Skip to content

Advertisement

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact us so we can address the problem.

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

Cancer Imaging201818:30

https://doi.org/10.1186/s40644-018-0159-3

  • Received: 3 April 2018
  • Accepted: 21 July 2018
  • Published:

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.

Keywords

  • Iodinated contrast media
  • Acute renal event
  • Cancer
  • Contrast-induced nephropathy
  • Contrast-induced acute kidney injury
  • Computed tomography

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).
Fig. 1
Fig. 1

Attrition Diagram

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

Fig. 2
Fig. 2

Renal Event: Multivariable Risk Decomposition – CT, CM, CKD, and Cancer Type, The percentages shown in Table 4, and in this figure in the columns and at the top of each column differ slightly due to rounding. +CT = record of CT; +Iodinated = record of iodinated contrast material (CM); +CKD = chronic kidney disease, The absolute risk of a renal event can be calculated based on a patient’s comorbidities. For example, a patient hospitalized for cancer who had a CT scan with iodinated CM and CKD stage 1, had a 4.9% risk of a renal event. The risk was calculated as follows: (baseline [.5%] + CT [.2%] with iodinated CM [.8%] + CKD stage 1 [2.5%] + cancer [.9%])

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.

Abbreviations

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

Declarations

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.

Authors’ contributions

All authors contributed to the concept and design of the study and contributed critical revision to the manuscript. MR and CG were responsible for the data analysis, MR, CG, EB were responsible for interpretation of results and drafting the manuscript. CN, SK, CG, MR, EB, and RM, approved the final version for journal submission. All authors read and approved the final manuscript.

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).

Consent for publication

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.

Authors’ Affiliations

(1)
MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA
(2)
University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, 75390-8834, TX, USA
(3)
CTI Clinical Trial & Consulting Services100 E, RiverCenter Blvd, Covington, KY 41011, USA
(4)
University of California San Diego 0892 UCSD Medical Center, 9500 Gilman Drive, La Jolla, CA 92037, USA

References

  1. Bottinor W, Polkampally P, Jovin I. Adverse reactions to iodinated contrast media. Int J Angiol. 2013;22:149–54.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Brockow K, Christiansen C, Kanny G, Clement O, Barbaud A, Bircher A, et al. Management of hypersensitivity reactions to iodinated contrast media. Allergy. 2005;60:150–8.View ArticlePubMedGoogle Scholar
  3. Morcos SK, Thomsen HS. Adverse reactions to iodinated contrast media. Eur Radiol. 2001;11:1267–75.View ArticlePubMedGoogle Scholar
  4. Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl. 2006;(100):S11–5.Google Scholar
  5. Mizuno T, Sato W, Ishikawa K, Shinjo H, Miyagawa Y, Noda Y, et al. KDIGO (kidney disease: improving global outcomes) criteria could be a useful outcome predictor of cisplatin-induced acute kidney injury. Oncology. 2012;82:354–9.View ArticlePubMedGoogle Scholar
  6. Rawson JV, Pelletier AL. When to order a contrast-enhanced CT. Am Fam Physician. 2013;88:312–6.PubMedGoogle Scholar
  7. American College of Radiology. ACR manual on contrast media Version 10.3 [https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf] Accessed 5 Oct 2017.
  8. Eng J, Wilson RF, Subramaniam RM, Zhang A, Suarez-Cuervo C, Turban S, et al. Comparative effect of contrast media type on the incidence of contrast-induced nephropathy: a systematic review and meta-analysis. Ann Intern Med. 2016;164:417–24.View ArticlePubMedGoogle Scholar
  9. Cicin I, Erdogan B, Gulsen E, Uzunoglu S, Sut N, Turkmen E, et al. Incidence of contrast-induced nephropathy in hospitalised patients with cancer. Eur Radiol. 2014;24:184–90.View ArticlePubMedGoogle Scholar
  10. Hong SI, Ahn S, Lee YS, Kim WY, Lim KS, Lee JH, et al. Contrast-induced nephropathy in patients with active cancer undergoing contrast-enhanced computed tomography. Support Care Cancer. 2016;24:1011–7.View ArticlePubMedGoogle Scholar
  11. Huang MK, Hsu TF, Chiu YH, Chiang SC, Kao WF, Yen DH, et al. Risk factors for acute kidney injury in the elderly undergoing contrast-enhanced computed tomography in the emergency department. J Chin Med Assoc. 2013;76:271–6.View ArticlePubMedGoogle Scholar
  12. Newhouse JH, Kho D, Rao QA, Starren J. Frequency of serum creatinine changes in the absence of iodinated contrast material: implications for studies of contrast nephrotoxicity. AJR Am J Roentgenol. 2008;191:376–82.View ArticlePubMedGoogle Scholar
  13. Farolfi A, Carretta E, Luna CD, Ragazzini A, Gentili N, Casadei C, et al. Does the time between CT scan and chemotherapy increase the risk of acute adverse reactions to iodinated contrast media in cancer patients? BMC Cancer. 2014;14:792.View ArticlePubMedPubMed CentralGoogle Scholar
  14. Farolfi A, Della Luna C, Ragazzini A, Carretta E, Gentili N, Casadei C, et al. Taxanes as a risk factor for acute adverse reactions to iodinated contrast media in cancer patients. Oncologist. 2014;19:823–8.View ArticlePubMedPubMed CentralGoogle Scholar
  15. Moos SI, van Vemde DN, Stoker J, Bipat S. Contrast induced nephropathy in patients undergoing intravenous (IV) contrast enhanced computed tomography (CECT) and the relationship with risk factors: a meta-analysis. Eur J Radiol. 2013;82:e387–99.View ArticlePubMedGoogle Scholar
  16. Dimopoulos MA, Kastritis E, Rosinol L, Blade J, Ludwig H. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia. 2008;22:1485–93.View ArticlePubMedGoogle Scholar
  17. Eleutherakis-Papaiakovou V, Bamias A, Gika D, Simeonidis A, Pouli A, Anagnostopoulos A, et al. Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma. 2007;48:337–41.View ArticlePubMedGoogle Scholar
  18. Gertz MA. Current therapy of myeloma induced renal failure. Leuk Lymphoma. 2008;49:833–4.View ArticlePubMedGoogle Scholar
  19. Pahade JK, LeBedis CA, Raptopoulos VD, Avigan DE, Yam CS, Kruskal JB, et al. Incidence of contrast-induced nephropathy in patients with multiple myeloma undergoing contrast-enhanced CT. AJR Am J Roentgenol. 2011;196:1094–101.View ArticlePubMedGoogle Scholar
  20. Premier Healthcare Database: Date that Informs and Preforms. [https://learn.premierinc.com/white-papers/premier-healthcare-database-whitepaper] Accessed Jul 2018.
  21. Ernst FR, Chen E, Lipkin C, Tayama D, Amin AN. Comparison of hospital length of stay, costs, and readmissions of alteplase versus catheter replacement among patients with occluded central venous catheters. J Hosp Med. 2014;9:490–6.Google Scholar
  22. Elixhauser A, Steiner C, Harris DR, Coffey RM. Comorbidity measures for use with administrative data. Med Care. 1998;36:8–27.View ArticlePubMedGoogle Scholar
  23. Davenport MS, Khalatbari S, Cohan RH, Dillman JR, Myles JD, Ellis JH. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration rate. Radiology. 2013;268:719–28.View ArticlePubMedGoogle Scholar
  24. McDonald RJ, McDonald JS, Carter RE, Hartman RP, Katzberg RW, Kallmes DF, et al. Intravenous contrast material exposure is not an independent risk factor for dialysis or mortality. Radiology. 2014;273:714–25.View ArticlePubMedGoogle Scholar
  25. Heiken JP. Contrast safety in the cancer patient: preventing contrast-induced nephropathy. Cancer Imaging. 2008;8 Spec No(A):S124–7.View ArticlePubMedPubMed CentralGoogle Scholar
  26. Sendur MA, Aksoy S, Yaman S, Arik Z, Tugba Kos F, Akinci MB, et al. Administration of contrast media just before cisplatin-based chemotherapy increases cisplatin-induced nephrotoxicity. J BUON. 2013;18:274–80.PubMedGoogle Scholar
  27. Owen RJ, Hiremath S, Myers A, Fraser-Hill M, Barrett BJ. Canadian Association of Radiologists consensus guidelines for the prevention of contrast-induced nephropathy: update 2012. Can Assoc Radiol J. 2014;65:96–105.View ArticlePubMedGoogle Scholar
  28. Terrenato I, Sperati F, Musicco F, Pozzi AF, di Turi A, Caterino M, et al. Iodixanol versus iopromide in cancer patients: evidence from a randomized clinical trial. J Cell Physiol. 2018;233(3):2572–80. Epub 2017 Sep 12.Google Scholar
  29. Salahudeen AK, Doshi SM, Pawar T, Nowshad G, Lahoti A, Shah P. Incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a comprehensive cancer center. Clin J Am Soc Nephrol. 2013;8:347–54.View ArticlePubMedGoogle Scholar
  30. Cosmai L, Porta C, Gallieni M, Perazella MA. Onco-nephrology: a decalogue. Nephrol Dial Transplant. 2016;31:515–9.View ArticlePubMedGoogle Scholar
  31. Perazella MA. Online Curricula: Onco-Nephrology [https://www.asn-online.org/education/distancelearning/curricula/onco/] Accessed 10 Nov 2017.

Copyright

Advertisement