM
0.81% (0.80, 0.83%)
< 0.0001
CKD Stage 1
2.55% (2.35, 2.74%)
< 0.0001
CKD Stage 2
4.64% (4.56, 4.71%)
< 0.0001
CKD Stage 3
7.24% (7.19, 7.28%)
< 0.0001
CKD Stage 4/5
8.14% (8.08, 8.19%)
< 0.0001
Cancer
0.87% (0.85, 0.89%)
< 0.0001
 Urinary
2.33% (2.28, 2.39%)
< 0.0001
 Leukemia
2.20% (2.09, 2.31%)
< 0.0001
 Colorectal
1.69% (1.63, 1.75%)
< 0.0001
 Hemolymph
1.22% (1.12, 1.33%)
< 0.0001
 Gynecological
1.03% (0.95, 1.11%)
< 0.0001
 Liver
1.00% (0.84, 1.16%)
< 0.0001
 Gastrointestinal
0.59% (0.54, 0.65%)
< 0.0001
 Lung
0.33% (0.27, 0.39%)
< 0.0001
 Endocrine
0.29% (0.18, 0.39%)
< 0.0001
CKD Chronic Kidney Disease, CM Contrast material
Figure 2 provides a cumulative visual for the regression estimates reported in Table 4. The first bar in the figure is the absolute risk of the renal AEs at baseline, 0.5%. Baseline risk represents patient visits without CT, CM, CKD or cancer. From left to right, the absolute risk associated with each variable is reported as well as how the risk accumulates with each additional variable. For example, a patient hospitalized for cancer that had a CT scan with iodinated CM and CKD stage 1, had a 4.9% risk of a renal event. The absolute risk of a renal event increases substantially for patients with CKD. Inpatients who underwent a CT with iodinated CM who do not have cancer had the following risk based on CKD severity: stage 1 (4.1%), stage 2 (6.2%), stage 3 (8.8%), stage 4 & 5 (9.7%).

Discussion

After controlling for patient demographics, comorbid conditions and hospital fixed effects, the risk of an acute renal event for hospitalized patients ranges from 0.5% at baseline (patient visits without CT, CM use, CKD or cancer experiencing AKI) to as high as 10.6% (patient visits with a CT with iodinated CM with CKD stage 4 or 5 and cancer). The increasing risk with CKD stage reflects the previously reported impact of compromised renal function and adds to the literature by showing the risk of renal AEs by cancer type. The effect of a cancer diagnosis on the risk of renal AEs was 0.9%, with specific cancers having up to 2.3% (for urinary cancer) added risk. The incremental risk of a renal event associated with a CT without contrast was 0.2%, which clinically may be counterintuitive. This incremental risk was most likely due to the CT being a proxy for sicker patients or other procedures not controlled for in the regression analysis. Regardless of the reason, the effect is small compared to the other factors.
Large retrospective single center studies have previously explored the risk of intravenous CM via propensity-matched cohort analyses [23, 24]. Such investigations differ from our current analysis in heterogeneity (or homogeneity) of population examined, this study specifically surveyed the inpatient setting while considering the impact of CKD stage and cancer diagnosis.
It is not difficult to surmise why cancer patients may be particularly susceptible to renal events given their high prevalence of renal insufficiency, concomitant nephrotoxic chemotherapeutic regimens, and predisposition to dehydration secondary to advanced age, poor appetite, nausea, and vomiting [25]. It has additionally been suggested that patients with active cancer undergoing CM enhanced CT are particularly at risk of CI-AKI even in the absence of significant renal impairment as underlying renal insufficiency may be masked due to falsely low creatinine concentration resulting from diminished muscle mass [10].
This study did not explore the potential additive effects of different types of CM and chemotherapy; however, it has been suggested that CI-AKI may develop 4.5 times more frequently in cancer patients who undergo recent chemotherapy [9] and that exposure to CM within a week prior to nephrotoxic chemotherapeutic agents, for example cisplatin, significantly increases the risk of nephropathy [26]. Similar nephrotoxic effects of iodinated CM and chemotherapeutic agents upon the renal vasculature may rationalize the amplified risk. Not surprisingly, chemotherapy has been increasingly identified as an additional risk factor, evident by inclusion into CI-AKI consensus statements and guideline recommendations [27].
While the current analysis did not assess renal AEs by class of CM, a recent prospective, multicenter, randomized controlled trial suggested more favorable safety profile of iso-osmolar CM (iodixanol) versus low-osmolar CM (iopromide) in low risk cancer patients defined by eGFR> 60 mL/min [28]. Adequately sized and designed studies of prospective nature are warranted to elucidate findings further.
Our findings quantify absolute risk of renal events and are noteworthy given the marked consequences that AKI may elicit within the oncology setting. Salahudeen et al. recently conducted cross-sectional analysis of prospectively collected data on 3558 patients admitted to the University of Texas, M.D. Anderson Cancer Center and found higher rates of AKI versus most non-cancer settings. In patients with AKI, length of stay (100%), cost (106%), and odds for mortality (4.7-fold) were significantly greater [29].
On account of these implications and due to the complex bidirectional relationship between cancer and kidney function, there is need for further investigation and periprocedural recommendations. The intra-arterial administration of CM within interventional cardiovascular procedures has been investigated at length, with subsequent guideline development central to patient risk assessment, hydration strategies, and emphasis on limiting volumes of CM administered. While it has been suggested that overall risk is lower with intravenous administration of CM, susceptible oncologic settings and vulnerable patients should be identified (particularly a patient’s state of kidney health and timing of treatment or imaging) and integrated strategies should be employed to minimize the risk of renal events among inpatient cancer patients undergoing CT with CM.
The intricate association and increasing prevalence of cancer and AKI/CKD has led to mounting interest in this complex environment and prompted evolution of the novel onco-nephrology subspecialty. Yet the relationship between cancer therapy and kidney disease remains underexplored. The burgeoning area of onco-nephrology suffers from lack of guidance for clinicians who encounter difficult and often complex problems in this complicated group of patients, and development of integrated guidelines is needed [30]. The 2016 American Society of Nephrology (ASN) Onco-Nephrology Curriculum may strengthen and expand understanding of this field by underscoring risk factors of CI-AKI and suggesting preventive measures be taken in patients with GFR < 60 mL/min including limiting contrast volume, using iso-osmolar contrast, prehydration with normal saline, and discontinuation of concurrent nephrotoxic agents [31].
To our understanding, this is the first study to quantify absolute risk of renal events in a robust multicenter cohort of patients undergoing CM enhanced CT with decomposed analysis of contributing factors to include CM, renal function, and cancer diagnosis. Our analysis suggests that patients who receive CM are at higher risk versus those who do not. Additionally, risk is heightened with progressively advanced stages of CKD. Further, our results substantiate multiple prior reports that cancer patients may be more uniquely susceptible to renal events undergoing CM enhanced CT versus non-cancer patients. Vulnerability of the oncologic cohort is likely multifactorial in nature and due, in part, to a high prevalence of renal insufficiency, dehydration, cachectic condition, and serial/additive renal insults induced by multiple exposures to CM, nephrotoxic medications and chemotherapeutic regimens. Results derived from our analysis may enable significant comparison of future analyses across procedures and selected high-risk populations, ultimately driving investigative research efforts and steering quality improvement endeavors.

Strengths and limitations

Strengths of this study include the use of a comprehensive data source and use of the hospital fixed-effect specification methodology that allowed for control of time-invariant within hospital variation that is otherwise unobservable, such as physician preferences and internal protocols. The limitations of this study are those that are inherent in retrospective database analyses, which include the unit of inference (which is the visit not the patient) and potential under coding of non-billable events. The data source for this study was the Premier Healthcare Database that represents 20% of all inpatient discharges in the US; however, given its reliance on ICD-9 Codes, there is a potential risk of coding errors. A second limitation of this data source is that it does not track patients longitudinally. Thus, it was not possible to determine if events occurred after the patient was discharged. Due to the administrative nature of the database, laboratory values (sCr and GFR) were not available, we could not define CI-AKI by sCr, and rather, the outcome was defined by the ICD-9 code for CI-AKI which may underestimate the occurrence of this event. Finally, due to limitations of the dataset, we were unable to ascertain total volumes of CM administered, use of hydration strategies, or concomitant use of nephrotoxic medications or chemotherapeutic regimens.

Conclusions

This large retrospective multicenter study decomposed the risk of acute renal events among hospitalized cancer patients having CT either with or without iodinated CM. The baseline risk for an acute renal event in patients without cancer or CKD and no CT or CM was 0.5%. When a CT procedure was performed with iodinated CM the risk increased to 1.5%. Patients with CKD having a CT with CM had an increased risk of an acute renal event from 2.5 to 8.1% depending on the stage of CKD. Among cancer patients, the overall risk increased from baseline by 0.9%. Risk increase from baseline by type of cancer ranged from 0.3 for endocrine and lung cancer to over 2% for leukemia and urinary cancer. Therefore, cancer patients having CT with iodinated CM without CKD have a risk increase of 2.4% and when CKD is present the risk ranges from 4.9 to 10.5% depending on CKD stage. In the changing healthcare landscape, with complex inpatient admissions, understanding the underlying risks of acute renal events will be an important consideration in treatment choices for oncology patients.

Funding

This study was funded by GE Healthcare.

Availability of data and materials

The data that support the findings of this study are available from Premier Hospital Database, but restrictions apply to the availability of these data and were used under license for the current study; therefore, they are not publicly available. The analyzable dataset is available from the authors upon reasonable request, and with permission of Premier Hospital Database.

Ethics approval

All data used to perform this analysis were de-identified and accessed in compliance with the Health Insurance Portability and Accountability Act. As a retrospective analysis of a de-identified database, the research was exempt from Institutional Review Board review under 45 Code of Federal Regulations 46.101(b)(4).
Not applicable.

Competing interests

CN has research grant funding from and is a consultant to GE Healthcare. CG, MR, and EB are employees of CTI Clinical Trial & Consulting Services which is a consultant to GE Healthcare. SK has research grant funding from Angiodynamics, Royalties from Springer and Elsevier, is an investor in Althea Healthcare and is a consultant to GE Healthcare and Koo Foundation (Taiwan). RM is a consultant to GE Healthcare.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
Anhänge

Appendix

Table 5
Cancer Coding
ICD-9 Diagnosis Code 3 Digit Group
ICD-9 Diagnosis Code Group Description
Cancer Category
140
MALIGNANT NEOPLASM LIP
Gastrointestinal
141
MALIG NEO TONGUE
Gastrointestinal
142
MAL NEO MAJOR SALIVARY
Gastrointestinal
143
MALIGNANT NEOPLASM GUM
Gastrointestinal
144
MALIG NEO MOUTH FLOOR
Gastrointestinal
145
MALIG NEO MOUTH NEC/NOS
Gastrointestinal
146
MALIG NEO OROPHARYNX
Gastrointestinal
147
MALIG NEO NASOPHARYNX
Respiratory
148
MALIG NEOPL HYPOPHARYNX
Respiratory
149
OTH MALIG NEO OROPHARYNX
Gastrointestinal
150
MALIGNANT NEO ESOPHAGUS
Gastrointestinal
151
MALIGNANT NEO STOMACH
Gastrointestinal
152
MALIG NEO SMALL BOWEL
Gastrointestinal
153
MALIGNANT NEOPLASM COLON
Colorectal
154
MALIG NEO RECTUM/ANUS
Colorectal
155
MALIGNANT NEOPLASM LIVER
Liver
156
MAL NEO GB/EXTRAHEPATIC
Gastrointestinal
157
MALIGNANT NEO PANCREAS
Gastrointestinal
158
MALIG NEO PERITONEUM
Gastrointestinal
159
OTH MALIG NEO GI/PERITON
Gastrointestinal
160
MAL NEO NASAL CAV/SINUS
Respiratory
161
MALIGNANT NEO LARYNX
Respiratory
162
MAL NEO TRACHEA/LUNG
Lung
163
MALIGNANT NEOPL PLEURA
Lung
164
MAL NEO THYMUS/MEDIASTIN
Lung
165
OTH/ILL-DEF MAL NEO RESP
Miscellaneous
170
MAL NEO BONE/ARTIC CART
Bone
171
MAL NEO SOFT TISSUE
Miscellaneous
172
MALIGNANT MELANOMA SKIN
Skin
173
OTHER MALIG NEOPL SKIN
Skin
174
MALIG NEO FEMALE BREAST
Breast
175
MALIG NEO MALE BREAST
Breast
176
KAPOSI’S SARCOMA
Miscellaneous
179
NEOPLASM, MALIGNANT, UTERUS NEC
Gynecological
180
MALIG NEOPL CERVIX UTERI
Gynecological
181
NEOPLASM, MALIGNANT, PLACENTA
Gynecological
182
MALIG NEOPL UTERUS BODY
Gynecological
183
MAL NEO UTERINE ADNEXA
Gynecological
184
MAL NEO FEM GEN NEC/NOS
Gynecological
185
NEOPLASM, MALIGNANT, PROSTATE
Urinary
186
MALIGN NEOPL TESTIS
Urinary
187
MAL NEO MALE GENITAL NEC
Urinary
188
MALIGN NEOPL BLADDER
Urinary
189
MAL NEO URINARY NEC/NOS
Urinary
190
MALIGNANT NEOPLASM EYE
Neurological
191
MALIGNANT NEOPLASM BRAIN
Neurological
192
MAL NEO NERVE NEC/NOS
Neurological
193
NEOPLASM, MALIGNANT, THYROID GLAND
Endocrine
194
MAL NEO OTHER ENDOCRINE
Endocrine
195
MAL NEO OTH/ILL-DEF SITE
Miscellaneous
196
MALIG NEO LYMPH NODES
Hemolymph
197
SECONDRY MAL NEO GI/RESP
Gastrointestinal
198
SEC MALIG NEO OTH SITES
Miscellaneous
199
MALIGNANT NEOPLASM NOS
Miscellaneous
200
LYMPHOSARC/RETICULOSARC
Hemolymph
201
HODGKIN’S DISEASE
Hemolymph
202
OTH MAL NEO LYMPH/HISTIO
Hemolymph
203
MULTIPLE MYELOMA ET AL
Leukemia
204
LYMPHOID LEUKEMIA
Leukemia
205
MYELOID LEUKEMIA
Leukemia
206
MONOCYTIC LEUKEMIA
Leukemia
207
OTHER SPECIFIED LEUKEMIA
Leukemia
208
LEUKEMIA-UNSPECIF CELL
Leukemia
209.0×-209.3×
NEUROENDOCRINE TUMORS
Endocrine
230
CA IN SITU DIGESTIVE ORG
Gastrointestinal
231
CA IN SITU RESPIRATORY
Respiratory
232
CARCINOMA IN SITU SKIN
Skin
233
CA IN SITU BREAST/GU
Breast
234
CA IN SITU NEC/NOS
Miscellaneous
235
UNC BEHAV NEO GI/RESP
Gastrointestinal
236
UNC BEHAV NEO GU
Urinary
237
UNCER NEO ENDOCRINE/NERV
Endocrine
238
UNC BEHAV NEO NEC/NOS
Miscellaneous
239
UNSPECIFIED NEOPLASM
Miscellaneous
Table 6
Safety Events
Adverse Event Category
ICD-9 Diagnosis Code(s)
Acute Kidney Injury
584.9
 Contrast-induced nephropathy (CIAKI)
584.9 + E947.8
 Acute Kidney Injury requiring dialysis
584.9 + 39.95
Renal Failure
586.x
Table 7
Radiologic Imaging
Code
Description
Sub-Category
Category
ICD-9
87.03
C.A.T. SCAN OF HEAD
CT - Diagnostic
CT
87.41
C.A.T. SCAN OF THORAX
CT - Diagnostic
CT
87.71
C.A.T. SCAN OF KIDNEY
CT - Diagnostic
CT
88.01
C.A.T. SCAN OF ABDOMEN
CT - Diagnostic
CT
88.38
OTHER C.A.T. SCAN
CT - Diagnostic
CT
CPT
70,450
CT HEAD/BRAIN W/O DYE
CT - Diagnostic
CT
70,460
CT HEAD/BRAIN W/DYE
CT - Diagnostic
CT
70,470
CT HEAD/BRAIN W/O & W/DYE
CT - Diagnostic
CT
70,480
CT ORBIT/EAR/FOSSA W/O DYE
CT - Diagnostic
CT
70,481
CT ORBIT/EAR/FOSSA W/DYE
CT - Diagnostic
CT
70,482
CT ORBIT/EAR/FOSSA W/O&W/DYE
CT - Diagnostic
CT
70,486
CT MAXILLOFACIAL W/O DYE
CT - Diagnostic
CT
70,487
CT MAXILLOFACIAL W/DYE
CT - Diagnostic
CT
70,488
CT MAXILLOFACIAL W/O & W/DYE
CT - Diagnostic
CT
70,490
CT SOFT TISSUE NECK W/O DYE
CT - Diagnostic
CT
70,491
CT SOFT TISSUE NECK W/DYE
CT - Diagnostic
CT
70,492
CT SFT TSUE NCK W/O & W/DYE
CT - Diagnostic
CT
70,496
CT ANGIOGRAPHY HEAD
CT Angiography - Diagnostic
CTA
70,498
CT ANGIOGRAPHY NECK
CT Angiography - Diagnostic
CTA
71,250
CT THORAX W/O DYE
CT - Diagnostic
CT
71,260
CT THORAX W/DYE
CT - Diagnostic
CT
71,270
CT THORAX W/O & W/DYE
CT - Diagnostic
CT
71,275
CT ANGIOGRAPHY CHEST
CT Angiography - Diagnostic
CTA
72,125
CT NECK SPINE W/O DYE
CT - Diagnostic
CT
72,126
CT NECK SPINE W/DYE
CT - Diagnostic
CT
72,127
CT NECK SPINE W/O & W/DYE
CT - Diagnostic
CT
72,128
CT CHEST SPINE W/O DYE
CT - Diagnostic
CT
72,129
CT CHEST SPINE W/DYE
CT - Diagnostic
CT
72,130
CT CHEST SPINE W/O & W/DYE
CT - Diagnostic
CT
72,131
CT LUMBAR SPINE W/O DYE
CT - Diagnostic
CT
72,132
CT LUMBAR SPINE W/DYE
CT - Diagnostic
CT
72,133
CT LUMBAR SPINE W/O & W/DYE
CT - Diagnostic
CT
72,191
CT ANGIOGRAPH PELV W/O&W/DYE
CT Angiography - Diagnostic
CTA
72,192
CT PELVIS W/O DYE
CT - Diagnostic
CT
72,193
CT PELVIS W/DYE
CT - Diagnostic
CT
72,194
CT PELVIS W/O & W/DYE
CT - Diagnostic
CT
73,200
CT UPPER EXTREMITY W/O DYE
CT - Diagnostic
CT
73,201
CT UPPER EXTREMITY W/DYE
CT - Diagnostic
CT
73,202
CT UPPR EXTREMITY W/O&W/DYE
CT - Diagnostic
CT
73,206
CT ANGIO UPR EXTRM W/O&W/DYE
CT Angiography - Diagnostic
CTA
73,700
CT LOWER EXTREMITY W/O DYE
CT - Diagnostic
CT
73,701
CT LOWER EXTREMITY W/DYE
CT - Diagnostic
CT
73,702
CT LWR EXTREMITY W/O&W/DYE
CT - Diagnostic
CT
73,706
CT ANGIO LWR EXTR W/O&W/DYE
CT Angiography - Diagnostic
CTA
74,150
CT ABDOMEN W/O DYE
CT - Diagnostic
CT
74,160
CT ABDOMEN W/DYE
CT - Diagnostic
CT
74,170
CT ABDOMEN W/O & W/DYE
CT - Diagnostic
CT
74,175
CT ANGIO ABDOM W/O & W/DYE
CT Angiography - Diagnostic
CTA
74,261
CT COLONOGRAPHY DX
CT - Diagnostic
CT
74,262
CT COLONOGRAPHY DX W/DYE
CT - Diagnostic
CT
74,263
CT COLONOGRAPHY SCREENING
CT - Diagnostic
CT
75,571
CT HRT W/O DYE W/CA TEST
CT - Diagnostic
CT
75,572
CT HRT W/3D IMAGE
CT - Diagnostic
CT
75,573
CT HRT W/3D IMAGE CONGEN
CT - Diagnostic
CT
75,574
CT ANGIO HRT W/3D IMAGE
CT Angiography - Diagnostic
CTA
75,635
CT ANGIO ABDOMINAL ARTERIES
CT Angiography - Diagnostic
CTA
76,380
CAT SCAN FOLLOW-UP STUDY
CT - Diagnostic
CT
76,497
CT PROCEDURE
CT - Diagnostic
CT
77,011
CT SCAN FOR LOCALIZATION
CT - Guidance
CT
77,012
CT SCAN FOR NEEDLE BIOPSY
CT - Guidance
CT
77,013
CT GUIDE FOR TISSUE ABLATION
CT - Guidance
CT
77,014
CT SCAN FOR THERAPY GUIDE
CT - Guidance
CT
77,078
CT BONE DENSITY AXIAL
CT - Diagnostic
CT
77,079
CT BONE DENSITY, PERIPHERAL
CT - Diagnostic
CT
0042 T
CT PERFUSION W/CONTRAST, CBF
CT - Diagnostic
CT & CTA
S8092
ELECTRON BEAM COMPUTED TOMOG
CT - Diagnostic
CT
Table 8
Chronic Kidney Disease
Chronic Kidney Disease Stage
ICD-9 Diagnosis Code(s)
Chronic Kidney Disease Stage 1
585.1
Chronic Kidney Disease Stage 2
585.2
Chronic Kidney Disease Stage 3
585.3
Chronic Kidney Disease Stage 4
585.4
Chronic Kidney Disease Stage 5
585.5
Chronic Kidney Disease, unspecified
585.9
Table 9
Elixhauser Comorbidity Index*
Comorbidity
Codes
Congestive Heart Failure
398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 425.4–425.9, 428.x
Cardiac Arrhythmia
426.0, 426.13, 426.7, 426.9, 426.10, 426.12, 427.0–427.4, 427.6–427.9, 785.0, 996.01, 996.04, V45.0, V53.3
Valvular Disease
093.2, 394.x–397.x, 424.x, 746.3–746.6, V42.2, V43.3
Pulmonary Circulation Disorders
415.0, 415.1, 416.x, 417.0, 417.8, 417.9
Peripheral Vascular Disorders
093.0, 437.3, 440.x, 441.x, 093.0, 437.3, 440.x, 441.x, 443.1–443.9, 447.1, 557.1, 557.9, V43.4
Hypertension (Uncomplicated)
401.x
Hypertension (Complicated)
402.x–405.x
Paralysis
334.1, 342.x, 343.x, 344.0–344.6, 344.9
Other Neurological Disorders
331.9, 332.0, 332.1, 333.4, 333.5, 333.92, 334.x–335.x, 336.2, 340.x, 341.x, 345.x, 348.1, 348.3, 780.3, 784.3
Chronic Pulmonary Disease
416.8, 416.9, 490.x − 505.x, 506.4, 508.1, 508.8
Diabetes (Uncomplicated)
250.0–250.3
Diabetes (Complicated)
250.4–250.9
Hypothyroidism
240.9, 243.x, 244.x, 246.1, 246.8
Renal Failure
403.01, 403.11, 403.91, 404.02, 404.03, 404.12, 404.13, 404.92, 404.93, 585.x, 586.x, except 585.6, 588.0, V42.0, V45.1, V56.x
End-stage renal disease
585.6
Liver Disease
070.22, 070.23, 070.32, 070.33, 070.44, 070.54, 070.6, 070.9, 456.0–456.2, 570.x, 571.x, 572.2–572.8, 573.3, 573.4, 573.8, 573.9, V42.7
Peptic Ulcer Disease (excluding bleeding)
531.7, 531.9, 532.7, 532.9, 533.7, 533.9, 534.7, 534.9
AIDS/HIV
042.x–044.x
Lymphoma
200.x–202.x, 203.0, 238.6
Metastatic Cancer
196.x–199.x
Solid Tumor without Metastasis
140.x–172.x, 174.x–195.x
Rheumatoid Arthritis Collagen
446.x, 701.0, 710.0–710.4, 710.8, 710.9, 711.2, 714.x, 719.3, 720.x, 725.x, 728.5, 728.89, 729.30
Coagulopathy
286.x, 287.1, 287.3–287.5
Obesity
278.0
Weight Loss
260.x–263.x, 783.2, 799.4
Fluid and Electrolyte Disorders
253.6, 276.x
Blood Loss Anemia
280.0
Deficiency Anemia
280.1–280.9, 281.x
Alcohol Abuse
265.2, 291.1–291.3, 291.5–291.9, 303.0, 303.9, 305.0, 357.5, 425.5, 535.3, 571.0–571.3, 980.x, V11.3
Drug Abuse
292.x, 304.x, 305.2–305.9, V65.42
Psychoses
293.8, 295.x, 296.04, 296.14, 296.44, 296.54, 297.x, 298.x
Depression
296.2, 296.3, 296.5, 300.4, 309.x, 311
*The ECI Score includes 31 categories (Table 9 in Appendix) of comorbidities, which are associated with mortality. Each category counts as 1 point for a potential ECI score range of 0–31. These comorbidities were identified using diagnosis codes that appear during the visit
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Metadaten
Titel
Risk of renal events following intravenous iodinated contrast material administration among inpatients admitted with cancer a retrospective hospital claims analysis
verfasst von
Chaan S. Ng
Sanjeeva P. Kalva
Candace Gunnarsson
Michael P. Ryan
Erin R. Baker
Ravindra L. Mehta
Publikationsdatum
01.12.2018
Verlag
BioMed Central
Erschienen in
Cancer Imaging / Ausgabe 1/2018
Elektronische ISSN: 1470-7330
DOI
https://doi.org/10.1186/s40644-018-0159-3

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