Use of questionnaires in outpatients at low-risk for post-contrast acute kidney injury scheduled for intravenous iodine-based contrast media administration: a proposal for computed tomography coronary angiography

Introduction

Iodine-based contrast media (ICM) are among the most commonly prescribed pharmaceutical agents, ordinarily utilized in computed tomography (CT) imaging (1). Post-contrast acute kidney injury (PC-AKI) is a possible adverse effect of ICM intravascular administration, defined as an increase in serum creatinine ≥0.3 mg/dL (or ≥26.5 µmol/L), or ≥1.5 times baseline, within 48–72 h of ICM injection (2). Given that chronic kidney disease (CKD) and AKI from other causes are the most significant predictors of PC-AKI, it is common practice to assess serum creatinine levels in all outpatient settings to calculate the estimated glomerular filtration rate (eGFR) before administering intravenous ICM. Contrast-enhanced CT scans are often postponed or the patient undergoes a hydration protocol if the eGFR is ≤30 mL/min/1.73 m² (3,4). The current guideline recommendations are predominantly derived from expert opinions and are motivated by practical considerations and logistical constraints within hospital settings. Under this strategy, patients without an up-to-date eGFR value may require an immediate eGFR measurement prior to the scan or rescheduling of the appointment, potentially impacting diagnostic and therapeutic timelines as well as increasing administrative costs and reducing scanner capacity for the imaging department (5). An alternative pathway could be to use a questionnaire to screen patients at higher risk of developing PC-AKI and only measure eGFR in these subjects, thus avoiding blood sampling in most cases. In particular, this approach could be safely applied to the growing number of outpatients accessing radiology departments for computed tomography coronary angiography (CTCA) scans to rule out coronary artery disease (CAD).

In this letter, through an overview of the main data present in the literature regarding PC-AKI and questionnaires, PC-AKI and guidelines, and PC-AKI and CTCA, we propose a questionnaire that could be easily integrated into future PC-AKI prevention guideline updates to screen the risk of PC-AKI before performing a CTCA in outpatients with chest pain but unknown CAD.

PC-AKI and questionnaires

Patient questionnaires have been proposed as a potential screening tool for PC-AKI since the mid-1990s. By identifying risk factors linked to PC-AKI, we can pinpoint patients at higher risk of kidney failure who might benefit from renal function assessment before receiving ICM, thus reducing the need for excessive eGFR testing. In an early landmark study by Choyke et al., patients with risk factors identified by a questionnaire, such as proteinuria, kidney disease (including renal surgery), hypertension, diabetes, or gout, had the highest odd-ratios for having a serum creatinine >150 µmol/L (6). This survey provided the framework for the European Society of Urogenital Radiology (ESUR)’s patient questionnaire, introduced in 2008 (7,8). A subsequent evaluation of the Choyke questionnaire in comparison with point-of-care serum creatinine testing showed 100% sensitivity, 100% negative predictive value, and 65% specificity for eGFR <30 mL/min/1.73 m². Furthermore, only a history of renal disease and diabetes mellitus was statistically significant predictor of eGFR <45 mL/min/1.73 m² (9). In another study, the most reliable indicators for eGFR <60 mL/min/1.73 m², in descending order, were identified as follows: the presence of renal disease, gout, previous renal surgery, diabetes mellitus, hypertension, proteinuria, and the use of nephrotoxic medication. Using these risk factors, the number of renal function tests could be restricted to 45% of subjects, with only 1.3% of patients having eGFR <30 mL/min/1.73 m² (10). Furthermore, 3–6% of subjects without any reported risk factors exhibited an eGFR <45 mL/min/1.73 m² and only 0.6–1% an eGFR <30 mL/min/1.73 m². Screening for previous renal disease had the highest correlation with a reduced eGFR (11,12). Also, a statistically significant association was observed between an eGFR <60 mL/min/1.73 m² and factors such as age over 60 years, diabetes mellitus, hypertension, and CKD. By exclusively targeting patients exhibiting one of these risk factors for eGFR evaluation prior to contrast-enhanced CT, all individuals with an eGFR <60 mL/min/1.73 m² were identified with 100% sensitivity and negative predictive value (13). In the United Kingdom, a cost-analysis of using a survey (including questions about the presence of kidney disease, diabetes, heart failure, or sickness in the last week) with point of care creatinine testing demonstrated potential for significant 5-year cost reductions (savings of £69,620). Indeed, 78% of patients did not show PC-AKI risk factors and could have avoided serum creatinine sampling (5).

These studies have therefore shown very promising results in identifying patients with low eGFR before performing contrast-enhanced imaging. As these are simple questions that can be provided to patients at the time of booking of the radiological examination, they potentially represent a valid alternative to the need to sample creatinine in all patients. Among the various risk factors analysed in the questionnaires, the one that seemed least understandable to patients was the presence of proteinuria (11,12), for which a more explanatory question could be used (e.g., “have proteins ever been detected in your urine?”).

PC-AKI and guidelines

In recent years, there has been a substantial shift in our comprehension of PC-AKI. Current research suggests that the risk of developing PC-AKI following ICM injection is not elevated compared to the risk associated with unenhanced CT examinations (14). Detecting PC-AKI and determining its prevalence is challenging due to the natural, physiological variability in serum creatinine levels. Additionally, other possible causes for fluctuations in creatinine levels should be considered. The American College of Radiology (ACR) and the National Kidney Foundation (NKF) made stricter discrimination for risk factors between the correlative diagnosis of PC-AKI and the causal diagnosis of contrast-induced acute kidney injury (CI-AKI), which requires study designs with appropriate control groups. Most published risk factors are associated with PC-AKI and include a decreased eGFR, diabetes, use of concurrent nephrotoxic drugs, hypovolemia, hypotension, albuminuria, and decreased renal perfusion from congestive heart failure. In contrast, multiple propensity score-matched studies showed that only severe CKD (eGFR of ≤30 mL/min/1.73 m²) or AKI are risk factors for CI-AKI (15-17). In a recent evaluation of the ACR-NKF consensus, only a prior diagnosis of renal disease or diabetes was statistically associated with an eGFR <30 mL/min/1.73 m², and it was recommended to favour diabetes over a history of renal surgery as a risk factor for identifying advanced CKD before contrast-enhanced CT in outpatients (18). These findings have led to the development of different guidelines globally concerning the screening for PC-AKI in outpatients.

For example, the ESUR recommends assessing eGFR before administering intravascular ICM, either for all patients or specifically for subjects with a history of diabetes, kidney disease, proteinuria, renal surgery, hyperuricemia and/or hypertension (19). The Italian College of Radiology (3) and the Radiological Society of the Netherlands (4) indicate that eGFR assessment should be performed for all subjects undergoing ICM injection. The ACR suggests that for patients scheduled for a routine intravascular study without a personal history of renal disease, diabetes mellitus, or metformin intake, a baseline serum creatinine determination before ICM administration is not necessary (20). The Canadian Association of Radiologists suggests assessing eGFR only for patients with kidney disease, a kidney transplant, or those referred to see a nephrologist/urologist (21).

This heterogeneity is an expression of the level of uncertainty in defining and managing PC-AKI and represents an index of the need to update and standardize international guidelines based on the current evidence.

PC-AKI and CTCA

CTCA is gaining popularity as a non-invasive method for examining the coronary arteries (22), significantly contributing to the diagnosis of heart conditions, prognostication, and treatment adjustment (23-26). It comes as no surprise that prominent guideline organizations are now more decisively advocating for the integration of CTCA into clinical practice (27).

One of the most frequent clinical indications for CTCA in outpatients is the study of subjects with stable chest pain but no known CAD. Determining the optimal management approach for these patients relies on assessing the pre-test probability of obstructive CAD using models incorporating age, gender, chest pain, and dyspnoea for risk assessment. Patients with a pre-test probability of less than 15% are categorized as low-risk, those with a probability between 15% and 50% are deemed intermediate-risk, and those with a probability exceeding 50% are classified as high-risk for CAD (28). American and European guidelines agree on the utility of CTCA in the following specific patient populations: asymptomatic patients with intermediate pre-test probability of CAD, where the symptoms could be attributable to coronary ischemia but are not diagnostic of the condition, and patients with equivocal or non-diagnostic stress test results, where CTCA can provide clear images of the coronary arteries to rule in or rule out significant stenosis (29,30). Conversely, the National Institute for Health and Care Excellence guidelines in the United Kingdom suggest CTCA as the initial diagnostic test for all patients exhibiting typical or atypical anginal symptoms (or those with electrocardiogram findings indicative of significant CAD even in the absence of symptoms), irrespective of pre-test probability (31).

CTCA employs modern electrocardiogram-gated/triggered multi-detector CT (>64 slice) scans to produce high-resolution, isotropic images of the coronary arteries following the intravenous administration of ICM (32). To achieve sufficient enhancement within the coronary arteries (>250 HU), the dose of ICM should be adjusted based on the patient’s weight (0.2–0.4 g iodine/kg body weight). It is recommended to use an iodine delivery rate (or iodine flux = flow rate × concentration) ranging from 1.5–2.0 g iodine/second. On average, for a contrast medium with 300 mg iodine/mL and a tube voltage of 120 kVp, this necessitates an injection rate of 5–6.6 mL/s and a volume of 50–100 mL of contrast medium (lower than a contrast-enhanced CT for parenchyma study) (33).

Recent research has assessed the risk of PC-AKI specifically in patients undergoing CTCA. Persistent renal dysfunction resulting from exposure to ICM was an uncommon and transitory occurrence, observed in only 0.2–1.2% of patients referred for CTCA to study suspected stable CAD (34-38). Moreover, individuals with potential risk factors, such as diabetes, did not exhibit a more significant increase in serum creatinine following ICM exposure compared to those without risk factors, and the average impact of ICM on serum creatinine did not surpass the inherent fluctuation in serum creatinine levels within individuals (35). This low rate of PC-AKI is in line with the baseline clinical profiles of the patients, who were predominantly outpatients with low-intermediate risk of stable CAD and an eGFR ≥60 mL/min/1.73 m² in 93% of cases (34). Given the low risk profile for PC-AKI demonstrated in these patients, they could be excellent candidates for using questionnaires to identify those who should undergo serum creatinine sampling before CTCA rather than measuring eGFR in all.

Data summary and our proposal

PC-AKI occurs less frequently than previously thought, particularly in patients referred for CTCA due to suspected stable CAD. The main risk factor for PC-AKI is an eGFR <30 mL/min/1.73 m², uncommon in outpatients with no known CAD undergoing CTCA. The use of patient questionnaires (Table 1) has proven to be a valid alternative method for identifying patients with eGFR <30 mL/min/1.73 m², and a diagnosis of diabetes and/or kidney disease is potentially linked to an eGFR <30 mL/min/1.73 m². Considering all this, we advocate the use of a questionnaire in outpatients with stable chest pain but no known CAD to identify subjects with possible impaired renal function who could benefit from eGFR evaluation before ICM administration. Based on the current ACR-NKF recommendations (15,18), the optimal questionnaire should include the points reported in Table 2 (39). Our proposal focuses primarily on those risk factors that, according to the latest evidence, are most strongly associated with kidney injury (history of nephropathy and/or diabetes), omitting some traditional risk factors found in older questionnaires (e.g., history of cardiovascular disease, gout, use of medications other than metformin) that, if included, would increase the number of patients undergoing eGFR testing without improving PC-AKI prevention.

This approach would result in cost savings by significantly reducing the number of serum creatinine tests required and would prevent the potential need for rescheduling CTCA examinations in many patients when eGFR is not available, with important implications for critical treatments (e.g., coronary artery interventions).

Future studies are needed to evaluate this practice and its cost-effectiveness, particularly among the growing number of outpatients undergoing CTCA scans.

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-968/coif). C.A.M. serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. A.J.v.d.M. received consultancy fees from Guerbet and royalties from Thieme Verlag KG. I.A.D. received consultancy fees from Guerbet. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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