Objectives 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 2 Topics reviewed include stratification of PC-AKI risk, the need to withdraw nephrotoxic medication, PC- AKI prophylaxis with hydration or drugs, the use of metformin in diabetic patients receiving contrast medium and the need to alter dialysis schedules in patients receiving contrast medium. Key points � In CKD, hydration reduces the PC-AKI risk � Intravenous normal saline and intravenous sodium bicarbonate provide equally effective prophylaxis � No drugs have been consistently shown to reduce the risk of PC-AKI � Stop metformin from the time of contrast medium administration if eGFR < 30 ml/min/1.73 m � Dialysis schedules need not change when intravascular contrast medium is given . . . . Keywords Contrast media Acute kidney injury Metformin Haemodialysis Practice guidelines AGREE Appraisal of Guidelines for Research and Abbreviations and acronyms Evaluation ACEI Angiotensin Converting Enzyme Inhibitor AHRQ Agency for Healthcare Research and Quality ACR American College of Radiology * Henrik S. Thomsen Department of Radiology, Assistance Publique-Hôpitaux de Paris, Henrik.Thomsen@regionh.dk Hôpital Européen Georges Pompidou, 20 rue Leblanc, Paris Cedex 15, F-71015 Paris, France Department of Radiology, C2-S, Leiden University Medical Center, Department of Radiology, Zentralinstitut für medizinische Albinusdreef 2, NL-2333 ZA Leiden, The Netherlands Radiologie, Diagnostik und Intervention, Landesklinikum St. Pölten, Institute for Diagnostic and Interventional Radiology Klinikum Propst Führer-Straße 4, AT-3100 St. Pölten, Austria Karlsruhe, Moltkestraße 90, D-76133 Karlsruhe, Germany S.C. Radiologia Ospedale Maggiore, Piazza Ospitale 1, Department of Diagnostic Radiology, University Hospitals of Basel, I-34129 Trieste, Italy Petersgaben 4, CH-4033 Basel, Switzerland 4 Department of Radiology, St. Bartholomew’s Hospital, University of Service Central de Radiologie Hôpital Paul Brousse 14, av. London, West Smithfield, EC1A 7BE, London, UK P.-V.-Couturier, F-94807 Villejuif, France 5 10 Department of Radiology, University of Trieste, Strada di Fiume 447, Department of Diagnostic Radiology 54E2, Copenhagen University I-34149 Trieste, Italy Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark Eur Radiol (2018) 28:2856–2869 2857 AKI Acute Kidney Injury acute kidney injury is not associated with gadolinium- ARB Angiotensin-II Receptor Blocker based contrast agents in doses approved for clinical mag- CA Coronary Angiography netic resonance imaging. CI-AKI Contrast-Induced Acute Kidney Injury In this second paper on PC-AKI, the following topics re- CIN Contrast-Induced Nephropathy lated to patient management are considered: CKD Chronic Kidney Disease CM Contrast Media 1. The role of questionnaires and risk scores to identify at- CMSC Contrast Media Safety Committee risk patients with reduced renal function CT Computed Tomography 2. The need to stop nephrotoxic medication before giving CTPA Computed Tomography Pulmonary Angiography D5W Dextrose 5% in Water CM eGFR Estimated Glomerular Filtration Rate 3. The optimal hydration protocols for protecting against ESUR European Society of Urogenital Radiology PC-AKI FDA Federal Drugs Administration 4. The possible role of prophylactic drug treatment in GFR Glomerular Filtration Rate preventing PC-AKI HD Haemodialysis 5. The need to adapt metformin administration when giving HF Haemofiltration CM IA Intra-Arterial 6. The need to alter schedules for dialysis in the period be- IV Intravenous fore and after CM administration NAc N-Acetylcysteine NaHCO Sodium Bicarbonate Recommendations are made for items 1–6. The recommen- NSAID Non-Steroidal Anti-Inflammatory Drug dations have been incorporated into version 10 of the ESUR NYHA New York Heart Association OCEBM Oxford Centre for Evidence Based Medicine CMSC guidelines, at the end of this paper (Table 4). PC-AKI Post-Contrast Acute Kidney Injury PCI Percutaneous Coronary Intervention PICO Patient–Intervention–Comparator–Outcome PS Propensity Score Materials and methods RAAS Renin–Angiotensin–Aldosterone System RSTN Radiological Society of the Netherlands The recommendations were prepared using the Appraisal RCT Randomised Controlled Trial of Guidelines for Research and Evaluation (AGREE) II RRT Renal Replacement Therapy document . A guideline Writing Group (WG) prepared sCr Serum Creatinine ten clinical questions in PICO format . Systematic WG Writing Group search strings were developed with a professional librari- an for four different biomedical literature databases (PubMed, Web of Science, Embase and the Cochrane Introduction Library). The titles and abstracts were screened for rele- vance and selected on predefined inclusion and exclusion The Contrast Media Safety Committee (CMSC) of the criteria. Emphasis was put on comparative studies with European Society of Urogenital Radiology (ESUR) pro- strong scientific evidence, such as meta-analyses and sys- duced their most recent guidelines on what was then tematic reviews, and prospective randomised controlled termed contrast-induced nephropathy (CIN) in 2011 . trials (RCTs). The six systematic searches in this manu- Guidelines on the use of contrast media (CM) in patients script yielded 3402 references of which 445 were selected on dialysis and on the use of CM in diabetic patients on the basis of title and abstract. After review of the full using metformin were published in 2002 and 2014 [2, text of these 445 publications, 145 were selected for in- 3]. This review provides recommendations for updating clusion in this paper. The quality of the evidence from the the CMSC guidelines which were obtained using a struc- selected articles was evaluated according to the Oxford tured literature review based on clinical questions and Centre for Evidence Based Medicine levels of evidence: Patient–Intervention–Comparator–Outcome (PICO) for- grade A, established scientific evidence; grade B, scien- matting. Since the literature related to the topics consid- tific presumption; grade C, low level of evidence . ered is so large, the results of the review have been split When there was no scientific evidence, recommendations into two papers. The review only considers post-contrast werebasedonWGconsensus andweregradedasexpert kidney injury (PC-AKI) after iodine-based CM because opinion (grade D). 2858 Eur Radiol (2018) 28:2856–2869 Table 1 PC-AKI: Risk stratification; use of nephrotoxic medication The full description of the materials and methods appears in part 1. Risk stratification The term intra-arterial injection with first pass renal In hospitals which use sCr measurements for all patients before exposure indicates that contrast medium reaches the kid- intravascular CM administration there is no benefit in using questionnaires for PC-AKI risk stratification. neys in a relatively undiluted form, e.g. injection into the left heart, thoracic and suprarenal abdominal aorta or the In hospitals which use sCr measurements selectively, Choyke questionnaires may be used to identify patients with eGFR < 45 renal arteries. The term intra-arterial injection with second ml/min/1.73 m before intra-arterial CM administration with first pass pass renal exposure indicates that contrast medium renal exposure. reaches the renal arteries after dilution either in the pul- Level of evidence D monary or peripheral circulation, e.g. injection into the Risk prediction scores are only available for coronary angiography and/or right heart, pulmonary artery, carotid, subclavian, coro- percutaneous coronary intervention, and have only modest abilities, so nary, mesenteric or infrarenal arteries. cannot be recommended to stratify the risk of PC-AKI. Level of evidence A Nephrotoxic medication Results In CKD patients receiving CM, optimal nephrologic care involves minimising the use of nephrotoxic drugs. Level of evidence D Question 5: Should questionnaires or scoring systems ACE inhibitors and angiotensin receptor blockers do not have to be be used for risk stratification by clinicians when they stopped before CM administration. request a contrast-enhanced imaging study? Level of evidence B There is insufficient evidence to recommend withholding nephrotoxic Patient questionnaires drugs such as NSAIDs, antimicrobial agents or chemotherapeutic agents before CM administration. Questionnaires, such as that proposed by Choyke , use Level of evidence C information about a history of renal disease or renal sur- gery, heart failure, diabetes, proteinuria, hypertension and gout to stratify patients for their PC-AKI risk so that sCr clinical outcome. In clinical practice, a prediction rule measurements need only be done selectively. This may would require a high discriminatory value, i.e. a C- work well and can save resources . Observational stud- statistic greater than 0.80 . ies have shown that these questionnaires can identify pa- The best-known risk model is the eight-variable Mehran tients with eGFR < 45 ml/min/1.73 m with adequate score , which has been studied in more than 15,000 pa- sensitivity, especially if they are aged less than 70 tients and has been externally validated in multiple studies, but [9–11]. Since eGFR measurement can detect more pa- with variable C-statistic values of 0.57–0.85 [16, 18–20]. The tients with renal dysfunction than questionnaires , Mehran score correlates relatively well with clinical outcomes with easier patient logistics and similar cost- . Newer risk scores with good discriminatory value, avail- effectiveness [13, 14], many hospitals have adopted a pol- able in user-friendly calculators or smartphone applications, icy of sCr measurements in all patients scheduled for in- still need external validation . A recent systematic review travenous (IV) CM and no longer use questionnaires for of 16 risk models concluded that they had only modest pre- risk stratification or selection for eGFR measurement dictive value  and a review and meta-analysis of 74 risk (Table 1). models noted their heterogeneity and concluded that further research was needed to evaluate the effect of such models on Risk prediction models clinical care (Table 1). No risk models have been produced yet for IV or IA CM administration with second pass renal exposure. For pa- Question 6: Should nephrotoxic medication be tients having coronary angiography (CA) or percutaneous withheld to reduce the risk of PC-AKI? coronary intervention (PCI), many different risk scores have been proposed to stratify the patient’s PC-AKI risk, Optimal nephrologic care involves minimizing the use of and most include pre-procedural and procedural data. A nephrotoxic drugs where clinically possible . Many fre- model with only pre-procedural data  would be more quently prescribed medications, such as nonselective practical for selecting suitable preventive measures. Risk NSAIDs, selective Cox-2 inhibitors, several classes of scores should be verified in relation to improvements in Eur Radiol (2018) 28:2856–2869 2859 Table 2 PC-AKI prophylaxis: Hydration, drugs, renal replacement therapy antimicrobial agents and chemotherapeutic agents have neph- rotoxic potential and can induce AKI . Hydration There is little good quality data about the relationship Preventive hydration should be used to reduce the incidence of PC-AKI between these drugs and PC-AKI . A retrospective in at-risk patients. cohort study showed that concurrent use of four or more Level of evidence B nephrotoxic agents was significantly predictive for PC- Intravenous saline and bicarbonate protocols have similar efficacy for hydration. AKI in patients given IV CM . A meta-analysis of PC-AKI incidence following CM-enhanced CT found that Level of evidence A concurrent administration of NSAIDs was an independent For intravenous and intra-arterial CM administration with second pass renal exposure hydrate the patient with either (a) 3 ml/kg/h bicarbonate risk factor for PC-AKI . 1.4% (or 154 mmol/l solution) for 1 h before CM or (b) 1 ml/kg/h The effect of withholding angiotensin converting en- saline 0.9% for 3–4hbeforeand 4–6hafter CM. zyme inhibitors (ACEI) and angiotensin-2 receptor Level of evidence D blockers (ARB) in chronic users has been extensively For intra-arterial CM administration with first pass renal exposure hydrate evaluated. Multiple RCTs [30, 31] and observational stud- the patient with either (a) 3 ml/kg/h bicarbonate 1.4% (or 154 mmol/l ies gave conflicting results and are limited by small sam- solution) for 1 h before CM followed by 1 ml/kg/h bicarbonate 1.4% (or 154 mmol/l) for 4–6h afterCM ple sizes and significant heterogeneity [32–34]. However, meta-analyses of RCTs found no lower risk . or (b) 1 ml/kg/h saline 0.9% for 3–4 h before and 4–6h afterCM. Withholding ACEI/ARB may be associated with a slight- Level of evidence D ly lowerriskofPC-AKIbut theevidenceisnot sufficient- Oral hydration as the sole means of prevention is not recommended. ly strong to recommend this (Table 1). Level of evidence D In patients with severe heart failure (NYHA grade 3–4) or patients with Question 7: What are the most cost- end-stage renal failure (CKD grade V) preventive IV hydration should be individualized by the clinician responsible for patient care. and time-effective protocols for oral and intravenous Level of evidence D hydration to reduce the risk of PC-AKI? Drugs N-Acetylcysteine has not been conclusively shown to reduce the risk of Hydration as a preventive strategy for PC-AKI PC-AKI in patients with eGFR < 45 ml/min/1.73 m receiving intravenous or intra-arterial CM, and its use is NOT recommended. Evidence for prevention of PC-AKI with IV saline hydration Level of evidence A (volume expansion) comes from RCTs in patients who re- Giving short-term, high-dose statins to patients not already taking statins ceived intra-arterial (IA) CM during percutaneous interven- has not been shown to reduce the risk of PC-AKI in patients with eGFR tion [35–37], and in patients who received bicarbonate hydra- < 45 ml/min/1.73 m receiving intravenous or intra-arterial CM, and its use is NOT recommended. tion before IV enhanced emergency CTPA . One RCT Level of evidence B evaluated the evidence for IA CM administration during CA ACE inhibitors or angiotensin receptor blockers have not been shown . These studies found that, for both IA and IV CM admin- conclusively to reduce the risk of PC-AKI in patients receiving istration, the incidence of PC-AKI was significantly lower in intravenous or intra-arterial CM, and their use is NOT recommended. patients who received IV hydration compared to placebo, and Level of evidence B that hydration prevented emergency dialysis . Significant Vitamin C has not been shown conclusively to reduce the risk of PC-AKI differences for mortality or other adverse events were not in patients receiving intravenous or intra-arterial CM, and its use is found. There were few patients with severe renal impairment NOT recommended. (eGFR < 30 ml/min/1.73 m ) in almost all studies. The recent Level of evidence B AMACING trial showed that for patients with eGFR > 30 ml/ Renal replacement therapy min/1.73 m receiving IV CM there was no difference be- Renal replacement therapy has not been shown conclusively to reduce the tween no hydration and hydration in preventing PC-AKI . risk of PC-AKI in patients receiving intravenous or intra-arterial CM, and its use is NOT recommended. Level of evidence B Oral hydration versus intravenous saline hydration Oral intake of clear fluids by patients as an alternative to IV saline to prevent PC-AKI is difficult to monitor or compared to IV hydration, but the studies were limited control. Nine studies evaluated oral hydration, but were by heterogeneity and lack of hard clinical outcomes limited by small patient numbers and by the absence of [49–51]. The CMSC does not recommend the use of oral patients with severe renal impairment [39, 41–48]. Three hydration as the sole preventive strategy for PC-AKI, but meta-analyses concluded that there is no evidence that unrestricted intake of clear oral fluids in addition to IV oral hydration is associated with more risk of PC-AKI volume expansion is supported (Table 2). 2860 Eur Radiol (2018) 28:2856–2869 Intravenous hydration: saline versus bicarbonate In which patients should the hydration protocol be individualized? Normal saline (NaCl 0.9%) and sodium bicarbonate solution (1.4% or 154 mmol NaHCO in D5W) are the two most com- There is no data to suggest that patients with severe renal monly studied crystalloid solutions. The rationale for using impairment (CKD grade V) or severe heart failure (NYHA bicarbonate is that alkalinisation can reduce the formation of grade 3–4) should receive different hydration protocols. free reactive oxygen species . Initial studies favoured bi- However, IV hydration with large volumes may exacerbate carbonate [53–56], but this was not replicated in later studies acute heart failure and induce pulmonary oedema . The [57–62], so IV hydration with bicarbonate can be considered opinion of the CMSC is that hydration protocols in these equivalent to normal saline. patients should be individualized for type, volume and There is no consensus on the optimal hydration re- duration. gime. Most studies have compared bicarbonate given pre- and post-CM for less than 6 h  to longer dura- Question 8: Which other strategies (pharmaceutical, tion saline pre- and post-CM protocols (12–24 h). In all vitamin, renal replacement therapy) have been studies, there are few patients with eGFR < 30 ml/min/ proved effective in preventing PC-AKI? 1.73 m , and evidence about whether short duration bi- carbonate is better than long duration saline is conflicting N-Acetylcysteine (NAc) [63–71]. There is limited evidence on whether pre- hydration only is inferior to pre- and post-hydration, Most recent RCTs or meta-analyses do not show a protective and only one very short duration bicarbonate protocol effect of NAc against PC-AKI following coronary or periph- has been evaluated [38, 72, 73]. eral angiography [66, 80–84]. NAc also failed to affect clinical Most studies have been performed in cardiac patients ad- outcome in coronary or peripheral angiography orto have mitted for CA or PCI. Three studies evaluated hydration pro- aprotective effect in CT [86, 87] or in patients with diabetes tocols in patients having contrast-enhanced CT, and did not mellitus undergoing coronary or peripheral angiography [88, favour bicarbonate over saline [38, 72, 74]. No studies were 89]. Comparative studies with NAc combined with saline or identified assessing the beneficial effect of other crystalloids. sodium bicarbonate protocols did not show any additional However, balanced crystalloid solutions, such as Ringer’slac- effect of protective effect of NAc [61, 90–93]. However, more tate, may be preferable in critical care populations, because recent meta-analyses showed a benefit of NAc, with or with- they avoid the harmful effects of hyperchloraemic acidosis. out high-dose statins, when added to hydration for preventing The CMSC considers that for IV and IA CM injection PC-AKI [94–96]. with second pass renal exposure either a short bicarbonate hydration regime before CM or a conventional protocol with Statins saline given before and after CM may be used. For IA CM injection with first pass renal exposure conventional proto- Several meta-analyses showed lower overall PC-AKI rates cols with either bicarbonate or saline given before and after with the use of high-dose, short-term statin treatment CM should be used (Table 2). compared to controls [95–105]. Lower PC-AKI rates were also found in subgroups, such as older patients, patients with acute coronary syndromes and for high-dose statin Forced diuresis versus conventional hydration regimes. Some of these meta-analyses showed a reduced need for RRT after statins, but no reduction in all-cause Newer approaches for patients with impaired left ventricular mortality [97, 102]. However, the US Agency for function combine controlled saline hydration with a forced Healthcare Research and Quality (AHRQ) meta-analysis high urinary flow rate to maintain euvolemia and avoid showed that the risk of PC-AKI was only significantly overhydration and several RCTs showed better results than reduced when statins were added to hydration and NAc. conventional hydration protocols [75–77]. Other catheter- A reduction in PC-AKI risk could not be shown when based strategies used left ventricular end-diastolic pressure statins plus hydration were compared to hydration alone or central venous pressure to guide hydration [78, 79]. In in patients not taking statins. The standard of evidence these RCTs the incidence of PC-AKI was lower than with grade was low in both analyses . standard IV hydration. Since the forced diuresis studies have Despite the many positive results, it is difficult to make a heterogeneous populations, interventions and control hydra- general recommendation for statins  because the patients tion protocols, their findings cannot be pooled. The CMSC studied were invariably cardiac, and a variety of statin and considers that there is not sufficient evidence to recommend hydration protocols were used. Patients with CKD grade forced diuresis. 3B–5 (eGFR < 45 ml/min/1.73 m ) are under-represented in Eur Radiol (2018) 28:2856–2869 2861 the studies and results in these patients remain inconclusive Question 9: Should administration of metformin be [102, 103, 107, 108]. Most patients undergoing CA/PCI are adapted to reduce the risk of metformin-associated already taking long-term statins, and results in these patients lactic acidosis in patients with type 2 diabetes mellitus are unclear. scheduled to receive intravascular contrast media? While the CMSC recognises the potential preventive ef- fects of short-term statins, it does not advise the use of short- Metformin is the standard drug for monotherapy of type 2 term, high-dose statins as a single strategy for preventing PC- diabetes mellitus . The effect of CM on the risk of AKI (Table 2). metformin-associated lactic acidosis is indirect, since an epi- sode of AKI following intravascular CM administration may lead to metformin accumulation. The use of metformin in RAAS blockade: ACE inhibitors and angiotensin-II receptor patients with eGFR 30–59 ml/min/1.73 m is considered safe blockers if doses are reduced appropriately [134, 135]. Limiting the metformin dose to a maximum of 2000 mg/day for eGFR Administration of renin–angiotensin–aldosterone system 45–60 ml/min/1.73 m and to a maximum of 1000 mg/day (RAAS) blockade as a preventive measure for patients not tak- for eGFR 30–44 ml/min/1.73 m has been recommended. In ing these drugs did not show a significant effect on the inci- patients with eGFR 30–59 ml/min/1.73 m metformin drug dence of PC-AKI in recent meta-analyses [32, 34](Table 2). levels remain within therapeutic ranges. For patients with eGFR < 30 ml/min/1.73 m metformin administration is not approved. Vitamin C Multiple studies and meta-analyses have shown that the risk of lactic acidosis is very low and linked more to the The majority of RCTs or meta-analyses do not demon- underlying disease and possible co-morbidities rather than strate a protective effect of vitamin C against PC-AKI in the use of metformin [134, 136, 137]. Because of the lack of patients with CKD predominantly undergoing coronary published evidence on metformin and CM, early guidelines angiography [109–111]orany benefitofthe use ofvita- about the need to stop metformin before intravascular CM min C, NAc or a combination of both over the standard were based on consensus, and were strict [138, 139]. As the hydration regimen in preventing PC-AKI [112, 113] low risk of lactic acidosis became apparent, guidelines have (Table 2). Combining vitamin C with pentoxifylline also become less restrictive . failed to show an advantage . Only two publications Since no new published evidence is available, the CMSC [115, 116] have shown a protective effect of vitamin C in has updated its recommendations based on recent patients with CKD undergoing CA. Renal replacement therapy (RRT) Table 3 Metformin administration, dialysis schedules There is no convincing evidence in favour of preventive Metformin administration in patients at risk of PC-AKI haemodialysis or RRT alone [117–119]or combined with hy- Note that these recommendations may deviate from current EMA/FDA recommendations. dration  in patients with CKD, predominantly undergo- Patients with eGFR > 30 ml/min/1.73 m and no evidence of AKI ing CA (Table 2). There is no evidence of an increased risk of receiving either intravenous CM or intra-arterial CM with second pass permanent anuria in patients on peritoneal dialysis undergoing renal exposure: continue taking metformin normally. CA . There is a single study showing better late-stage Patients (a) with eGFR < 30 ml/min/1.73 m receiving either intravenous (day 5–30) renal protection against PC-AKI with simulta- CM or intra-arterial CM with second pass renal exposure or (b) neous haemodialysis . receiving intra-arterial CM with first pass renal exposure or (c) with AKI: stop taking metformin from the time of CM administration: measure eGFR within 48 hours and restart metformin if renal function has not changed significantly. Miscellaneous Level of evidence D Dialysis schedules in relation to CM administration The data on the protective effects of several agents, such It is not necessary to adapt the timing of intravascular CM administration as trimatizidine [123, 124], theophylline [95, 125–127], in relation to the dialysis schedule in patients undergoing chronic alprostadil [128, 129], nebivolol , fenoldopam  dialysis or haemofiltration, but it may be done to minimise volume overload. and iloprost , is not conclusive and does not sup- port recommending their use to reduce the risk of PC- Level of evidence D AKI. 2862 Eur Radiol (2018) 28:2856–2869 Table 4 ESUR CMSC guideline Definitions (version 10) for post-contrast acute kidney injury (PC-AKI) Post-contrast acute kidney injury (PC-AKI) is defined as an increase in serum creatinine ≥ 0.3 mg/dl (or ≥ 26.5 μmol/l), or ≥ 1.5 times baseline, within 48–72 h of intravascular administration of a contrast medium. Intra-arterial injection with first pass renal exposure indicates that contrast medium reaches the renal arteries in a relatively undiluted form, e.g. injection into the left heart, thoracic and suprarenal abdominal aorta or the renal arteries. Intra-arterial injection with second pass renal exposure indicates that contrast medium reaches the renal arteries after dilution either in the pulmonary or peripheral circulation e.g. injection into the right heart, pulmonary artery, carotid, subclavian, coronary, mesenteric or infra-renal arteries. Measurement of renal function � Estimated glomerular filtration rate (eGFR), calculated from the serum creatinine, is recommended to estimate renal function before administration of contrast medium. � In adults ≥ 18 years, the CKD-EPI formula to estimate GFR is recommended. eGFR (ml/min/1.73 m )= −0.329 Age Female sCr ≤ 62 μmol/l: 144 × (sCr/62) ×0.993 −1.209 Age Female sCr > 62 μmol/l: 144 × (sCr/62) ×0.993 −0.411 Age Male sCr ≤ 80 μmol/l: 141 × (sCr/80) ×0.993 −1.209 Age Male sCr > 80 μmol/l: 141 × (sCr/80) ×0.993 (sCr in μmol/l; age in years) All equations × 1.159 if African American race � In children, the revised Schwartz formula to estimate GFR is recommended, eGFR (ml/min/1.73 m ) = 36.5 × Length/sCr (sCr in μmol/l; length in cm) Note: Neither serum nor plasma creatinine is an ideal indicator of renal function and may miss decreased renal function. Renal adverse reactions to iodine-based contrast media RISK FACTORS FOR PC-AKI Patient-related � eGFR less than 45 ml/min/1.73 m before intra-arterial contrast medium administration with first pass renal exposure or in ICU patients � eGFR less than 30 ml/min/1.73 m before intravenous contrast medium or intra-arterial contrast medium administration with second pass renal exposure � Known or suspected acute renal failure Procedure-related � Intra-arterial contrast medium administration with first pass renal exposure � Large doses of contrast medium given intra-arterially with first pass renal exposure � High osmolality contrast media � Multiple contrast medium injections within 48-72h Time of referral ELECTIVE EXAMINATION MEASUREMENT OF RENAL FUNCTION � Measure eGFR before administering intravascular iodine-based contrast medium either (a) In all patients or (b) In patients who have a history of - Renal disease (eGFR < 60 ml/min/1.73 m ) - Kidney surgery - Proteinuria - Hypertension - Hyperuricemia - Diabetes mellitus � Timing of eGFR measurement - Within 7 days before contrast medium administration in patients with an acute disease, an acute deterioration of a chronic disease or who are hospital inpatients Eur Radiol (2018) 28:2856–2869 2863 Table 4 (continued) - Within 3 months before contrast medium administration in all other patients EMERGENCY EXAMINATION Identify at-risk patients (see above), if possible: � Determine eGFR if the procedure can be deferred until the result is available without harm to the patient. � If eGFR cannot be obtained, follow the protocols for patients with eGFR less than 45 ml/min/1.73 m for intra- arterial administration with first pass renal exposure and eGFR less than 30 ml/min/1.73 m for intravenous and intra-arterial administration with second pass renal exposure as closely as clinical circumstances permit. Before the examination ELECTIVE EXAMINATION At-risk patients (see above) � Consider an alternative imaging method not using iodine-based contrast media � Intravenous saline and bicarbonate have similar efficacy for preventive hydration � For intravenous contrast media administration and intra-arterial contrast media administration with second pass renal exposure hydrate the patient either with intravenous sodium bicarbonate 1.4% (or 154 mmol/l in dextrose 5% water): 3 ml/kg/h for 1 h before contrast medium or with intravenous saline 0.9%, 1 ml/kg/h for 3–4 h before and 4–6h after contrast medium � For intra-arterial contrast media administration with first renal exposure hydrate the patient either with intravenous sodium bicarbonate 1.4% (or 154 mmol/l in dextrose 5% water): 3 ml/kg/h for 1 h before and 1 ml/kg/h for 4–6 h after contrast medium or with intravenous saline 0.9%, 1 ml/kg/h for 3–4 h before and 4–6 h after contrast medium � The clinician responsible for patient care should individualize preventive hydration in patients with severe congestive heart failure (NYHA grade 3–4) or patients with end-stage renal failure (eGFR < 15 ml/min/1.73 m ) � Oral hydration is not recommended as the sole method of preventive hydration EMERGENCY EXAMINATION At-risk patients (see above) � Consider an alternative imaging method not using iodine-based contrast media � Use preventive hydration before contrast medium administration (see ‘Elective Examination’ for protocols) Time of examination All patients � Use low or iso-osmolar contrast media � Use the lowest dose of contrast medium consistent with a diagnostic result � For intra-arterial contrast medium administration with first pass renal exposure keep either the ratio CM dose (in gram I)/absolute eGFR (in ml/min) < 1.1 or the ratio CM volume (in ml)/eGFR (in ml/min/1.73 m ) < 3.0 (assuming a contrast medium concentration of 350 mg iodine/ ml) After the examination At-risk patients � Continue preventive hydration if appropriate (see protocols above) � Determine eGFR 48 h after administration of contrast medium � If at 48 h there is a diagnosis of PC-AKI, monitor the patient clinically for at least 30 days and determine eGFR at regular intervals Note: No pharmacological prophylaxis (with statins, renal vasodilators, receptor antagonists of endogenous vasoactive mediators or cytoprotective drugs) has been shown to offer consistent protection against PC-AKI. Patients with diabetes mellitus taking metformin � Patients with eGFR > 30 ml/min/1.73 m and no evidence of AKI receiving either intravenous or intra-arterial iodine-based contrast medium with second pass renal exposure: Continue taking metformin normally. � Patients (a) with eGFR < 30 ml/min/1.73 m receiving either intravenous or intra-arterial contrast medium with second pass renal exposure or (b) receiving intra-arterial contrast medium with first pass renal exposure or (c) with AKI: Stop taking metformin from the time of contrast medium administration. Measure eGFR within 48 h and restart metformin if renal function has not changed significantly. Dialysis and contrast medium administration � All iodine-based contrast media can be removed by haemodialysis or peritoneal dialysis. � There is no evidence that haemodialysis protects patients with normal or impaired renal function from PC-AKI. � In all patients, avoid osmotic and fluid overload. 2864 Eur Radiol (2018) 28:2856–2869 Table 4 (continued) PATIENTS ON DIALYSIS Patients on haemodialysis � Co-ordinating the time of the iodine-based contrast medium injection with the haemodialysis session is unnecessary � Extra haemodialysis session to remove iodine-based contrast medium is unnecessary Patients on continuous Haemodialysis to remove iodine-based contrast medium is unnecessary ambulatory peritoneal dialysis recommendations from the FDA , and on guidelines AKI. There is no need to adapt dialysis schedules in patients from the ACR and RSTN [14, 141](Table 3). being given intravascular CM. The recommendations made in this paper have been incor- porated into the ESUR CMSC guidelines version 10 (Table 4). Question 10: Should the timing of CM administration be adapted to the schedule of haemodialysis Funding The authors state that this work has not received any funding. or haemofiltration sessions in patients on renal replacement therapy? Compliance with ethical standards Guarantor The scientific guarantor of this publication is Prof. Henrik S. Iodine-based CM can be safely removed by haemodialysis Thomsen. (HD) or haemofiltration (HF). Many factors influence the ef- fectiveness of HD, such as flow rate of blood and dialysate, Conflict of interest Aart van der Molen has received incidental pay- dialysis membrane permeability, HD duration, and CM char- ments for lectures and chairmanships at scientific meetings for contrast acteristics such as molecular size, protein binding, hydrophi- agent safety related issues (contrast agent reactions, Gd-retention) from GE, Bayer, Bracco and Guerbet. licity and electrical charge . Fulvio Stacul has received lecture fees from Bracco and Guerbet. Although HF concomitant with radiological procedures Olivier Clément has received lecture fees from Bracco and Guerbet. has been shown to be feasible and well tolerated [143, 144], The other authors of this manuscript declare no relationships with any the fractional removal of iodine-based CM contrast agents is companies whose products and services may be related to the subject matter of this article. modest and several HF or HD sessions are needed to remove 95% of the administered CM . Also, there is no evidence Statistics and biometry No complex statistical methods were necessary for the necessity of emergency HD after administration of for this paper. iodine-based CM in patients on chronic HD . However, to avoid volume overload, CM administration may be Informed consent Written informed consent was not required for this synchronised with scheduled HF or HD (Table 3). study because this is a special paper based on other publications. Thus informed consent is not necessary. Ethical approval Institutional review board approval was not required because it is a retrospective study based on other studies. Conclusion Methodology Assessment of the risk of PC-AKI before intravascular CM is � retrospective administered is best done by measuring eGFR but the alterna- � multicentre study tive of a questionnaire for patients detects most patients with eGFR less than 45 ml/min/1.73 m . Volume expansion with Open Access This article is distributed under the terms of the Creative normal saline or sodium bicarbonate remains the mainstay of Commons Attribution 4.0 International License (http:// PC-AKI prevention, but there is still uncertainty about the creativecommons.org/licenses/by/4.0/), which permits unrestricted use, optimal protocol. The additional benefit of a number of drugs, distribution, and reproduction in any medium, provided you give appro- priate credit to the original author(s) and the source, provide a link to the such as N-acetylcysteine, statins, ACE inhibitors and Creative Commons license, and indicate if changes were made. angiotensin-II receptor blockers, and vitamin C in preventing PC-AKI has not been proved conclusively. Stopping nephro- toxic medications appears to be of limited value in preventing PC-AKI. Recommendations for discontinuing metformin References when CM is given have been relaxed and now only apply to patients with eGFR < 30 ml/min/1.73 m receiving IV CM or 1. Stacul F, van der Molen AJ, Reimer P, Contrast Media Safety IA CM with second pass renal exposure, and to all patients Committee of European Society of Urogenital Radiology receiving IA CM with first pass renal exposure or who have (ESUR) et al (2011) Contrast induced nephropathy: updated Eur Radiol (2018) 28:2856–2869 2865 ESUR Contrast Media Safety Committee guidelines. Eur Radiol 19. Tziakas D, Chalikias G, Stakos D et al (2014) Validation of a new risk score to predict contrast-induced nephropathy after percuta- 21:2527–2541 neous coronary intervention. Am J Cardiol 113:1487–1493 2. Morcos SK, Thomsen HS, Webb JA, Contrast Media Safety 20. Abellas-Sequeiros RA, Raposeiras-Roubin S, Abu-Assi E et al Committee of the European Society of Urogenital Radiology (2016) Mehran contrast nephropathy risk score: is it still useful (ESUR) et al (2002) Dialysis and contrast media. Eur Radiol 12: 10 years later? J Cardiol 67:262–267 3026–3030 21. Sato A, Hoshi T, Kakefuda Yet al (2015) Effect of the Mehran risk 3. Contrast Media Safety Committee ESUR. Guidelines on Contrast score for the prediction of clinical outcomes after percutaneous Media v9. CMSC, 2014. http://www.esur-cm.org/index.php/en/. coronary intervention. J Cardiol 66:417–422 15 December 2017 22. Gurm HS, Seth M, Kooiman J, Share D (2013) A novel tool for 4. Brouwers M, Kho ME, Browman GP, on behalf of the AGREE reliable and accurate prediction of renal complications in patients Next Steps Consortium et al (2010) AGREE II: Advancing guide- undergoing percutaneous coronary intervention. J Am Coll line development, reporting and evaluation in healthcare. Can Cardiol 61:2242–2248 Med Assoc J 182:E839–E842 23. Silver SA, Shah PS, Chertow GM, Harel S, Wald R, Harel Z 5. Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines: (2015) Risk prediction models for contrast induced nephropathy: 2. Framing the question and deciding on important outcomes. J systematic review. BMJ 351:h4395 Clin Epidemiol 64:395–400 24. Allen DW, Ma B, Leung KC et al (2017) Risk prediction models 6. OCEBM Levels of Evidence Working Group. The Oxford 2011 for contrast-induced acute kidney injury accompanying cardiac Levels of Evidence. Oxford Centre for Evidence-Based Medicine. catheterization: systematic review and meta-analysis. Can J http://www.cebm.net/index.aspx?o=5653. Accessed 15 December Cardiol 33(6):724-736 25. Dutch Federation of Nephrology. Guideline diagnosis and manage- 7. Choyke PL, Cady J, DePollar SL, Austin H (1998) Determination ment of chronic kidney disease 2016. https://www.nefro.nl/ of serum creatinine prior to iodinated contrast media: is it neces- richtlijnen/diagnostiek-en-behandeling-van-chronische-nierschade- sary in all patients? Tech Urol 4:65–69 voorlopige-richtlijn-2016-0. Accessed 15 December 2017 8. Tippins RB, Torres WE, Baumgartner BR, Baumgarten DA 26. Perazella MA (2005) Drug-induced nephropathy: an update. (2000) Are screening serum creatinine levels necessary prior to Expert Opin Drug Saf 4:689–704 outpatient CT examinations? Radiology 216:481–484 27. Diogo LP, Saitovitch D, Biehl M et al (2010) Is there an associa- 9. Azzouz M, Romsing J, Thomsen HS (2014) Can a structured tion between non-steroidal anti-inflammatory drugs and contrast questionnaire identify patients with reduced renal function? Eur nephropathy? Arq Bras Cardiol 95:726–731 Radiol 24:780–784 28. Ho YF, Hsieh KL, Kung FL, et al (2015) Nephrotoxic 10. Too CW, Ng WY, Tan CC, Mahmood MI, Tay KH (2015) polypharmacy and risk of contrast medium-induced nephropathy Screening for impaired renal function in outpatients before iodin- in hospitalized patients undergoing contrast-enhanced CT. AJR ated contrast injection: comparing the Choyke questionnaire with Am J Roentgenol 205:703–708 a rapid point-of-care-test. Eur J Radiol 84:1227–1231 29. Moos SI, van Vemde DN, Stoker J, Bipat S (2013) Contrast in- 11. Zähringer C, Potthast S, Tyndall AJ, Bongartz G, Hohmann J duced nephropathy in patients undergoing intravenous (IV) con- (2015) Serum creatinine measurements: evaluation of a question- trast enhanced computed tomography (CECT) and the relationship with risk factors: a meta-analysis. Eur J Radiol 82:e387–e399 naire according to the ESUR guidelines. Acta Radiol 56:628–634 30. Rosenstock JL, Bruno R, Kim JK et al (2008) The effect of with- 12. Chang P, Saddleton E, Laumann AE et al (2012) Comparison of drawal of ACE inhibitors or angiotensin receptor blockers prior to the sensitivity of a pre-MRI questionnaire and point of care eGFR coronary angiography on the incidence of contrast-induced ne- testing for detection of impaired renal function. Acad Radiol 19: phropathy. Int Urol Nephrol 40:749–755 1181–1185 31. Bainey KR, Rahim S, Etherington K, CAPTAIN Investigators 13. Moos SI, de Weijert RS, Nagan G, Stoker J, Bipat S (2014) Cost of et al (2015) Effects of withdrawing vs. continuing renin- screening for kidney disease before intravenous contrast adminis- angiotensin blockers on incidence of acute kidney injury in pa- tration. Neth J Med 72:271–280 tients with renal insufficiency undergoing cardiac catheterization: 14. Van der Molen AJ, Geenen RWF, Dekkers HM et al for the results from the angiotensin converting enzyme inhibitor/ Radiological Society of the Netherlands (RSTN). Guideline safe angiotensin receptor blocker and contrast induced nephropathy use of contrast media, part 1. Vught, RSTN: 2017. https://www. in patients receiving cardiac catheterization (CAPTAIN) trial. radiologen.nl/secties/nvvr/documenten/richtlijn-veilig-gebruik-van- Am Heart J 170:110–116 contrastmiddelen-deel-1-full-english. Accessed 15 December 2017 32. Jo SH, Lee JM, Park J, Kim HS (2015) The impact of renin- 15. Tsai TT, Patel UD, Chang TI et al (2014) Validated contemporary angiotensin-aldosterone system blockade on contrast-induced ne- risk model of acute kidney injury in patients undergoing percuta- phropathy: a meta-analysis of 12 studies with 4,493 patients. neous coronary interventions: insights from the National Cardiology 130:4–14 Cardiovascular Data Registry Cath-PCI Registry. J Am Heart 33. Peng F, Su J, Lin J, Niu W (2015) Impact of renin-angiotensin- Assoc 3:e001380 aldosterone system-blocking agents on the risk of contrast- 16. Kooiman J, Gurm HS (2014) Predicting contrast-induced renal induced acute kidney injury: a prospective study and meta-analy- complications in the catheterization laboratory. Intervent Cardiol sis. J Cardiovasc Pharmacol 65:262–268 Clin 3:369–377 34. Wu Z, Zhang H, Jin Wet al (2015) The effect of renin-angiotensin- 17. Mehran R, Aymong ED, Nikolsky E et al (2004) A simple risk aldosterone system blockade medications on contrast-induced ne- score for prediction of contrast-induced nephropathy after percu- phropathy in patients undergoing coronary angiography: a meta- taneous coronary intervention: development and initial validation. analysis. PLoS One 10:e0129747 J Am Coll Cardiol 44:1393–1399 35. Chen SL, Zhang J, Yei F et al (2008) Clinical outcomes of 18. Sgura FA, Bertelli L, Monopoli D et al (2010) Mehran contrast- contrast-induced nephropathy in patients undergoing percutane- induced nephropathy risk score predicts short- and long-term clin- ous coronary intervention: a prospective, multicenter, randomized ical outcomes in patients with ST-elevation-myocardial infarction. study to analyze the effect of hydration and acetylcysteine. Int J Circ Cardiovasc Interv 3:491–498 Cardiol 126:407–413 2866 Eur Radiol (2018) 28:2856–2869 36. Luo Y, Wang X, Ye Z, et al (2014) Remedial hydration reduces the 52. Heyman SN, Rosen S, Khamaisi M, Idée JM, Rosenberger C (2010) Reactive oxygen species and the pathogenesis of incidence of contrast-induced nephropathy and short-term adverse events in patients with ST-segment elevation myocardial infarc- radiocontrast-induced nephorpathy. Invest Radiol 45:188–193 tion: a single-center, randomized trial. Intern Med 53:2265–2272 53. Merten GJ, Burgess WP, Gray LV et al (2004) Prevention of contrast-induced nephropathy with sodium bicarbonate: a ran- 37. Jurado-Roman A, Hernandez-Hernandez F, Garcia-Tejada J et al domized controlled trial. JAMA 291:2328–2334 (2015) Role of hydration in contrast-induced nephropathy in pa- 54. Masuda M, Yamada T, Mine T et al (2007) Comparison of useful- tients who underwent primary percutaneous coronary interven- ness of sodium bicarbonate versus sodium chloride to prevent tion. Am J Cardiol 115:1174–1178 contrast-induced nephropathy in patients undergoing an emergent 38. Kooiman J, Sijpkens YW, van Buren M et al (2014) Randomised coronary procedure. Am J Cardiol 100:781–786 trial of no hydration vs. sodium bicarbonate hydration in patients with 55. Ozcan EE, Guneri S, Akdeniz B et al (2007) Sodium bicarbonate, chronic kidney disease undergoing acute computed tomography- N-acetylcysteine, and saline for prevention of radiocontrast- pulmonary angiography. J Thromb Haemost 12:1658–1666 induced nephropathy. A comparison of 3 regimens for protecting 39. Trivedi HS, Moore H, Nasr S et al (2003) A randomized prospec- contrast-induced nephropathy in patients undergoing coronary tive trial to assess the role of saline hydration on the development procedures. A single-center prospective controlled trial. Am of contrast nephrotoxicity. Nephron Clin Pract 93:C29–C34 Heart J 154:539–544 40. Nijssen EC, Rennenberg RJ, Nelemans PJ et al (2017) Prophylactic 56. Recio-Mayoral A, Chaparro M, Prado B et al (2007) The reno- hydration to protect renal function from intravascular iodinated con- protective effect of hydration with sodium bicarbonate plus N- trast material in patients at high risk of contrast-induced nephropa- acetylcysteine in patients undergoing emergency percutaneous thy (AMACING): a prospective, randomised, phase 3, controlled, coronary intervention: the RENO Study. J Am Coll Cardiol 49: open-label, non-inferiority trial. Lancet 389:1312–1322 1283–1288 41. Taylor AJ, Hotchkiss D, Morse RW, McCabe J (1998) PREPARED: 57. Adolph E, Holdt-Lehmann B, Chatterjee T et al (2008) Renal preparation for Angiography in Renal Dysfunction: a randomized trial Insufficiency Following Radiocontrast Exposure Trial of inpatient vs outpatient hydration protocols for cardiac catheteriza- (REINFORCE): a randomized comparison of sodium bicarbonate tion in mild-to-moderate renal dysfunction. Chest 114:1570–1574 versus sodium chloride hydration for the prevention of contrast- 42. Dussol B, Morange S, Loundoun A, Auquier P, Berland Y (2006) induced nephropathy. Coron Artery Dis 19:413–419 A randomized trial of saline hydration to prevent contrast ne- 58. Brar SS, Shen AY, Jorgensen MB et al (2008) Sodium bicarbonate phropathy in chronic renal failure patients. Nephrol Dial vs sodium chloride for the prevention of contrast medium-induced Transplant 21:2120–2126 nephropathy in patients undergoing coronary angiography: a ran- 43. Lawlor DK, Moist L, DeRose G et al (2007) Prevention of domized trial. JAMA 300:1038–1046 contrast-induced nephropathy in vascular surgery patients. Ann 59. Boucek P, Havrdova T, Oliyarnyk O et al (2013) Prevention of Vasc Surg 21:593–597 contrast-induced nephropathy in diabetic patients with impaired 44. Wrobel W, Sinkiewicz W, Gordon M, Wozniak-Wisniewska A renal function: a randomized, double blind trial of sodium bicar- (2010) Oral versus intravenous hydration and renal function in bonate versus sodium chloride-based hydration. Diabetes Res Clin diabetic patients undergoing percutaneous coronary interventions. Pract 101:303–308 Kardiol Pol 68:1015–1020 60. Gomes VO, Lasevitch R, Lima VC et al (2012) Hydration with 45. Akyuz S, Karaca M, Kemaloglu OT et al (2014) Efficacy of oral sodium bicarbonate does not prevent contrast nephropathy: a mul- hydration in the prevention of contrast-induced acute kidney inju- ticenter clinical trial. Arq Bras Cardiol 99:1129–1134 ry in patients undergoing coronary angiography or intervention. 61. Ratcliffe JA, Thiagarajah P, Chen J et al (2009) Prevention of Nephron Clin Pract 128:95–100 contrast-induced nephropathy: a randomized controlled trial of so- 46. Cho R, Javed N, Traub D, Kodali S, Atem F, Srinivasan V (2010) dium bicarbonate and N-acetylcysteine. Int J Angiol 18:193–197 Oral hydration and alkalinization is noninferior to intravenous 62. Solomon R, Gordon P, Manoukian SV et al (2015) Randomized therapy for prevention of contrast-induced nephropathy in patients trial of bicarbonate or saline study for the prevention of contrast- with chronic kidney disease. J Interv Cardiol 23:460–466 induced nephropathy in patients with CKD. Clin J Am Soc 47. Kong DG, Hou YF, Ma LL, Yao DK, Wang LX (2012) Nephrol 10:1519–1524 Comparison of oral and intravenous hydration strategies for the 63. Briguori C, Airoldi F, D'Andrea D et al (2007) Renal Insufficiency prevention of contrast-induced nephropathy in patients undergo- Following Contrast Media Administration Trial (REMEDIAL): a ing coronary angiography or angioplasty: a randomized clinical randomized comparison of 3 preventive strategies. Circulation trial. Acta Cardiol 67:565–569 115:1211–1217 48. Martin-Moreno PL, Varo N, Martinez-Anso E et al (2015) 64. Castini D, Lucreziotti S, Bosotti L et al (2010) Prevention of Comparison of intravenous and oral hydration in the prevention contrast-induced nephropathy: a single center randomized study. of contrast-induced acute kidney injury in low-risk patients: a Clin Cardiol 33:E63–E68 randomized trial. Nephron 131:51–58 65. Chong E, Poh KK, Lu Q et al (2015) Comparison of combination 49. Hiremath S, Akbari A, Shabana W, Fergusson DA, Knoll GA therapy of high-dose oral N-acetylcysteine and intravenous sodi- (2013) Prevention of contrast-induced acute kidney injury: is sim- um bicarbonate hydration with individual therapies in the reduc- ple oral hydration similar to intravenous? A systematic review of tion of Contrast-induced Nephropathy during Cardiac the evidence. PLoS One 8:e60009 Catheterisation and Percutaneous Coronary Intervention 50. Cheungpasitporn W, Thongprayoon C, Brabec BA, Edmonds PJ, (CONTRAST): a multi-centre, randomised, controlled trial. Int J O'Corragain OA, Erickson SB (2014) Oral hydration for preven- Cardiol 201:237–242 tion of contrast-induced acute kidney injury in elective radiologi- 66. Hafiz AM, Jan MF, Mori N et al (2012) Prevention of contrast- cal procedures: a systematic review and meta-analysis of random- induced acute kidney injury in patients with stable chronic renal ized controlled trials. N Am J Med Sci 6:618–624 disease undergoing elective percutaneous coronary and peripheral 51. Agarwal SK, Mohareb S, Patel A et al (2015) Systematic oral interventions: randomized comparison of two preventive strate- hydration with water is similar to parenteral hydration for preven- gies. Catheter Cardiovasc Interv 79:929–937 tion of contrast-induced nephropathy: an updated meta-analysis of 67. Koc F, Ozdemir K, Altunkas F et al (2013) Sodium bicarbonate randomised clinical data. Open Heart 2:e000317 versus isotonic saline for the prevention of contrast-induced Eur Radiol (2018) 28:2856–2869 2867 nephropathy in patients with diabetes mellitus undergoing coro- 83. O'Sullivan S, Healy DA, Moloney MC, Grace PA, Walsh SR (2013) The role of N-acetylcysteine in the prevention of nary angiography and/or intervention: a multicenter prospective randomized study. J Investig Med 61:872–877 contrast-induced nephropathy in patients undergoing peripheral angiography: a structured review and meta-analysis. Angiology 68. Klima T, Christ A, Marana I et al (2012) Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium- 64:576–582 induced nephropathy: a randomized controlled trial. Eur Heart J 84. Sun Z, Fu Q, Cao L, Jin W, Cheng L, Li Z (2013) Intravenous N- 33:2071–2079 acetylcysteine for prevention of contrast-induced nephropathy: a 69. Lee SW, Kim WJ, Kim YH et al (2011) Preventive strategies of meta-analysis of randomized, controlled trials. PLoS One 8: e55124 renal insufficiency in patients with diabetes undergoing interven- tion or arteriography (the PREVENT Trial). Am J Cardiol 107: 85. Loomba RS, Shah PH, Aggarwal S, Arora RR (2016) Role of N- 1447–1452 acetylcysteine to prevent contrast-induced nephropathy: a meta- 70. Maioli M, Toso A, Leoncini M et al (2008) Sodium bicarbonate analysis. Am J Ther 23:e172–e183 versus saline for the prevention of contrast-induced nephropathy 86. Traub SJ, Mitchell AM, Jones AE et al (2013) N-acetylcysteine in patients with renal dysfunction undergoing coronary angiogra- plus intravenous fluids versus intravenous fluids alone to prevent phy or intervention. J Am Coll Cardiol 52:599–604 contrast-induced nephropathy in emergency computed tomogra- phy. Ann Emerg Med 62:511–520 71. Shavit L, Korenfeld R, Lifschitz M, Butnaru A, Slotki I (2009) Sodium bicarbonate versus sodium chloride and oral N- 87. Poletti PA, Platon A, De Seigneux S et al (2013) N-acetylcysteine acetylcysteine for the prevention of contrast-induced nephropathy does not prevent contrast nephropathy in patients with renal im- in advanced chronic kidney disease. J Interv Cardiol 22:556–563 pairment undergoing emergency CT: a randomized study. BMC 72. Kooiman J, Sijpkens YW, de Vries JP et al (2014) A randomized Nephrol 14:119 comparison of 1-h sodium bicarbonate hydration versus standard 88. Berwanger O, Cavalcanti AB, Sousa AM et al (2013) peri-procedural saline hydration in patients with chronic kidney Ac etylcysteine for the prevention of renal outcomes in patients disease undergoing intravenous contrast-enhanced computerized with diabetes mellitus undergoing coronary and peripheral vascu- tomography. Nephrol Dial Transplant 29:1029–1036 lar angiography: a substudy of the acetylcysteine for contrast- 73. Kooiman J, de Vries JP, van der Heyden J et al (2014) induced nephropathy trial. Circ Cardiovasc Interv 6:139–145 Randomized trial of 1-hour sodium bicarbonate vs. Standard sa- 89. Kang X, Hu DY, Li CB, Ai ZS, Peng A (2015) N-acetylcysteine line hydration in patients with chronic kidney disease undergoing for the prevention of contrast-induced nephropathy in patients intra-arterial contrast administration [abstr]. Circulation 130: with pre-existing renal insufficiency or diabetes: a systematic re- A17645 view and meta-analysis. Ren Fail 37:297–303 74. Kama A, Yilmaz S, Yaka E et al (2014) Comparison of short-term 90. Brown JR, Block CA, Malenka DJ, O'Connor GT, Schoolwerth infusion regimens of N-acetylcysteine plus intravenous fluids, so- AC, Thompson CA (2009) Sodium bicarbonate plus N- dium bicarbonate plus intravenous fluids, and intravenous fluids acetylcysteine prophylaxis: a meta-analysis. JACC Cardiovasc alone for prevention of contrast-induced nephropathy in the emer- Interv 2:1116–1124 gency department. Acad Emerg Med 21:615–622 91. Carbonell N, Blasco M, Sanjuan R et al (2007) Intravenous N- 75. Briguori C, Visconti G, Focaccio A et al (2011) Renal acetylcysteine for preventing contrast-induced nephropathy: a Insufficiency After Contrast Media Administration Trial II randomised trial. Int J Cardiol 115:57–62 (REMEDIAL II): RenalGuard System in high-risk patients for 92. Heng AE, Cellarier E, Aublet-Cuvelier B et al (2008) Is treatment contrast-induced acute kidney injury. Circulation 124:1260–1269 with N-acetylcysteine to prevent contrast-induced nephropathy 76. Marenzi G, Ferrari C, Marana I et al (2012) Prevention of contrast when using bicarbonate hydration out of date? Clin Nephrol 70: nephropathy by furosemide with matched hydration: the 475–484 MYTHOS (Induced Diuresis With Matched Hydration 93. Staniloae CS, Doucet S, Sharma SK et al (2009) N-Acetylcysteine Compared to Standard Hydration for Contrast Induced added to volume expansion with sodium bicarbonate does not Nephropathy Prevention) trial. JACC Cardiovasc Interv 5:90–97 further prevent contrast-induced nephropathy: results from the 77. Usmiani T, Andreis A, Budano C et al (2016) AKIGUARD cardiac angiography in renally impaired patients study. J Interv (Acute Kidney Injury GUARding Device) trial: in-hospital and Cardiol 22:261–265 one-year outcomes. J Cardiovasc Med 17:530–537 94. Subramaniam RM, Suarez-Cuervo C, Wilson RF et al (2016) 78. Brar SS, Aharonian V, Mansukhani P et al (2014) Haemodynamic- Effectiveness of prevention strategies for contrast-induced ne- guided fluid administration for the prevention of contrast-induced phropathy: a systematic review and meta-analysis. Ann Intern acute kidney injury: the POSEIDON randomised controlled trial. Med 164:406–416 Lancet 383:1814–1823 95. Ali-Hassan-Sayegh S, Mirhosseini SJ, Ghodratipour Z et al (2017) 79. Qian G, Fu Z, Guo J, Cao F, Chen Y (2016) Prevention of Strategies preventing contrast-induced nephropathy after coronary contrast-induced nephropathy by central venous pressure-guided angiography: a comprehensive meta-analysis and systematic re- fluid administration in chronic kidney disease and congestive view of 125 randomized controlled trials. Angiology 68:389–413 heart failure patients. JACC Cardiovasc Interv 9:89–96 96. Su X, Xie X, Liu L et al (2017) Comparative effectiveness of 12 80. Aslanger E, Uslu B, Akdeniz C, Polat N, Cizgici Y, Oflaz H treatment strategies for preventing contrast-induced acute kidney (2012) Intrarenal application of N-acetylcysteine for the preven- injury: A systematic review and Bayesian network analysis. Am J tion of contrast medium-induced nephropathy in primary angio- Kidney Dis 69:69–77 plasty. Coron Artery Dis 23:265–270 97. Briasoulis A, Mallikethi-Reddy S, Sharma S, Briasouli AA, 81. Inda-Filho AJ, Caixeta A, Manggini M, Schor N (2014) Do intra- Afonso L (2015) 3-Hydroxy-3-methylglutaryl-CoA reductase en- venous N-acetylcysteine and sodium bicarbonate prevent high os- zyme inhibitors for prevention of contrast-induced nephropathy: a molal contrast-induced acute kidney injury? A randomized con- meta-analysis of prospective randomized controlled studies. Am J trolled trial. PLoS One 9:e107602 Ther 22:e158–e166 82. Jaffery Z, Verma A, White CJ et al (2012) A randomized trial of 98. Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, et al intravenous n-acetylcysteine to prevent contrast induced nephrop- (2015) Periprocedural effects of statins on the incidence of contrast- athy in acute coronary syndromes. Catheter Cardiovasc Interv 79: induced acute kidney injury: a systematic review and meta-analysis 921–926 of randomized controlled trials. Ren Fail 37:664–671 2868 Eur Radiol (2018) 28:2856–2869 99. Li H, Wang C, Liu C, Li R, Zou M, Cheng G (2016) Efficacy of 115. Sadat U, Usman A, Gillard JH, Boyle JR (2013) Does ascorbic acid protect against contrast-induced acute kidney injury in pa- short-term statin treatment for the prevention of contrast-induced acute kidney injury in patients undergoing coronary angiography/ tients undergoing coronary angiography: a systematic review with percutaneous coronary intervention: a meta-analysis of 21 ran- meta-analysis of randomized, controlled trials. J Am Coll Cardiol domized controlled trials. Am J Cardiovasc Drugs 16:201–219 62:2167–2175 100. Liu YH, Liu Y, Duan CYet al (2015) Statins for the prevention of 116. Wang XT, Yan J, Li L, Su Q (2014) Anti-oxidative vitamin for the contrast-induced nephropathy after coronary angiography/ prevention of contrast-induced acute kidney injury in patients with percutaneous interventions: a meta-analysis of randomized con- chronic kidney disease: meta-analysis of randomized controlled trolled trials. J Cardiovasc Pharmacol Ther 20:181–192 trials. Exp Clin Cardiol 20:1385–1410 101. Marenzi G, Cosentino N, Werba JP, Tedesco CC, Veglia F, 117. Cruz DN, Perazella MA, Bellomo R et al (2006) Extracorporeal Bartorelli AL (2015) A meta-analysis of randomized controlled blood purification therapies for prevention of radiocontrast- trials on statins for the prevention of contrast-induced acute kid- induced nephropathy: a systematic review. Am J Kidney Dis 48: ney injury in patients with and without acute coronary syndromes. 361–371 Int J Cardiol 183:47–53 118. Cruz DN, Goh CY, Marenzi G, Corradi V, Ronco C, Perazella MA 102. Thompson K, Razi R, Lee MS et al (2016) Statin use prior to (2012) Renal replacement therapies for prevention of angiography for the prevention of contrast-induced acute kidney radiocontrast-induced nephropathy: a systematic review. Am J injury: a meta-analysis of 19 randomised trials. EuroIntervention Med 125:66–78 12:366–374 119. Song K, Jiang S, Shi Y, Shen H, Shi X, Jing D (2010) Renal 103. Wang N, Qian P, Yan TD, Phan K (2016) Periprocedural effects of replacement therapy for prevention of contrast-induced acute kid- statins on the incidence of contrast-induced acute kidney injury: A ney injury: a meta-analysis of randomized controlled trials. Am J systematic review and trial sequential analysis. Int J Cardiol 206: Nephrol 32:497–504 143–152 120. Reinecke H, Fobker M, Wellmann J et al (2007) A randomized 104. Wu H, Li D, Fang M, Han H, Wang H (2015) Meta-analysis of controlled trial comparing hydration therapy to additional hemo- short-term high versus low doses of atorvastatin preventing dialysis or N-acetylcysteine for the prevention of contrast contrast-induced acute kidney injury in patients undergoing coro- medium-induced nephropathy: the Dialysis-versus-Diuresis nary angiography/percutaneous coronary intervention. J Clin (DVD) trial. Clin Res Cardiol 96:130–139 Pharmacol 55:123–131 121. Weisbord SD, Bernardini J, Mor MK et al (2006) The effect of 105. Yang Y, Wu YX, Hu YZ (2015) Rosuvastatin treatment for coronary angiography on residual renal function in patients on preventing contrast-induced acute kidney injury after cardiac cath- peritoneal dialysis. Clin Cardiol 29:494–497 eterization: a meta-analysis of randomized controlled trials. 122. Choi MJ, Yoon JW, Han SJ et al (2014) The prevention of Medicine 94:e1226 contrast-induced nephropathy by simultaneous hemofiltration 106. Vanmassenhove J, Vanholder R, Lameire N (2016) Statins for the during coronary angiographic procedures: a comparison with prevention of contrast-induced acute kidney injury. Curr Opin periprocedural hemofiltration. Int J Cardiol 176:941–945 Nephrol Hypertens 25:508–517 123. Nadkarni GN, Konstantinidis I, Patel A et al (2015) Trimetazidine decreases risk of contrast-induced nephropathy in patients with 107. Giacoppo D, Capodanno D, Capranzano P, Aruta P, Tamburino C chronic kidney disease: a meta-analysis of randomized controlled (2014) Meta-analysis of randomized controlled trials of trials. J Cardiovasc Pharmacol Ther 20:539–546 preprocedural statin administration for reducing contrast-induced acute kidney injury in patients undergoing coronary catheteriza- 124. Ye Z, Lu H, Su Q et al (2017) Clinical effect of trimetazidine on tion. Am J Cardiol 114:541–548 prevention of contrast-induced nephropathy in patients with renal 108. Han Y, Zhu G, Han L et al (2014) Short-term rosuvastatin therapy insufficiency: an updated systematic review and meta-analysis. for prevention of contrast-induced acute kidney injury in patients Medicine 96:e6059 with diabetes and chronic kidney disease. J Am Coll Cardiol 63: 125. Bilasy ME, Oraby MA, Ismail HM, Maklady FA (2012) 62–70 Effectiveness of theophylline in preventing contrast-induced ne- 109. Brueck M, Cengiz H, Hoeltgen R et al (2013) Usefulness of N- phropathy after coronary angiographic procedures. J Interv acetylcysteine or ascorbic acid versus placebo to prevent contrast- Cardiol 25:404–410 induced acute kidney injury in patients undergoing elective cardi- 126. Dai B, Liu Y, Fu L, Li Y, Zhang J, Mei C (2012) Effect of theoph- ac catheterization: a single-center, prospective, randomized, dou- ylline on prevention of contrast-induced acute kidney injury: a ble-blind, placebo-controlled trial. J Invasive Cardiol 25:276–283 meta-analysis of randomized controlled trials. Am J Kidney Dis 60:360–370 110. Dvorsak B, Kanic V, Ekart R, Bevc S, Hojs R (2013) Ascorbic acid for the prevention of contrast-induced nephropathy after cor- 127. Matejka J, Varvarovsky I, Vojtisek P et al (2010) Prevention of onary angiography in patients with chronic renal impairment: a contrast-induced acute kidney injury by theophylline in elderly randomized controlled trial. Ther Apher Dial 17:384–390 patients with chronic kidney disease. Heart Vessels 25:536–542 111. Li R, Chen H (2012) Prevention of contrast-induced nephropathy 128. Miao Y, Zhong Y, Yan H, Li W, Wang BY, Jin J (2013) Alprostadil with ascorbic acid. Heart 98:E211 plays a protective role in contrast-induced nephropathy in the el- 112. Albabtain MA, Almasood A, Alshurafah H, Alamri H, Tamim H derly. Int Urol Nephrol 45:1179–1185 (2013) Efficacy of ascorbic acid, N-acetylcysteine, or combination 129. Ye Z, Lu H, Guo W et al (2016) The effect of alprostadil on of both on top of saline hydration versus saline hydration alone on preventing contrast induced nephropathy for percutaneous coro- prevention of contrast-Induced nephropathy: a prospective ran- nary intervention in diabetic patients: a systematic review and domized study. J Interv Cardiol 26:90–96 meta-analysis. Medicine 95:e5306 113. Zhou L, Chen H (2012) Prevention of contrast-induced nephrop- 130. Thamcharoen N, Thongprayoon C, Edmonds PJ, Cheungpasitporn athy with ascorbic acid. Intern Med 51:531–535 W (2015) Periprocedural nebivolol for the prevention of contrast- 114. Shakeryan F, Sanati H, Fathi H et al (2013) Evaluation of combi- induced acute kidney injury: a systematic review and meta-analy- nation therapy with vitamin C and pentoxifylline on preventing sis. N Am J Med Sci 7:446–451 kidney failure secondary to intravenous contrast material in coro- 131. Naeem M, McEnteggart GE, Murphy TP, Prince E, Ahn S, Soares nary angioplasty. Iran Heart J 14:17–21 G (2015) Fenoldopam for the prevention of contrast-induced Eur Radiol (2018) 28:2856–2869 2869 nephropathy (CIN) - do we need more trials? A meta-analysis. lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology 254:261–269 Clin Imaging 39:759–764 132. Kassis HM, Minsinger KD, McCullough PA, Block CA, Sidhu 139. Thomsen HS, Morcos SK, ESUR CMSC (1999) Contrast media MS, Brown JR (2015) A review of the use of Iloprost, a synthetic and metformin: guidelines to diminish the risk of lactic acidosis in prostacyclin, in the prevention of radiocontrast nephropathy in non-insulin-dependent diabetics after administration of contrast patients undergoing coronary angiography and intervention. Clin media. Eur Radiol 9:738-740 Cardiol 38:492–498 140. Food and Drug Administration (FDA) (2016) FDA revises warn- 133. Inzucchi SE, Bergenstal RM, Buse JB et al (2015) Management of ings regarding use of the diabetes medicine metformin in certain hyperglycemia in type 2 diabetes, 2015: a patient-centered ap- patients with reduced kidney function. http://www.fda.gov/Drugs/ proach: update to a position statement of the American Diabetes DrugSafety/ucm493244.htm. Accessed 15 December 2017 Association and the European Association for the Study of 141. ACR Committee on Drugs and Contrast Media (2017) ACR man- Diabetes. Diabetes Care 38:140–149 ual on contrast media, v10.3. American College of Radiology. 134. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK (2014) https://www.acr.org/-/media/ACR/Files/Clinical-Resources/ Metformin in patients with type 2 diabetes and kidney disease: a Contrast_Media.pdf. Accessed 15 December 2017 systematic review. JAMA 312:2668–2675 142. Morcos SK, Thomsen HS, Webb JA (2002) Dialysis and contrast 135. Lu WR, Defilippi J, Braun A (2013) Unleash metformin: recon- media. Eur Radiol 12:3026–3030 sideration of the contraindication in patients with renal impair- 143. Gabutti L (2003) Does continuous venovenous hemodiafiltration ment. Ann Pharmacother 47:1488–1497 concomitant with radiological procedures provide a significant 136. Richy FF, Sabido-Espin M, Guedes S, Corvino FA, Gottwald- and safe removal of the iodinated contrast ioversol? Blood Purif Hostalek U (2014) Incidence of lactic acidosis in patients 21:152–157 with type 2 diabetes with and without renal impairment treat- 144. Shinoda T, Hata T, Nakajima K, Yoshimoto H, Niwa A (2002) ed with metformin: a retrospective cohort study. Diabetes Time-course of iodine elimination by hemodialysis in patients Care 37:2291–2295 with renal failure after angiography. Ther Apher 6:437–442 137. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE (2010) Risk of 145. Younathan CM, Kaude JV, Cook MD, Shaw GS, Peterson JC (1994) fatal and nonfatal lactic acidosis with metformin use in type 2 Dialysis is not indicated immediately after administration of nonion- diabetes mellitus. Cochrane Database Syst Rev 14:CD002967 ic contrast agents in patients with end-stage renal disease treated by 138. Goergen SK, Rumbold G, Compton G, Harris C (2010) Systematic maintenance dialysis. AJR Am J Roentgenol 163:969–971 review of current guidelines, and their evidence base, on risk of
European Radiology – Springer Journals
Published: Feb 7, 2018
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
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
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.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera