Post-contrast acute kidney injury – Part 1: Definition, clinical features, incidence, role of contrast medium and risk factors

Post-contrast acute kidney injury – Part 1: Definition, clinical features, incidence, role of... Purpose The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. Areas covered in part 1 Topics reviewed include the terminology used, the best way to measure eGFR, the definition of PC-AKI, and the risk factors for PC-AKI, including whether the risk with intravenous and intra-arterial contrast medium differs. Key Points � PC-AKI is the preferred term for renal function deterioration after contrast medium. � PC-AKI has many possible causes. � The risk of AKI caused by intravascular contrast medium has been overstated. � Important patient risk factors for PC-AKI are CKD and dehydration. . . . . Keywords Contrast media Acute kidney injury Glomerular filtration rate Risk factors Practice guidelines as topic Abbreviations CM Contrast media ACR American College of Radiology CMSC Contrast Media Safety Committee ADQI Acute Dialysis Quality Initiative CT Computed tomography AGREE Appraisal of Guidelines for Research and eGFR Estimated glomerular filtration rate Evaluation EBM Evidence-based medicine AKI Acute kidney injury ERBP European Renal Best Practice AKIN Acute Kidney Injury Network ESUR European Society of Urogenital Radiology BIS Berlin Initiative Study FAS Full age spectrum BUN Blood urea nitrogen GFR Glomerular filtration rate CA Coronary angiography IA Intra-arterial CI Confidence interval ICU Intensive care unit IDMS Isotope Dilution Mass Spectroscopy CI-AKI Contrast-induced acute kidney injury IV Intravenous CIN Contrast-induced nephropathy KDIGO Kidney Disease Improving Global Outcome CKD Chronic kidney disease LM Lund Malmö CKD-EPI ChronicKidneyDiseaseEpidemiologyCollaboration MDRD Modification of Diet in Renal Disease NICE National Institute for Health and Care Excellence OCEBM Oxford Center for Evidence Based Medicine * Henrik S. Thomsen PC-AKI Post-contrast acute kidney injury Henrik.Thomsen@regionh.dk PCI Percutaneous coronary intervention Extended author information available on the last page of the article PICO Patient-Intervention-Comparator-Outcome 2846 Eur Radiol (2018) 28:2845–2855 PoC Point of Care Clinical features and incidence of PC-AKI PS Propensity Score RANZCR Royal Australian and New Zealand College of The term PC-AKI is used to describe a decrease in renal func- Radiology tion that follows intravascular administration of CM. The de- RCR Royal College of Radiologists crease in renal function is usually mild, peaking at 2–3days, RCT Randomised controlled trials and renal function usually returns to baseline values within 1– RRT Renal replacement therapy 3 weeks. Like all forms of AKI, an episode of PC-AKI is a RSTN Radiological Society of The Netherlands marker for increased short- and long-term morbidity and mor- sCr Serum creatinine tality and prolonged hospital stay [4–10]. WG Writing Group The risk of PC-AKI after intravenous (IV) CM has proba- bly been overestimated. Two meta-analyses of 19,000 patients who had received IV CM showed PC-AKI incidences of 6.4 %(95 %CI 5.0–8.1) and 5.0 % (95 % CI 3.8–6.5) [11, 12]. In Introduction 1 % of all patients the decline in renal function persisted for 2 months, but the weighted incidence of renal replacement ther- The Contrast Media Safety Committee (CMSC) of the apy (RRT) was as low as 0.06 % [11]. European Society of Urogenital Radiology (ESUR) produced It has been suggested that intra-arterial (IA) CM adminis- their most recent guidelines on what was then termed contrast tration during catheter-based angiography, with or without induced nephropathy (CIN) in 2011 [1]. Guidelines on the use percutaneous coronary intervention (PCI), is associated with of contrast media (CM) in patients on dialysis and the use of a higher incidence of PC-AKI than IV CM administration [13, CM in diabetic patients using metformin were published in 14]. However, there are many causes of AKI following angi- 2002 and 2014 [2, 3]. This review provides the information to ography, and AKI may wrongly be attributed to the CM [15]. support the new CMSC guidelines, which were obtained Catheter-based procedures may be complicated by haemody- using a structured literature review based on clinical questions namic instability, and by embolization of cholesterol or throm- and patient-intervention-comparator outcome (PICO) format- bi to the renal arteries caused by catheter manipulations [16]. ting. Since the literature related to the topics considered is so Any of these may lead to post-interventional AKI, which is large, the results of the review have been split into two papers. often misinterpreted as contrast-induced acute kidney injury The review only considers post-contrast kidney injury (PC- (CI-AKI) [17, 18]. A large meta-analysis of cardiovascular AKI) after intravascular iodine-based CM. Acute kidney inju- outcomes after coronary angiography (CA) showed that the ry (AKI) is not associated with intravascular gadolinium- association between PC-AKI and mortality was strongly con- based contrast agents in doses approved for clinical magnetic founded by baseline clinical features that predisposed to both resonance imaging. kidney injury and mortality [6]. The risk of PC-AKI reported In this first paper on PC-AKI, the following topics related in studies adjusted for confounding features was much lower to diagnosis and risk are considered: than that from unadjusted studies. The incidence of AKI was 2.3 % and need for RRT 0.3 % in a recent retrospective anal- 1. The clinical features and incidence of PC-AKI. ysis using propensity matching with controls of over 2,000 2. The choice of terms for renal function deterioration after patients who had PCI [7]. CM, the degree of renal function deterioration used to diagnose PC-AKI, and the definitions of intravenous and intra-arterial CM administration. 3. The reliability of the various equations used to measure Materials and methods eGFR and the appropriate timing of eGFR measurement before CM administration. The guidelines were developed using the Appraisal of 4. The evidence that CM can cause AKI, the levels of renal Guidelines for Research and Evaluation (AGREE) II docu- function at which there is a risk of PC-AKI, and the recent ment [19]. A guideline Writing Group (WG) prepared ten evidence suggesting that the risk of PC-AKI may be lower clinical questions in Patient – Intervention – Comparison – after intravenous than after intra-arterial contrast medium. Outcome (PICO) format [20]. Systematic search strings were 5. The importance of the many risk factors for PC-AKI de- developed with a professional librarian for four different bio- scribed in the literature. medical literature databases (PubMed, Web of Science, Embase, and the Cochrane Library). Language was limited Recommendations are made for items 2–5. The recommen- to English and German. Where necessary, additional system- dations have been incorporated into version 10 of the ESUR atic searches on specific topics, such as pediatric PC-AKI, CMSC guidelines (see Table 4 in Part 2). were performed. Eur Radiol (2018) 28:2845–2855 2847 The titles and abstracts were screened for relevance and suggested Acute Kidney Injury (AKI) as the preferred term for selected on predefined in- and exclusion criteria. Emphasis acute renal failure to be used for all forms of AKI [24]. was put on comparative studies with strong scientific evidence, The CMSC recommends that the term PC-AKI should re- such as meta-analyses and systematic reviews, and prospective place the older term of contrast-induced nephropathy (CIN) and randomized controlled trials (RCTs). In addition, evidence was suggests using the terms recommended by the ACR Committee collected from comparative cohort, patient-control and non- on Drugs and Contrast Media [25] when AKI follows CM comparative studies. Other important quality criteria were size administration (Table 1). They state that post-contrast acute of population studied, duration of follow-up and control for kidney injury (PC-AKI) is a general term that should be used bias. Cross-referencing was used to find additional data. The if there is a sudden deterioration in renal function within 48 h of four systematic searches for paper 1 yielded 3,086 references, the intravascular administration of iodine-based CM. They de- of which 705 were selected from their title and abstract. The full scribe PC-AKI as a correlative diagnosis. They recommend texts of these 705 publications were reviewed and 105 were that the term contrast-induced acute kidney injury (CI-AKI) is selected for inclusion in this paper. The quality of evidence reserved for cases where a causal relation can be shown be- was evaluated according to the Oxford Centre for Evidence tween the administered CM and the deterioration in renal func- Based Medicine (OCEBM) 2011 levels of evidence: Grade tion. However, in clinical practice it is usually difficult to dis- A: established scientific evidence; Grade B: scientific presump- tinguish CI-AKI from PC-AKI and very few of the published tion; Grade C: low level of evidence [21]. Where there was no studies have a suitable control group to allow the two condi- scientific evidence, recommendations were based on WG con- tions to be separated. Thus, many cases of PC-AKI seen in sensus and graded as expert opinion (Grade D). clinical practice or reported in clinical studies are likely to be Other factors such as availability of techniques or expertise, coincident to, but not caused by, CM administration. organizational consequences, financial costs and patient prefer- ences were also considered. CM manuals and guidelines Renal function definitions of PC-AKI (American College of Radiology (ACR), Royal Australian and New Zealand College of Radiology (RANZCR), National The diagnosis of PC-AKI is usually based on surrogate measures Institute for Health and Care Excellence (NICE), Royal College of absolute or relative change in serum creatinine (sCr), rather of Radiologists (RCR), and Radiological Society of the than patient outcomes, such as renal failure, need for RRT or Netherlands (RSTN)) were consulted where appropriate. mortality. The KDIGO Practice Guidelines [26, 27] adopted the The recommendations prepared by the WG are the result of older AKIN criteria [24] and recommended division of AKI into the available scientific evidence combined with these other three stages dependent on sCr and/or urine output (Table 2). sources of information. They were discussed at the CMSC The ESUR CMSC defined Contrast-Induced Nephropathy meeting in Copenhagen, Denmark in February 2017 and the (CIN) in their first survey-based guideline as “aconditionin text of the final recommendations and guidelines was subse- which an impairment in renal function (an increase in sCr by quently approved by the academic members of the CMSC. more than 25 % or 44 μmol/L, or 0.5 mg/dl) occurs within 3 Once published in print, the validity of the CMSC guidelines days following the intravascular administration of a contrast will be routinely set at 6 years. However, the CMSC members medium in the absence of an alternative aetiology” [28]. constantly monitor the validity of the guidelines, and can pro- Multiple studies have shown that the incidence of PC-AKI pose revision at an earlier date if deemed necessary. is largely dependent on the definition used [29–31]. A relative increase in sCr of > 25 % has been the most sensitive indica- tor, with absolute values being less sensitive. In coronary an- Results giography studies, relative definitions had more prognostic Table 1 PC-AKI: Terminology and definition QUESTION 1: What are the preferred terms and definitions to be used in PC-AKI? The preferred term for acute kidney injury associated with CM administration when no control population is available is Terminology Post-Contrast Acute Kidney Injury (PC-AKI). The term Contrast-Induced Acute Kidney Injury (CI-AKI) should be used only when comparison with a control allows CM to be shown Until recently there has not been a generally accepted term for to be the cause of the acute kidney injury. acute renal failure, which is a complex disorder with many possi- Level of Evidence D blecausesandriskfactors.Severalnephrologygroups, suchasthe PC-AKI and CI-AKI should be defined as an increase in sCr of ≥ Acute Dialysis Quality Initiative (ADQI) [22] and Kidney 0.3mg/dl, or of ≥ 1.5–1.9 times baseline (KDIGO definition of AKI) Disease:ImprovingGlobalOutcome(KDIGO)[23],haveworked in the 48–72 h following CM administration. on finding a suitable term. The Acute Kidney Injury Network Level of Evidence C (AKIN), a group of experts in Critical Care and Nephrology, 2848 Eur Radiol (2018) 28:2845–2855 Table 2 Acute Kidney Injury Staging (KDIGO) and CKD-EPI and Schwartz Equations for calculating eGFR (a) KDIGO staging for AKI Stage Serum creatinine Urine output 1sCr ≥ 0.3 mg/dl (≥ 26.5 μmol/L), or < 0.5 ml/kg/h for 6–12h sCr increase of 1.5–1.9xbaseline 2 sCr increase of 2.0–2.9 x baseline < 0.5 ml/kg/h for ≥ 12h 3sCr ≥ 4.0 mg/dl (≥ 354 μmol/L) or < 0.3 ml/kg/h for ≥ 24h sCr increase > 3.0x baseline or Anuria for ≥ 12h or need for renal replacement therapy (b) CKD-EPI equation (sCr in μmol/L; age in years). eGFR (ml/min/1.73 m )= -0.329 Age Female sCr ≤ 62 μmol/L: 144 x (sCr / 62) x0.993 -1.209 Age Female sCr > 62 μmol/L: 144 x (sCr / 62) x0.993 -0.411 Age Male sCr ≤ 80 μmol/L: 141 x (sCr / 80) x0.993 -1.209 Age Male sCr > 80 μmol/L: 141 x (sCr / 80) x0.993 All equations x 1.159 if African American race (c) Revised Schwartz equation (sCr in μmol/L; patient length in cm). eGFR (ml/min/1.73 m2) = 36.5 × Length / sCr relevance [29]. In other studies, however, relative increases in heart and pulmonary arteries and via catheters directly in the sCr were found to overestimate PC-AKI and absolute values carotid, subclavian, brachial, coronary and mesenteric arteries, were considered preferable [32]. Relative values seem to be as well as into the infrarenal aorta and the iliac, femoral and more sensitive for patients with CKD 3B (eGFR 30–44 ml/ crural arteries. Note: Because of backflow during this type of 2 2 min/1.73m ) and CKD 2 (eGFR 60–89 ml/min//1.73m ), and IA injection, small doses of CM may reach the kidney in a absolute values seem to be more sensitive for patients with relatively undiluted form. CKD 3A (eGFR 45–59 ml/min/1.73m )[33, 34]. Studies in The term intra-arterial CM administration with first-pass critically ill populations using the AKIN definition found that renal exposure indicates that CM reaches the renal arteries dur- development of AKI correlated with ICU mortality [35]. ing its first pass in a relatively undiluted form, depending on the The KDIGO criteria are more rigorously derived than the distance of the site of injection from the renal arteries. This CIN definition and are now being adopted as the standard for occurs with injections through catheters into the left heart, the PC-AKI studies [36]. The CMSC, like the European Renal thoracic and suprarenal abdominal aorta, and selectively into the Best Practice (ERBP) working group, recommends that the renal arteries. Note: In suprarenal aortic injections, some of the definition of PC- AKI (or CI-AKI) should use the KDIGO injected CM escapes via suprarenal aortic side-branches and definition of AKI: an increase in sCr of ≥ 0.3 mg/dl, or a sCr reaches the kidney after dilution in the circulation. increase of ≥ 1.5– 1.9 times baseline [37, 38](Table 1). The KDIGO recommendation is that the renal function change should be within 48 h, but the CMSC recommends retaining QUESTION 2: What are the best equations for GFR a period of 48–72 h after CM as being more practical for estimation in European populations? diagnosing PC-AKI in radiological practice, the majority of which involves outpatients. Total glomerular filtration rate (GFR) is considered the best overall index of kidney function, but cannot be measured eas- Intravenous and direct and indirect intra-arterial CM ily in clinical practice, so GFR is estimated using sCr as an administration: definition of terms endogenous filtration marker. In 1999, the Modification of Diet in Renal Disease (MDRD) equation [39] was introduced The term intravenous CM administration indicates that CM for estimating GFR. The quality of GFR estimates largely reaches the renal arteries after dilution by circulation through depends on the accuracy of the creatinine measurements, the right heart and pulmonary circulation or a systemic capil- and should be based on sCr assays standardized to reference lary bed. methods [40]. The MDRD equation has therefore been re- The same is true for intra-arterial CM administration with expressed for use with sCr assays standardized using isotope second-pass renal exposure, such as via catheters into the right dilution mass spectroscopy (IDMS) [41]. Eur Radiol (2018) 28:2845–2855 2849 In 2009, the CKD-EPI equation was proposed by the Chronic [49] was revised in 2009 to include the IDMS method and Kidney Disease Epidemiology Collaboration (CKD-EPI), and plasma iohexol clearance as standardized reference methods was shown to be superior to the MDRD equation, especially at [50](Tables 2 and 3). higher GFRs (Table 2)[42]. The National Kidney Foundation A Cystatin C-based equation has been proposed that recommended replacing the MDRD by the CKD-EPI equation showed the best accuracy (91 %) when combined with for routine clinical use [43]. The CMSC therefore recommends height/SCr, height, sex and blood urea nitrogen (BUN) [49]. the CKD-EPI equation for routine use in adults (Table 3). All However, this requires an additional BUN, which lacks stan- creatinine-based equations should be used with caution in people dardized measurement, and Cystatin C requires standardiza- with abnormally high or low muscle mass. Caution should also tion and calibration [51]. In children with increased muscle be exercised in patients with AKI, because sCr takes several days mass both the sCr and Cystatin C based Schwartz formulas to stabilize and may not reflect current GFR. tend to overestimate GFR. There are other equations for specific subgroups, such as the Lund-Malmö (LM) revised equation for the Swedish Point-of-care creatinine measurements population [44], the Berlin Initiative Study (BIS-1) equa- tion for the elderly German population [45], and the full age Point-of-care (PoC) whole blood creatinine may be measured spectrum (FAS) equation for children and adults [46]. with the older Jaffe (alkaline picrate) method or by enzymatic However, these equations have not been validated in other methods, with the latter considered more accurate. Although populations. Cystatin C equations for estimation of GFR such measurements have practical advantages in patients may have advantages over sCr-based equations but are lim- with increased risk of PC-AKI, PoC devices may lead to ited by additional costs and lack of an international refer- overestimation of renal function in severe kidney failure ence system for calibration [47]. with resultant incorrect risk stratification [52]. Laboratory professionals should be consulted about analytical perfor- Estimation of GFR in children mance and quality assurance of whole blood PoC creati- nine measurement. When estimating GFR in children, sCr levels should be mea- sured by standardized reference methods because serum con- centrations are lower than in adults [48]. The CMSC therefore For how long do GFR estimations remain valid? recommends the revised Schwartz equation for routine clinical use in children (Table 3). The widely-used Schwartz equation There are no studies available on how long eGFR mea- surements remain valid for estimating the PC-AKI risk. Table 3 Formulae for eGFR and timing of eGFR measurement The eGFR measurements can be regarded as stable in individuals without CKD or underlying co-morbidities The CKD-EPI equation for estimated GFR (eGFR) is recommended for adults. As with all creatinine-based eGFRs, results should be such as heart failure or hypertension who are not taking interpreted with caution in people with abnormally high or low nephrotoxic drugs. muscle mass The CMSC considers eGFR measurements before intra- Level of Evidence A vascular CM exposure valid for a maximum of: The revised Schwartz formula (2009) for eGFR is recommended for children. As with all creatinine-based eGFRs, results should be (1) 7 days* if the patient interpreted with caution in people with abnormally high or low muscle mass a) has an acute disease, an acute deterioration of a Level of Evidence C known chronic disease or any other adverse event that eGFR is not reliable in patients with known AKI could have negatively influenced renal function Level of Evidence A (eGFR), or The CMSC considers eGFR measurements before intravascular b) is a hospital inpatient CM exposure valid for a maximum of: 1) 7 days* if the patient has (a) an acute disease, an acute deterioration of a known chronic disease or any other adverse event that could (2) 3months have negatively influenced renal function (eGFR), or (b) is a hospital inpatient a) if the patient has a chronic disease with stable renal 2) 3 months (a) if the patient has a chronic disease with stable function (eGFR), and renal function (eGFR) and (b) in all other patients b) in all other patients (Table 3) Level of Evidence D *Note: In patients with AKI, eGFR should be monitored *Note: in patients with AKI it is advisable to monitor eGFR frequently, so a maximum of 1-2 days may be advisable. frequently, and a maximum of 1–2 days is advisable. 2850 Eur Radiol (2018) 28:2845–2855 QUESTION 3: What is the evidence that contrast based studies. Remaining major limitations of observa- media are truly a causative factor in AKI and what are tional studies are the low numbers of patients with severe the eGFR values below which there is a risk of PC-AKI? renal impairment, and the variability of data available on, for example, prophylactic volume expansion and the CM Contrast-induced nephropathy was accepted for many years, dose administered. but more recently it has been questioned whether CM causes the deterioration in renal function that may occur after CM administration [17, 53]. There are important limitations in Comparison of intra-arterial and intravenous CM many studies that assess whether CM causes AKI. Most stud- administration in the same patients ies evaluate the use of IA CM in CA and/or percutaneous coronary intervention (PCI) in patients with significant co- A limited number of studies have directly compared IV to IA morbidities and therefore may not be relevant for intravenous CM administration, using the patient as their own control. The administration, and most studies do not have adequate control risk of PC-AKI as well as its clinical course was independent groups [54, 55]. of the route of administration in four retrospective studies of patient populations with varying degrees of renal impairment Intravenous CM administration [67–70], and PC-AKI rates were similar to the rates for unenhanced CT [70]. However, these studies suffer from There is controversy about the causal relationship be- selection bias and procedures with IA CM administra- tween exposure to IV CM and PC-AKI, since there are tion with first- and second-pass renal exposure were not no prospective RCTs confirming this association [56, 57]. separated. Without controlled studies, many factors such as diet, hy- dration, physiological variation in sCr over time, and a variety of nephrotoxic risk factors, including medications, Intra-arterial CM administration which may influence renal function, cannot be distin- guished from any effect of the CM [17, 18, 58]. The PC-AKI incidence following direct IA CM administration Although RCTs have the strongest research design for with first-pass renal exposure is frequently reported to be assessing the effects of interventions, assessment of rare higher than after IV administration, but this remains contro- conditions such as PC-AKI by RCT would require large versial [71, 72]. Problems with confounding factors are most numbers of patients [53]. significant in studies on patients that undergo catheter-based Based on comparisons of the relatively few studies CA and/or PCI because it is impossible to separate the effects of contrast media from the effects of co-morbidity, catheter with and without control populations it has been sug- gested that the risk of PC-AKI after IV CM has been manipulations or other procedural variables. In large meta- overestimated [53, 59]. A meta-analysis that retrospec- analyses on cardiovascular outcome the PC-AKI inci- tively studied 13 non-randomised controlled studies was dence may have been strongly confounded by baseline unable to find an increased incidence of AKI in patients clinical characteristics, both for first- and second-pass IA who received intravenous contrast medium [60]. CM administration [6, 73]. Nonetheless, AKI in general Evidence from observational studies may need to be is a significant problem in these patients and is associat- used, despite the recognised methodological problems ed with increased morbidity, longer length of hospital [61]. Recently, a few large-scale studies using propensity stay and higher cost [74], and may be associated with score (PS)-matching for the evaluation of PC-AKI in pa- mortality in a significant percentage of cardiac patients tients undergoing contrast-enhanced CT, which stratified [7]. Second-pass IA CM administration is considered to subjects according to their baseline sCr or eGFR, have have no higher risk than IV CM administration. been published [62–65]. These studies were unable to Since it is difficult to separate the effects of the proce- identify a risk of PC-AKI in patients with eGFR ≥ 30 dure from those of the CM, the CMSC decided, for opti- ml/min/1.73m , but there is conflicting evidence on mal safety, to choose a higher cut-off eGFR level for whether patients with severe renal impairment (eGFR preventive measures in patients undergoing catheter- <30 ml/min/1.73m ) are at increased risk of PC-AKI based diagnostic or interventional examinations using IA [63, 65]. Lack of information on hydration status was a CM administration with first-pass renal exposure, even limitation in these studies, but when hydration status was though some of the risk may relate to the procedure. added to an improved PS model, the findings were similar Also, the CMSC decided to include CA and/or PCI in this [66]. The failure to adjust for the various predictor vari- category because these examinations frequently combine ables in previous observational studies may explain the IA CM administration with both first- and second-pass renal exposure (Table 4). differences between them and the recent PS matching- Eur Radiol (2018) 28:2845–2855 2851 Table 4 Risk of PC-AKI Paediatric PC-AKI (a) Levels of eGFR at which there is a risk There are very few studies on paediatric PC-AKI [83–85]. As The risk of PC-AKI in patients with eGFR ≥ 30 ml/min/1.73m after the incidence of PC-AKI seems similar in children and ado- intravenous and intra-arterial CM administration with second-pass lescents to that in adults, the CMSC considers that for optimal renal exposure is very low, but there is conflicting evidence on the risk safety the recommendations for sCr determination and pre- for intra-arterial CM administration with first-pass renal exposure vention of PC-AKI, which are predominantly based on studies Level of Evidence: B in adults (aged 18+ years), should also be used for children Preventive measures are recommended for patients with eGFR < 30 and adolescents (Table 4). ml/min/1.73m before intravenous and intra-arterial CM administration with second-pass renal exposure Level of Evidence: C Preventive measures are recommended for patients with eGFR < 45 QUESTION 4: What are the patient- ml/min/1.73m if they are in ICU or if they will receive intra-arterial and procedure-related risk factors for developing CM administration with first-pass renal exposure PC-AKI and which patient populations have a higher Level of Evidence: C risk for developing PC-AKI? Recommendations for prevention of PC-AKI in adults may also be used in children and adolescents Patient-related risk factors Level of Evidence D Impaired renal function is the most important patient risk fac- (b) Risk factors tor for PC-AKI. Many meta-analyses and systematic reviews The principal risk factor for PC-AKI is impaired renal function. Most of uncontrolled studies have identified a wealth of possible other published patient-related risk factors are risk factors for the clinical risk factors for AKI in general such as old age, female presence of chronic kidney disease or AKI, and are not specific for gender, low BMI, classic cardiovascular and metabolic risk PC-AKI factors, malignancy, inflammation, bleeding, anaemia and Level of Evidence B hyperuricaemia [11, 12, 86–96]. However, uncontrolled stud- There is no difference in PC-AKI risk between IOCM and LOCM. The ies cannot reliably differentiate baseline clinical risk factors use of ionic, high-osmolar CM and repeated CM injections in a short period (48–72 h) should be avoided from effects attributable specifically to CM. In a meta-analysis Level of Evidence C of controlled studies, no additional risk factors specific for When CM are injected intravenously, there is insufficient evidence that CM were demonstrated [60](Table 4). The effect of two or CM dose is a risk factor. When CM are injected intra-arterially, the more risk factors is additive and increases the risk of PC-AKI. ratio of CM dose (in gram Iodine) / absolute eGFR (in ml/min) should be kept below 1.1 or the ratio of CM volume (in ml) / eGFR (in ml/min/1.73m ) should be kept below 3.0 when using a CM concentration of 350 mgl/ml Procedure-related risk factors: CM type and dose Level of Evidence C A variety of risk factors have been related to the type of CM and the way it is administered. Special populations Multiple meta-analyses have shown no evidence that iso- osmolar CM (IOCM) are associated with a significantly lower There is limited evidence about PC-AKI in several special rate of PC-AKI than non-ionic, low osmolar CM agents populations, such as patients with renal or renal and pancreatic (LOCM) [97–100]. However, the risk of PC-AKI is increased transplants, or critically ill patients. In renal transplant recipi- when ionic, high-osmolar CM are used [101]. Repeated CM ents, the incidence of PC-AKI in patients receiving either IVor administration within a short interval (48–72 h) has been IA CM was not higher than in patients without transplants, shown to increase the risk of PC-AKI [86](Table 4). and there was no graft loss or need for dialysis [75–77]. Evidence about the influence of CM dose (CM volume x Critically ill patients in ICU with multi-organ disease have a CM concentration) indicates dependence on the route of ad- greater risk profile for AKI than other inpatients, and AKI ministration. There is insufficient evidence that dose is a prob- incidence varies with subpopulation, study design and hydra- lem with IV CM. However, for direct IA CM administration in tion status [33, 78, 79]. Without properly controlled studies, it coronary angiographic intervention it is advisable to keep the is impossible to know the role of CM in causing the AKI. ratio of CM dose (in grams Iodine) to absolute eGFR (in ml/ Although earlier studies failed to show a role of CM [80, min; corrected for body surface area) below 1.1 [102, 103]or 81], a recent large PS-matched controlled study suggested an to keep the ratio of CM volume (in ml) to eGFR (in ml/min/ increased PC-AKI risk for ICU patients with eGFR < 45 ml/ 1.73m ) below 3.0 when using a CM concentration of 350 min/1.73m [82]. mgl/ml [104, 105](Table 4). 2852 Eur Radiol (2018) 28:2845–2855 (ESUR) et al (2011) Contrast induced nephropathy: updated Conclusion ESUR Contrast Media Safety Committee guidelines. Eur Radiol 21:2527–2541 PC-AKI has been adopted as the best term to apply to renal 2. Morcos SK, Thomsen HS, Webb JA, Contrast Media Safety function deterioration after intravascular CM administration Committee of the European Society of Urogenital Radiology (ESUR) et al (2002) Dialysis and contrast media. Eur Radiol 12: because, unlike some of the older terms, it does not imply that 3026–3030 CM is the cause. Stage 1 of the KDIGO classification of AKI 3. Contrast Media Safety Committee ESUR. Guidelines on Contrast is recommended as the change in renal function used to diag- Media v9. CMSC, 2014. Available via: http://www.esur-cm.org/ nose PC-AKI. The principal risk factor for PC-AKI is im- index.php/en/ Accessed: 14 December 2017 paired renal function, and the recommended ways to measure 4. Gruberg L, Mintz GS, Mehran R et al (2000) The prognostic implications of further renal function deterioration within 48 h of this are by the CKD-EPI equation in adults and the Schwartz interventional coronary procedures in patients with pre-existent equation in children. In recent years, it has become apparent chronic renal insufficiency. J Am Coll Cardiol 36:1542–1548 that the risk of true CI-AKI was overstated in the past. When 5. Gupta R, Gurm HS, Bhatt DL et al (2005) Renal failure after properly corrected for the many other possible causes of AKI percutaneous coronary intervention is associated with high mor- tality. Catheter Cardiovasc Interv 64:442–448 in patients with chronic kidney disease, the risk of CI-AKI 6. James MT, Samuel SM, Manning MA et al (2013) Contrast- when modern low osmolar CM are administered IV or IA is induced acute kidney injury and risk of adverse clinical outcomes low. Repeated CM administration within a 24- to 48-h period after coronary angiography a systematic review and meta-analy- increases the risk of CI-AKI. The evidence of a higher risk sis. Circ Cardiovasc Interv 6:37–43 with IA than with IV CM administration is limited, but the 7. Kooiman J, Seth M, Nallamothu BK et al (2015) Association between acute kidney injury and in-hospital mortality in patients CMSC nonetheless considers that the cut-off levels of eGFR undergoing percutaneous coronary interventions. Circ Cardiovasc used to indicate the need for prophylaxis before IA adminis- Interv 8:e002212 tration with first-pass renal exposure should be stricter, and 8. Mitchell AM, Kline JA, Jones AE et al (2015) Major adverse that there should be a maximum volume of CM given intra- events one year after acute kidney injury after contrast-enhanced arterially during any examination or procedure with first-pass computed tomography. Ann Emerg Med 66:267–274.e4 9. Rihal CS, Textor SC, Grill DE et al (2002) Incidence and prog- renal exposure. nostic importance of acute renal failure after percutaneous coro- The recommendations made in this paper have been incor- nary intervention. Circulation 105:2259–2264 porated into the ESUR CMSC guidelines (see Table 4,Part2). 10. Rudnick M, Feldman H (2008) Contrast-induced nephropathy: what are the true clinical consequences? Clin J Am Soc Nephrol Funding The authors state that this work has not received any funding. 3:263–272 11. Kooiman J, Pasha SM, Zondag W et al (2012) Meta-analysis: Compliance with ethical standards serum creatinine changes following contrast enhanced CT imag- ing. Eur J Radiol 81:2554–2561 12. Moos SI, van Vemde DN, Stoker J et al (2013) Contrast induced Guarantor The scientific guarantor of this publication is Prof. Henrik S. nephropathy in patients undergoing intravenous (IV) contrast en- Thomsen. hanced computed tomography (CECT) and the relationship with risk factors: a meta-analysis. Eur J Radiol 82:e387–e399 Conflict of interest Aart van der Molen has received incidental pay- 13. Solomon R (2008) Contrast-induced acute kidney injury: is there a ments for lectures and chairmanships at scientific meetings for contrast risk after intravenous contrast? Clin J Am Soc Nephrol 3:1242–1243 agent safety related issues (contrast agent reactions, Gd-retention) from 14. Dong M, Jiao Z, Liu T et al (2012) Effect of administration route GE, Bayer, Bracco and Guerbet on the renal safety of contrast agents: a meta-analysis of random- Fulvio Stacul has received lecture fees from Bracco and Guerbet ized controled trials. J Nephrol 25:290–301. https://www. Olivier Clément has received lecture fees from Bracco and Guerbet radiologen.nl/secties/nvvr/documenten/richtlijn-veilig-gebruik- The other authors of this manuscript declare no relationships with any vancontrastmiddelen-deel-1-full-english companies whose products and services may be related to the subject matter of this article. 15. Keeley EC (1998) Grines CL (1998) Scraping of aortic debris by coronary guiding catheters: a prospective evaluation of 1,000 cases. J Am Coll Cardiol 32:1861–1865 Open Access This article is distributed under the terms of the Creative 16. Wichmann JL, Katzberg RW, Litwin SE et al (2015) Contrast- Commons Attribution 4.0 International License (http:// induced nephropathy. Circulation 132:1931–1936 creativecommons.org/licenses/by/4.0/), which permits unrestricted use, 17. Newhouse JH, Kho D, Rao QA et al (2008) Frequency of serum distribution, and reproduction in any medium, provided you give appro- creatinine changes in the absence of iodinated contrast material: priate credit to the original author(s) and the source, provide a link to the implications for studies of contrast nephrotoxicity. AJR Am J Creative Commons license, and indicate if changes were made. Roentgenol 191:376–382 18. Bruce RJ, Djamali A, Shinki K et al (2009) Background fluctua- tion of kidney function versus contrast-induced nephrotoxicity. AJR American Journal of Roentgenology 192:711–718 References 19. Brouwers M, Kho ME, Browman GP, on behalf of the AGREE Next Steps Consortium et al (2010) AGREE II: Advancing guide- line development, reporting and evaluation in healthcare. Can 1. Stacul F, van der Molen AJ, Reimer P, Contrast Media Safety Med Assoc J 182:E839–E842 Committee of European Society of Urogenital Radiology Eur Radiol (2018) 28:2845–2855 2853 20. Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines: management and contrast-induced nephropathy. Nephrol Dial Transplant 27:4263–4272 2. Framing the question and deciding on important outcomes. J Clin Epidemiol 64:395–400 39. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D 21. OCEBM Levels of Evidence Working Group. The Oxford 2011 (1999) A more accurate method to estimate glomerular filtration Levels of Evidence. Oxford Centre for Evidence-Based Medicine. rate from serum creatinine: a new prediction equation. Available via: http://www.cebm.net/index.aspx?o=5653 Accessed Modification of Diet in Renal Disease Study Group. Ann Intern 14 December 2017 Med 130:461–470 22. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute 40. Levey AS, Coresh J, Greene T et al (2007) Expressing the MDRD Dialysis Quality Initiative workgroup (2004) Acute renal failure - study equation for estimating GFR with standardized serum cre- definition, outcome measures, animal models, fluid therapy and atinine values. Clin Chem 53:766–772 information technology needs: the Second International 41. Levey AS, Coresh J, Greene T, Chronic Kidney Disease Consensus Conference of the Acute Dialysis Quality Initiative Epidemiology Collaboration et al (2006) Using standardized se- (ADQI) Group. Crit Care 8:R204–R212 rum creatinine values in the modification of diet in renal disease 23. Levey AS, Eckardt KU, Tsukamoto Y et al (2005) Definition and study equation for estimating glomerular filtration rate. Ann classification of chronic kidney disease: a position statement from Intern Med 145:247–254. https://www.acr.org/-/media/ACR/ Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Files/Clinical-Resources/Contrast_Media.pdf Int 67:2089–2100 42. Levey AS, Stevens LA, Schmid CH, CKD-EPI (Chronic Kidney 24. Mehta RL, Kellum JA, Shah SVet al (2007) Acute Kidney Injury Disease Epidemiology Collaboration) et al (2009) A new equation Network. Acute Kidney Injury Network: report of an initiative to to estimate glomerular filtration rate. Ann Intern Med 150:604–612 improve outcomes in acute kidney injury. Crit Care 11:R31 43. Stevens LA, Li S, Kurella Tamura M et al (2011) Comparison of 25. ACR Committee on Drugs and Contrast Media. ACR Manual on the CKD Epidemiology Collaboration (CKD-EPI) and Contrast Media, v10.3. American College of Radiology, 2017 Modification of Diet in Renal Disease (MDRD) study equations: Available via: https://www.acr.org/-/media/ACR/Files/Clinical- risk factors for and complications of CKD and mortality in the Resources/Contrast_Media.pdf Accessed: 14 December 2017 Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 26. KellumJA,LameireN(2013)Diagnosis,evaluation,andmanagement 57:S9–S16 of acute kidney injury: a KDIGO summary (Part 1). Crit Care 17:204 44. Björk J, Jones I, Nyman U, Sjostrom P (2012) Validation of the 27. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Lund-Malmo, Chronic Kidney Disease Epidemiology (CKD-EPI) Kidney Injury Work Group (2012) KDIGO Clinical Practice and Modification of Diet in Renal Disease (MDRD) equations to Guideline for Acute Kidney Injury. Kidney Int Suppl 2:1–138 estimate glomerular filtration rate in a large Swedish clinical pop- 28. Morcos SK, Thomsen HS, Webb JA (1999) Contrast-media- ulation. Scand J Urol Nephrol 46:212–222 induced nephrotoxicity: a consensus report. Contrast Media 45. Schäffner ES, Ebert N, Delanaye P et al (2012) Two novel equa- Safety Committee, European Society of Urogenital Radiology tions to estimate kidney function in persons aged 70 years or older. (ESUR). Eur Radiol 9:1602–1613 Ann Intern Med 157:471–481 29. Pyxaras SA, Zhang Y, Wolf A, Schmitz T, Naber CK (2015) Effect of 46. Pottel H, Hoste L, Dubourg L et al (2016) An estimated glomer- varying definitions of contrast-induced acute kidney injury and left ular filtration rate equation for the full age spectrum. Nephrol Dial ventricular ejection fraction on one-year mortality in patients having Transplant 31:798–806 transcatheter aortic valve implantation. Am J Cardiol 116:426–430 47. Florkowski CM, Chew-Harris JSC (2011) Methods of Estimating 30. Slocum NK, Grossman PM, Moscucci M et al (2012) The chang- GFR – Different Equations Including CKD-EPI. Clin Biochem ing definition of contrast-induced nephropathy and its clinical im- Rev 32:75–79 plications: insights from the Blue Cross Blue Shield of Michigan 48. Delanaye P, Ebert N (2012) Assessment of kidney function: esti- Cardiovascular Consortium (BMC2). Am Heart J 163:829–834 mating GFR in children. Nat Rev Nephrol 8:503–504 31. Weisbord SD,MorMK,ResnickAL,HartwigKC,PalevskyPM,Fine 49. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A MJ(2008)Incidenceandoutcomesof contrast-inducedAKI following simple estimate of glomerular filtration rate in children derived computed tomography. Clin J Am Soc Nephrol 3:1274–1281 from body length and plasma creatinine. Pediatrics 58:259–263 32. Budano C, Levis M, D'Amico M et al (2011) Impact of contrast- 50. Schwartz GJ, Munoz A, Schneider MF et al (2009) New equations to induced acute kidney injury definition on clinical outcomes. Am estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637 Heart J 161:963–971 51. Schwartz GJ, Schneider MF, Maier PS et al (2012) Improved 33. Azzouz M, Rømsing J, Thomsen HS (2014) Fluctuations in eGFR equations estimating GFR in children with chronic kidney disease in relation to unenhanced and enhanced MRI and CT outpatients. using an immunonephelometric determination of cystatin C. Eur J Radiol 83:886–892 Kidney Int 82:445–453 34. Thomsen HS, Morcos SK (2009) Risk of iodinated contrast 52. Martinez Lomakin F, Tobar C (2014) Accuracy of point-of-care serum material-induced nephropathy with intravenous administration. creatinine devices for detecting patients at risk of contrast-induced ne- Eur Radiol 19:891–897 phropathy: a critical overview. Crit Rev Clin Lab Sci 51:332–343 35. Lakhal K, Ehrmann S, Chaari A et al (2011) Acute Kidney Injury 53. Rao QA, Newhouse JH (2006) Risk of nephropathy after intrave- Network definition of contrast-induced nephropathy in the criti- nous administration of contrast material: a critical literature anal- cally ill: incidence and outcome. J Crit Care 26:593–599 ysis. Radiology 239:392–397 36. Garfinkle MA, Stewart S, Basi R (2015) Incidence of CT contrast 54. Katzberg RW, Newhouse JH (2010) Intravenous contrast agent-induced nephropathy: toward a more accurate estimation. medium-induced nephrotoxicity: is the medical risk really as great AJR Am J Roentgenol 204:1146–1151 as we have come to believe? Radiology 256:21–28 37. Thomas ME, Blaine C, Dawnay A et al (2015) The defi- nition of acute kidney injury and its use in practice. Kidney 55. Stratta P, Bozzola C, Quaglia M (2012) Pitfall in nephrology: Int 87:62–73 contrast nephropathy has to be differentiated from renal damage 38. Fliser D, Laville M, Covic A et al (2012) A European Renal Best due to atheroembolic disease. J Nephrol 25:282–289 Practice (ERBP) position statement on the Kidney Disease 56. McDonald RJ, McDonald JS, Newhouse JH, Davenport MS Improving Global Outcomes (KDIGO) clinical practice guidelines (2015) Controversies in contrast material-induced acute kidney on acute kidney injury: part 1: definitions, conservative injury: closing in on the truth? Radiology 277:627–632 2854 Eur Radiol (2018) 28:2845–2855 57. Nyman U, Aspelin P, Jakobsen J, Bjork J (2015) Controversies in 75. Haider M, Yessayan L, Venkat KK, Goggins M, Patel A, Karthikeyan V (2015) Incidence of contrast-induced nephropathy contrast material-induced acute kidney injury: Propensity Score matching of patients with different dose/absolute glomerular fil- in kidney transplant recipients. Transplant Proc 47:379–383 tration rate ratios. Radiology 277:633–637 76. Fananapazir G, Troppmann C, Corwin MT, Bent CK, Vu CT, 58. Ricos C, Iglesias N, Garcia-Lario JV et al (2007) Within-subject Lamba R (2016) Incidence of contrast-induced nephropathy after biological variation in disease: collated data and clinical conse- renal graft catheter arteriography using iodine-based contrast me- quences. Ann Clin Biochem 44:343–352 dium. AJR Am J Roentgenol 206:783–786 59. Wilhelm-Leen E, Montez-Rath ME, Chertow G (2017) Estimating 77. Fananapazir G, Troppmann C, Corwin MT, Nikpour AM, Naderi the risk of radiocontrast-associated nephropathy. J Am Soc , Lamba R (2016) Incidences of acute kidney injury, dialysis, and Nephrol 28:653–659 graft loss following intravenous administration of low-osmolality 60. McDonaldJS,McDonaldRJ,CominJetal(2013)Frequencyofacute iodinated contrast in patients with kidney transplants. Abdom kidney injuryfollowing intravenous contrastmediumadministration: Radiol 41:2182–2186 a systematic review and meta-analysis. Radiology 267:119–128 78. Haveman JW, Gansevoort RT, Bongaerts AH, Nijsten MW (2006) 61. SchünemannHJ,TugwellP,ReevesBCetal(2013)Non-randomized Low incidence of nephropathy in surgical ICU patients receiving studies as a source of complementary, sequential or replacement ev- intravenous contrast: a retrospective analysis. Intensive Care Med idence for randomized controlled trials in systematic reviews on the 32:1199–1205 effects of interventions. Res Synth Methods 4:49–62 79. Hoste EA, Doom S, De Waele J et al (2011) Epidemiology of 62. DavenportMS,KhalatbariS,DillmanJR,CohanRH,CaoiliEM,Ellis contrast-associated acute kidney injury in ICU patients: a retro- JH (2013) Contrast material-induced nephrotoxicity and intravenous spective cohort analysis. Intensive Care Med 37:1921–1931 low-osmolality iodinated contrast material. Radiology 267:94–105 80. Cely CM, Schein RM, Quartin AA (2012) Risk of contrast in- 63. DavenportMS,KhalatbariS,CohanRH,DillmanJR,MylesJD,Ellis duced nephropathy in the critically ill: a prospective, case matched JH (2013) Contrast material-induced nephrotoxicity and intravenous study. Crit Care 16:R67 low-osmolalityiodinatedcontrastmaterial:riskstratificationbyusing 81. Ehrmann S, Badin J, Savath L et al (2013) Acute kidney injury in estimated glomerular filtration rate. Radiology 268:719–728 the critically ill: is iodinated contrast medium really harmful? Crit 64. McDonald RJ, McDonald JS, Bida JP et al (2013) Intravenous Care Med 41:1017–1026 contrast material-induced nephropathy: causal or coincident phe- 82. McDonald JS, McDonald RJ, Williamson EE, Kallmes DF, nomenon? Radiology 267:106–118 Kashani K (2017) Post-contrast acute kidney injury in intensive 65. McDonald JS, McDonald RJ, Carter RE, Katzberg RW, Kallmes care unit patients: a propensity score-adjusted study. Intensive DF, Williamson EE (2014) Risk of intravenous contrast material- Care Med 43:774–784 mediated acute kidney injury: a propensity score-matched study 83. Senthilnathan S, Gauvreau K, Marshall AC, Lock JE, Bergersen L stratified by baseline-estimated glomerular filtration rate. (2009) Contrast administration in pediatric cardiac catheterization: Radiology 271:65–73 dose and adverse events. Catheter Cardiovasc Interv 73:814–820 66. McDonald JS, McDonald RJ, Lieske JC et al (2015) Risk of acute 84. Huggins N, Nugent A, Modem V et al (2014) Incidence of acute kidney injury, dialysis, and mortality in patients with chronic kid- kidney injury following cardiac catheterization prior to cardiopulmo- ney disease after intravenous contrast material exposure. Mayo nary bypass in children. Catheter Cardiovasc Interv 84:615–619 Clin Proc 90:1046–1053 85. Cantais A, Hammouda Z, Mory O et al (2016) Incidence of 67. Karlsberg RP, Dohad SY, Sheng R (2011) Iodixanol peripheral contrast-induced acute kidney injury in a pediatric setting: a cohort computed tomographic angiography study investigator panel. study. Pediatr Nephrol 31:1355–1362 Contrast medium acute kidney injury: comparison of intravenous 86. Balemans CE, Reichert LJ, van Schelven BI, van den Brand JA, and intra-arterial administration of iodinated contrast medium. J Wetzels JF (2012) Epidemiology of contrast material-induced ne- Vasc Intervent Radiol 22:1159–1165 phropathy in the era of hydration. Radiology 263:706–713 68. Kooiman J, Le Haen PA, Gezgin G et al (2013) Contrast-induced 87. Kanbay M, Solak Y, Afsar B et al (2017) Serum uric acid and risk for acute kidney injury and clinical outcomes after intra-arterial and acute kidney injury following contrast: an evaluation of epidemiolo- intravenous contrast administration: risk comparison adjusted for gy, clinical trials, and potential mechanisms. Angiology 68:132–144 patient characteristics by design. Am Heart J 165:793–799 88. Kiski D, Stepper W, Breithardt G, Reinecke H (2010) Impact of 69. McDonald JS, Leake CB, McDonald RJ et al (2016) Acute kidney female gender on frequency of contrast medium-induced nephrop- injury after intravenous versus intra-arterial contrast material ad- athy: post hoc analysis of dialysis versus diuresis trial. J Womens ministration in a paired cohort. Invest Radiol 51:804–809 Health 19:1363–1368 70. Tong GE, Kumar S, Chong KC et al (2016) Risk of contrast- 89. Kwasa EA, Vinayak S, Armstrong R (2014) The role of inflam- induced nephropathy for patients receiving intravenous vs. intra- mation in contrast-induced nephropathy. Br J Radiol 87:20130738 arterial iodixanol administration. Abdom Radiol 41:91–99 90. Medalion B, Cohen H, Assali A et al (2010) The effect of cardiac 71. From AM, Bartholmai BJ, Williams AW, Cha SS, McDonald FS angiography timing, contrast media dose, and preoperative renal (2008) Mortality associated with nephropathy after radiographic function on acute renal failure after coronary artery bypass contrast exposure. Mayo Clin Proc 83:1095–1100 grafting. J Thorac Cardiovasc Surg 139:1539–1544 72. Nyman U, Almén T, Jacobsson B, Aspelin P (2012) Are intrave- 91. Ohno Y, Maekawa Y, Miyata H et al (2013) Impact of nous injections of contrast media really less nephrotoxic than periprocedural bleeding on incidence of contrast-induced acute intra-arterial injections? Eur Radiol 22:1366–1371 kidney injury in patients treated with percutaneous coronary in- 73. Prasad A, Ortiz-Lopez C, Khan A, Levin D, Kaye DM (2016) tervention. J Am Coll Cardiol 62:1260–1266 Acute kidney injury following peripheral angiography and 92. Pannu N, Wiebe N, Tonelli M (2006) Prophylaxis strategies for endovascular therapy: a systematic review of the literature. contrast-induced nephropathy. JAMA 295:2765–2779 Catheter Cardiovasc Interv 88:264–273 74. Aubry P, Brillet G, Catella L, Schmidt A, Bénard S (2016) 93. Song W, Zhang T, Pu J, Shen L, He B (2014) Incidence and risk of Outcomes, risk factors and health burden of contrast-induced developing contrast-induced acute kidney injury following intravascu- acute kidney injury: an observational study of one million hospi- larcontrastadministrationinelderlypatients.ClinIntervAging9:85–93 talizations with image-guided cardiovascular procedures. BMC 94. Toprak O, Cirit M (2006) Risk factors for contrast-induced ne- Nephrol 17:167 phropathy. Kidney Blood Press Res 29:84–93 Eur Radiol (2018) 28:2845–2855 2855 95. Yang JQ, Ran P, Chen JY et al (2014) Development of contrast- nephropathy: a systematic review and meta-analysis. Ann Intern Med 164:417–424 induced acute kidney injury after elective contrast media exposure in patients with type 2 diabetes mellitus: effect of albuminuria. 101. Barrett BJ, Carlisle EJ (1993) Meta-analysis of the relative neph- PLoS One 9:e106454 rotoxicity of high- and low-osmolality iodinated contrast media. 96. Zuo T, Jiang L, Mao S, Liu X, Yin X, Guo L (2016) Radiology 188:171–178 Hyperuricemia and contrast-induced acute kidney injury: A sys- 102. Gurm HS, Dixon SR, Smith DE, BMC2 (Blue Cross Blue Shield tematic review and meta-analysis. Int J Cardiol 224:286–294 of Michigan Cardiovascular Consortium) Registry et al (2011) 97. McDonald JS, McDonald RJ, Williamson EE, Kallmes DF (2017) Is Renal function-based contrast dosing to define safe limits of ra- intravenous administration of iodixanol associated with increased risk diographic contrast media in patients undergoing percutaneous of acute kidney injury, dialysis, or mortality? a Propensity Score- coronary interventions. J Am Coll Cardiol 58:907–914 adjusted study. Radiology. 285: 414-424 103. Kooiman J, Seth M, Share D, Dixon S, Gurm HS (2014) The associ- 98. Heinrich MC, Häberle L, Müller V, Bautz W, Uder M (2009) ation between contrast dose and renal complications post-PCI across Nephrotoxicity of iso-osmolar iodixanol compared with nonionic the continuum of procedural estimated risk. PLoS One 9:e90233 low-osmolar contrast media: meta-analysis of randomized con- 104. Nyman U, Björk J, Aspelin P, Marenzi G (2008) Contrast medium trolled trials. Radiology 250:68–86 dose-to-GFR ratio: a measure of systemic exposure to predict 99. From AM, Al Badarin FJ, McDonald FS, Bartholmai BJ, Cha SS, contrast-induced nephropathy after percutaneous coronary inter- Rihal CS (2010) Iodixanol versus low-osmolar contrast media for vention. Acta Radiol 49:658–667 prevention of contrast induced nephropathy: meta-analysis of ran- 105. Nyman U (2016) Contrast dose, estimated GFR and techniques to domized, controlled trials. Circ Cardiovasc Interv 3:351–358 reduce contrast dose in PCI – time to consider some basic princi- 100. Eng J, Wilson RF, Subramaniam RM et al (2016) Comparative ples! J Invas Cardiol 28:E126–E127 effect of contrast media type on the incidence of contrast-induced Affiliations 1 2 1 3 4 Aart J. van der Molen & Peter Reimer & Ilona A. Dekkers & Georg Bongartz & Marie-France Bellin & 5 6 7 8 9 Michele Bertolotto & Olivier Clement & Gertraud Heinz-Peer & Fulvio Stacul & Judith A. W. Webb & Henrik S. Thomsen 1 6 Department of Radiology, C2-S, Leiden University Medical Center, Department of Radiology, Assistance Publique-Hôpitaux de Paris, Albinusdreef 2, NL-2333 ZA Leiden, The Netherlands Hôpital Européen Georges Pompidou, 20, rue Leblanc, Paris Cedex 15, F-71015 Paris, France Institute for Diagnostic and Interventional Radiology, Klinikum Karlsruhe, Academic Teaching Hospital of the University of Department of Radiology, Zentralinstitut für medizinische Freiburg, Moltkestraße 90, D-76133 Karlsruhe, Germany Radiologie, Diagnostik und Intervention, Landesklinikum St. Pölten, Propst Führer-Straße 4, AT-3100 St. Pölten, Austria Department of Diagnostic Radiology, University Hospitals of Basel, Petersgaben 4, CH-4033 Basel, Switzerland S.C. Radiologia Ospedale Maggiore, Piazza Ospitale 1 I-34129 Trieste, Italy Service Central de Radiologie Hôpital Paul Brousse 14, av. P.-V.- Couturier, F-94807 Villejuif, France Department of Radiology, St. Bartholomew’s Hospital, University of London, West Smithfield, London EC1A 7BE, UK Department of Radiology, University of Trieste, Strada di Fiume 447, I-34149 Trieste, Italy Department of Diagnostic Radiology 54E2, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Radiology Springer Journals

Post-contrast acute kidney injury – Part 1: Definition, clinical features, incidence, role of contrast medium and risk factors

Free
11 pages

Loading next page...
 
/lp/springer_journal/post-contrast-acute-kidney-injury-part-1-definition-clinical-features-wFO8VAkgJg
Publisher
Springer Journals
Copyright
Copyright © 2018 by The Author(s)
Subject
Medicine & Public Health; Imaging / Radiology; Diagnostic Radiology; Interventional Radiology; Neuroradiology; Ultrasound; Internal Medicine
ISSN
0938-7994
eISSN
1432-1084
D.O.I.
10.1007/s00330-017-5246-5
Publisher site
See Article on Publisher Site

Abstract

Purpose The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. Areas covered in part 1 Topics reviewed include the terminology used, the best way to measure eGFR, the definition of PC-AKI, and the risk factors for PC-AKI, including whether the risk with intravenous and intra-arterial contrast medium differs. Key Points � PC-AKI is the preferred term for renal function deterioration after contrast medium. � PC-AKI has many possible causes. � The risk of AKI caused by intravascular contrast medium has been overstated. � Important patient risk factors for PC-AKI are CKD and dehydration. . . . . Keywords Contrast media Acute kidney injury Glomerular filtration rate Risk factors Practice guidelines as topic Abbreviations CM Contrast media ACR American College of Radiology CMSC Contrast Media Safety Committee ADQI Acute Dialysis Quality Initiative CT Computed tomography AGREE Appraisal of Guidelines for Research and eGFR Estimated glomerular filtration rate Evaluation EBM Evidence-based medicine AKI Acute kidney injury ERBP European Renal Best Practice AKIN Acute Kidney Injury Network ESUR European Society of Urogenital Radiology BIS Berlin Initiative Study FAS Full age spectrum BUN Blood urea nitrogen GFR Glomerular filtration rate CA Coronary angiography IA Intra-arterial CI Confidence interval ICU Intensive care unit IDMS Isotope Dilution Mass Spectroscopy CI-AKI Contrast-induced acute kidney injury IV Intravenous CIN Contrast-induced nephropathy KDIGO Kidney Disease Improving Global Outcome CKD Chronic kidney disease LM Lund Malmö CKD-EPI ChronicKidneyDiseaseEpidemiologyCollaboration MDRD Modification of Diet in Renal Disease NICE National Institute for Health and Care Excellence OCEBM Oxford Center for Evidence Based Medicine * Henrik S. Thomsen PC-AKI Post-contrast acute kidney injury Henrik.Thomsen@regionh.dk PCI Percutaneous coronary intervention Extended author information available on the last page of the article PICO Patient-Intervention-Comparator-Outcome 2846 Eur Radiol (2018) 28:2845–2855 PoC Point of Care Clinical features and incidence of PC-AKI PS Propensity Score RANZCR Royal Australian and New Zealand College of The term PC-AKI is used to describe a decrease in renal func- Radiology tion that follows intravascular administration of CM. The de- RCR Royal College of Radiologists crease in renal function is usually mild, peaking at 2–3days, RCT Randomised controlled trials and renal function usually returns to baseline values within 1– RRT Renal replacement therapy 3 weeks. Like all forms of AKI, an episode of PC-AKI is a RSTN Radiological Society of The Netherlands marker for increased short- and long-term morbidity and mor- sCr Serum creatinine tality and prolonged hospital stay [4–10]. WG Writing Group The risk of PC-AKI after intravenous (IV) CM has proba- bly been overestimated. Two meta-analyses of 19,000 patients who had received IV CM showed PC-AKI incidences of 6.4 %(95 %CI 5.0–8.1) and 5.0 % (95 % CI 3.8–6.5) [11, 12]. In Introduction 1 % of all patients the decline in renal function persisted for 2 months, but the weighted incidence of renal replacement ther- The Contrast Media Safety Committee (CMSC) of the apy (RRT) was as low as 0.06 % [11]. European Society of Urogenital Radiology (ESUR) produced It has been suggested that intra-arterial (IA) CM adminis- their most recent guidelines on what was then termed contrast tration during catheter-based angiography, with or without induced nephropathy (CIN) in 2011 [1]. Guidelines on the use percutaneous coronary intervention (PCI), is associated with of contrast media (CM) in patients on dialysis and the use of a higher incidence of PC-AKI than IV CM administration [13, CM in diabetic patients using metformin were published in 14]. However, there are many causes of AKI following angi- 2002 and 2014 [2, 3]. This review provides the information to ography, and AKI may wrongly be attributed to the CM [15]. support the new CMSC guidelines, which were obtained Catheter-based procedures may be complicated by haemody- using a structured literature review based on clinical questions namic instability, and by embolization of cholesterol or throm- and patient-intervention-comparator outcome (PICO) format- bi to the renal arteries caused by catheter manipulations [16]. ting. Since the literature related to the topics considered is so Any of these may lead to post-interventional AKI, which is large, the results of the review have been split into two papers. often misinterpreted as contrast-induced acute kidney injury The review only considers post-contrast kidney injury (PC- (CI-AKI) [17, 18]. A large meta-analysis of cardiovascular AKI) after intravascular iodine-based CM. Acute kidney inju- outcomes after coronary angiography (CA) showed that the ry (AKI) is not associated with intravascular gadolinium- association between PC-AKI and mortality was strongly con- based contrast agents in doses approved for clinical magnetic founded by baseline clinical features that predisposed to both resonance imaging. kidney injury and mortality [6]. The risk of PC-AKI reported In this first paper on PC-AKI, the following topics related in studies adjusted for confounding features was much lower to diagnosis and risk are considered: than that from unadjusted studies. The incidence of AKI was 2.3 % and need for RRT 0.3 % in a recent retrospective anal- 1. The clinical features and incidence of PC-AKI. ysis using propensity matching with controls of over 2,000 2. The choice of terms for renal function deterioration after patients who had PCI [7]. CM, the degree of renal function deterioration used to diagnose PC-AKI, and the definitions of intravenous and intra-arterial CM administration. 3. The reliability of the various equations used to measure Materials and methods eGFR and the appropriate timing of eGFR measurement before CM administration. The guidelines were developed using the Appraisal of 4. The evidence that CM can cause AKI, the levels of renal Guidelines for Research and Evaluation (AGREE) II docu- function at which there is a risk of PC-AKI, and the recent ment [19]. A guideline Writing Group (WG) prepared ten evidence suggesting that the risk of PC-AKI may be lower clinical questions in Patient – Intervention – Comparison – after intravenous than after intra-arterial contrast medium. Outcome (PICO) format [20]. Systematic search strings were 5. The importance of the many risk factors for PC-AKI de- developed with a professional librarian for four different bio- scribed in the literature. medical literature databases (PubMed, Web of Science, Embase, and the Cochrane Library). Language was limited Recommendations are made for items 2–5. The recommen- to English and German. Where necessary, additional system- dations have been incorporated into version 10 of the ESUR atic searches on specific topics, such as pediatric PC-AKI, CMSC guidelines (see Table 4 in Part 2). were performed. Eur Radiol (2018) 28:2845–2855 2847 The titles and abstracts were screened for relevance and suggested Acute Kidney Injury (AKI) as the preferred term for selected on predefined in- and exclusion criteria. Emphasis acute renal failure to be used for all forms of AKI [24]. was put on comparative studies with strong scientific evidence, The CMSC recommends that the term PC-AKI should re- such as meta-analyses and systematic reviews, and prospective place the older term of contrast-induced nephropathy (CIN) and randomized controlled trials (RCTs). In addition, evidence was suggests using the terms recommended by the ACR Committee collected from comparative cohort, patient-control and non- on Drugs and Contrast Media [25] when AKI follows CM comparative studies. Other important quality criteria were size administration (Table 1). They state that post-contrast acute of population studied, duration of follow-up and control for kidney injury (PC-AKI) is a general term that should be used bias. Cross-referencing was used to find additional data. The if there is a sudden deterioration in renal function within 48 h of four systematic searches for paper 1 yielded 3,086 references, the intravascular administration of iodine-based CM. They de- of which 705 were selected from their title and abstract. The full scribe PC-AKI as a correlative diagnosis. They recommend texts of these 705 publications were reviewed and 105 were that the term contrast-induced acute kidney injury (CI-AKI) is selected for inclusion in this paper. The quality of evidence reserved for cases where a causal relation can be shown be- was evaluated according to the Oxford Centre for Evidence tween the administered CM and the deterioration in renal func- Based Medicine (OCEBM) 2011 levels of evidence: Grade tion. However, in clinical practice it is usually difficult to dis- A: established scientific evidence; Grade B: scientific presump- tinguish CI-AKI from PC-AKI and very few of the published tion; Grade C: low level of evidence [21]. Where there was no studies have a suitable control group to allow the two condi- scientific evidence, recommendations were based on WG con- tions to be separated. Thus, many cases of PC-AKI seen in sensus and graded as expert opinion (Grade D). clinical practice or reported in clinical studies are likely to be Other factors such as availability of techniques or expertise, coincident to, but not caused by, CM administration. organizational consequences, financial costs and patient prefer- ences were also considered. CM manuals and guidelines Renal function definitions of PC-AKI (American College of Radiology (ACR), Royal Australian and New Zealand College of Radiology (RANZCR), National The diagnosis of PC-AKI is usually based on surrogate measures Institute for Health and Care Excellence (NICE), Royal College of absolute or relative change in serum creatinine (sCr), rather of Radiologists (RCR), and Radiological Society of the than patient outcomes, such as renal failure, need for RRT or Netherlands (RSTN)) were consulted where appropriate. mortality. The KDIGO Practice Guidelines [26, 27] adopted the The recommendations prepared by the WG are the result of older AKIN criteria [24] and recommended division of AKI into the available scientific evidence combined with these other three stages dependent on sCr and/or urine output (Table 2). sources of information. They were discussed at the CMSC The ESUR CMSC defined Contrast-Induced Nephropathy meeting in Copenhagen, Denmark in February 2017 and the (CIN) in their first survey-based guideline as “aconditionin text of the final recommendations and guidelines was subse- which an impairment in renal function (an increase in sCr by quently approved by the academic members of the CMSC. more than 25 % or 44 μmol/L, or 0.5 mg/dl) occurs within 3 Once published in print, the validity of the CMSC guidelines days following the intravascular administration of a contrast will be routinely set at 6 years. However, the CMSC members medium in the absence of an alternative aetiology” [28]. constantly monitor the validity of the guidelines, and can pro- Multiple studies have shown that the incidence of PC-AKI pose revision at an earlier date if deemed necessary. is largely dependent on the definition used [29–31]. A relative increase in sCr of > 25 % has been the most sensitive indica- tor, with absolute values being less sensitive. In coronary an- Results giography studies, relative definitions had more prognostic Table 1 PC-AKI: Terminology and definition QUESTION 1: What are the preferred terms and definitions to be used in PC-AKI? The preferred term for acute kidney injury associated with CM administration when no control population is available is Terminology Post-Contrast Acute Kidney Injury (PC-AKI). The term Contrast-Induced Acute Kidney Injury (CI-AKI) should be used only when comparison with a control allows CM to be shown Until recently there has not been a generally accepted term for to be the cause of the acute kidney injury. acute renal failure, which is a complex disorder with many possi- Level of Evidence D blecausesandriskfactors.Severalnephrologygroups, suchasthe PC-AKI and CI-AKI should be defined as an increase in sCr of ≥ Acute Dialysis Quality Initiative (ADQI) [22] and Kidney 0.3mg/dl, or of ≥ 1.5–1.9 times baseline (KDIGO definition of AKI) Disease:ImprovingGlobalOutcome(KDIGO)[23],haveworked in the 48–72 h following CM administration. on finding a suitable term. The Acute Kidney Injury Network Level of Evidence C (AKIN), a group of experts in Critical Care and Nephrology, 2848 Eur Radiol (2018) 28:2845–2855 Table 2 Acute Kidney Injury Staging (KDIGO) and CKD-EPI and Schwartz Equations for calculating eGFR (a) KDIGO staging for AKI Stage Serum creatinine Urine output 1sCr ≥ 0.3 mg/dl (≥ 26.5 μmol/L), or < 0.5 ml/kg/h for 6–12h sCr increase of 1.5–1.9xbaseline 2 sCr increase of 2.0–2.9 x baseline < 0.5 ml/kg/h for ≥ 12h 3sCr ≥ 4.0 mg/dl (≥ 354 μmol/L) or < 0.3 ml/kg/h for ≥ 24h sCr increase > 3.0x baseline or Anuria for ≥ 12h or need for renal replacement therapy (b) CKD-EPI equation (sCr in μmol/L; age in years). eGFR (ml/min/1.73 m )= -0.329 Age Female sCr ≤ 62 μmol/L: 144 x (sCr / 62) x0.993 -1.209 Age Female sCr > 62 μmol/L: 144 x (sCr / 62) x0.993 -0.411 Age Male sCr ≤ 80 μmol/L: 141 x (sCr / 80) x0.993 -1.209 Age Male sCr > 80 μmol/L: 141 x (sCr / 80) x0.993 All equations x 1.159 if African American race (c) Revised Schwartz equation (sCr in μmol/L; patient length in cm). eGFR (ml/min/1.73 m2) = 36.5 × Length / sCr relevance [29]. In other studies, however, relative increases in heart and pulmonary arteries and via catheters directly in the sCr were found to overestimate PC-AKI and absolute values carotid, subclavian, brachial, coronary and mesenteric arteries, were considered preferable [32]. Relative values seem to be as well as into the infrarenal aorta and the iliac, femoral and more sensitive for patients with CKD 3B (eGFR 30–44 ml/ crural arteries. Note: Because of backflow during this type of 2 2 min/1.73m ) and CKD 2 (eGFR 60–89 ml/min//1.73m ), and IA injection, small doses of CM may reach the kidney in a absolute values seem to be more sensitive for patients with relatively undiluted form. CKD 3A (eGFR 45–59 ml/min/1.73m )[33, 34]. Studies in The term intra-arterial CM administration with first-pass critically ill populations using the AKIN definition found that renal exposure indicates that CM reaches the renal arteries dur- development of AKI correlated with ICU mortality [35]. ing its first pass in a relatively undiluted form, depending on the The KDIGO criteria are more rigorously derived than the distance of the site of injection from the renal arteries. This CIN definition and are now being adopted as the standard for occurs with injections through catheters into the left heart, the PC-AKI studies [36]. The CMSC, like the European Renal thoracic and suprarenal abdominal aorta, and selectively into the Best Practice (ERBP) working group, recommends that the renal arteries. Note: In suprarenal aortic injections, some of the definition of PC- AKI (or CI-AKI) should use the KDIGO injected CM escapes via suprarenal aortic side-branches and definition of AKI: an increase in sCr of ≥ 0.3 mg/dl, or a sCr reaches the kidney after dilution in the circulation. increase of ≥ 1.5– 1.9 times baseline [37, 38](Table 1). The KDIGO recommendation is that the renal function change should be within 48 h, but the CMSC recommends retaining QUESTION 2: What are the best equations for GFR a period of 48–72 h after CM as being more practical for estimation in European populations? diagnosing PC-AKI in radiological practice, the majority of which involves outpatients. Total glomerular filtration rate (GFR) is considered the best overall index of kidney function, but cannot be measured eas- Intravenous and direct and indirect intra-arterial CM ily in clinical practice, so GFR is estimated using sCr as an administration: definition of terms endogenous filtration marker. In 1999, the Modification of Diet in Renal Disease (MDRD) equation [39] was introduced The term intravenous CM administration indicates that CM for estimating GFR. The quality of GFR estimates largely reaches the renal arteries after dilution by circulation through depends on the accuracy of the creatinine measurements, the right heart and pulmonary circulation or a systemic capil- and should be based on sCr assays standardized to reference lary bed. methods [40]. The MDRD equation has therefore been re- The same is true for intra-arterial CM administration with expressed for use with sCr assays standardized using isotope second-pass renal exposure, such as via catheters into the right dilution mass spectroscopy (IDMS) [41]. Eur Radiol (2018) 28:2845–2855 2849 In 2009, the CKD-EPI equation was proposed by the Chronic [49] was revised in 2009 to include the IDMS method and Kidney Disease Epidemiology Collaboration (CKD-EPI), and plasma iohexol clearance as standardized reference methods was shown to be superior to the MDRD equation, especially at [50](Tables 2 and 3). higher GFRs (Table 2)[42]. The National Kidney Foundation A Cystatin C-based equation has been proposed that recommended replacing the MDRD by the CKD-EPI equation showed the best accuracy (91 %) when combined with for routine clinical use [43]. The CMSC therefore recommends height/SCr, height, sex and blood urea nitrogen (BUN) [49]. the CKD-EPI equation for routine use in adults (Table 3). All However, this requires an additional BUN, which lacks stan- creatinine-based equations should be used with caution in people dardized measurement, and Cystatin C requires standardiza- with abnormally high or low muscle mass. Caution should also tion and calibration [51]. In children with increased muscle be exercised in patients with AKI, because sCr takes several days mass both the sCr and Cystatin C based Schwartz formulas to stabilize and may not reflect current GFR. tend to overestimate GFR. There are other equations for specific subgroups, such as the Lund-Malmö (LM) revised equation for the Swedish Point-of-care creatinine measurements population [44], the Berlin Initiative Study (BIS-1) equa- tion for the elderly German population [45], and the full age Point-of-care (PoC) whole blood creatinine may be measured spectrum (FAS) equation for children and adults [46]. with the older Jaffe (alkaline picrate) method or by enzymatic However, these equations have not been validated in other methods, with the latter considered more accurate. Although populations. Cystatin C equations for estimation of GFR such measurements have practical advantages in patients may have advantages over sCr-based equations but are lim- with increased risk of PC-AKI, PoC devices may lead to ited by additional costs and lack of an international refer- overestimation of renal function in severe kidney failure ence system for calibration [47]. with resultant incorrect risk stratification [52]. Laboratory professionals should be consulted about analytical perfor- Estimation of GFR in children mance and quality assurance of whole blood PoC creati- nine measurement. When estimating GFR in children, sCr levels should be mea- sured by standardized reference methods because serum con- centrations are lower than in adults [48]. The CMSC therefore For how long do GFR estimations remain valid? recommends the revised Schwartz equation for routine clinical use in children (Table 3). The widely-used Schwartz equation There are no studies available on how long eGFR mea- surements remain valid for estimating the PC-AKI risk. Table 3 Formulae for eGFR and timing of eGFR measurement The eGFR measurements can be regarded as stable in individuals without CKD or underlying co-morbidities The CKD-EPI equation for estimated GFR (eGFR) is recommended for adults. As with all creatinine-based eGFRs, results should be such as heart failure or hypertension who are not taking interpreted with caution in people with abnormally high or low nephrotoxic drugs. muscle mass The CMSC considers eGFR measurements before intra- Level of Evidence A vascular CM exposure valid for a maximum of: The revised Schwartz formula (2009) for eGFR is recommended for children. As with all creatinine-based eGFRs, results should be (1) 7 days* if the patient interpreted with caution in people with abnormally high or low muscle mass a) has an acute disease, an acute deterioration of a Level of Evidence C known chronic disease or any other adverse event that eGFR is not reliable in patients with known AKI could have negatively influenced renal function Level of Evidence A (eGFR), or The CMSC considers eGFR measurements before intravascular b) is a hospital inpatient CM exposure valid for a maximum of: 1) 7 days* if the patient has (a) an acute disease, an acute deterioration of a known chronic disease or any other adverse event that could (2) 3months have negatively influenced renal function (eGFR), or (b) is a hospital inpatient a) if the patient has a chronic disease with stable renal 2) 3 months (a) if the patient has a chronic disease with stable function (eGFR), and renal function (eGFR) and (b) in all other patients b) in all other patients (Table 3) Level of Evidence D *Note: In patients with AKI, eGFR should be monitored *Note: in patients with AKI it is advisable to monitor eGFR frequently, so a maximum of 1-2 days may be advisable. frequently, and a maximum of 1–2 days is advisable. 2850 Eur Radiol (2018) 28:2845–2855 QUESTION 3: What is the evidence that contrast based studies. Remaining major limitations of observa- media are truly a causative factor in AKI and what are tional studies are the low numbers of patients with severe the eGFR values below which there is a risk of PC-AKI? renal impairment, and the variability of data available on, for example, prophylactic volume expansion and the CM Contrast-induced nephropathy was accepted for many years, dose administered. but more recently it has been questioned whether CM causes the deterioration in renal function that may occur after CM administration [17, 53]. There are important limitations in Comparison of intra-arterial and intravenous CM many studies that assess whether CM causes AKI. Most stud- administration in the same patients ies evaluate the use of IA CM in CA and/or percutaneous coronary intervention (PCI) in patients with significant co- A limited number of studies have directly compared IV to IA morbidities and therefore may not be relevant for intravenous CM administration, using the patient as their own control. The administration, and most studies do not have adequate control risk of PC-AKI as well as its clinical course was independent groups [54, 55]. of the route of administration in four retrospective studies of patient populations with varying degrees of renal impairment Intravenous CM administration [67–70], and PC-AKI rates were similar to the rates for unenhanced CT [70]. However, these studies suffer from There is controversy about the causal relationship be- selection bias and procedures with IA CM administra- tween exposure to IV CM and PC-AKI, since there are tion with first- and second-pass renal exposure were not no prospective RCTs confirming this association [56, 57]. separated. Without controlled studies, many factors such as diet, hy- dration, physiological variation in sCr over time, and a variety of nephrotoxic risk factors, including medications, Intra-arterial CM administration which may influence renal function, cannot be distin- guished from any effect of the CM [17, 18, 58]. The PC-AKI incidence following direct IA CM administration Although RCTs have the strongest research design for with first-pass renal exposure is frequently reported to be assessing the effects of interventions, assessment of rare higher than after IV administration, but this remains contro- conditions such as PC-AKI by RCT would require large versial [71, 72]. Problems with confounding factors are most numbers of patients [53]. significant in studies on patients that undergo catheter-based Based on comparisons of the relatively few studies CA and/or PCI because it is impossible to separate the effects of contrast media from the effects of co-morbidity, catheter with and without control populations it has been sug- gested that the risk of PC-AKI after IV CM has been manipulations or other procedural variables. In large meta- overestimated [53, 59]. A meta-analysis that retrospec- analyses on cardiovascular outcome the PC-AKI inci- tively studied 13 non-randomised controlled studies was dence may have been strongly confounded by baseline unable to find an increased incidence of AKI in patients clinical characteristics, both for first- and second-pass IA who received intravenous contrast medium [60]. CM administration [6, 73]. Nonetheless, AKI in general Evidence from observational studies may need to be is a significant problem in these patients and is associat- used, despite the recognised methodological problems ed with increased morbidity, longer length of hospital [61]. Recently, a few large-scale studies using propensity stay and higher cost [74], and may be associated with score (PS)-matching for the evaluation of PC-AKI in pa- mortality in a significant percentage of cardiac patients tients undergoing contrast-enhanced CT, which stratified [7]. Second-pass IA CM administration is considered to subjects according to their baseline sCr or eGFR, have have no higher risk than IV CM administration. been published [62–65]. These studies were unable to Since it is difficult to separate the effects of the proce- identify a risk of PC-AKI in patients with eGFR ≥ 30 dure from those of the CM, the CMSC decided, for opti- ml/min/1.73m , but there is conflicting evidence on mal safety, to choose a higher cut-off eGFR level for whether patients with severe renal impairment (eGFR preventive measures in patients undergoing catheter- <30 ml/min/1.73m ) are at increased risk of PC-AKI based diagnostic or interventional examinations using IA [63, 65]. Lack of information on hydration status was a CM administration with first-pass renal exposure, even limitation in these studies, but when hydration status was though some of the risk may relate to the procedure. added to an improved PS model, the findings were similar Also, the CMSC decided to include CA and/or PCI in this [66]. The failure to adjust for the various predictor vari- category because these examinations frequently combine ables in previous observational studies may explain the IA CM administration with both first- and second-pass renal exposure (Table 4). differences between them and the recent PS matching- Eur Radiol (2018) 28:2845–2855 2851 Table 4 Risk of PC-AKI Paediatric PC-AKI (a) Levels of eGFR at which there is a risk There are very few studies on paediatric PC-AKI [83–85]. As The risk of PC-AKI in patients with eGFR ≥ 30 ml/min/1.73m after the incidence of PC-AKI seems similar in children and ado- intravenous and intra-arterial CM administration with second-pass lescents to that in adults, the CMSC considers that for optimal renal exposure is very low, but there is conflicting evidence on the risk safety the recommendations for sCr determination and pre- for intra-arterial CM administration with first-pass renal exposure vention of PC-AKI, which are predominantly based on studies Level of Evidence: B in adults (aged 18+ years), should also be used for children Preventive measures are recommended for patients with eGFR < 30 and adolescents (Table 4). ml/min/1.73m before intravenous and intra-arterial CM administration with second-pass renal exposure Level of Evidence: C Preventive measures are recommended for patients with eGFR < 45 QUESTION 4: What are the patient- ml/min/1.73m if they are in ICU or if they will receive intra-arterial and procedure-related risk factors for developing CM administration with first-pass renal exposure PC-AKI and which patient populations have a higher Level of Evidence: C risk for developing PC-AKI? Recommendations for prevention of PC-AKI in adults may also be used in children and adolescents Patient-related risk factors Level of Evidence D Impaired renal function is the most important patient risk fac- (b) Risk factors tor for PC-AKI. Many meta-analyses and systematic reviews The principal risk factor for PC-AKI is impaired renal function. Most of uncontrolled studies have identified a wealth of possible other published patient-related risk factors are risk factors for the clinical risk factors for AKI in general such as old age, female presence of chronic kidney disease or AKI, and are not specific for gender, low BMI, classic cardiovascular and metabolic risk PC-AKI factors, malignancy, inflammation, bleeding, anaemia and Level of Evidence B hyperuricaemia [11, 12, 86–96]. However, uncontrolled stud- There is no difference in PC-AKI risk between IOCM and LOCM. The ies cannot reliably differentiate baseline clinical risk factors use of ionic, high-osmolar CM and repeated CM injections in a short period (48–72 h) should be avoided from effects attributable specifically to CM. In a meta-analysis Level of Evidence C of controlled studies, no additional risk factors specific for When CM are injected intravenously, there is insufficient evidence that CM were demonstrated [60](Table 4). The effect of two or CM dose is a risk factor. When CM are injected intra-arterially, the more risk factors is additive and increases the risk of PC-AKI. ratio of CM dose (in gram Iodine) / absolute eGFR (in ml/min) should be kept below 1.1 or the ratio of CM volume (in ml) / eGFR (in ml/min/1.73m ) should be kept below 3.0 when using a CM concentration of 350 mgl/ml Procedure-related risk factors: CM type and dose Level of Evidence C A variety of risk factors have been related to the type of CM and the way it is administered. Special populations Multiple meta-analyses have shown no evidence that iso- osmolar CM (IOCM) are associated with a significantly lower There is limited evidence about PC-AKI in several special rate of PC-AKI than non-ionic, low osmolar CM agents populations, such as patients with renal or renal and pancreatic (LOCM) [97–100]. However, the risk of PC-AKI is increased transplants, or critically ill patients. In renal transplant recipi- when ionic, high-osmolar CM are used [101]. Repeated CM ents, the incidence of PC-AKI in patients receiving either IVor administration within a short interval (48–72 h) has been IA CM was not higher than in patients without transplants, shown to increase the risk of PC-AKI [86](Table 4). and there was no graft loss or need for dialysis [75–77]. Evidence about the influence of CM dose (CM volume x Critically ill patients in ICU with multi-organ disease have a CM concentration) indicates dependence on the route of ad- greater risk profile for AKI than other inpatients, and AKI ministration. There is insufficient evidence that dose is a prob- incidence varies with subpopulation, study design and hydra- lem with IV CM. However, for direct IA CM administration in tion status [33, 78, 79]. Without properly controlled studies, it coronary angiographic intervention it is advisable to keep the is impossible to know the role of CM in causing the AKI. ratio of CM dose (in grams Iodine) to absolute eGFR (in ml/ Although earlier studies failed to show a role of CM [80, min; corrected for body surface area) below 1.1 [102, 103]or 81], a recent large PS-matched controlled study suggested an to keep the ratio of CM volume (in ml) to eGFR (in ml/min/ increased PC-AKI risk for ICU patients with eGFR < 45 ml/ 1.73m ) below 3.0 when using a CM concentration of 350 min/1.73m [82]. mgl/ml [104, 105](Table 4). 2852 Eur Radiol (2018) 28:2845–2855 (ESUR) et al (2011) Contrast induced nephropathy: updated Conclusion ESUR Contrast Media Safety Committee guidelines. Eur Radiol 21:2527–2541 PC-AKI has been adopted as the best term to apply to renal 2. Morcos SK, Thomsen HS, Webb JA, Contrast Media Safety function deterioration after intravascular CM administration Committee of the European Society of Urogenital Radiology (ESUR) et al (2002) Dialysis and contrast media. Eur Radiol 12: because, unlike some of the older terms, it does not imply that 3026–3030 CM is the cause. Stage 1 of the KDIGO classification of AKI 3. Contrast Media Safety Committee ESUR. Guidelines on Contrast is recommended as the change in renal function used to diag- Media v9. CMSC, 2014. Available via: http://www.esur-cm.org/ nose PC-AKI. The principal risk factor for PC-AKI is im- index.php/en/ Accessed: 14 December 2017 paired renal function, and the recommended ways to measure 4. Gruberg L, Mintz GS, Mehran R et al (2000) The prognostic implications of further renal function deterioration within 48 h of this are by the CKD-EPI equation in adults and the Schwartz interventional coronary procedures in patients with pre-existent equation in children. In recent years, it has become apparent chronic renal insufficiency. J Am Coll Cardiol 36:1542–1548 that the risk of true CI-AKI was overstated in the past. When 5. Gupta R, Gurm HS, Bhatt DL et al (2005) Renal failure after properly corrected for the many other possible causes of AKI percutaneous coronary intervention is associated with high mor- tality. Catheter Cardiovasc Interv 64:442–448 in patients with chronic kidney disease, the risk of CI-AKI 6. James MT, Samuel SM, Manning MA et al (2013) Contrast- when modern low osmolar CM are administered IV or IA is induced acute kidney injury and risk of adverse clinical outcomes low. Repeated CM administration within a 24- to 48-h period after coronary angiography a systematic review and meta-analy- increases the risk of CI-AKI. The evidence of a higher risk sis. Circ Cardiovasc Interv 6:37–43 with IA than with IV CM administration is limited, but the 7. Kooiman J, Seth M, Nallamothu BK et al (2015) Association between acute kidney injury and in-hospital mortality in patients CMSC nonetheless considers that the cut-off levels of eGFR undergoing percutaneous coronary interventions. Circ Cardiovasc used to indicate the need for prophylaxis before IA adminis- Interv 8:e002212 tration with first-pass renal exposure should be stricter, and 8. Mitchell AM, Kline JA, Jones AE et al (2015) Major adverse that there should be a maximum volume of CM given intra- events one year after acute kidney injury after contrast-enhanced arterially during any examination or procedure with first-pass computed tomography. Ann Emerg Med 66:267–274.e4 9. Rihal CS, Textor SC, Grill DE et al (2002) Incidence and prog- renal exposure. nostic importance of acute renal failure after percutaneous coro- The recommendations made in this paper have been incor- nary intervention. Circulation 105:2259–2264 porated into the ESUR CMSC guidelines (see Table 4,Part2). 10. Rudnick M, Feldman H (2008) Contrast-induced nephropathy: what are the true clinical consequences? Clin J Am Soc Nephrol Funding The authors state that this work has not received any funding. 3:263–272 11. Kooiman J, Pasha SM, Zondag W et al (2012) Meta-analysis: Compliance with ethical standards serum creatinine changes following contrast enhanced CT imag- ing. Eur J Radiol 81:2554–2561 12. Moos SI, van Vemde DN, Stoker J et al (2013) Contrast induced Guarantor The scientific guarantor of this publication is Prof. Henrik S. nephropathy in patients undergoing intravenous (IV) contrast en- Thomsen. hanced computed tomography (CECT) and the relationship with risk factors: a meta-analysis. Eur J Radiol 82:e387–e399 Conflict of interest Aart van der Molen has received incidental pay- 13. Solomon R (2008) Contrast-induced acute kidney injury: is there a ments for lectures and chairmanships at scientific meetings for contrast risk after intravenous contrast? Clin J Am Soc Nephrol 3:1242–1243 agent safety related issues (contrast agent reactions, Gd-retention) from 14. Dong M, Jiao Z, Liu T et al (2012) Effect of administration route GE, Bayer, Bracco and Guerbet on the renal safety of contrast agents: a meta-analysis of random- Fulvio Stacul has received lecture fees from Bracco and Guerbet ized controled trials. J Nephrol 25:290–301. https://www. Olivier Clément has received lecture fees from Bracco and Guerbet radiologen.nl/secties/nvvr/documenten/richtlijn-veilig-gebruik- The other authors of this manuscript declare no relationships with any vancontrastmiddelen-deel-1-full-english companies whose products and services may be related to the subject matter of this article. 15. Keeley EC (1998) Grines CL (1998) Scraping of aortic debris by coronary guiding catheters: a prospective evaluation of 1,000 cases. J Am Coll Cardiol 32:1861–1865 Open Access This article is distributed under the terms of the Creative 16. Wichmann JL, Katzberg RW, Litwin SE et al (2015) Contrast- Commons Attribution 4.0 International License (http:// induced nephropathy. Circulation 132:1931–1936 creativecommons.org/licenses/by/4.0/), which permits unrestricted use, 17. Newhouse JH, Kho D, Rao QA et al (2008) Frequency of serum distribution, and reproduction in any medium, provided you give appro- creatinine changes in the absence of iodinated contrast material: priate credit to the original author(s) and the source, provide a link to the implications for studies of contrast nephrotoxicity. AJR Am J Creative Commons license, and indicate if changes were made. Roentgenol 191:376–382 18. Bruce RJ, Djamali A, Shinki K et al (2009) Background fluctua- tion of kidney function versus contrast-induced nephrotoxicity. AJR American Journal of Roentgenology 192:711–718 References 19. Brouwers M, Kho ME, Browman GP, on behalf of the AGREE Next Steps Consortium et al (2010) AGREE II: Advancing guide- line development, reporting and evaluation in healthcare. Can 1. Stacul F, van der Molen AJ, Reimer P, Contrast Media Safety Med Assoc J 182:E839–E842 Committee of European Society of Urogenital Radiology Eur Radiol (2018) 28:2845–2855 2853 20. Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines: management and contrast-induced nephropathy. Nephrol Dial Transplant 27:4263–4272 2. Framing the question and deciding on important outcomes. J Clin Epidemiol 64:395–400 39. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D 21. OCEBM Levels of Evidence Working Group. The Oxford 2011 (1999) A more accurate method to estimate glomerular filtration Levels of Evidence. Oxford Centre for Evidence-Based Medicine. rate from serum creatinine: a new prediction equation. Available via: http://www.cebm.net/index.aspx?o=5653 Accessed Modification of Diet in Renal Disease Study Group. Ann Intern 14 December 2017 Med 130:461–470 22. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute 40. Levey AS, Coresh J, Greene T et al (2007) Expressing the MDRD Dialysis Quality Initiative workgroup (2004) Acute renal failure - study equation for estimating GFR with standardized serum cre- definition, outcome measures, animal models, fluid therapy and atinine values. Clin Chem 53:766–772 information technology needs: the Second International 41. Levey AS, Coresh J, Greene T, Chronic Kidney Disease Consensus Conference of the Acute Dialysis Quality Initiative Epidemiology Collaboration et al (2006) Using standardized se- (ADQI) Group. Crit Care 8:R204–R212 rum creatinine values in the modification of diet in renal disease 23. Levey AS, Eckardt KU, Tsukamoto Y et al (2005) Definition and study equation for estimating glomerular filtration rate. Ann classification of chronic kidney disease: a position statement from Intern Med 145:247–254. https://www.acr.org/-/media/ACR/ Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Files/Clinical-Resources/Contrast_Media.pdf Int 67:2089–2100 42. Levey AS, Stevens LA, Schmid CH, CKD-EPI (Chronic Kidney 24. Mehta RL, Kellum JA, Shah SVet al (2007) Acute Kidney Injury Disease Epidemiology Collaboration) et al (2009) A new equation Network. Acute Kidney Injury Network: report of an initiative to to estimate glomerular filtration rate. Ann Intern Med 150:604–612 improve outcomes in acute kidney injury. Crit Care 11:R31 43. Stevens LA, Li S, Kurella Tamura M et al (2011) Comparison of 25. ACR Committee on Drugs and Contrast Media. ACR Manual on the CKD Epidemiology Collaboration (CKD-EPI) and Contrast Media, v10.3. American College of Radiology, 2017 Modification of Diet in Renal Disease (MDRD) study equations: Available via: https://www.acr.org/-/media/ACR/Files/Clinical- risk factors for and complications of CKD and mortality in the Resources/Contrast_Media.pdf Accessed: 14 December 2017 Kidney Early Evaluation Program (KEEP). Am J Kidney Dis 26. KellumJA,LameireN(2013)Diagnosis,evaluation,andmanagement 57:S9–S16 of acute kidney injury: a KDIGO summary (Part 1). Crit Care 17:204 44. Björk J, Jones I, Nyman U, Sjostrom P (2012) Validation of the 27. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Lund-Malmo, Chronic Kidney Disease Epidemiology (CKD-EPI) Kidney Injury Work Group (2012) KDIGO Clinical Practice and Modification of Diet in Renal Disease (MDRD) equations to Guideline for Acute Kidney Injury. Kidney Int Suppl 2:1–138 estimate glomerular filtration rate in a large Swedish clinical pop- 28. Morcos SK, Thomsen HS, Webb JA (1999) Contrast-media- ulation. Scand J Urol Nephrol 46:212–222 induced nephrotoxicity: a consensus report. Contrast Media 45. Schäffner ES, Ebert N, Delanaye P et al (2012) Two novel equa- Safety Committee, European Society of Urogenital Radiology tions to estimate kidney function in persons aged 70 years or older. (ESUR). Eur Radiol 9:1602–1613 Ann Intern Med 157:471–481 29. Pyxaras SA, Zhang Y, Wolf A, Schmitz T, Naber CK (2015) Effect of 46. Pottel H, Hoste L, Dubourg L et al (2016) An estimated glomer- varying definitions of contrast-induced acute kidney injury and left ular filtration rate equation for the full age spectrum. Nephrol Dial ventricular ejection fraction on one-year mortality in patients having Transplant 31:798–806 transcatheter aortic valve implantation. Am J Cardiol 116:426–430 47. Florkowski CM, Chew-Harris JSC (2011) Methods of Estimating 30. Slocum NK, Grossman PM, Moscucci M et al (2012) The chang- GFR – Different Equations Including CKD-EPI. Clin Biochem ing definition of contrast-induced nephropathy and its clinical im- Rev 32:75–79 plications: insights from the Blue Cross Blue Shield of Michigan 48. Delanaye P, Ebert N (2012) Assessment of kidney function: esti- Cardiovascular Consortium (BMC2). Am Heart J 163:829–834 mating GFR in children. Nat Rev Nephrol 8:503–504 31. Weisbord SD,MorMK,ResnickAL,HartwigKC,PalevskyPM,Fine 49. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A MJ(2008)Incidenceandoutcomesof contrast-inducedAKI following simple estimate of glomerular filtration rate in children derived computed tomography. Clin J Am Soc Nephrol 3:1274–1281 from body length and plasma creatinine. Pediatrics 58:259–263 32. Budano C, Levis M, D'Amico M et al (2011) Impact of contrast- 50. Schwartz GJ, Munoz A, Schneider MF et al (2009) New equations to induced acute kidney injury definition on clinical outcomes. Am estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637 Heart J 161:963–971 51. Schwartz GJ, Schneider MF, Maier PS et al (2012) Improved 33. Azzouz M, Rømsing J, Thomsen HS (2014) Fluctuations in eGFR equations estimating GFR in children with chronic kidney disease in relation to unenhanced and enhanced MRI and CT outpatients. using an immunonephelometric determination of cystatin C. Eur J Radiol 83:886–892 Kidney Int 82:445–453 34. Thomsen HS, Morcos SK (2009) Risk of iodinated contrast 52. Martinez Lomakin F, Tobar C (2014) Accuracy of point-of-care serum material-induced nephropathy with intravenous administration. creatinine devices for detecting patients at risk of contrast-induced ne- Eur Radiol 19:891–897 phropathy: a critical overview. Crit Rev Clin Lab Sci 51:332–343 35. Lakhal K, Ehrmann S, Chaari A et al (2011) Acute Kidney Injury 53. Rao QA, Newhouse JH (2006) Risk of nephropathy after intrave- Network definition of contrast-induced nephropathy in the criti- nous administration of contrast material: a critical literature anal- cally ill: incidence and outcome. J Crit Care 26:593–599 ysis. Radiology 239:392–397 36. Garfinkle MA, Stewart S, Basi R (2015) Incidence of CT contrast 54. Katzberg RW, Newhouse JH (2010) Intravenous contrast agent-induced nephropathy: toward a more accurate estimation. medium-induced nephrotoxicity: is the medical risk really as great AJR Am J Roentgenol 204:1146–1151 as we have come to believe? Radiology 256:21–28 37. Thomas ME, Blaine C, Dawnay A et al (2015) The defi- nition of acute kidney injury and its use in practice. Kidney 55. Stratta P, Bozzola C, Quaglia M (2012) Pitfall in nephrology: Int 87:62–73 contrast nephropathy has to be differentiated from renal damage 38. Fliser D, Laville M, Covic A et al (2012) A European Renal Best due to atheroembolic disease. J Nephrol 25:282–289 Practice (ERBP) position statement on the Kidney Disease 56. McDonald RJ, McDonald JS, Newhouse JH, Davenport MS Improving Global Outcomes (KDIGO) clinical practice guidelines (2015) Controversies in contrast material-induced acute kidney on acute kidney injury: part 1: definitions, conservative injury: closing in on the truth? Radiology 277:627–632 2854 Eur Radiol (2018) 28:2845–2855 57. Nyman U, Aspelin P, Jakobsen J, Bjork J (2015) Controversies in 75. Haider M, Yessayan L, Venkat KK, Goggins M, Patel A, Karthikeyan V (2015) Incidence of contrast-induced nephropathy contrast material-induced acute kidney injury: Propensity Score matching of patients with different dose/absolute glomerular fil- in kidney transplant recipients. Transplant Proc 47:379–383 tration rate ratios. Radiology 277:633–637 76. Fananapazir G, Troppmann C, Corwin MT, Bent CK, Vu CT, 58. Ricos C, Iglesias N, Garcia-Lario JV et al (2007) Within-subject Lamba R (2016) Incidence of contrast-induced nephropathy after biological variation in disease: collated data and clinical conse- renal graft catheter arteriography using iodine-based contrast me- quences. Ann Clin Biochem 44:343–352 dium. AJR Am J Roentgenol 206:783–786 59. Wilhelm-Leen E, Montez-Rath ME, Chertow G (2017) Estimating 77. Fananapazir G, Troppmann C, Corwin MT, Nikpour AM, Naderi the risk of radiocontrast-associated nephropathy. J Am Soc , Lamba R (2016) Incidences of acute kidney injury, dialysis, and Nephrol 28:653–659 graft loss following intravenous administration of low-osmolality 60. McDonaldJS,McDonaldRJ,CominJetal(2013)Frequencyofacute iodinated contrast in patients with kidney transplants. Abdom kidney injuryfollowing intravenous contrastmediumadministration: Radiol 41:2182–2186 a systematic review and meta-analysis. Radiology 267:119–128 78. Haveman JW, Gansevoort RT, Bongaerts AH, Nijsten MW (2006) 61. SchünemannHJ,TugwellP,ReevesBCetal(2013)Non-randomized Low incidence of nephropathy in surgical ICU patients receiving studies as a source of complementary, sequential or replacement ev- intravenous contrast: a retrospective analysis. Intensive Care Med idence for randomized controlled trials in systematic reviews on the 32:1199–1205 effects of interventions. Res Synth Methods 4:49–62 79. Hoste EA, Doom S, De Waele J et al (2011) Epidemiology of 62. DavenportMS,KhalatbariS,DillmanJR,CohanRH,CaoiliEM,Ellis contrast-associated acute kidney injury in ICU patients: a retro- JH (2013) Contrast material-induced nephrotoxicity and intravenous spective cohort analysis. Intensive Care Med 37:1921–1931 low-osmolality iodinated contrast material. Radiology 267:94–105 80. Cely CM, Schein RM, Quartin AA (2012) Risk of contrast in- 63. DavenportMS,KhalatbariS,CohanRH,DillmanJR,MylesJD,Ellis duced nephropathy in the critically ill: a prospective, case matched JH (2013) Contrast material-induced nephrotoxicity and intravenous study. Crit Care 16:R67 low-osmolalityiodinatedcontrastmaterial:riskstratificationbyusing 81. Ehrmann S, Badin J, Savath L et al (2013) Acute kidney injury in estimated glomerular filtration rate. Radiology 268:719–728 the critically ill: is iodinated contrast medium really harmful? Crit 64. McDonald RJ, McDonald JS, Bida JP et al (2013) Intravenous Care Med 41:1017–1026 contrast material-induced nephropathy: causal or coincident phe- 82. McDonald JS, McDonald RJ, Williamson EE, Kallmes DF, nomenon? Radiology 267:106–118 Kashani K (2017) Post-contrast acute kidney injury in intensive 65. McDonald JS, McDonald RJ, Carter RE, Katzberg RW, Kallmes care unit patients: a propensity score-adjusted study. Intensive DF, Williamson EE (2014) Risk of intravenous contrast material- Care Med 43:774–784 mediated acute kidney injury: a propensity score-matched study 83. Senthilnathan S, Gauvreau K, Marshall AC, Lock JE, Bergersen L stratified by baseline-estimated glomerular filtration rate. (2009) Contrast administration in pediatric cardiac catheterization: Radiology 271:65–73 dose and adverse events. Catheter Cardiovasc Interv 73:814–820 66. McDonald JS, McDonald RJ, Lieske JC et al (2015) Risk of acute 84. Huggins N, Nugent A, Modem V et al (2014) Incidence of acute kidney injury, dialysis, and mortality in patients with chronic kid- kidney injury following cardiac catheterization prior to cardiopulmo- ney disease after intravenous contrast material exposure. Mayo nary bypass in children. Catheter Cardiovasc Interv 84:615–619 Clin Proc 90:1046–1053 85. Cantais A, Hammouda Z, Mory O et al (2016) Incidence of 67. Karlsberg RP, Dohad SY, Sheng R (2011) Iodixanol peripheral contrast-induced acute kidney injury in a pediatric setting: a cohort computed tomographic angiography study investigator panel. study. Pediatr Nephrol 31:1355–1362 Contrast medium acute kidney injury: comparison of intravenous 86. Balemans CE, Reichert LJ, van Schelven BI, van den Brand JA, and intra-arterial administration of iodinated contrast medium. J Wetzels JF (2012) Epidemiology of contrast material-induced ne- Vasc Intervent Radiol 22:1159–1165 phropathy in the era of hydration. Radiology 263:706–713 68. Kooiman J, Le Haen PA, Gezgin G et al (2013) Contrast-induced 87. Kanbay M, Solak Y, Afsar B et al (2017) Serum uric acid and risk for acute kidney injury and clinical outcomes after intra-arterial and acute kidney injury following contrast: an evaluation of epidemiolo- intravenous contrast administration: risk comparison adjusted for gy, clinical trials, and potential mechanisms. Angiology 68:132–144 patient characteristics by design. Am Heart J 165:793–799 88. Kiski D, Stepper W, Breithardt G, Reinecke H (2010) Impact of 69. McDonald JS, Leake CB, McDonald RJ et al (2016) Acute kidney female gender on frequency of contrast medium-induced nephrop- injury after intravenous versus intra-arterial contrast material ad- athy: post hoc analysis of dialysis versus diuresis trial. J Womens ministration in a paired cohort. Invest Radiol 51:804–809 Health 19:1363–1368 70. Tong GE, Kumar S, Chong KC et al (2016) Risk of contrast- 89. Kwasa EA, Vinayak S, Armstrong R (2014) The role of inflam- induced nephropathy for patients receiving intravenous vs. intra- mation in contrast-induced nephropathy. Br J Radiol 87:20130738 arterial iodixanol administration. Abdom Radiol 41:91–99 90. Medalion B, Cohen H, Assali A et al (2010) The effect of cardiac 71. From AM, Bartholmai BJ, Williams AW, Cha SS, McDonald FS angiography timing, contrast media dose, and preoperative renal (2008) Mortality associated with nephropathy after radiographic function on acute renal failure after coronary artery bypass contrast exposure. Mayo Clin Proc 83:1095–1100 grafting. J Thorac Cardiovasc Surg 139:1539–1544 72. Nyman U, Almén T, Jacobsson B, Aspelin P (2012) Are intrave- 91. Ohno Y, Maekawa Y, Miyata H et al (2013) Impact of nous injections of contrast media really less nephrotoxic than periprocedural bleeding on incidence of contrast-induced acute intra-arterial injections? Eur Radiol 22:1366–1371 kidney injury in patients treated with percutaneous coronary in- 73. Prasad A, Ortiz-Lopez C, Khan A, Levin D, Kaye DM (2016) tervention. J Am Coll Cardiol 62:1260–1266 Acute kidney injury following peripheral angiography and 92. Pannu N, Wiebe N, Tonelli M (2006) Prophylaxis strategies for endovascular therapy: a systematic review of the literature. contrast-induced nephropathy. JAMA 295:2765–2779 Catheter Cardiovasc Interv 88:264–273 74. Aubry P, Brillet G, Catella L, Schmidt A, Bénard S (2016) 93. Song W, Zhang T, Pu J, Shen L, He B (2014) Incidence and risk of Outcomes, risk factors and health burden of contrast-induced developing contrast-induced acute kidney injury following intravascu- acute kidney injury: an observational study of one million hospi- larcontrastadministrationinelderlypatients.ClinIntervAging9:85–93 talizations with image-guided cardiovascular procedures. BMC 94. Toprak O, Cirit M (2006) Risk factors for contrast-induced ne- Nephrol 17:167 phropathy. Kidney Blood Press Res 29:84–93 Eur Radiol (2018) 28:2845–2855 2855 95. Yang JQ, Ran P, Chen JY et al (2014) Development of contrast- nephropathy: a systematic review and meta-analysis. Ann Intern Med 164:417–424 induced acute kidney injury after elective contrast media exposure in patients with type 2 diabetes mellitus: effect of albuminuria. 101. Barrett BJ, Carlisle EJ (1993) Meta-analysis of the relative neph- PLoS One 9:e106454 rotoxicity of high- and low-osmolality iodinated contrast media. 96. Zuo T, Jiang L, Mao S, Liu X, Yin X, Guo L (2016) Radiology 188:171–178 Hyperuricemia and contrast-induced acute kidney injury: A sys- 102. Gurm HS, Dixon SR, Smith DE, BMC2 (Blue Cross Blue Shield tematic review and meta-analysis. Int J Cardiol 224:286–294 of Michigan Cardiovascular Consortium) Registry et al (2011) 97. McDonald JS, McDonald RJ, Williamson EE, Kallmes DF (2017) Is Renal function-based contrast dosing to define safe limits of ra- intravenous administration of iodixanol associated with increased risk diographic contrast media in patients undergoing percutaneous of acute kidney injury, dialysis, or mortality? a Propensity Score- coronary interventions. J Am Coll Cardiol 58:907–914 adjusted study. Radiology. 285: 414-424 103. Kooiman J, Seth M, Share D, Dixon S, Gurm HS (2014) The associ- 98. Heinrich MC, Häberle L, Müller V, Bautz W, Uder M (2009) ation between contrast dose and renal complications post-PCI across Nephrotoxicity of iso-osmolar iodixanol compared with nonionic the continuum of procedural estimated risk. PLoS One 9:e90233 low-osmolar contrast media: meta-analysis of randomized con- 104. Nyman U, Björk J, Aspelin P, Marenzi G (2008) Contrast medium trolled trials. Radiology 250:68–86 dose-to-GFR ratio: a measure of systemic exposure to predict 99. From AM, Al Badarin FJ, McDonald FS, Bartholmai BJ, Cha SS, contrast-induced nephropathy after percutaneous coronary inter- Rihal CS (2010) Iodixanol versus low-osmolar contrast media for vention. Acta Radiol 49:658–667 prevention of contrast induced nephropathy: meta-analysis of ran- 105. Nyman U (2016) Contrast dose, estimated GFR and techniques to domized, controlled trials. Circ Cardiovasc Interv 3:351–358 reduce contrast dose in PCI – time to consider some basic princi- 100. Eng J, Wilson RF, Subramaniam RM et al (2016) Comparative ples! J Invas Cardiol 28:E126–E127 effect of contrast media type on the incidence of contrast-induced Affiliations 1 2 1 3 4 Aart J. van der Molen & Peter Reimer & Ilona A. Dekkers & Georg Bongartz & Marie-France Bellin & 5 6 7 8 9 Michele Bertolotto & Olivier Clement & Gertraud Heinz-Peer & Fulvio Stacul & Judith A. W. Webb & Henrik S. Thomsen 1 6 Department of Radiology, C2-S, Leiden University Medical Center, Department of Radiology, Assistance Publique-Hôpitaux de Paris, Albinusdreef 2, NL-2333 ZA Leiden, The Netherlands Hôpital Européen Georges Pompidou, 20, rue Leblanc, Paris Cedex 15, F-71015 Paris, France Institute for Diagnostic and Interventional Radiology, Klinikum Karlsruhe, Academic Teaching Hospital of the University of Department of Radiology, Zentralinstitut für medizinische Freiburg, Moltkestraße 90, D-76133 Karlsruhe, Germany Radiologie, Diagnostik und Intervention, Landesklinikum St. Pölten, Propst Führer-Straße 4, AT-3100 St. Pölten, Austria Department of Diagnostic Radiology, University Hospitals of Basel, Petersgaben 4, CH-4033 Basel, Switzerland S.C. Radiologia Ospedale Maggiore, Piazza Ospitale 1 I-34129 Trieste, Italy Service Central de Radiologie Hôpital Paul Brousse 14, av. P.-V.- Couturier, F-94807 Villejuif, France Department of Radiology, St. Bartholomew’s Hospital, University of London, West Smithfield, London EC1A 7BE, UK Department of Radiology, University of Trieste, Strada di Fiume 447, I-34149 Trieste, Italy Department of Diagnostic Radiology 54E2, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark

Journal

European RadiologySpringer Journals

Published: Feb 9, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off