European Radiology (2022) 32:8432–8442

https://doi.org/10.1007/s00330-022-08916-y

CONTRAST MEDIA

Risk of acute kidney injury after contrast-enhanced computerized

tomography: a systematic review and meta-analysis of 21 propensity
score–matched cohort studies
Mikal Obed 1 & Maria Magdalena Gabriel 2 & Eva Dumann 1 & Clara Vollmer Barbosa 1 & Karin Weißenborn 2 &
Bernhard Magnus Wilhelm Schmidt 1

Received: 25 March 2022 / Revised: 7 May 2022 / Accepted: 30 May 2022 / Published online: 21 June 2022
# The Author(s) 2022

Abstract
Objectives Intravenous application of contrast media is part of a wide spectrum of diagnostic procedures for better imaging
quality. Clinical avoidance of contrast-enhanced imaging is an ever-present quandary in patients with impaired kidney function.
The objective of this study was to estimate the risk for acute kidney injury (AKI), dialysis and mortality among patients
undergoing contrast-enhanced CT compared to propensity score–matched controls (i.e. contrast-unenhanced CT). Selected
cohort studies featured high-risk patients with advanced kidney disease and critical illness.
Methods This review was designed to conform to the Preferred Reporting Items in Systematic Reviews and Meta-Analysis
(PRISMA) guidelines. PubMed was searched from August 2021 to November 2021 for all-language articles without date
restriction. A random-effects model (DerSimonian and Laird method) was used for meta-analysis.
Results Twenty-one articles were included, comprising data of 169,455 patients. The overall risk of AKI was similar in the
contrast-enhanced and unenhanced groups (OR: 0.97 [95% CI: 0.85; 1.11], p = 0.64), regardless of baseline renal function and
underlying disease. Substantial heterogeneity was detected (I2 = 90%, p ≤ 0.0001). Multivariable logistic regression identified
hypertension (p = 0.03) and estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 (p = 0.0001) as factors associated
with greater risk of post-contrast AKI.
Conclusions Based on propensity score–matched pairs obtained from 21 cohort studies, we found no evidence for increased risk for
AKI, dialysis or mortality after contrast-enhanced CT among patients with eGFR ≥ 45 mL/min/1.73 m2. In congruence with the
emerging evidence in the literature, caution should be exercised in patients with hypertension and eGFR ≤ 30 mL/min/1.73 m2.
Key Points
• The application of contrast media for medical imaging is not associated with higher odds for AKI, induction of renal
replacement therapy, or mortality. Many comorbidities traditionally associated with greater risk for acute kidney injury do
not appear to predispose for renal decline after contrast media exposure.
• Underlying hypertension and eGFR less than or equal to 30 mL/min/1.73 m2 seem to predispose for post-contrast acute kidney
injury.
• Propensity score matching cannot account for unmeasured influences on AKI incidence, which needs to be addressed in the
interpretation of results.

Keywords Acute kidney injury . Contrast media . Computed tomography . Glomerular filtration rate . Propensity score matching

Abbreviations
AKI Acute kidney injury
* Mikal Obed
[email protected] AKIN Acute Kidney Injury Network
CA-AKI Contrast-associated acute kidney injury
1 CI-AKI Contrast-induced acute kidney injury
Department of Nephrology and Hypertension, Hannover Medical
School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany CIN Contrast-induced nephropathy
2 CM Contrast media
Department of Neurology, Hannover Medical School,
Carl-Neuberg-Straße 1, 30625 Hannover, Germany SCr Serum creatinine
European Radiology (2022) 32:8432–8442 8433

CT Computed tomography demographically similar controls undergoing contrast-

KDIGO Kidney Disease: Improving Global Outcomes unenhanced CT. As secondary outcomes of interest, we eval-
RIFLE Risk, injury, failure, loss of kidney function, uated the risks of dialysis and mortality in patients with CM–
and end-stage kidney disease enhanced and unenhanced CT.
95%CI 95% confidence interval
PS Propensity score
PSM Propensity score matching Materials and methods
CKD Chronic kidney disease
Protocol and registration
Introduction The protocol for this systematic review was registered at the
International Prospective Register of Systematic Reviews
Contrast-induced nephropathy (CIN), also known as contrast- (PROSPERO) under the identification number 197088, and
associated acute kidney injury (CA-AKI) or contrast-induced was accepted on September 6, 2020.
acute kidney injury (CI-AKI), is defined as a rapid decline of
renal function within days following intravascular exposure to
contrast media (CM) [1, 2]. CA-AKI is traditionally suggested Data sources and search
to be a leading cause of hospital-acquired acute kidney injury
(AKI), presenting 12% of all cases [3]. The absolute and rel- Two investigators (M.O. and B.M.W.S.) reviewed all
ative definitions of CA-AKI are diverse. Most commonly, it is English-language publications in Cochrane Library, PubMed
characterized by an absolute increase in serum creatinine and MEDLINE using the search terms “propensity score
(SCr) levels of ≥ 0.3 mg/dL or ≥ 0.5 mg/dL from baseline. It AND contrast media“ and “(AKI OR nephropathy) AND (io-
can also be defined as a relative SCr increase of more than dinated contrast OR contrast media OR CT OR angiography)
25% of baseline or 1.5 times baseline within 1–3 or 4–5 days AND propensity score” with no date restrictions. Data extrac-
after intravenous or intra-arterial CM application [4–6]. By tion was performed until November 2021, using a predefined
definition, no factors other than previous CM exposure can set of inclusion and exclusion criteria. In case of differing
provide sufficient explanation for the renal decline [7, 8]. results between both researchers, a third (K.W.) and a fourth
Post-contrast AKI is strongly associated with short- and (E.D.) investigator reviewed and adjudicated the results.
long-standing adverse and potentially irreversible outcomes
[9, 10]. Eligibility criteria
Contrast-enhanced computed tomography (CT) is an indis-
pensable component of medical imaging. Although low- and All studies reporting on the effects of CM exposure on AKI
iso-osmolar contrast agents are generally considered safe, incidence using a propensity score–matching model were con-
their intravenous administration for greater imaging quality sidered for inclusion. Eligible studies required two arms: one
and diagnostic accuracy has been assumed one of the most group of patients undergoing CM–enhanced CT and a control
frequent causes of AKI in clinical practice [7]. group undergoing unenhanced CT. Studies were included for
However, numerous cohort studies have challenged this meta-analysis if AKI was defined by Acute Kidney Injury
historic belief by using the propensity score (PS) to match Network (AKIN); Kidney Disease: Improving Global
CM–exposed subjects with unexposed controls. Propensity Outcomes (KDIGO); Risk, Injury, Failure, Loss of kidney
score matching (PSM) is an analytical approach to estimate function, and End-stage Kidney Disease (RIFLE); or
the weight of CM exposure on the incidence of AKI [11]. contrast-induced nephropathy (CIN) criteria [13–16]. The
Applying logistic regression, patients are matched according presence of SCr measurements or glomerular filtration rates
to similar distributions of baseline characteristics [11, 12]. (GFRs) before and after CT scans was required for inclusion.
Studies applying the PS have revealed equal rates of AKI in No age restriction was applied. Trials comparing different
matched cohorts (i.e. CM exposed and unexposed), pointing doses of the same intervention or applying re-randomization
out the underestimated role of underlying comorbidities in the of the same sample (i.e. crossover design) and trials that
development of AKI. Thus, it is suggested that the dreaded lacked either PSM or a proper comparator arm were excluded.
deterioration of kidney function following contrast-enhanced Studies reporting on solitary kidneys or procedures other than
imaging might have been falsely attributed to CM rather than CT scans were also excluded. The same applied to patient
the susceptibility of particular patient collectives. cohorts undergoing multiple CT scans within 72 h.
The objective of this systematic review and meta-analysis Systematic reviews and meta-analyses were excluded; how-
was to determine the risks of acute nephropathy in patients ever, the references of all identified reviews were searched for
undergoing contrast-enhanced CT compared with additional citations [17–19].
8434 European Radiology (2022) 32:8432–8442

Study selection and data collection process Our initial search identified 297 publications (Fig. 1).
After duplicates were removed, the remaining 99 articles
The data of selected studies was independently extracted by were reviewed by title, leading to the exclusion of 58
three investigators (M.O., M.M.G., C.V.B.). In case of dis- records. The remaining 41 articles were screened by
crepancies on study findings, outcomes were discussed (with abstract. All papers fulfilling the inclusion criteria (n =
E.D., supervised by B.M.W.S. and K.W.), and consensus was 26) were assessed by full-text review. Potential doubling
established. Points of discussion included the handling of ar- or reutilization of study populations was thoroughly
ticles with mixed CM pathways (i.e. intravenous and intra- checked. Ultimately, 21 articles were selected for final
arterial), overlapping study populations, differing matching data extraction, comprising data of 169,455 patients un-
models and the consideration of multiple AKI criteria in the dergoing CT.
same study.

Fig. 1 Flowchart showing the

study selection process. The
numbers of studies identified,
assessed for eligibility, and
included in the meta-analysis
European Radiology (2022) 32:8432–8442 8435

Data items and statistical analyses pooled odds ratios (ORs) for primary (i.e. AKI) and secondary
outcomes (i.e. dialysis, death) in CM–exposed and unexposed
The number of subjects and the study type were retrieved for cohorts [21]. Additional meta-regression analysis was performed
each study (Table 1). Additionally, the applied matching ratios to determine heterogeneity by patient-related factors (e.g. age,
(i.e. 1:1, 1:3), type of study population (e.g. general population, gender, comorbidities).
septic patients) and applied AKI definition (i.e. AKIN, KDIGO, All analyses were performed using Comprehensive Meta-
RIFLE or CIN) were identified. The Newcastle–Ottawa Scale Analysis (CMA, Version 2.2.064) and R 4.0.2.
was implemented to assess the risk of bias [20]. The calculated
scores were converted to the Agency for Healthcare Research
and Quality (AHRQ) standards, marking the risk of bias as un- Results
clear, high, moderate or low. Cochrane’s Q and I2 were used to
indicate the heterogeneity between studies, and a funnel plot was The initial literature search identified 297 articles fulfilling our
applied to examine the risk of publication bias. A random-effects inclusion criteria. After performing full-text article workups, 26
model (DerSimonian and Laird method) was used to calculate studies were initially declared eligible for inclusion. In the course

Table 1 Study characteristics and study populations

Study AKI Matching Study population Number of Number of Odds ratio (OR) [95%
type definition method exposed controls confidence interval]

Davenport, 2013a RCS AKIN* 1:1 General inpatient population 10,121 10,121 0.96 [0.87 to 1.06]
Davenport, 2013° RCS AKIN 1:1 General inpatient population 8826 8826 1.02 [0.91 to 1.15]
Ehrmann, 2013 PCS CIN+ 1:1 ICU patients 146 146 1.00 [0.38 to 2.66]
McDonald, 2013 RCS CIN 1:1 General inpatient population 10,686 10,686 0.94 [0.83 to 1.07]
McDonald, RCS AKIN 1:1 CKD patients 1639 1639 0.78 [0.64 to 0.95]
2015°
Hinson, 2016 RCS AKIN N/A^ ED patients 7201 5499 0.75 [0.66 to 0.85]
Tao, 2017 RCS AKIN 1:1 Nephrotic syndrome patients 543 543 0.54 [0.32 to 0.91]
Chaudhury, 2018 RCS CIN 1:1 CKD patients 200 200 1.00 [0.63 to 1.58]
Latcha, 2018 RCS RIFLE& 1:1 Cancer patients 2252 2252 0.98 [0.85 to 1.12]
Ellis, 2019 RCS AKIN 1:1 Patients with stage IIIb–V CKD 599 599 1.23 [0.91 to 1.67]
Goto, 2019 RCS KDIGO§ 1:1 Septic patients 100 100 0.96 [0.54 to 1.71]
Hinson, 2019 RCS KDIGO N/A Septic patients 1464 976 0.75 [0.56 to 1.0]
Puchol, 2019 RCS AKIN N/A ED patients 6642 6193 0.73 [0.64 to 0.83]
Williams, 2019 RCS KDIGO 1:1 ICU patients 2306 2306 1.09 [0.94 to 1.26]
Gilligan, 2020 RCS AKIN 1:1 Pediatric patients 925 925 0.92 [0.51 to 1.64]
Elias, 2021 RCS AKIN 1:1 Patients with suspected 969 969 1.00 [0.79 to 1.27]
pulmonary embolism
Guo, 2021 RCS KDIGO 1:1 Infants and young children 159 159 1.09 [0.68 to 1.76]
undergoing cardiac surgery
Gorelik, 2021 RCS KDIGO 1:1 General inpatient population 11,664 11,664 0.86 [0.78 to 0.95]
Kene, 2021 RCS AKIN 1:1 Emergency patients with 5589 5589 1.68 [1.49 to 1.90]
chronic kidney disease
Su, 2021 RCS KDIGO N/A Emergency patients 10,143 11,921 1.36 [1.25 to 1.49]
Yan, 2021 RCS AKIN 1:1 Hospitalized acute kidney 1172 1172 0.86 [0.64 to 1.15]
injury patients
*
Acute Kidney Injury Network (AKIN) Definition: Absolute increase of ≥ 0.3 mg from baseline serum creatinine at 48 to 72 hours
+
Contrast-induced nephropathy (CIN) definition by the European Society of Urogenital Radiology: absolute SCr increase of 0.5 mg/dL or > 25% of the
baseline within 72 h of contrast administration
§
Kidney Disease: Improving Global Outcomes (KDIGO) definition: absolute SCr increase of ≥ 0.3 mg/dL (26.5 μmol/L) from baseline serum creatinine
within 48 h or > 1.5-fold from baseline within 7 days
&
Risk, Injury, Failure; Loss, End-Stage Renal (RIFLE) definition of AKI: relative increase of 1.5–1.9 over baseline SCr at 48 to 72 h or glomerular
filtration rate (GFR) decrease of > 50%
° Studies not included in the main analysis
^ Not applicable
8436 European Radiology (2022) 32:8432–8442

of our statistical analysis, we detected a high degree of overlap- Meta-regression analysis

ping samples in the studies by Davenport et al and McDonald
et al, respectively. In order to address single author bias and To further explore possible origins of heterogeneity, we per-
increased subject weighting, we decided to remove all duplicates formed meta-regression analyses for 7 relevant covariates
and consider only one study of each author. Based on the largest (Table 3). Here, a larger proportion of patients with hyperten-
sample size, the studies from Davenport et al from 2013 [22] and sion was associated with higher odds for AKI after CM expo-
McDonald et al from 2013 [23] were chosen for meta-analysis. sure (p = 0.03) (Fig. 4). Other clinically plausible variables
As both studies lacked further subdivision into eGFR groups, the related to the use of CM showed no significant influence on
2013 study by Davenport et al [24] and 2015 article by AKI rates. Therefore, hypertension and eGFR less than or
McDonald et al [25] were chosen for the analysis of cohorts with equal to 30 mL/min/1.73 m2 likely are conditions accounting
eGFR less than or equal to 30 mL/min/1.73 m2. for the observed heterogeneity (Figs. 3 and 4).
Ultimately, 21 studies were selected for final data extrac-
tion and analysis, six of which consisted of general population Effects of contrast media on dialysis and mortality
cohorts [22–27] (Table 1). Two studies focused on critically ill
[28, 29] and two on pediatric patients [30, 31]. Four studies A total of 1517 patients from 11 studies required renal replace-
consisted of patients admitted via emergency department ment therapy after CM exposure, including 729 cases from the
[32–35]; one study examined nephrotic syndrome patients CM–exposed cohorts (n = 18,493) and 788 from the control
[36]; two focused on patients with chronic kidney disease groups (n = 11,202). No significant difference in the rate of
(CKD) [37, 38]; and two on patients hospitalized with AKI dialysis was observed between CM exposed and controls
[39, 40]. Two groups studied septic [38, 41] and one cancer (OR: 0.97 [0.75; 1.25]; p = 0.81) (Table 2).
patients [42]. AKI was defined by RIFLE criteria in 1 study; Further, 3400 deaths were reported in 7 studies (n = 10,312),
by AKIN in 11 studies; by KDIGO criteria in 6 studies, and by including 1649 cases among 8030 CM–exposed patients (13%)
CIN criteria in 3 studies. If studies applied AKIN and CIN and 1751 fatal events in 2282 controls (13%). No significant
criteria to define AKI, the 2007 definition by AKIN was pre- difference in mortality was detected between the CM groups
ferred over CIN. Each study comprised two cohorts that were and controls (OR: 0.94 [0.86; 1.03]; p = 0.18) (Table 2).
assigned by PSM. Here, 17 studies (80%) applied a 1:1
matching ratio. Low-osmolar contrast agents were adminis- Serum creatinine measurements for AKI diagnosis
tered in 14 studies (70%), iso-osmolar CM in one study
(5%) and a combination of both in five studies (25%). One Our selected studies applied different observation periods to
study (5%) did not specify the type of CM used. The use of diagnose AKI after CT imaging. Here, SCr levels were ac-
high-osmolar CM was declared by none. quired within 24 h [22, 24, 29], 48 h [22, 24, 30, 31], 72 h
[22, 24, 26, 42] or 96 h after the index CT scan [28, 37]. In
three studies, the window for post-contrast SCr measurement
Effects of contrast media administration on kidney reached from 48 to 72 h [33, 34, 41], one of which added a
function second time point between 48 h and 1 week. One group mea-
sured the SCr levels for 1 month after index CT [40], while
Overall, 7425 AKI events were detected in 60,367 patients one study refrained from defining the time period [39].
with CM exposure and 7346 events in 51,980 controls The frequency of SCr measurements following contrast-
(Table 2). There was a tendency towards lower odds of AKI based imaging differed markedly among our studies. While
in CM–exposed cohorts compared with unexposed controls three groups obtained only one SCr level after imaging [32,
(OR 0.97 [0.85; 1.11], p = 0.64) (Fig. 2). Substantial hetero- 33, 41], two studies measured at least three early SCr values in
geneity was detected (I2 = 90.1%, Q = 40.74, p ≤ 0.0001). each 24-h period for the first 72 h after index CT [22, 24].
Since the risk for AKI after CM exposure is presumably Eight groups reported more than one SCr measurement with-
higher among patients with impaired kidney function, we per- out disclosing the exact number [24, 26, 32, 39, 43–46]. For
formed additional subgroup analysis by aggregating data from the remaining studies, the number of measurements was not
patients with eGFR ≤ 30 mL/min/1.73 m2 (Fig. 3). Here, we disclosed [23, 25, 27, 30, 31, 34, 35, 38].
detected a significantly higher risk of AKI in CM–exposed
patients compared with unexposed controls (OR: 1.68 [1.29; Risk of bias within studies
2.19], p = 0.0001; 55; I2 = 42%, Q = 10.3, p = 0.1125) (Fig. 3).
Notably, the absolute risk increase in CM–exposed patients The Newcastle–Ottawa Scale indicated a low risk of bias
with eGFR ≤ 30 mL/min/1.73 m2 remains rather low (334/ for all studies according to the AHRQ standard (Table 4).
1757, 19% vs. 863/5698, 15%) with an absolute risk increase The funnel plot (Suppl. Fig. 1) revealed no evidence of
of 4%. relevant publication bias. Because we hypothesized that
European Radiology (2022) 32:8432–8442 8437

Table 2 Acute kidney injury (AKI), dialysis and mortality in exposed and control populations

Study AKI in exposed AKI in control Dialysis in exposed Dialysis in control Mortality in exposed Mortality in control

Davenport, 2013 835 867 N/A N/A N/A N/A

Davenport, 2013a 619 606 N/A N/A N/A N/A
Ehrmann, 2013 8 8 3 4 N/A N/A
McDonald, 2013 515 544 N/A N/A N/A N/A
McDonald, 2015 215 266 12 8 189 218
Hinson, 2016 488 488 27 49 N/A N/A
Tao, 2017 22 40 16 21 0 0
Chaudhury, 2018 48 48 N/A N/A N/A N/A
Latcha, 2018 529 538 N/A N/A N/A N/A
Ellis, 2019 106 89 N/A N/A N/A N/A
Goto, 2019 34 35 26 23 17 17
Hinson, 2019 106 92 N/A N/A N/A N/A
Puchol, 2019 475 593 N/A N/A N/A N/A
Williams, 2019 444 414 10 6 N/A N/A
Gilligan, 2020 22 24 N/A N/A N/A N/A
Elias, 2021 158 158 9 12 N/A N/A
Guo, 2021 50 47 N/A N/A 0 0
Gorelik, 2021 817 939 60 45 1000 985
Kene, 2021 738 464 39 17 397 475
Su, 2021 1105 981 500 564 N/A N/A
Yan, 2021 91 105 27 39 46 56

differences in propensity score–matching methods might Discussion

introduce between-study heterogeneity, an additional
meta-regression analysis was performed to verify the ade- For years, the literature has been shaped by the assumption
quacy of matching procedures (Suppl. Fig. 2). Here, we that post-contrast AKI is attributable to the iodinated CM itself
found that the inclusion of more variables in the matching rather than preexisting nephrotoxic risk factors. Building on
model (range: 3 to 42) was associated with a greater ten- prior studies, we sought to facilitate clinical decision-making
dency towards similar incidences of AKI between exposed and prevent both over- and underestimation of AKI risk dur-
and unexposed groups (p = 0.093). ing CT examination. Risk overestimation might deprive

Fig. 2 Forest plot with overall

odds ratio (OR) of the association
of CM application and AKI. 95%-
CI, 95% confidence interval; CM,
contrast media
8438 European Radiology (2022) 32:8432–8442

Fig. 3 Forest plot with overall

odds ratio (OR) of the association
of CM application and AKI in
patients with eGFR ≤ 30. 95%-CI,
95% confidence interval; CM,
contrast media

Table 3 Results of meta-

regression (mixed-effects Covariates n studies Mixed-effects model p value
regression)
Point estimate Standard error

Female gender (%) 11 0.02 0.01 0.15

CHF (%) 11 0.00 0.00 0.88
Diabetes mellitus (%) 10 0.01 0.1 0.2
CKD (%) 11 0.00 0.00 0.88
Hypertension (%) 8 0.01 0.00 0.03
GFR < 60 (%) 9 0.01 0.01 0.31
GFR < 30 (%) 11 0.00 0.01 0.0001

patients of clinical benefits of contrast-enhanced imaging out after single administration of CM during CT scan in eGFR
of fear of causing AKI. However, an underestimation could groups above 45 mL/min/1.73 m2. These results appear ro-
expose patients to preventable nephrotoxic insults with high bust, even in subgroups with chronic and critical illness.
potential for adverse outcomes. However, our analysis revealed an increased risk of AKI in
We performed a systematic review and meta-analysis of 21 patients with eGFR of less than or equal to 30 mL/min/1.73
cohort studies utilizing a propensity-matched multivariate m2 and hypertensive disease.
model, in order to isolate the role of CM exposure on the Previous studies on CM nephrotoxicity were limited either
incidence of post-contrast AKI. In line with the growing body by a lack of control groups or by absence of adjustments for
of literature, we found no evidence from state-of-the-art co- predisposing risk factors [43, 44, 47, 48]. The study by Moos
hort studies for an increased risk for AKI, dialysis or mortality et al [48] has stood out by including four studies with

Fig. 4 Balloon plot with log odds

ratio (OR) of the association of
CM application and AKI in pa-
tients with hypertension. 95%-CI,
95% confidence interval; CM,
contrast media
European Radiology (2022) 32:8432–8442 8439

Table 4 Risk of bias assessment with the Newcastle–Ottawa Scale

Selection Comparability Outcome

Study and Representative Selection of Ascertainment Outcome not Comparability Outcome Duration Adequacy of
Year Cohort Non-Exposed of exposure present at outset assessment Follow-Up Follow-Up

Davenport, * * * * ** * * *
2013
Davenport, * * * * ** * * *
2013a
Ehrmann, * * * ** * * *
2013
Mcdonald, * * * * ** * * *
2013
Mcdonald, * * ** * * *
2015
Hinson, * * * ** * * *
2016
Tao, 2017 * * ** * * *
Chaudhury, * * * ** * * *
2018
Latcha, * * * * ** * * *
2018
Ellis, 2019 * * ** * * *
Goto, 2019 * * * ** * * *
Hinson, * * * ** * * *
2019
Puchol, * * * * ** * * *
2019
Williams, * * * ** * * *
2019
Gilligan, * * * * ** * * *
2020
Elias, 2021 * * * * ** * * *
Guo, 2021 * * * ** * * *
Gorelik, ** * * * ** * * *
2021
Kene, 2021 * * ** * * *
Su, 2021 * * * * ** * * *
Yan, 2021 * * ** * *

The Newcastle–Ottawa Scales were used to assess the risk of bias for the cohort studies. Each domain was rated on a scale of zero or one star, except
comparability, which can be awarded up to two stars. 0 = High or unclear risk of bias; 1 or 2 = Low risk of bias

unexposed controls (out of a total of 41 studies). Retrospective [49] or entirely [50] lacked matched controls, or featured con-
observational studies followed, showing similar rates of AKI siderably fewer studies [19].
following CT examination regardless of CM administration Our findings reverberate the conflicting data in the adult
[45, 46]. Moreover, a substantial number of patients without literature regarding renal risks after intravenous CM adminis-
CM exposure displayed changes in SCr levels that would have tration and prompt a differential analysis for patients with high
met the criteria for CIN, had they undergone CM administra- disease burden.
tion [45]. This emphasized the need for a proper comparator Assessing a broad range of comorbidities, no other associ-
arm. Observational controlled studies followed, presenting ation with higher AKI risk was found. This is particularly
similar rates of AKI between CM–exposed patients and unex- noteworthy considering that our study populations featured
posed controls. Currently, PSM protocols are employed to critically [28, 29, 34, 35] and chronically ill patients [25, 37,
adjust for patient-related factors (e.g. age, sex) and various 39]. In daily clinical practice, these patients are most likely to
underlying comorbidities amongst study cohorts, thereby ap- experience exclusion from CM–enhanced procedures out of
proximating a randomized distribution. Our study further ex- fear of causing contrast-induced AKI. Our findings do not
pands upon contemporary meta-analyses that either partly support the clinical avoidance of CM where otherwise
8440 European Radiology (2022) 32:8432–8442

indicated. Similarly, van der Molen et al recently demonstrat- on the recency of publication (i.e. 2019), the use of high-
ed no need for emergency haemodialysis after administration osmolar CM for CT is quite unlikely. Further, neither fluid
of iodine-based CM in patients with dialysis-requiring CKD administration during and after CT nor nephrotoxic medica-
[51]. The observed shift in the medical literature may be ex- tions were consistently documented throughout the studies.
plained by adjustments in CM osmolality and administered This would have been preferable, as hydration is known to
volumes in recent years. reduce the risk of post-contrast renal impairment [51]. With
Similar to other authors, we observed a trend towards lower regard to total volumes of injected CM, only weight-adjusted
risk for renal impairment after CM exposure [32, 33]. Puchol ranges were provided (n = 15). Notably, none of the groups
et al explained this with the hydration occurring in the course described the flow rate of intravenous CM administration and
of administering the CM volume, and its subsequent osmotic only eight disclosed CM concentrations. We strongly recom-
diuretic effects [32]. Since CM is not nephroprotective, we mend the disclosure of all periprocedural circumstances for
assume the presence of factors affecting the AKI incidence. accurate risk estimation and effective periprocedural
These are not easily measurable and, as it seems, not entirely management.
rectified by PSM. Investigators who applied PSM models This also applies to post-contrast serial measurements of
have reported similar results [52]. Studies cannot consider SCr in clinical settings. Since AKI is not necessarily associat-
factors that conceivably bias the decision to administer CM ed with permanent changes in renal function, consistent SCr
in the first place. Therefore, it remains crucial to consider the measurement protocols following CM administration would
possible impact of these variables before and after PSM, in be of great value to improve the diagnostic algorithm in
order to avoid misleading inferences of causality. Selection suspected AKI. Diagnostic standardization with longer obser-
bias may also cause the higher number of AKI among controls vation periods may help differentiate between subclinical re-
(i.e. unenhanced CT). This arises when presumed high-risk nal damage and potentially reversible background fluctuations
patients are excluded from CM exposure under the assump- of SCr. Lastly, the majority of studies failed to report AKI
tion that CM causes AKI, which precipitates a less healthy stages, which would have been beneficial to understand the
control cohort. Likewise, discrepancies in matching method- severity of kidney injury and show the risk of progression to
ologies or small sample sizes may contribute to this finding higher AKI stages.
[22]. Conceivably, patients with contrast-enhanced imaging Currently, no adjunctive medication can effectively pre-
might receive a better fluid management as part of the CM vent or treat post-contrast AKI. Therefore, it remains crucial
administration protocol. to anticipate and obviate post-contrast renal decline with com-
Our study displays various methodological strengths. We prehensive risk prediction scores and preprocedural volume
focused on cohort studies originally designed to compare the expansion, even in emergencies and time-sensitive conditions
nephrotoxicity of CM–enhanced CT with unenhanced CT ex- [54]. The clinical practice of withholding CM–enhanced im-
aminations. By restricting the analysis to studies that applied aging for concern of CI-AKI appears not to be justified.
PSM, we further narrowed limitations of inherent biases in However, despite the low incremental risk, caution remains
observational study designs [53]. Our findings affirm that warranted in individuals with hypertension or eGFR less
PSM does not account for all influencing factors and that all than or equal to 30 mL/min/1.73 m2.
outcomes require careful interpretation. However, since ran-
domized controlled trials evaluating post-contrast AKI remain Supplementary Information The online version contains supplementary
material available at https://doi.org/10.1007/s00330-022-08916-y.
unlikely for ethical reasons, our findings summarize the best
available evidence in absence of randomization. By excluding
Funding Open Access funding enabled and organized by Projekt DEAL.
all studies that lacked controls, we further enhanced the rigor
of our analysis. AKI diagnosis was made based on interna-
Declarations
tionally recognized guidelines, the anticipated primary event
of interest was documented and standardization across all Guarantor The scientific guarantor of this publication is Professor
studies was established in terms of design (i.e. observational Bernhard Magnus Wilhelm Schmidt, MD, SM/M.Sc.
cohort study), intervention (i.e. CT scan) and primary out-
come (i.e. AKI). Conflict of interest The authors of this manuscript declare no relation-
To the best of our knowledge, we provide the first and most ships with any companies, whose products or services may be related to
the subject matter of the article.
extensive study that systematically assesses the renal risks
after CT examination attributable to CM after controlling for Statistics and biometry One of the authors has significant statistical
demographic variables. Despite this, we note limitations in our expertise.
study, which deserve mention. Our data relies on retrospective
cohort studies with limited numbers of participants. One study Informed consent Written informed consent was not required, because
did not disclose the osmolality of CM used. However, based this work is a systematic review and meta-analysis.
European Radiology (2022) 32:8432–8442 8441

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