UBC Faculty Research and Publications

Effectiveness of contrast-associated acute kidney injury prevention methods; a systematic review and… Ahmed, Khalid; McVeigh, Terri; Cerneviciute, Raminta; Mohamed, Sara; Tubassam, Mohammad; Karim, Mohammad; Walsh, Stewart Nov 13, 2018

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata


52383-12882_2018_Article_1113.pdf [ 2.19MB ]
JSON: 52383-1.0373703.json
JSON-LD: 52383-1.0373703-ld.json
RDF/XML (Pretty): 52383-1.0373703-rdf.xml
RDF/JSON: 52383-1.0373703-rdf.json
Turtle: 52383-1.0373703-turtle.txt
N-Triples: 52383-1.0373703-rdf-ntriples.txt
Original Record: 52383-1.0373703-source.json
Full Text

Full Text

RESEARCH ARTICLE Open AccessEffectiveness of contrast-associated acutekidney injury prevention methods; asystematic review and network meta-analysisKhalid Ahmed1,2* , Terri McVeigh1, Raminta Cerneviciute1, Sara Mohamed1, Mohammad Tubassam2,Mohammad Karim3 and Stewart Walsh1,2,4AbstractBackground: Different methods to prevent contrast-associated acute kidney injury (CA-AKI) have been proposed inrecent years. We performed a mixed treatment comparison to evaluate and rank suggested interventions.Methods: A comprehensive Systematic review and a Bayesian network meta-analysis of randomised controlledtrials was completed. Results were tabulated and graphically represented using a network diagram; forest plots andleague tables were shown to rank treatments by the surface under the cumulative ranking curve (SUCRA). A stackedbar chart rankogram was generated. We performed main analysis with 200 RCTs and three analyses according tocontrast media and high or normal baseline renal profile that includes 173, 112 & 60 RCTs respectively.Results: We have included 200 trials with 42,273 patients and 44 interventions. The primary outcome was CI-AKI,defined as ≥25% relative increase or≥ 0.5 mg/dl increase from baseline creatinine one to 5 days post contrastexposure. The top ranked interventions through different analyses were Allopurinol, Prostaglandin E1 (PGE1) & Oxygen(0.9647, 0.7809 & 0.7527 in the main analysis). Comparatively, reference treatment intravenous hydration was rankedlower but better than Placebo (0.3124 VS 0.2694 in the main analysis).Conclusion: Multiple CA-AKI preventive interventions have been tested in RCTs. This network evaluates data for all theexplored options. The results suggest that some options (particularly allopurinol, PGE1 & Oxygen) deserve furtherevaluation in a larger well-designed RCTs.Keywords: Contrast induced acute kidney injury, Contrast nephropathy, Prevention methods, Contrast associatedacute kidney injuryBackgroundRationaleContrast Associated acute kidney injury (CA-AKI) alsoknown as Contrast-induced acute kidney injury (CI-AKI)previously known as contrast induced nephropathy(CIN) is the third leading cause of hospital-acquiredacute renal injury, accounting for 12% of cases [1]. It isdefined as an abrupt deterioration in renal functionfollowing exposure to contrast media (CM) in the ab-sence of other aetiological factors [2]. The absolute andrelative values used to define CI-AKI vary, but are mostcommonly quoted as a relative increase of > 25% or anabsolute increase of 0.5 mg/dL and ≥ 0.3 mg from base-line serum creatinine measurement within 1–3 (4–5 daysless frequently used) of contrast exposure [3–7]. InCI-AKI, the serum creatinine level begins to rise within24 h of contrast exposure, peaking after 72 h, andusually returning to baseline within 1–3 weeks [6].The proposed pathophysiology of CI-AKI is acute tubu-lar necrosis. The underlying mechanisms are thought tobe vasoconstriction, leading to cellular hypoxia, or direct* Correspondence: Khalidmd20@gmail.com1Lambe Institute for Translational Research, Discipline of Surgery NationalUniversity of Ireland, Galway, Republic of Ireland2Department of Vascular surgery, Galway University Hospital, Galway,Republic of IrelandFull list of author information is available at the end of the article© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Ahmed et al. BMC Nephrology          (2018) 19:323 https://doi.org/10.1186/s12882-018-1113-0toxicity of contrast media to renal tubular cells [8, 9].Multiple therapies have been postulated to preventCI-AKI act by affecting these mechanisms or their meta-bolic mediators.There is ongoing discussion about the impact of newcontrast media on the size of the problem and the out-comes of prevention methods or even the existence ofthe problem, on the other side these conclusions werechallenged as coming only from retrospective studiesthat does not take in account patients factors or indica-tions for using contrast media in deferent cases with def-erent baseline renal profile [10, 11].In recent years, there have been many systematic re-views and meta-analyses for direct pair-wise compari-sons of individual interventions suggested for CI-AKIprevention. With so many options explored, it is difficultto determine the treatment options most likely to showbenefit in large-scale trials. Unlike conventionalmeta-analysis, Network facilitates simultaneous compari-son of indirect relationships between multiple interven-tions. The network can establish an estimate ofcomparative efficacy between two or more treatmentscompared to the same control intervention [12–14]. Weundertook a network-meta-analysis of preventive strat-egies for CA-AKI to determine the treatment most likelyto be beneficial based upon currently available evidence.MethodsWe conducted a systematic review and networkmeta-analysis in accordance with the PRISMA extensionfor Network Meta-Analyses [15].Protocol and registrationNo registered protocol.Eligibility criteriaWe consider all randomized controlled trials in whichpatients underwent a contrast-enhanced procedure withCI-AKI as a primary or secondary outcome. We evaluatestudies in which a prevention method was compared toplacebo, control or other intervention. Excluded fromthe analysis were other research designs, includingnon-randomised control trials; clinical trials; trials com-paring different doses of the same intervention and trialsusing re-randomization of the same sample (Crossoverdesign). For this review, we defined CI-AKI as an in-crease of more than or equal to 0.5 mg/dl and/or 25%increase in baseline serum Creatinine one to 5 days postcontrast exposure [3].Information sourcesWe searched for English-language trials in PubMed,Embase and Cochrane Central Register of ControlledTrials without any date restrictions. The final search wasundertaken on 25th April 2017.Search strategy and study selectionTwo authors (Ahmed, Walsh) searched Electronic data-bases using Mesh terms “contrast nephropathy”, “con-trast nephropathy prophylaxis”, “contrast nephropathyprevention”, with the Boolean operator “OR” as appro-priate. Titles and abstracts of identified studies wereassessed first, with full texts reviewed thereafter. Thestudy was included if the methodology fulfilled inclusioncriterion.Data collectionData were recorded concerning sample size, adverseevents, procedures performed, study inclusion and ex-clusion criteria, intervention type and dose, contrastmedia volume, CI-AKI definition, and contrast mediumtype and osmolality.The geometry of the networkA network diagram was created using NetMetaXL tool tographically represent the size of the trial and the numberof pairwise comparisons between interventions. The sizeof each intervention node is proportional to a number ofpatients included in the trial, while the thickness of inter-connecting lines is proportional to the number of pairwisecomparisons between any two interventions.Risk of biasThe Cochrane tool for risk of bias assessment (RevMan5.3) was used to assess bias within individual studies. Abias graph was generated to portray the risk of bias over-all across the included trials.Summary measuresOdds ratios with 95% confidence intervals were calcu-lated and presented in the form of Forest plots we gen-erated a league table, which ranks summary estimates inorder of the impact of the intervention on the primaryoutcome measure [10]. In the league table, interventionswere ranked from those with the highest effect to thelowest. A stacked bar chart rankogram was also createdto represent ranking probabilities and their uncertainty.Analysis methodsData with respect to events and number of patients inindividual trials were prepared and entered using Net-MetaXL [16], to facilitate completion of a Bayesian net-work meta-analysis using WinBUGS version 1.4.3 fromwithin Microsoft excel. We used the Markov ChainMonte Carlo method of parameter estimation to obtainposterior estimates of effects. Both vague prior and in-formative prior results were presented in the Forest Plot.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 2 of 18Zero cells were adjusted using an adjusted continuitycorrection factor accounting for potential differences insample size, centered around 0.5.As NetMetaXL is a relatively new tool, we run a separ-ate set of analyses for the same data on GeMTC R pack-age to validate our results with no noticeable differences.We performed analysis with both fixed effects modelsand random effects random-effect hierarchical models.For Bayesian computation; detailed statistical approachand diagnostics are provided in Additional file 1.Assessment of consistency, model fit, and convergenceIn NetMetaXL, ‘inconsistency plot’ was generated to fa-cilitate visual assessment of conflicts between direct andindirect evidence with limitation in our analysis due to asubstantial number of nodes on excel. Heterogeneity forvague and informative priors was provided within theforest plot results & Monte Carlo error < 5% of thestandard deviation (SD) used to assess convergence.For GeMTC R package Gelman-Rubin statistics usednumerically and graphically to evaluate convergence whiledeviance information criterion (DIC) was used for deter-mining model fits and the model with smaller DIC valuewas considered better.Additional analysesIn addition to the main analysis we performed three otheranalysis, the first excluding RCTs with any partial use ofhyperosmolar contrast media and in the other two RCTswere divided according to baseline renal profile.For each of the four analyses we performed sub-analysisexcluding studies with zero values as corresponding ef-fects estimates may be subject to numerical instability,generally over-estimate the effect, and that can be ob-served in the wide associated confidence intervals.ResultsStudy selectionA total of 32,596 study titles were identified in the initialliterature search, of which 200 fulfilled criteria for inclu-sion [4, 5, 7, 17–209] (Fig. 1). Some studies were excludedas some data were partially included or re-analyzed in aFig. 1 Flow DiagramAhmed et al. BMC Nephrology          (2018) 19:323 Page 3 of 18follow-up study involved in our review [210–215]. A totalof 32,399 studies were excluded after remove duplicationthe most common reasons for exclusions after full exam-ination included observational methodology; different out-come measures, inadequate definition of CI-AKI; unclearevidence of randomization; old studies that did not com-ply with eligibility criteria for more than one reason [216–279]. The twelve studies published in a non-English lan-guage included those from centers in Germany [280, 281],China [282–287], Spain [288], France [289], Turkey [290]and Italy [291]. Eight further potentially suitable studieswere identified in abstract form only, but were excludedas no full-text article could be identified [292–299].Study characteristicsAdditional file 2 outlines individual study characteristics(study inclusion and exclusion criteria; procedure per-formed; baseline renal function; definition of CI-AKIused in the study; contrast medium volume and osmolal-ity). In total, 197studies fulfilled the inclusion criteria,including three which had multiple trial arms requiringseparate analyses (Yang 2014, Kumar 2014 & Chen2008). A total of 200 comparative analyses were there-fore included in our analyses. Coronary angiographyaccounted for 145 (72.5%) of the contrast-dependentprocedures were. Less frequently reported proceduresincluded contrast-enhanced CT imaging (n = 16, 8%),peripheral angiography with/without angioplasty andstenting (n = 3, 1.5%) endovascular aneurysm repairs(EVAR) (n = 1, 0.5. %). Multiple procedures were in-cluded in 35 studies (17.5%). Low osmolar contrastagents were used in 111 (55.5%), iso-osmolar agents in44 studies (22%), and hi-osmolar media in 3 studies(1.5%). Twenty-six (13%) trials permitted physician dis-cretion in the selection of contrast media, while a fur-ther 16 (8%) did not specify the contrast mediumutilized. More recent studies we observed better designwith an exclusion for patients using alternative CI-AKIprevention interventions from participation or stratifiedthose methods among arms of the trial.Network structureThe relationship and comparisons between includedstudies are demonstrated in the network diagram (Fig. 2).Forty-four interventions are included in this network(Table 1).Network geometryData from 42,273 patients recruited to 200 trials investi-gating 44 interventions were included in our analyses; asummary of network characteristics is provided in(Table 2). Nine hundred and forty-six pair-wise compari-sons were possible, of which 81 used data from directcomparisons in Additional file 3. The most commonlyinvestigated comparisons are between N-acetylcysteine(NAC) and placebo (36 studies, 8,202patients); andintravenous normal saline and intravenous sodium bicar-bonate (24 studies, 5,481patients). The interventionsmost commonly investigated were NAC, NaHCO3, Sta-tins, Intravenous Hydration (I.V), and placebo or con-trol. The characteristics of individual interventions areoutlined in Additional file 3.Risk of biasRisk of bias assessed by two authors (Khalid, Walsh). Incase of disagreement, other authors were consulted. Sum-mary for individual studies provided in Additional file 4while (Fig. 3) shows the risk of bias graph across all stud-ies. Most of the studies demonstrated unclear to low riskof bias while most of the high risk of bias were observedin attrition bias domain. As the outcome measure (CA-AKI) is dependent on laboratory results it seems reason-able to assume the risk of bias attributed to blinding ofoutcome assessment domain was low by default.Synthesis of resultsThe Renal Association, British Cardiovascular Interven-tion Society and the Royal College of Radiologists amongmany other medical bodies recommend using intravenousvolume expansion as a prevention method for CA-AKI[300]. Thus, we considered intravenous hydration clinic-ally the reference intervention in this analysis, in additionto the node size and the multiple arms within the networkwhich make it very good comparator.A forest plot was generated to demonstrate odds ratiogenerated from direct and indirect pair-wise compari-sons. Effect estimates, and confidence intervals were in-cluded for both vague and informative priors using arandom effects model. The overall heterogeneity for thevague prior was 0.54 (95% CI 0.41–0.69), while that forinformative prior was 0.498 (95% CI 0.366–0.6403). TheSUCRA (surface under the cumulative ranking curve)was utilized to generate a stacked bar chart rankogram(Fig. 4). A league table arranging summary of effectestimate, and ranking interventions according to impacton the outcome can be found in Additional file 3 inaddition to the Forest Plot, characteristics of interven-tions and comparisons and analysis specifications. Theprobabilities of being ranked for the best each interven-tion is summarized in (Table 3) while the numericalvalues follow the Rankogram results the list of interven-tions in the first column follow the league table hier-archy and a good example is Allopurinol which includedin 4 studies ranked best in both Rankogram (0.9647) andLeague Table while Silymarin was 3rd (0.7934) and lastrespectively and was included in one study.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 4 of 18Sensitivity analysisFlow chart for the main analyses and sub-analyses isincluded in Additional file 1. From the main analysis200 RCTs we run sub-analysis that includes 184RCTS in which we exclude all studies with zerovalues (n = 7). All figures and tables are included inAdditional file 3.The second analysis involved 173 RCTs after excludingstudies reporting any use of hyperosmolar contrastmedia, the sub-analysis without zero values RCTs in-clude 159 RCTS.Trials with high baseline renal profile were in analysis 3which includes 112 RCTs and sub-analysis for 105 RCTS.The 4th analysis includes 60 and 53 RCTs respectively.Analysis specifications, figures and tables provided inAdditional file 5, Additional file 6 and Additional file 7.When interpreting sub-analyses results in conventionaldirect pairwise comparisons the main effect results fromthe size of the excluded studies because there is no ex-clusion for interventions and they will always be presentat both sides of the forest plot. This impact the overalldiamond shape effect estimates size and confidenceFig. 2 Network Diagram: The size of each intervention node is proportional to the number of patients included in the trials, while the thicknessof interconnecting lines is proportional to the number of pairwise comparisons between any two interventionsAhmed et al. BMC Nephrology          (2018) 19:323 Page 5 of 18interval will either shift towards one treatment or touch-ing the line of no effect indicating no superiority for anyintervention. This is different in Network Meta-analysisin which we can see changes in connections dynamic(Network Diagram) and interventions numbers repre-sented by node sizes and number of connections be-tween them both can be affected or totally removed bythe excluding studies. In the latter case the NetworkDiagram and characteristics of interventions and com-parisons provide detailed visualization to help comparethe main vs sub-analysis. In Additional file 3, Additionalfile 5, Additional file 6 and Additional file 7 we detailedall excluded studies, the affected interventions, NetworkDiagrams and the characteristics of the interventionsand comparisons.Assessment of consistencyAn ‘inconsistency plot’ (Fig. 5) was generated to assessinconsistency. Inconsistency in network meta-analysis issimilar to heterogeneity in conventional meta-analysis butconsistency concerns the relation between the treatmentswhereas heterogeneity concerns the variation betweentrials within a pairwise comparison between two treat-ments. Inconsistency is caused by imbalances in the distri-bution of effect modifiers in the direct and indirectevidence. Effects modifiers in this large sample includebut are not limited to patient factors, drug interactions,contrast media volume and type and renal function pre-intervention. Inevitably, some modifiers exist that cannotbe completely eliminated in large multi-treatment networkmeta-analysis, leading to some inconsistency, indicating aneed for careful interpretation of the results [301]. Theconsistency plot shows individual data points’ posteriormean deviance contributions for the consistency model(horizontal axis) and the unrelated mean effects model(vertical axis) along with the line of equality. In our analysis,the main limitation is excel inability to handle a largeamount of nodes. However, there should be a considerationTable 1 Interventions within Network DiagramNO Drug Abbreviation Patients1 I.V Hydration I.V 51362 Statins Sta 30403 Furosemide Fur 5544 NAC NAC 60955 Trimetazidine Tri 3526 NaHCO3 NaH 33937 PGE1 PGE 3048 MgSO4 MgS 629 Pentoxifylline Pen 43810 Placebo Pla 704411 Control Con 912012 Allopurinol All 20413 BNP BNP 74414 Probucol Pro 19815 α-tocopherol α-t 31216 γ-tocopherol γ-t 10217 Oxygen Oxy 34618 Amlodipine and Valsartan Aml 4519 K/Na citrate K/N 20320 Nicorandil Nic 29121 Ascorbic Acid Asc 55222 Alpha-Lipoic Acid Alp 13923 Oral Hydration Ora 25424 Nebivolol Neb 4025 Anisodamine Ani 19226 RIPC RIP 60827 Theophylline The 38428 Hypothermia Hyp 5829 Glutathione Glu 42130 MESNA MES 5131 ACEI AC 12932 Aminophylline Ami 4533 Iloprost Ilo 11834 Acetazolamide Ace 9435 ANP ANP 20236 Zinc Zin 1837 Dialysis Dia 29338 Fenoldopam Fe 33339 ERAs ER 7740 CCB CC 4241 Dopamine Do 4842 Mannitol Ma 3543 Cordyceps Co 8844 Silymarin Si 69ACEI Angiotensin Converting-Enzyme Inhibitor, ANP Atrial Natriuretic Peptide,BNP B-Type Natriuretic Peptide, CCB Calcium Channels Blockers, CI-AKI ContrastInduced Acute Kidney Injury, CIN Contrast Induced Nephropathy, ERAsEndothelin Receptor Antagonism, MESNA 2-Mercaptoethane Sulfonate Sodium,MgSo4 Magnesium Sulphate, NAC N-acetyl cysteine, NaHco3 SodiumBicarbonate, PGE1 Prostaglandin E1, RIPC Remote Ischemic PreconditioningTable 2 Network CharacteristicsCharacteristic NumberNumber of Interventions 44Number of Studies 200Total Number of Patients in Network 42,273Total Number of Events in Network 4602Total Possible Pairwise Comparisons 946Total Number Pairwise Comparisons with Direct Data 81Number of Two-arm Studies 179Number of Multi-Arms Studies 21Number of Studies with No Zero Events 184Number of Studies With At Least One Zero Event 16Number of Studies with All Zero Events 2Ahmed et al. BMC Nephrology          (2018) 19:323 Page 6 of 18Fig. 3 Risk of Bias GraphFig. 4 Rankogram: ranking the interventions for the probability of being the best, the interventions are colour coded; the first column representsthe chance of being first best and 2nd column is the chance of being 2nd best and so on. i.e. the first column represent the chance of being firstbest cmparing all interventions out of100% and the second represent the chance of being second best out of 100% up to last column in thiscase number 44 (nuber of interventions); the overall ranking for each treatment is the sum of scores through out the 44 compasrisons. Theoverall numerical value is presented in Table 3Ahmed et al. BMC Nephrology          (2018) 19:323 Page 7 of 18of individual pairwise comparisons effect estimates gener-ated within the forest plot.In GeMTC R analyses I2 statistics and DIC was muchsmaller for Random effect indicating less heterogeneitycompared with a fixed effect which is expected to pro-vide the nature of the network. Detailed scores are pre-sented in Additional file 1 while Gelman and Rubin’sconvergence diagnostics were added to correspondedanalyses in Additional file 3, Additional file 5, Additionalfile 6 and Additional file 7.In general, the main analysis reviled some interesting re-sults with Allopurinol, Prostaglandin E1 (PGE1) & Oxygenwere ranked high with good both statistical and clinicaloutcomes in relatively fewer number of studies comparingwith other interventions studied in larger number of RCTse.g. NAC, Statins, Hydration, NaHco3 and RIPC. The re-sults were stable throughout different sub analysis consid-ering the changes in network diagram being affected byexcluded studies in all 7 networks. The model fitting andthe consistency within the network was good consideringthe large size and it is understandable that it was better fit-ted in the 7 sub-groups analysis specially after excludingzero values studies. It is very important here to rememberin network ranking is the probability of being the bestwithin the interventions and we need to look at the forestplot for each comparison.DiscussionSummary of evidenceThis is a systematic review and network meta-analysis(multi-treatment comparison) of studies investigatingmethods for the prevention of contrast-induced nephrop-athy. We identified 200 eligible trials, of which 3 had 2different arms and thus analysed separately. Data from atotal of 42,273 patients undergoing 44 different interven-tions were included. Intravenous hydration (Nacl) wasused as the reference treatment as there is a consensussupported by evidence accepting it as a method of preven-tion with no clear superiority for other I.V fluids [81]. inour network it was also included in many multiple armsTable 3 Interventions ranking the treatments names columnfollow the league table (which arranges the presentation ofsummary estimates by ranking the treatments in order of mostpronounced impact on the outcome under consideration) thenumerical values represents the cumulative results of theprobability of being best in which the highest score is 1 or100% (see Rankogram)Treatment SUCRA Treatment SUCRAAllopurinol 0.9647 NaHCO3 0.3419MESNA 0.9427 Pentoxifylline 0.3391PGE1 0.7809 I.V Hydration 0.3124α-tocopherol 0.7614 Placebo 0.2694Oxygen 0.7527 Oral Hydration 0.2517K/Na citrate 0.7469 Hypothermia 0.2021Trimetazidine 0.7151 Control 0.1658Probucol 0.7042 Amlodipine and Valsartan 0.05485γ-tocopherol 0.689 ACEI 0.5783BNP 0.6767 Aminophylline 0.6593Anisodamine 0.6594 Iloprost 0.7481Nicorandil 0.6442 Acetazolamide 0.6242Theophylline 0.629 ANP 0.3291RIPC 0.5692 Zinc 0.198Statins 0.5497 Dialysis 0.4319MgSO4 0.5177 Fenoldopam 0.2296NAC 0.4592 ERAs 0.06734Nebivolol 0.4543 CCB 0.7249Ascorbic Acid 0.4433 Dopamine 0.1916Alpha-Lipoic Acid 0.4322 Mannitol 0.1905Furosemide 0.4027 Cordyceps 0.4459Glutathione 0.3554 Silymarin 0.7934Analysis Random Effects (Vague)Fig. 5 Inconsistency Plot: Inconsistency is similar to heterogeneity in conventional meta-analysis, but consistency concerns the relation betweenthe direct and indirect evidence. The consistency plot shows individual data points’ posterior mean deviance contributions for the consistencymodel (horizontal axis) and the unrelated mean effects model (vertical axis) along with the line of equalityAhmed et al. BMC Nephrology          (2018) 19:323 Page 8 of 18RCTs which make it statistically a very good comparator.While only randomized control trials were included, de-fining the outcome and inclusion criteria, help tominimize the number of effect modifiers at play in differ-ent studies, thus minimising inconsistency. However, theassumption of homogeneity should be accepted with cau-tion in light of the large numbers of trials and patientsincluded.It is very important for readers more familiar withgeneral probability measure in which the value one isassigned to the entire probability space to recognizethat SUCRA use posterior probabilities for each treat-ment to be among the n - best options (cumulativeprobabilities) thus the sum add to > 1. The word bestreferred to the number of times that an interventionranks first out of the total number of random sam-ples [14] In Rankogram the first column representthe chance of being first best out of100% and the sec-ond represent the chance of being second best up tolast column; the overall ranking for each treatment isthe sum and that the reason each treatment probabil-ity is calculated out of 100%.We can generally categorize the 44 ranked interven-tions in groups. The first group is high ranked interven-tions with relatively fewer number of studies and thisgroup is mainly for further research consideration des-pite good design RCTs, good clinical outcomes, and ourconscious effort to eliminate the effect of small node ef-fect on the network and the fact we accommodate andaccounted for the different in interventions size whencalculating the probability but we cannot ignore that thismay still play in favour of small studies and we thinkthey deserve another look with larger well-designed tri-als, this group includes mainly Allopurinol, Prostaglan-din E1 (PGE1) & Oxygen; Allopurinol a xanthineoxidase Inhibitor used for treatment of gout and man-agement of hyperuricemia associated with chemotherapyand was assessed in 4 trials with 204 patients with recentpublished evidence suggesting some benefits [302] whilePGE1 in 4 trails with total 304 patients. InterestinglyOxygen was highly ranked before and after exclusion ofzero events studies and the total number of patients was346 in 2 studies.The scorned group is the middle group which includedin decent number of studies and the interventions in thisgroup with safe and or well tested profile can be used inpatient care at the same time continuously evaluatedand this group can include RIPC, Statins (which usuallyin use specially by cardiac and vascular patients), NAC,NaHco3, I.V hydration, Oral hydration and hypothermia.This group needed the physician to consult his localguidelines after evaluating each patient individually andsome interventions like hypothermia is not applicablefor all patients.The sub-analyses in our network for was performedafter excluding studies with zero events to eliminate favor-able effect profile. It produced better statistical results andhelped compare the results without the interventions in-volved in a small number of trials.Research & Clinical impactFor health care providers, the results of this meta-analysisdo not suggest changes to current clinical practice. Theprevention methods assessed in large studies should beevaluated on a case-by-case basis, bearing in mind the co-morbidities, clinical needs and prior risk factors of the in-dividual patient with special consideration to national andlocal guidelines. Interventions with safe profile and sup-portive evidence from direct pair-wise meta-analysis canbe considered as additional or second-line therapies forCA-AKI prevention. For clinical researchers, the highly-ranked treatments with relatively small number of trialsmerit further examonation in larger RCTs.LimitationsOne limitation of this meta-analysis is the exclusion ofnon-English language studies (n = 12). The inclusion ofthese studies may add to the supportive evidence for theuse of some interventions, although the effect size ofthese trials is likely to be minimal in light of the samplesizes in question. Another limitation is the difference incontrast media used which may affect the outcomes; weexcluded studies that used hyperosmolar contrast mediato minimise this effect with some evidence suggestingsimilar CIN incidence for iso and low-osmolar CM incoronary angiography patients [303]. In large Network,another consideration is our inability to account forother possible effect modifiers, and our assumptions re-garding homogeneity and similarity across a large num-ber of studies thus it is important to look at eachintervention ranking through the multiple analyses pro-vided in the supplemnts.While preparing this network meta-analysis a pairwisemeta-analysis was published .comparing N-acetylcysteine,sodium bicarbonate, statins and ascorbic acid for CA-AKIreduction [304]. The data was obtained from controlledtrials that used intravenous (IV) or intra-arterial contrast.The results of statins plus I.V saline vs I.V saline showclinically but not statistically significant difference. Whencomparing Sodium bicarbonate to I.V saline it was clinic-ally better, but again the difference was not statistically sig-nificant. However Ascorbic acid was better both clinicallyand statistically vs I.V saline and show no such differencewhen compared with NAC. A similar result can be ob-served in our ranking table with 0.5497, 0.4433, 0.3419and 0.3124 probability of being rank for statins, ascorbicacid, Sodium bicarbonate and I.V saline consequently. Al-though direct comparisons results were provided withinAhmed et al. BMC Nephrology          (2018) 19:323 Page 9 of 18forest plot in our network, we think the results from pair-wise reviews is important; the nature of conventionalmeta-analysis prevent utilization of multiple arms trialsand creating indirect comparison but it can be used tolook at sections of more comprehensive network-meta-analysis in addition to the fact that It is more flexible interms of subgroup analysis and thus assessment of effectsmodifiers e.g. type of contrast media in this case.ConclusionThis systematic review and network meta-analysis pro-vide a comprehensive analysis of currently utilized CA-AKI prevention interventions. Results arising from thisnetwork identified some highly-ranked interventionsthroughout analyses and sub-analyses (e.g., Allopurinol,PGE1 & Oxygen) which were included in small numberof trials and merit further examination on a larger scalein the context of a well-designed RCTs.Additional filesAdditional file 1: Analysis flow chart and statistical approach. (DOCX 125 kb)Additional file 2: Studies characteristics. (DOCX 889 kb)Additional file 3: Main Analysis 200–184 RCTs. (DOCX 46108 kb)Additional file 4: Risk of Bias Table. (DOCX 1056 kb)Additional file 5: Excluding hyperosmolar 173–159 RCTs. (DOCX 41962 kb)Additional file 6: High Baseline Renal Profile 112–105 RCTs. (DOCX 32278 kb)Additional file 7: Normal Baseline Renal Profile 60–53 RCTs. (DOCX 16081 kb)AbbreviationsACEI: Angiotensin Converting-Enzyme Inhibitor; ANP: Atrial NatriureticPeptide; BNP: B-Type Natriuretic Peptide; CCB: Calcium Channels Blockers; CI-AKI: Contrast Induced Acute Kidney Injury; CIN: Contrast InducedNephropathy; CM: Contrast Media; ERAs: Endothelin Receptor Antagonism;MESNA: 2-Mercaptoethane Sulfonate Sodium; MgSo4: Magnesium Sulphate;NAC: N-acetyl cysteine; NaHco3: Sodium Bicarbonate; PGE1: Prostaglandin E1;RCT: Randomise Control Trails; RIPC: Remote Ischemic PreconditioningAcknowledgementsWe acknowledge Ms. Geraldine Curtin and the staff in the James Hardimanlibrary, NUI Galway, for their kind assistance in acquiring relevant papers andInformation.FundingThis research was funded by the National University of Ireland Galway.Availability of data and materialsN/A (2ndry data from published studies).Authors’ contributionsKA: Study design, Literature search, figures, data collection, data Analysis, datainterpretation and writing. TM: Critical appraisal, review and edit. RC FiguresEditing: SM Figures Editing. MT Critical appraisal, review and edit. MKMethodology, statistical data analysis, data interpretation, review and edit.Professor SW: Methodology, literature search, data interpretation Criticalappraisal, review, and edit. All authors read and approved the final manuscript.Ethics approval and consent to participateN/A.Consent for publicationN/A.Competing interestsThe authors declare that they have no competing interests.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in publishedmaps and institutional affiliations.Author details1Lambe Institute for Translational Research, Discipline of Surgery NationalUniversity of Ireland, Galway, Republic of Ireland. 2Department of Vascularsurgery, Galway University Hospital, Galway, Republic of Ireland. 3School ofPopulation and Public Health, University of British Columbia, Scientist /Biostatistician, Centre for Health Evaluation and Outcome Sciences (CHEOS),St. Paul’s Hospital, Vancouver, Canada. 4HRB Clinical Research Facility Galway,Galway, Republic of Ireland.Received: 13 November 2017 Accepted: 22 October 2018References1. Mohammed NM, Mahfouz A, Achkar K, Rafie IM, Hajar R. Contrast-inducednephropathy. Heart Views. 2013;14(3):106–16.2. Goldfarb S, McCullough PA, McDermott J, Gay SB. Contrast-induced acutekidney injury: specialty-specific protocols for interventional radiology,diagnostic computed tomography radiology, and interventional cardiology.Mayo Clin Proc. 2009;84(2):170–9.3. Goldenberg I, Matetzky S. Nephropathy induced by contrast media:pathogenesis, risk factors and preventive strategies. CMAJ. 2005;172(11):1461–71.4. Castini D, Lucreziotti S, Bosotti L, Salerno Uriarte D, Sponzilli C, Verzoni A, etal. Prevention of contrast-induced nephropathy: a single center randomizedstudy. Clin Cardiol. 2010;33(3):E63–8.5. Maioli M, Toso A, Leoncini M, Gallopin M, Tedeschi D, Micheletti C, et al.Sodium bicarbonate versus saline for the prevention of contrast-inducednephropathy in patients with renal dysfunction undergoing coronaryangiography or intervention. J Am Coll Cardiol. 2008;52(8):599–604.6. Mehran R, Nikolsky E. Contrast-induced nephropathy: definition,epidemiology, and patients at risk. Kidney Int Suppl. 2006;100:S11–5.7. Spargias K, Alexopoulos E, Kyrzopoulos S, Iokovis P, Greenwood DC,Manginas A, et al. Ascorbic acid prevents contrast-mediated nephropathy inpatients with renal dysfunction undergoing coronary angiography orintervention. Circulation. 2004;110(18):2837–42.8. Tumlin J, Stacul F, Adam A, Becker CR, Davidson C, Lameire N, et al.Pathophysiology of contrast-induced nephropathy. Am J Cardiol. 2006;98(6A):14K–20K.9. Wong PC, Li Z, Guo J, Zhang A. Pathophysiology of contrast-inducednephropathy. Int J Cardiol. 2012;158(2):186–92.10. Ehrmann S, Aronson D, Hinson JS. Contrast-associated acute kidney injury isa myth: yes. Intensive Care Med. 2018;44(1):104–6.11. Weisbord SD, du Cheryon D. Contrast-associated acute kidney injury is amyth: no. Intensive Care Med. 2018;44(1):107–9.12. Thorlund K, Druyts E, Toor K, Jansen JP, Mills EJ. Incorporatingalternative design clinical trials in network meta-analyses. ClinEpidemiol. 2015;7:29–35.13. Salanti G, Higgins JP, Ades AE, Ioannidis JP. Evaluation of networks ofrandomized trials. Stat Methods Med Res. 2008;17(3):279–301.14. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numericalsummaries for presenting results from multiple-treatment meta-analysis: anoverview and tutorial. J Clin Epidemiol. 2011;64(2):163–71.15. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al.The PRISMA extension statement for reporting of systematic reviewsincorporating network meta-analyses of health care interventions: checklistand explanations. Ann Intern Med. 2015;162(11):777–84.16. Brown S, Hutton B, Clifford T, Coyle D, Grima D, Wells G, et al. AMicrosoft-excel-based tool for running and critically appraising networkmeta-analyses—an overview and application of NetMetaXL. Syst Rev.2014;3:110.17. Abaci O, Arat Ozkan A, Kocas C, Cetinkal G, Sukru Karaca O, Baydar O, et al.Impact of Rosuvastatin on contrast-induced acute kidney injury in patientsat high risk for nephropathy undergoing elective angiography. Am JCardiol. 2015;115(7):867–71.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 10 of 1818. Adolph E, Holdt-Lehmann B, Chatterjee T, Paschka S, Prott A, Schneider H,et al. Renal insufficiency following radiocontrast exposure trial (REINFORCE):a randomized comparison of sodium bicarbonate versus sodium chloridehydration for the prevention of contrast-induced nephropathy. Coron ArteryDis. 2008;19(6):413–9.19. Akyuz S, Karaca M, Kemaloglu Oz T, Altay S, Gungor B, Yaylak B, et al.Efficacy of oral hydration in the prevention of contrast-induced acutekidney injury in patients undergoing coronary angiography or intervention.Nephron Clin Pract. 2014;128(1–2):95–100.20. Albabtain MA, Almasood A, Alshurafah H, Alamri H, Tamim H. Efficacyof ascorbic acid, N-acetylcysteine, or combination of both on top ofsaline hydration versus saline hydration alone on prevention ofcontrast-induced nephropathy: a prospective randomized study. J IntervCardiol. 2013;26(1):90–6.21. Allaqaband S, Tumuluri R, Malik AM, Gupta A, Volkert P, Shalev Y, et al.Prospective randomized study of N-acetylcysteine, fenoldopam, and salinefor prevention of radiocontrast-induced nephropathy. Catheter CardiovascInterv. 2002;57(3):279–83.22. Amini M, Salarifar M, Amirbaigloo A, Masoudkabir F, Esfahani F. N-acetylcysteine does not prevent contrast-induced nephropathy after cardiaccatheterization in patients with diabetes mellitus and chronic kidneydisease: a randomized clinical trial. Trials. 2009;10:45.23. Angoulvant D, Cucherat M, Rioufol G, Finet G, Beaune J, Revel D, et al. Preventingacute decrease in renal function induced by coronary angiography (PRECORD): aprospective randomized trial. Arch Cardiovasc Dis. 2009;102(11):761–7.24. Aslanger E, Uslu B, Akdeniz C, Polat N, Cizgici Y, Oflaz H. Intrarenal applicationof N-acetylcysteine for the prevention of contrast medium-inducednephropathy in primary angioplasty. Coron Artery Dis. 2012;23(4):265–70.25. Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapidprotocol for the prevention of contrast-induced renal dysfunction: theRAPPID study. J Am Coll Cardiol. 2003;41(12):2114–8.26. Balderramo DC, Verdu MB, Ramacciotti CF, Cremona LS, Lemos PA, Orias M,et al. Renoprotective effect of high periprocedural doses of oral N-acetylcysteine in patients scheduled to undergo a same-day angiography.Rev Fac Cien Med Univ Nac Cordoba. 2004;61(2):13–9.27. Baskurt M, Okcun B, Abaci O, Dogan GM, Kilickesmez K, Ozkan AA, et al. N-acetylcysteine versus N-acetylcysteine + theophylline for the prevention ofcontrast nephropathy. Eur J Clin Investig. 2009;39(9):793–9.28. Berwanger O, Cavalcanti AB, Sousa AM, Buehler A, Castello-Junior HJ,Cantarelli MJ, et al. Acetylcysteine for the prevention of renal outcomes inpatients with diabetes mellitus undergoing coronary and peripheralvascular angiography: a substudy of the acetylcysteine for contrast-inducednephropathy trial. Circ Cardiovasc Interv. 2013;6(2):139–45.29. Bidram P, Roghani F, Sanei H, Hedayati Z, Golabchi A, Mousavi M, et al.Atorvastatin and prevention of contrast induced nephropathy followingcoronary angiography. J Res Med Sci. 2015;20(1):1–6.30. Bilasy ME, Oraby MA, Ismail HM, Maklady FA. Effectiveness of theophylline inpreventing contrast-induced nephropathy after coronary angiographicprocedures. J Interv Cardiol. 2012;25(4):404–10.31. Boscheri A, Weinbrenner C, Botzek B, Reynen K, Kuhlisch E, Strasser RH.Failure of ascorbic acid to prevent contrast-media induced nephropathy inpatients with renal dysfunction. Clin Nephrol. 2007;68(5):279–86.32. Boucek P, Havrdova T, Oliyarnyk O, Skibova J, Pecenkova V, Pucelikova T, etal. Prevention of contrast-induced nephropathy in diabetic patients withimpaired renal function: a randomized, double blind trial of sodiumbicarbonate versus sodium chloride-based hydration. Diabetes Res ClinPract. 2013;101(3):303–8.33. Brar SS, Shen AY, Jorgensen MB, Kotlewski A, Aharonian VJ, Desai N, et al.Sodium bicarbonate vs sodium chloride for the prevention of contrastmedium-induced nephropathy in patients undergoing coronaryangiography: a randomized trial. JAMA. 2008;300(9):1038–46.34. Briguori C, Airoldi F, D’Andrea D, Bonizzoni E, Morici N, Focaccio A, et al.Renal insufficiency following contrast media administration trial (REMEDIAL):a randomized comparison of 3 preventive strategies. Circulation. 2007;115(10):1211–7.35. Briguori C, Colombo A, Airoldi F, Violante A, Castelli A, Balestrieri P, et al. N-acetylcysteine versus fenoldopam mesylate to prevent contrast agent-associated nephrotoxicity. J Am Coll Cardiol. 2004;44(4):762–5.36. Briguori C, Manganelli F, Scarpato P, Elia PP, Golia B, Riviezzo G, et al.Acetylcysteine and contrast agent-associated nephrotoxicity. J Am CollCardiol. 2002;40(2):298–303.37. Brueck M, Cengiz H, Hoeltgen R, Wieczorek M, Boedeker RH,Scheibelhut C, et al. Usefulness of N-acetylcysteine or ascorbic acidversus placebo to prevent contrast-induced acute kidney injury inpatients undergoing elective cardiac catheterization: a single-center,prospective, randomized, double-blind, placebo-controlled trial. JInvasive Cardiol. 2013;25(6):276–83.38. Burns KE, Priestap F, Martin C. N-acetylcysteine in critically ill patientsundergoing contrast-enhanced computed tomography: a randomized trial.Clin Nephrol. 2010;74(4):323–6.39. Carbonell N, Blasco M, Sanjuan R, Perez-Sancho E, Sanchis J, Insa L, et al.Intravenous N-acetylcysteine for preventing contrast-induced nephropathy:a randomised trial. Int J Cardiol. 2007;115(1):57–62.40. Carbonell N, Sanjuan R, Blasco M, Jorda A, Miguel A. N-acetylcysteine: short-term clinical benefits after coronary angiography in high-risk renal patients.Rev Esp Cardiol. 2010;63(1):12–9.41. Chen SL, Zhang J, Yei F, Zhu Z, Liu Z, Lin S, et al. Clinical outcomes of contrast-induced nephropathy in patients undergoing percutaneous coronaryintervention: a prospective, multicenter, randomized study to analyze theeffect of hydration and acetylcysteine. Int J Cardiol. 2008;126(3):407–13.42. Cho R, Javed N, Traub D, Kodali S, Atem F, Srinivasan V. Oral hydration andalkalinization is noninferior to intravenous therapy for prevention ofcontrast-induced nephropathy in patients with chronic kidney disease. JInterv Cardiol. 2010;23(5):460–6.43. Cicek M, Yildirir A, Okyay K, Yazici AC, Aydinalp A, Kanyilmaz S, et al. Use ofalpha-lipoic acid in prevention of contrast-induced nephropathy in diabeticpatients. Ren Fail. 2013;35(5):748–53.44. Coyle LC, Rodriguez A, Jeschke RE, Simon-Lee A, Abbott KC, Taylor AJ.Acetylcysteine In Diabetes (AID): a randomized study of acetylcysteine forthe prevention of contrast nephropathy in diabetics. Am Heart J. 2006;151(5):1032 e9–12.45. Durham JD, Caputo C, Dokko J, Zaharakis T, Pahlavan M, Keltz J, et al. Arandomized controlled trial of N-acetylcysteine to prevent contrastnephropathy in cardiac angiography. Kidney Int. 2002;62(6):2202–7.46. Dussol B, Morange S, Loundoun A, Auquier P, Berland Y. A randomized trialof saline hydration to prevent contrast nephropathy in chronic renal failurepatients. Nephrol Dial Transplant. 2006;21(8):2120–6.47. Dvorsak B, Kanic V, Ekart R, Bevc S, Hojs R. Ascorbic acid for the preventionof contrast-induced nephropathy after coronary angiography in patientswith chronic renal impairment: a randomized controlled trial. Ther ApherDial. 2013;17(4):384–90.48. Efrati S, Dishy V, Averbukh M, Blatt A, Krakover R, Weisgarten J, et al. Theeffect of N-acetylcysteine on renal function, nitric oxide, and oxidative stressafter angiography. Kidney Int. 2003;64(6):2182–7.49. Er F, Nia AM, Dopp H, Hellmich M, Dahlem KM, Caglayan E, et al.Ischemic preconditioning for prevention of contrast medium-inducednephropathy: randomized pilot RenPro trial (renal protection trial).Circulation. 2012;126(3):296–303.50. Erley CM, Duda SH, Rehfuss D, Scholtes B, Bock J, Muller C, et al. Preventionof radiocontrast-media-induced nephropathy in patients with pre-existingrenal insufficiency by hydration in combination with the adenosineantagonist theophylline. Nephrol Dial Transplant. 1999;14(5):1146–9.51. Erol T, Tekin A, Katircibasi MT, Sezgin N, Bilgi M, Tekin G, et al. Efficacy ofallopurinol pretreatment for prevention of contrast-induced nephropathy: arandomized controlled trial. Int J Cardiol. 2013;167(4):1396–9.52. Erturk M, Uslu N, Gorgulu S, Akbay E, Kurtulus G, Akturk IF, et al. Does intravenousor oral high-dose N-acetylcysteine in addition to saline prevent contrast-inducednephropathy assessed by cystatin C? Coron Artery Dis. 2014;25(2):111–7.53. Ferrario F, Barone MT, Landoni G, Genderini A, Heidemperger M, Trezzi M, et al.Acetylcysteine and non-ionic isosmolar contrast-induced nephropathy—arandomized controlled study. Nephrol Dial Transplant. 2009;24(10):3103–7.54. Firouzi A, Eshraghi A, Shakerian F, Sanati HR, Salehi N, Zahedmehr A, et al.Efficacy of pentoxifylline in prevention of contrast-induced nephropathy inangioplasty patients. Int Urol Nephrol. 2012;44(4):1145–9.55. Firouzi A, Maadani M, Kiani R, Shakerian F, Sanati HR, Zahedmehr A, et al.Intravenous magnesium sulfate: new method in prevention of contrast-induced nephropathy in primary percutaneous coronary intervention. IntUrol Nephrol. 2015;47(3):521–5.56. Fung JW, Szeto CC, Chan WW, Kum LC, Chan AK, Wong JT, et al. Effect of N-acetylcysteine for prevention of contrast nephropathy in patients withmoderate to severe renal insufficiency: a randomized trial. Am J Kidney Dis.2004;43(5):801–8.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 11 of 1857. Gare M, Haviv YS, Ben-Yehuda A, Rubinger D, Bdolah-Abram T, Fuchs S, etal. The renal effect of low-dose dopamine in high-risk patients undergoingcoronary angiography. J Am Coll Cardiol. 1999;34(6):1682–8.58. Geng W, Fu XH, Gu XS, Wang YB, Wang XC, Li W, et al. Preventive effects ofanisodamine against contrast-induced nephropathy in type 2 diabetics withrenal insufficiency undergoing coronary angiography or angioplasty. ChinMed J. 2012;125(19):3368–72.59. Goldenberg I, Shechter M, Matetzky S, Jonas M, Adam M, Pres H, et al. Oralacetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy following coronary angiography. A randomized controlledtrial and review of the current literature. Eur Heart J. 2004;25(3):212–8.60. Gomes VO, Lasevitch R, Lima VC, Brito FS Jr, Perez-Alva JC, Moulin B, et al.Hydration with sodium bicarbonate does not prevent contrast nephropathy:a multicenter clinical trial. Arq Bras Cardiol. 2012;99(6):1129–34.61. Gomes VO, Poli de Figueredo CE, Caramori P, Lasevitch R, Bodanese LC,Araujo A, et al. N-acetylcysteine does not prevent contrast inducednephropathy after cardiac catheterisation with an ionic low osmolalitycontrast medium: a multicentre clinical trial. Heart. 2005;91(6):774–8.62. Gu GQ, Lu R, Cui W, Liu F, Zhang Y, Yang XH, et al. Low-dose furosemideadministered with adequate hydration reduces contrast-inducednephropathy in patients undergoing coronary angiography. Cardiology.2013;125(2):69–73.63. Gulel O, Keles T, Eraslan H, Aydogdu S, Diker E, Ulusoy V. Prophylacticacetylcysteine usage for prevention of contrast nephropathy after coronaryangiography. J Cardiovasc Pharmacol. 2005;46(4):464–7.64. Gunebakmaz O, Kaya MG, Koc F, Akpek M, Kasapkara A, Inanc MT, et al.Does nebivolol prevent contrast-induced nephropathy in humans? ClinCardiol. 2012;35(4):250–4.65. Gupta RK, Kapoor A, Tewari S, Sinha N, Sharma RK. Captopril for preventionof contrast-induced nephropathy in diabetic patients: a randomised study.Indian Heart J. 1999;51(5):521–6.66. Hafiz AM, Jan MF, Mori N, Shaikh F, Wallach J, Bajwa T, et al. Prevention ofcontrast-induced acute kidney injury in patients with stable chronic renaldisease undergoing elective percutaneous coronary and peripheralinterventions: randomized comparison of two preventive strategies.Catheter Cardiovasc Interv. 2012;79(6):929–37.67. Han Y, Zhu G, Han L, Hou F, Huang W, Liu H, et al. Short-term rosuvastatintherapy for prevention of contrast-induced acute kidney injury in patients withdiabetes and chronic kidney disease. J Am Coll Cardiol. 2014;63(1):62–70.68. Hashemi M, Kharazi A, Shahidi S. Captopril for prevention of contrast inducednephropathy in patients undergoing coronary angioplasty: a double blindplacebo controlled clinical trial. J Res Med Sci. 2005;10(5):305–8.69. Heguilen RM, Liste AA, Payaslian M, Ortemberg MG, Albarracin LM,Bernasconi AR. N-acethyl-cysteine reduces the occurrence of contrast-induced acute kidney injury in patients with renal dysfunction: a single-center randomized controlled trial. Clin Exp Nephrol. 2013;17(3):396–404.70. Heng AE, Cellarier E, Aublet-Cuvelier B, Decalf V, Motreff P, Marcaggi X, et al. Istreatment with N-acetylcysteine to prevent contrast-induced nephropathy whenusing bicarbonate hydration out of date? Clin Nephrol. 2008;70(6):475–84.71. Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, et al.Cardiac remote ischemic preconditioning in coronary stenting (CRISP stent)study: a prospective, randomized control trial. Circulation. 2009;119(6):820–7.72. Hsu TF, Huang MK, Yu SH, Yen DH, Kao WF, Chen YC, et al. N-acetylcysteinefor the prevention of contrast-induced nephropathy in the emergencydepartment. Intern Med. 2012;51(19):2709–14.73. Huber W, Schipek C, Ilgmann K, Page M, Hennig M, Wacker A, et al.Effectiveness of theophylline prophylaxis of renal impairment after coronaryangiography in patients with chronic renal insufficiency. Am J Cardiol. 2003;91(10):1157–62.74. Inda-Filho AJ, Caixeta A, Manggini M, Schor N. Do intravenous N-acetylcysteine and sodium bicarbonate prevent high osmolal contrast-induced acute kidney injury? A randomized controlled trial. PLoS One. 2014;9(9):e107602.75. Investigators ACT. Acetylcysteine for prevention of renal outcomes inpatients undergoing coronary and peripheral vascular angiography: mainresults from the randomized acetylcysteine for contrast-inducednephropathy trial (ACT). Circulation. 2011;124(11):1250–9.76. Jaffery Z, Verma A, White CJ, Grant AG, Collins TJ, Grise MA, et al. Arandomized trial of intravenous n-acetylcysteine to prevent contrastinduced nephropathy in acute coronary syndromes. Catheter CardiovascInterv. 2012;79(6):921–6.77. Jo SH, Kim SA, Kim HS, Han SJ, Park WJ, Choi YJ. Alpha-lipoic acid for theprevention of contrast-induced nephropathy in patients undergoingcoronary angiography: the ALIVE study - a prospective randomized trial.Cardiology. 2013;126(3):159–66.78. Jo SH, Koo BK, Park JS, Kang HJ, Cho YS, Kim YJ, et al. Prevention of radiocontrastmedium-induced nephropathy using short-term high-dose simvastatin inpatients with renal insufficiency undergoing coronary angiography (PROMISS)trial—a randomized controlled study. Am Heart J. 2008;155(3):499 e1–8.79. Jo SH, Koo BK, Park JS, Kang HJ, Kim YJ, Kim HL, et al. N-acetylcysteine versusAScorbic acid for preventing contrast-induced nephropathy in patients withrenal insufficiency undergoing coronary angiography NASPI study-aprospective randomized controlled trial. Am Heart J. 2009;157(3):576–83.80. Jurado-Roman A, Hernandez-Hernandez F, Garcia-Tejada J, Granda-Nistal C,Molina J, Velazquez M, et al. Role of hydration in contrast-inducednephropathy in patients who underwent primary percutaneous coronaryintervention. Am J Cardiol. 2015;115(9):1174–8.81. Kama A, Yilmaz S, Yaka E, Dervisoglu E, Dogan NO, Erimsah E, et al.Comparison of short-term infusion regimens of N-acetylcysteine plusintravenous fluids, sodium bicarbonate plus intravenous fluids, andintravenous fluids alone for prevention of contrast-induced nephropathy inthe emergency department. Acad Emerg Med. 2014;21(6):615–22.82. Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A, et al. Acetylcysteine forprevention of acute deterioration of renal function following electivecoronary angiography and intervention: a randomized controlled trial.JAMA. 2003;289(5):553–8.83. Kefer JM, Hanet CE, Boitte S, Wilmotte L, De Kock M. Acetylcysteine,coronary procedure and prevention of contrast-induced worsening of renalfunction: which benefit for which patient? Acta Cardiol. 2003;58(6):555–60.84. Khoury Z, Schlicht JR, Como J, Karschner JK, Shapiro AP, Mook WJ, et al. Theeffect of prophylactic nifedipine on renal function in patients administeredcontrast media. Pharmacotherapy. 1995;15(1):59–65.85. Kimmel M, Butscheid M, Brenner S, Kuhlmann U, Klotz U, Alscher DM.Improved estimation of glomerular filtration rate by serum cystatin C inpreventing contrast induced nephropathy by N-acetylcysteine orzinc—preliminary results. Nephrol Dial Transplant. 2008;23(4):1241–5.86. Kinbara T, Hayano T, Ohtani N, Furutani Y, Moritani K, Matsuzaki M. Efficacyof N-acetylcysteine and aminophylline in preventing contrast-inducednephropathy. J Cardiol. 2010;55(2):174–9.87. Kitzler TM, Jaberi A, Sendlhofer G, Rehak P, Binder C, Petnehazy E, et al. Efficacyof vitamin E and N-acetylcysteine in the prevention of contrast induced kidneyinjury in patients with chronic kidney disease: a double blind, randomizedcontrolled trial. Wien Klin Wochenschr. 2012;124(9–10):312–9.88. Klima T, Christ A, Marana I, Kalbermatter S, Uthoff H, Burri E, et al. Sodium chloridevs. sodium bicarbonate for the prevention of contrast medium-inducednephropathy: a randomized controlled trial. Eur Heart J. 2012;33(16):2071–9.89. Ko YG, Lee BK, Kang WC, Moon JY, Cho YH, Choi SH, et al. Preventive effectof pretreatment with intravenous nicorandil on contrast-inducednephropathy in patients with renal dysfunction undergoing coronaryangiography (PRINCIPLE study). Yonsei Med J. 2013;54(4):957–64.90. Koc F, Ozdemir K, Altunkas F, Celik A, Dogdu O, Karayakali M, et al. Sodiumbicarbonate versus isotonic saline for the prevention of contrast-inducednephropathy in patients with diabetes mellitus undergoing coronaryangiography and/or intervention: a multicenter prospective randomizedstudy. J Investig Med. 2013;61(5):872–7.91. Koc F, Ozdemir K, Kaya MG, Dogdu O, Vatankulu MA, Ayhan S, et al.Intravenous N-acetylcysteine plus high-dose hydration versus high-dosehydration and standard hydration for the prevention of contrast-inducednephropathy: CASIS—a multicenter prospective controlled trial. Int J Cardiol.2012;155(3):418–23.92. Koch JA, Plum J, Grabensee B, Modder U. Prostaglandin E1: a new agent for theprevention of renal dysfunction in high risk patients caused by radiocontrastmedia? PGE1 study group. Nephrol Dial Transplant. 2000;15(1):43–9.93. Kong DG, Hou YF, Ma LL, Yao DK, Wang LX. Comparison of oral andintravenous hydration strategies for the prevention of contrast-inducednephropathy in patients undergoing coronary angiography or angioplasty:a randomized clinical trial. Acta Cardiol. 2012;67(5):565–9.94. Kooiman J, Sijpkens YW, de Vries JP, Brulez HF, Hamming JF, van der MolenAJ, et al. A randomized comparison of 1-h sodium bicarbonate hydrationversus standard peri-procedural saline hydration in patients with chronickidney disease undergoing intravenous contrast-enhanced computerizedtomography. Nephrol Dial Transplant. 2014;29(5):1029–36.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 12 of 1895. Kooiman J, Sijpkens YW, van Buren M, Groeneveld JH, Ramai SR, van derMolen AJ, et al. Randomised trial of no hydration vs. sodium bicarbonatehydration in patients with chronic kidney disease undergoing acutecomputed tomography-pulmonary angiography. J Thromb Haemost. 2014;12(10):1658–66.96. Kotlyar E, Keogh AM, Thavapalachandran S, Allada CS, Sharp J, Dias L, et al.Prehydration alone is sufficient to prevent contrast-induced nephropathyafter day-only angiography procedures—a randomised controlled trial.Heart Lung Circ. 2005;14(4):245–51.97. Kumar A, Bhawani G, Kumari N, Murthy KS, Lalwani V, Raju CN. Comparativestudy of renal protective effects of allopurinol and N-acetyl-cysteine oncontrast induced nephropathy in patients undergoing cardiaccatheterization. J Clin Diagn Res. 2014;8(12):HC03–7.98. Kurnik BR, Allgren RL, Genter FC, Solomon RJ, Bates ER, Weisberg LS.Prospective study of atrial natriuretic peptide for the prevention ofradiocontrast-induced nephropathy. Am J Kidney Dis. 1998;31(4):674–80.99. Kurnik BR, Weisberg LS, Cuttler IM, Kurnik PB. Effects of atrial natriureticpeptide versus mannitol on renal blood flow during radiocontrast infusionin chronic renal failure. J Lab Clin Med. 1990;116(1):27–36.100. Lavi S, D’Alfonso S, Diamantouros P, Camuglia A, Garg P, Teefy P, et al.Remote ischemic postconditioning during percutaneous coronaryinterventions: remote ischemic postconditioning-percutaneous coronaryintervention randomized trial. Circ Cardiovasc Interv. 2014;7(2):225–32.101. Lawlor DK, Moist L, DeRose G, Harris KA, Lovell MB, Kribs SW, et al.Prevention of contrast-induced nephropathy in vascular surgery patients.Ann Vasc Surg. 2007;21(5):593–7.102. Lee SW, Kim WJ, Kim YH, Park SW, Park DW, Yun SC, et al. Preventive strategiesof renal insufficiency in patients with diabetes undergoing intervention orarteriography (the PREVENT trial). Am J Cardiol. 2011;107(10):1447–52.103. Lehnert T, Keller E, Gondolf K, Schaffner T, Pavenstadt H, Schollmeyer P.Effect of haemodialysis after contrast medium administration in patientswith renal insufficiency. Nephrol Dial Transplant. 1998;13(2):358–62.104. Leoncini M, Toso A, Maioli M, Tropeano F, Villani S, Bellandi F. Early high-dose rosuvastatin for contrast-induced nephropathy prevention in acutecoronary syndrome: results from the PRATO-ACS study (protective effect ofRosuvastatin and antiplatelet therapy on contrast-induced acute kidneyinjury and myocardial damage in patients with acute coronary syndrome). JAm Coll Cardiol. 2014;63(1):71–9.105. Li G, Yin L, Liu T, Zheng X, Xu G, Xu Y, et al. Role of probucol in preventingcontrast-induced acute kidney injury after coronary interventionalprocedure. Am J Cardiol. 2009;103(4):512–4.106. Li W, Fu X, Wang Y, Li X, Yang Z, Wang X, et al. Beneficial effects of high-dose atorvastatin pretreatment on renal function in patients with acute ST-segment elevation myocardial infarction undergoing emergencypercutaneous coronary intervention. Cardiology. 2012;122(3):195–202.107. Li WH, Li DY, Qian WH, Liu JL, Xu TD, Zhu H, et al. Prevention of contrast-induced nephropathy with prostaglandin E1 in high-risk patients undergoingpercutaneous coronary intervention. Int Urol Nephrol. 2014;46(4):781–6.108. Li XM, Cong HL, Li TT, He LJ, Zhou YJ. Impact of benazepril on contrast-induced acute kidney injury for patients with mild to moderate renalinsufficiency undergoing percutaneous coronary intervention. Chin Med J.2011;124(14):2101–6.109. Ludwig U, Riedel MK, Backes M, Imhof A, Muche R, Keller F. MESNA (sodium2-mercaptoethanesulfonate) for prevention of contrast medium-inducednephrotoxicity - controlled trial. Clin Nephrol. 2011;75(4):302–8.110. Luo SJ, Zhou YJ, Shi DM, Ge HL, Wang JL, Liu RF. Remote ischemicpreconditioning reduces myocardial injury in patients undergoing coronarystent implantation. Can J Cardiol. 2013;29(9):1084–9.111. Luo Y, Wang X, Ye Z, Lai Y, Yao Y, Li J, et al. Remedial hydration reduces theincidence of contrast-induced nephropathy and short-term adverse eventsin patients with ST-segment elevation myocardial infarction: a single-center,randomized trial. Intern Med. 2014;53(20):2265–72.112. MacNeill BD, Harding SA, Bazari H, Patton KK, Colon-Hernadez P, DeJoseph D,et al. Prophylaxis of contrast-induced nephropathy in patients undergoingcoronary angiography. Catheter Cardiovasc Interv. 2003;60(4):458–61.113. Maioli M, Toso A, Leoncini M, Micheletti C, Bellandi F. Effects of hydration incontrast-induced acute kidney injury after primary angioplasty: arandomized, controlled trial. Circ Cardiovasc Interv. 2011;4(5):456–62.114. Malhis M, Al-Bitar S, Al-Deen ZK. The role of theophylline in preventionof radiocontrast media-induced nephropathy. Saudi J Kidney DisTranspl. 2010;21(2):276–83.115. Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. NEngl J Med. 2006;354(26):2773–82.116. Marenzi G, Ferrari C, Marana I, Assanelli E, De Metrio M, Teruzzi G, et al.Prevention of contrast nephropathy by furosemide with matched hydration:the MYTHOS (induced diuresis with matched hydration compared tostandard hydration for contrast induced nephropathy prevention) trial. JACCCardiovasc Interv. 2012;5(1):90–7.117. Marenzi G, Marana I, Lauri G, Assanelli E, Grazi M, Campodonico J, et al. Theprevention of radiocontrast-agent-induced nephropathy by hemofiltration.N Engl J Med. 2003;349(14):1333–40.118. Markota D, Markota I, Starcevic B, Tomic M, Prskalo Z, Brizic I.Prevention of contrast-induced nephropathy with Na/K citrate. EurHeart J. 2013;34(30):2362–7.119. Masuda M, Yamada T, Mine T, Morita T, Tamaki S, Tsukamoto Y, et al.Comparison of usefulness of sodium bicarbonate versus sodium chloride toprevent contrast-induced nephropathy in patients undergoing an emergentcoronary procedure. Am J Cardiol. 2007;100(5):781–6.120. Matejka J, Varvarovsky I, Vojtisek P, Herman A, Rozsival V, Borkova V, et al.Prevention of contrast-induced acute kidney injury by theophylline inelderly patients with chronic kidney disease. Heart Vessel. 2010;25(6):536–42.121. Menting TP, Sterenborg TB, de Waal Y, Donders R, Wever KE, LemsonMS, et al. Remote ischemic preconditioning to reduce contrast-inducednephropathy: a randomized controlled trial. Eur J Vasc Endovasc Surg.2015;50(4):527–32.122. Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, etal. Prevention of contrast-induced nephropathy with sodium bicarbonate: arandomized controlled trial. JAMA. 2004;291(19):2328–34.123. Miao Y, Zhong Y, Yan H, Li W, Wang BY, Jin J. Alprostadil plays aprotective role in contrast-induced nephropathy in the elderly. Int UrolNephrol. 2013;45(4):1179–85.124. Miner SE, Dzavik V, Nguyen-Ho P, Richardson R, Mitchell J, Atchison D, et al.N-acetylcysteine reduces contrast-associated nephropathy but not clinicalevents during long-term follow-up. Am Heart J. 2004;148(4):690–5.125. Moore NN, Lapsley M, Norden AG, Firth JD, Gaunt ME, Varty K, et al. DoesN-acetylcysteine prevent contrast-induced nephropathy duringendovascular AAA repair? A randomized controlled pilot study. J EndovascTher. 2006;13(5):660–6.126. Morikawa S, Sone T, Tsuboi H, Mukawa H, Morishima I, Uesugi M, et al. Renalprotective effects and the prevention of contrast-induced nephropathy byatrial natriuretic peptide. J Am Coll Cardiol. 2009;53(12):1040–6.127. Motohiro M, Kamihata H, Tsujimoto S, Seno T, Manabe K, Isono T, et al. Anew protocol using sodium bicarbonate for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography. Am JCardiol. 2011;107(11):1604–8.128. Ng TM, Shurmur SW, Silver M, Nissen LR, O’Leary EL, Rigmaiden RS, et al.Comparison of N-acetylcysteine and fenoldopam for preventing contrast-induced nephropathy (CAFCIN). Int J Cardiol. 2006;109(3):322–8.129. Ochoa A, Pellizzon G, Addala S, Grines C, Isayenko Y, Boura J, et al. Abbreviateddosing of N-acetylcysteine prevents contrast-induced nephropathy afterelective and urgent coronary angiography and intervention. J Interv Cardiol.2004;17(3):159–65.130. Oguzhan N, Cilan H, Sipahioglu M, Unal A, Kocyigit I, Kavuncuoglu F, et al.The lack of benefit of a combination of an angiotensin receptor blocker andcalcium channel blocker on contrast-induced nephropathy in patients withchronic kidney disease. Ren Fail. 2013;35(4):434–9.131. Oldemeyer JB, Biddle WP, Wurdeman RL, Mooss AN, Cichowski E, HillemanDE. Acetylcysteine in the prevention of contrast-induced nephropathy aftercoronary angiography. Am Heart J. 2003;146(6):E23.132. Onbasili AO, Yeniceriglu Y, Agaoglu P, Karul A, Tekten T, Akar H, et al.Trimetazidine in the prevention of contrast-induced nephropathy aftercoronary procedures. Heart. 2007;93(6):698–702.133. Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O, Baris N, et al.Sodium bicarbonate, N-acetylcysteine, and saline for prevention ofradiocontrast-induced nephropathy. A comparison of 3 regimens forprotecting contrast-induced nephropathy in patients undergoingcoronary procedures. A single-center prospective controlled trial. AmHeart J. 2007;154(3):539–44.134. Ozhan H, Erden I, Ordu S, Aydin M, Caglar O, Basar C, et al. Efficacy of short-term high-dose atorvastatin for prevention of contrast-induced nephropathy inpatients undergoing coronary angiography. Angiology. 2010;61(7):711–4.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 13 of 18135. Pakfetrat M, Nikoo MH, Malekmakan L, Tabandeh M, Roozbeh J, Nasab MH,et al. A comparison of sodium bicarbonate infusion versus normal salineinfusion and its combination with oral acetazolamide for prevention ofcontrast-induced nephropathy: a randomized, double-blind trial. Int UrolNephrol. 2009;41(3):629–34.136. Patti G, Ricottini E, Nusca A, Colonna G, Pasceri V, D’Ambrosio A, et al. Short-term, high-dose atorvastatin pretreatment to prevent contrast-inducednephropathy in patients with acute coronary syndromes undergoingpercutaneous coronary intervention from the ARMYDA-CIN [atorvastatin forreduction of myocardial damage during angioplasty—contrast-inducednephropathy] trial. Am J Cardiol. 2011;108(1):1–7.137. Poletti PA, Platon A, De Seigneux S, Dupuis-Lozeron E, Sarasin F, Becker CD,et al. N-acetylcysteine does not prevent contrast nephropathy in patientswith renal impairment undergoing emergency CT: a randomized study.BMC Nephrol. 2013;14:119.138. Qiao B, Deng J, Li Y, Wang X, Han Y. Rosuvastatin attenuated contrast-induced nephropathy in diabetes patients with renal dysfunction. Int J ClinExp Med. 2015;8(2):2342–9.139. Quintavalle C, Fiore D, De Micco F, Visconti G, Focaccio A, Golia B, et al.Impact of a high loading dose of atorvastatin on contrast-induced acutekidney injury. Circulation. 2012;126(25):3008–16.140. Rahman MM, Haque SS, Rokeya B, Siddique MA, Banerjee SK, Ahsan SA, etal. Trimetazidine in the prevention of contrast induced nephropathy aftercoronary angiogram. Mymensingh Med J. 2012;21(2):292–9.141. Rashid ST, Salman M, Myint F, Baker DM, Agarwal S, Sweny P, et al.Prevention of contrast-induced nephropathy in vascular patientsundergoing angiography: a randomized controlled trial of intravenous N-acetylcysteine. J Vasc Surg. 2004;40(6):1136–41.142. Reinecke H, Fobker M, Wellmann J, Becke B, Fleiter J, Heitmeyer C, et al. Arandomized controlled trial comparing hydration therapy to additionalhemodialysis or N-acetylcysteine for the prevention of contrast medium-induced nephropathy: the Dialysis-versus-diuresis (DVD) trial. Clin ResCardiol. 2007;96(3):130–9.143. Rohani A. Effectiveness of aminophylline prophylaxis of renal impairmentafter coronary angiography in patients with chronic renal insufficiency.Indian J Nephrol. 2010;20(2):80–3.144. Sadat U, Walsh SR, Norden AG, Gillard JH, Boyle JR. Does oral N-acetylcysteine reduce contrast-induced renal injury in patients withperipheral arterial disease undergoing peripheral angiography? Arandomized-controlled study. Angiology. 2011;62(3):225–30.145. Saitoh T, Satoh H, Nobuhara M, Machii M, Tanaka T, Ohtani H, et al. Intravenousglutathione prevents renal oxidative stress after coronary angiography moreeffectively than oral N-acetylcysteine. Heart Vessel. 2011;26(5):465–72.146. Sandhu C, Belli AM, Oliveira DB. The role of N-acetylcysteine in the prevention ofcontrast-induced nephrotoxicity. Cardiovasc Intervent Radiol. 2006;29(3):344–7.147. Sanei H, Hajian-Nejad A, Sajjadieh-Kajouei A, Nazemzadeh N, Alizadeh N,Bidram P, et al. Short term high dose atorvastatin for the prevention ofcontrast-induced nephropathy in patients undergoing computedtomography angiography. ARYA Atheroscler. 2014;10(5):252–8.148. Sar F, Saler T, Ecebay A, Saglam ZA, Ozturk S, Kazancioglu R. The efficacy ofn-acetylcysteine in preventing contrast-induced nephropathy in type 2diabetic patients without nephropathy. J Nephrol. 2010;23(4):478–82.149. Savaj S, Savoj J, Jebraili I, Sezavar SH. Remote ischemic preconditioning forprevention of contrast-induced acute kidney injury in diabetic patients. IranJ Kidney Dis. 2014;8(6):457–60.150. Sekiguchi H, Ajiro Y, Uchida Y, Ishida I, Otsuki H, Hattori H, et al. Oxygenpre-conditioning prevents contrast-induced nephropathy (OPtion CINstudy). J Am Coll Cardiol. 2013;62(2):162–3.151. Seyon RA, Jensen LA, Ferguson IA, Williams RG. Efficacy of N-acetylcysteineand hydration versus placebo and hydration in decreasing contrast-inducedrenal dysfunction in patients undergoing coronary angiography with orwithout concomitant percutaneous coronary intervention. Heart Lung. 2007;36(3):195–204.152. Shehata M. Impact of trimetazidine on incidence of myocardial injury andcontrast-induced nephropathy in diabetic patients with renal dysfunctionundergoing elective percutaneous coronary intervention. Am J Cardiol.2014;114(3):389–94.153. Shehata M, Hamza M. Impact of high loading dose of atorvastatin indiabetic patients with renal dysfunction undergoing electivepercutaneous coronary intervention: a randomized controlled trial.Cardiovasc Ther. 2015;33(2):35–41.154. Shyu KG, Cheng JJ, Kuan P. Acetylcysteine protects against acute renaldamage in patients with abnormal renal function undergoing a coronaryprocedure. J Am Coll Cardiol. 2002;40(8):1383–8.155. Solomon R, Werner C, Mann D, D’Elia J, Silva P. Effects of saline, mannitol,and furosemide to prevent acute decreases in renal function induced byradiocontrast agents. N Engl J Med. 1994;331(21):1416–20.156. Spargias K, Adreanides E, Demerouti E, Gkouziouta A, Manginas A, PavlidesG, et al. Iloprost prevents contrast-induced nephropathy in patients withrenal dysfunction undergoing coronary angiography or intervention.Circulation. 2009;120(18):1793–9.157. Spargias K, Adreanides E, Giamouzis G, Karagiannis S, Gouziouta A,Manginas A, et al. Iloprost for prevention of contrast-mediated nephropathyin high-risk patients undergoing a coronary procedure. Results of arandomized pilot study. Eur J Clin Pharmacol. 2006;62(8):589–95.158. Stone GW, McCullough PA, Tumlin JA, Lepor NE, Madyoon H, Murray P, etal. Fenoldopam mesylate for the prevention of contrast-inducednephropathy: a randomized controlled trial. JAMA. 2003;290(17):2284–91.159. Stone GW, Vora K, Schindler J, Diaz C, Mann T, Dangas G, et al. Systemichypothermia to prevent radiocontrast nephropathy (from the COOL-RCNrandomized trial). Am J Cardiol. 2011;108(5):741–6.160. Tamura A, Goto Y, Miyamoto K, Naono S, Kawano Y, Kotoku M, et al. Efficacyof single-bolus administration of sodium bicarbonate to prevent contrast-induced nephropathy in patients with mild renal insufficiency undergoingan elective coronary procedure. Am J Cardiol. 2009;104(7):921–5.161. Tanaka A, Suzuki Y, Suzuki N, Hirai T, Yasuda N, Miki K, et al. Does N-acetylcysteine reduce the incidence of contrast-induced nephropathy andclinical events in patients undergoing primary angioplasty for acutemyocardial infarction? Intern Med. 2011;50(7):673–7.162. Tasanarong A, Piyayotai D, Thitiarchakul S. Protection of radiocontrastinduced nephropathy by vitamin E (alpha tocopherol): a randomizedcontrolled pilot study. J Med Assoc Thail. 2009;92(10):1273–81.163. Tasanarong A, Vohakiat A, Hutayanon P, Piyayotai D. New strategy of alpha-and gamma-tocopherol to prevent contrast-induced acute kidney injury inchronic kidney disease patients undergoing elective coronary procedures.Nephrol Dial Transplant. 2013;28(2):337–44.164. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W.Prevention of radiographic-contrast-agent-induced reductions in renalfunction by acetylcysteine. N Engl J Med. 2000;343(3):180–4.165. Thiele H, Hildebrand L, Schirdewahn C, Eitel I, Adams V, Fuernau G, et al.Impact of high-dose N-acetylcysteine versus placebo on contrast-inducednephropathy and myocardial reperfusion injury in unselected patients withST-segment elevation myocardial infarction undergoing primarypercutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouSCoronary Intervention Acute Myocardial Infarction N-ACC) Trial. J Am CollCardiol. 2010;55(20):2201–9.166. Toso A, Maioli M, Leoncini M, Gallopin M, Tedeschi D, Micheletti C, et al. Usefulnessof atorvastatin (80 mg) in prevention of contrast-induced nephropathy in patientswith chronic renal disease. Am J Cardiol. 2010;105(3):288–92.167. Traub SJ, Mitchell AM, Jones AE, Tang A, O’Connor J, Nelson T, et al. N-acetylcysteine plus intravenous fluids versus intravenous fluids alone toprevent contrast-induced nephropathy in emergency computedtomography. Ann Emerg Med. 2013;62(5):511–20 e25.168. Trivedi HS, Moore H, Nasr S, Aggarwal K, Agrawal A, Goel P, et al. A randomizedprospective trial to assess the role of saline hydration on the development ofcontrast nephrotoxicity. Nephron Clin Pract. 2003;93(1):C29–34.169. Tumlin JA, Wang A, Murray PT, Mathur VS. Fenoldopam mesylate blocksreductions in renal plasma flow after radiocontrast dye infusion: a pilot trialin the prevention of contrast nephropathy. Am Heart J. 2002;143(5):894–903.170. Vasheghani-Farahani A, Sadigh G, Kassaian SE, Khatami SM, Fotouhi A,Razavi SA, et al. Sodium bicarbonate in preventing contrast nephropathy inpatients at risk for volume overload: a randomized controlled trial. JNephrol. 2010;23(2):216–23.171. Vasheghani-Farahani A, Sadigh G, Kassaian SE, Khatami SM, Fotouhi A,Razavi SA, et al. Sodium bicarbonate plus isotonic saline versus salinefor prevention of contrast-induced nephropathy in patients undergoingcoronary angiography: a randomized controlled trial. Am J Kidney Dis.2009;54(4):610–8.172. Vogt B, Ferrari P, Schonholzer C, Marti HP, Mohaupt M, Wiederkehr M, et al.Prophylactic hemodialysis after radiocontrast media in patients with renalinsufficiency is potentially harmful. Am J Med. 2001;111(9):692–8.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 14 of 18173. Wang A, Holcslaw T, Bashore TM, Freed MI, Miller D, Rudnick MR, et al.Exacerbation of radiocontrast nephrotoxicity by endothelin receptorantagonism. Kidney Int. 2000;57(4):1675–80.174. Wang Y, Fu X, Wang X, Jia X, Gu X, Zhang J, et al. Protective effects ofanisodamine on renal function in patients with ST-segment elevationmyocardial infarction undergoing primary percutaneous coronaryintervention. Tohoku J Exp Med. 2011;224(2):91–7.175. Webb JG, Pate GE, Humphries KH, Buller CE, Shalansky S, Al Shamari A, et al.A randomized controlled trial of intravenous N-acetylcysteine for theprevention of contrast-induced nephropathy after cardiac catheterization:lack of effect. Am Heart J. 2004;148(3):422–9.176. Weisberg LS, Kurnik PB, Kurnik BR. Dopamine and renal blood flow inradiocontrast-induced nephropathy in humans. Ren Fail. 1993;15(1):61–8.177. Wrobel W, Sinkiewicz W, Gordon M, Wozniak-Wisniewska A. Oral versusintravenous hydration and renal function in diabetic patients undergoingpercutaneous coronary interventions. Kardiol Pol. 2010;68(9):1015–20.178. Xu X, Zhou Y, Luo S, Zhang W, Zhao Y, Yu M, et al. Effect of remoteischemic preconditioning in the elderly patients with coronary arterydisease with diabetes mellitus undergoing elective drug-eluting stentimplantation. Angiology. 2014;65(8):660–6.179. Yamanaka T, Kawai Y, Miyoshi T, Mima T, Takagaki K, Tsukuda S, et al.Remote ischemic preconditioning reduces contrast-induced acute kidneyinjury in patients with ST-elevation myocardial infarction: a randomizedcontrolled trial. Int J Cardiol. 2015;178:136–41.180. Yang K, Liu W, Ren W, Lv S. Different interventions in preventing contrast-induced nephropathy after percutaneous coronary intervention. Int UrolNephrol. 2014;46(9):1801–7.181. Yavari V, Ostovan MA, Kojuri J, Afshariani R, Hamidian Jahromi A, Roozbeh J,et al. The preventive effect of pentoxifylline on contrast-inducednephropathy: a randomized clinical trial. Int Urol Nephrol. 2014;46(1):41–6.182. Yeganehkhah MR, Iranirad L, Dorri F, Pazoki S, Akbari H, Miryounesi M, et al.Comparison between three supportive treatments for prevention ofcontrast-induced nephropathy in high-risk patients undergoing coronaryangiography. Saudi J Kidney Dis Transpl. 2014;25(6):1217–23.183. Yin L, Li G, Liu T, Yuan R, Zheng X, Xu G, et al. Probucol for the preventionof cystatin C-based contrast-induced acute kidney injury following primaryor urgent angioplasty: a randomized, controlled trial. Int J Cardiol. 2013;167(2):426–9.184. Zhang J, Fu X, Jia X, Fan X, Gu X, Li S, et al. B-type natriuretic peptidefor prevention of contrast-induced nephropathy in patients with heartfailure undergoing primary percutaneous coronary intervention. ActaRadiol. 2010;51(6):641–8.185. Zhao K, Lin Y, Li YJ, Gao S. Efficacy of short-term cordyceps sinensis forprevention of contrast-induced nephropathy in patients with acutecoronary syndrome undergoing elective percutaneous coronaryintervention. Int J Clin Exp Med. 2014;7(12):5758–64.186. Zhou L, Chen H. Prevention of contrast-induced nephropathy with ascorbicacid. Intern Med. 2012;51(6):531–5.187. Abouzeid SM, ElHossary HE. Na/K citrate versus sodium bicarbonate inprevention of contrast-induced nephropathy. Saudi J Kidney Dis Transpl.2016;27(3):519–25.188. Arabmomeni M, Najafian J, Abdar Esfahani M, Samadi M, Mirbagher L.Comparison between theophylline, N-acetylcysteine, and theophylline plusN-acetylcysteine for the prevention of contrast-induced nephropathy. ARYAAtheroscler. 2015;11(1):43–9.189. Balbir Singh G, Ann SH, Park J, Chung HC, Lee JS, Kim ES, et al. Remoteischemic preconditioning for the prevention of contrast-induced acutekidney injury in diabetics receiving elective percutaneous coronaryintervention. PLoS One. 2016;11(10):e0164256.190. Chong E, Poh KK, Lu Q, Zhang JJ, Tan N, Hou XM, et al. Comparison ofcombination therapy of high-dose oral N-acetylcysteine and intravenoussodium bicarbonate hydration with individual therapies in the reduction ofcontrast-induced nephropathy during cardiac catheterisation andpercutaneous coronary intervention (CONTRAST): a multi-Centre,randomised, controlled trial. Int J Cardiol. 2015;201:237–42.191. Eshraghi A, Naranji-Sani R, Pourzand H, Vojdanparast M, Morovatfar N,Ramezani J, et al. Pentoxifylline and prevention of contrast-inducednephropathy: is it efficient in patients with myocardial infarctionundergoing coronary angioplasty? ARYA atheroscler[Internet]. 2017;12(5):1–5Available from: http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/737/CN-01298737/frame.html.192. Fan Y, Wei Q, Cai J, Shi Y, Zhang Y, Yao L, et al. Preventive effect of oralnicorandil on contrast-induced nephropathy in patients with renalinsufficiency undergoing elective cardiac catheterization. Heart Vessel. 2016;31(11):1776–82.193. Healy DA, Feeley I, Keogh CJ, Scanlon TG, Hodnett PA, Stack AG, et al.Remote ischemic conditioning and renal function after contrast-enhancedCT scan: a randomized trial. Clin Invest Med. 2015;38(3):E110–8.194. Izani WMW, Darus Z, Yusof Z. Oral N-acetylcysteine in prevention of contrastinduced nephropathy following coronary angiogram. Int Med J [Internet].2008;15(5):353–61 Available from: http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/905/CN-00754905/frame.html.195. Kai Z, Yongjian L, Sheng G, Yu L. Effect of Dongchongxiacao (Cordyceps)therapy on contrast-induced nephropathy in patients with type 2 diabetesand renal insufficiency undergoing coronary angiography. J Tradit ChinMed. 2015;35(4):422–7.196. Khosravi A, Dolatkhah M, Hashemi HS, Rostami Z. Preventive effect ofatorvastatin (80 mg) on contrast-induced nephropathy after angiography inhigh-risk patients: double-blind randomized clinical trial. Nephrourol Mon.2016;8(3):e29574.197. Liu J, Xie Y, He F, Gao Z, Hao Y, Zu X, et al. Recombinant brain natriureticpeptide for the prevention of contrast-induced nephropathy in patientswith chronic kidney disease undergoing nonemergent percutaneouscoronary intervention or coronary angiography: a randomized controlledtrial. Biomed Res Int. 2016;2016:5985327.198. Liu W, Ming Q, Shen J, Wei Y, Li W, Chen W, et al. Trimetazidine preventionof contrast-induced nephropathy in coronary angiography. Am J Med Sci.2015;350(5):398–402.199. Minoo F, Lessan-Pezeshki M, Firouzi A, Nikfarjam S, Gatmiri SM, Ramezanzade E.Prevention of contrast-induced nephropathy with oxygen supplementation: arandomized controlled trial. Iran J Kidney Dis. 2016;10(5):291–8.200. Nawa T, Nishigaki K, Kinomura Y, Tanaka T, Yamada Y, Kawasaki M, et al.Continuous intravenous infusion of nicorandil for 4 hours before and 24 hoursafter percutaneous coronary intervention protects against contrast-inducednephropathy in patients with poor renal function. Int J Cardiol. 2015;195:228–34.201. Nijssen EC, Rennenberg RJ, Nelemans PJ, Essers BA, Janssen MM, VermeerenMA, et al. Prophylactic hydration to protect renal function from intravasculariodinated contrast material in patients at high risk of contrast-inducednephropathy (AMACING): a prospective, randomised, phase 3, controlled,open-label, non-inferiority trial. Lancet. 2017;389(10076):1312–22.202. Rezaei Y, Khademvatani K, Rahimi B, Khoshfetrat M, Arjmand N, Seyyed-Mohammadzad MH. Short-term high-dose vitamin E to prevent contrastmedium-induced acute kidney injury in patients with chronic kidneydisease undergoing elective coronary angiography: a randomized placebo-controlled trial. J Am Heart Assoc. 2016;5(3):e002919.203. Sadineni R, Karthik KR, Swarnalatha G, Das U, Taduri G. N-acetyl cysteine versusallopurinol in the prevention of contrast nephropathy in patients with chronickidney disease: a randomized controlled trial. Indian J Nephrol. 2017;27(2):93–8.204. Sedighifard Z, Roghani F, Bidram P, Harandi SA, Molavi S. Silymarin for theprevention of contrast-induced nephropathy: a placebo-controlled clinicaltrial. Int J Prev Med. 2016;7:23.205. Solomon R, Gordon P, Manoukian SV, Abbott JD, Kereiakes DJ, Jeremias A,et al. Randomized trial of bicarbonate or saline study for the prevention ofcontrast-induced nephropathy in patients with CKD. Clin J Am Soc Nephrol.2015;10(9):1519–24.206. Sun C, Zhi J, Bai X, Li X, Xia H. Comparison of the efficacy of recombinanthuman brain natriuretic peptide with saline hydration in preventing contrast-induced nephropathy in patients undergoing coronary angiography with orwithout concomitant percutaneous coronary intervention. Int J Clin Exp Med.2015;8(8):14166–72.207. Wang C, Wang W, Ma S, Lu J, Shi H, Ding F. Reduced glutathione forprevention of renal outcomes in patients undergoing selective coronaryangiography or intervention. J Interv Cardiol. 2015;28(3):249–56.208. Xu RH, Ma GZ, Cai ZX, Chen P, Zhu ZD, Wang WL. Combined use ofhydration and alprostadil for preventing contrast-induced nephropathyfollowing percutaneous coronary intervention in elderly patients. Exp TherMed. 2013;6(4):863–7.209. Zagidullin NS, Dunayeva AR, Plechev VV, Gilmanov AZ, Zagidullin SZ, Er F, etal. Nephroprotective effects of remote ischemic preconditioning in coronaryangiography. Clin Hemorheol Microcirc. 2017;65(3):299–307.210. Droppa M, Desch S, Blase P, Eitel I, Fuernau G, Schuler G, et al. Impact of N-acetylcysteine on contrast-induced nephropathy defined by cystatin C inAhmed et al. BMC Nephrology          (2018) 19:323 Page 15 of 18patients with ST-elevation myocardial infarction undergoing primaryangioplasty. Clin Res Cardiol. 2011;100(11):1037–43.211. Huber W, Ilgmann K, Page M, Hennig M, Schweigart U, Jeschke B, et al.Effect of theophylline on contrast material-nephropathy in patients withchronic renal insufficiency: controlled, randomized, double-blinded study.Radiology. 2002;223(3):772–9.212. Marenzi G, Bartorelli AL. Hemofiltration in the prevention of radiocontrastagent induced nephropathy. Minerva Anestesiol. 2004;70(4):189–91.213. Masuda M, Yamada T, Okuyama Y, Morita T, Sanada S, Furukawa Y, et al.Sodium bicarbonate improves long-term clinical outcomes compared withsodium chloride in patients with chronic kidney disease undergoing anemergent coronary procedure. Circ J. 2008;72(10):1610–4.214. Zhang J, Li Y, Tao GZ, Chen YD, Hu TH, Cao XB, et al. Short-termrosuvastatin treatment for the prevention of contrast-induced acute kidneyinjury in patients receiving moderate or high volumes of contrast media: asub-analysis of the TRACK-D study. Chin Med J. 2015;128(6):784–9.215. Sketch MH Jr, Whelton A, Schollmayer E, Koch JA, Bernink PJ, Woltering F, etal. Prevention of contrast media-induced renal dysfunction withprostaglandin E1: a randomized, double-blind, placebo-controlled study. AmJ Ther. 2001;8(3):155–62.216. Acikel S, Muderrisoglu H, Yildirir A, Aydinalp A, Sade E, Bayraktar N, et al.Prevention of contrast-induced impairment of renal function by short-termor long-term statin therapy in patients undergoing elective coronaryangiography. Blood Coagul Fibrinolysis. 2010;21(8):750–7.217. Allie DE, Lirtzman MD, Wyatt CH, Keller VA, Mitran EV, Hebert CJ, et al.Targeted renal therapy and contrast-induced nephropathy duringendovascular abdominal aortic aneurysm repair: results of a feasibility pilottrial. J Endovasc Ther. 2007;14(4):520–7.218. Assadi F. Acetazolamide for prevention of contrast-induced nephropathy: anew use for an old drug. Pediatr Cardiol. 2006;27(2):238–42.219. Avci E, Yesil M, Bayata S, Postaci N, Arikan E, Cirit M. The role of nebivolol inthe prevention of contrast-induced nephropathy in patients with renaldysfunction. Anadolu Kardiyol Derg. 2011;11(7):613–7.220. Awal A, Ahsan SA, Siddique MA, Banerjee S, Hasan MI, Zaman SM, etal. Effect of hydration with or without n-acetylcysteine on contrastinduced nephropathy in patients undergoing coronary angiographyand percutaneous coronary intervention. Mymensingh Med J. 2011;20(2):264–9.221. Azmus AD, Gottschall C, Manica A, Manica J, Duro K, Frey M, et al.Effectiveness of acetylcysteine in prevention of contrast nephropathy. JInvasive Cardiol. 2005;17(2):80–4.222. Bader BD, Berger ED, Heede MB, Silberbaur I, Duda S, Risler T, et al. What isthe best hydration regimen to prevent contrast media-inducednephrotoxicity? Clin Nephrol. 2004;62:1):1–7.223. Barrett BJ, Parfrey PS, Vavasour HM, McDonald J, Kent G, Hefferton D, et al.Contrast nephropathy in patients with impaired renal function: high versuslow osmolar media. Kidney Int. 1992;41(5):1274–9.224. Boccalandro F, Amhad M, Smalling RW, Sdringola S. Oral acetylcysteine doesnot protect renal function from moderate to high doses of intravenousradiographic contrast. Catheter Cardiovasc Interv. 2003;58(3):336–41.225. Brar SS, Aharonian V, Mansukhani P, Moore N, Shen AY, Jorgensen M, et al.Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial.Lancet. 2014;383(9931):1814–23.226. Briguori C. Renalguard system in high-risk patients for contrast-inducedacute kidney injury. Minerva Cardioangiol. 2012;60(3):291–7.227. Briguori C, Colombo A, Violante A, Balestrieri P, Manganelli F, Paolo Elia P, etal. Standard vs double dose of N-acetylcysteine to prevent contrast agentassociated nephrotoxicity. Eur Heart J. 2004;25(3):206–11.228. Briguori C, Visconti G, Focaccio A, Airoldi F, Valgimigli M, Sangiorgi GM, etal. Renal insufficiency after contrast media administration trial II (REMEDIALII): RenalGuard system in high-risk patients for contrast-induced acutekidney injury. Circulation. 2011;124(11):1260–9.229. Buyukhatipoglu H, Sezen Y, Yildiz A, Bas M, Kirhan I, Ulas T, et al. N-acetylcysteine fails to prevent renal dysfunction and oxidative stress afternoniodine contrast media administration during percutaneous coronaryinterventions. Pol Arch Med Wewn. 2010;120(10):383–9.230. Clavijo LC, Pinto TL, Kuchulakanti PK, Torguson R, Chu WW, Satler LF, et al.Effect of a rapid intra-arterial infusion of dextrose 5% prior to coronaryangiography on frequency of contrast-induced nephropathy in high-riskpatients. Am J Cardiol. 2006;97(7):981–3.231. Deray G, Bellin MF, Boulechfar H, Baumelou B, Koskas F, Baumelou A, et al.Nephrotoxicity of contrast media in high-risk patients with renalinsufficiency: comparison of low- and high-osmolar contrast agents. Am JNephrol. 1991;11(4):309–12.232. Dorval JF, Dixon SR, Zelman RB, Davidson CJ, Rudko R, Resnic FS. Feasibilitystudy of the RenalGuard balanced hydration system: a novel strategy forthe prevention of contrast-induced nephropathy in high risk patients. Int JCardiol. 2013;166(2):482–6.233. Drager LF, Andrade L, Barros de Toledo JF, Laurindo FR, Machado Cesar LA,Seguro AC. Renal effects of N-acetylcysteine in patients at risk for contrastnephropathy: decrease in oxidant stress-mediated renal tubular injury.Nephrol Dial Transplant. 2004;19(7):1803–7.234. Erley CM, Duda SH, Schlepckow S, Koehler J, Huppert PE, Strohmaier WL, etal. Adenosine antagonist theophylline prevents the reduction of glomerularfiltration rate after contrast media application. Kidney Int. 1994;45(5):1425–31.235. Frank H, Werner D, Lorusso V, Klinghammer L, Daniel WG, Kunzendorf U, etal. Simultaneous hemodialysis during coronary angiography fails to preventradiocontrast-induced nephropathy in chronic renal failure. Clin Nephrol.2003;60(3):176–82.236. Gandhi MR, Brown P, Romanowski CA, Morcos SK, Campbell S, el Nahas AM,et al. The use of theophylline, an adenosine antagonist in the prevention ofcontrast media induced nephrotoxicity. Br J Radiol. 1992;65(777):838.237. Goo JJ, Kim JJ, Kang JH, Kim KN, Byun KS, Kim MK, et al. Effect of renin-angiotensin-system blockers on contrast-medium-induced acute kidneyinjury after coronary angiography. Korean J Intern Med. 2014;29(2):203–9.238. Han S, Li XM, Mohammed Ali LA, Fu NK, Jin DX, Cong HL. Effect of short-term different statins loading dose on renal function and CI-AKI incidencein patients undergoing invasive coronary procedures. Int J Cardiol. 2013;168(5):5101–3.239. Harris KG, Smith TP, Cragg AH, Lemke JH. Nephrotoxicity from contrastmaterial in renal insufficiency: ionic versus nonionic agents. Radiology. 1991;179(3):849–52.240. Hoffmann U, Fischereder M, Kruger B, Drobnik W, Kramer BK. The value ofN-acetylcysteine in the prevention of radiocontrast agent-inducednephropathy seems questionable. J Am Soc Nephrol. 2004;15(2):407–10.241. Hoshi T, Sato A, Kakefuda Y, Harunari T, Watabe H, Ojima E, et al. Preventiveeffect of statin pretreatment on contrast-induced acute kidney injury inpatients undergoing coronary angioplasty: propensity score analysis from amulticenter registry. Int J Cardiol. 2014;171(2):243–9.242. Huber W, Eckel F, Hennig M, Rosenbrock H, Wacker A, Saur D, et al.Prophylaxis of contrast material-induced nephropathy in patients inintensive care: acetylcysteine, theophylline, or both? A randomized study.Radiology. 2006;239(3):793–804.243. Huber W, Jeschke B, Page M, Weiss W, Salmhofer H, Schweigart U, et al.Reduced incidence of radiocontrast-induced nephropathy in ICU patientsunder theophylline prophylaxis: a prospective comparison to series ofpatients at similar risk. Intensive Care Med. 2001;27(7):1200–9.244. Igarashi G, Iino K, Watanabe H, Ito H. Remote ischemic pre-conditioningalleviates contrast-induced acute kidney injury in patients with moderatechronic kidney disease. Circ J. 2013;77(12):3037–44.245. Katholi RE, Taylor GJ, McCann WP, Woods WT Jr, Womack KA, McCoy CD, etal. Nephrotoxicity from contrast media: attenuation with theophylline.Radiology. 1995;195(1):17–22.246. Kaya A, Kurt M, Tanboga IH, Isik T, Ekinci M, Aksakal E, et al. Rosuvastatinversus atorvastatin to prevent contrast induced nephropathy in patientsundergoing primary percutaneous coronary intervention (ROSA-cIN trial).Acta Cardiol. 2013;68(5):489–94.247. Khanal S, Attallah N, Smith DE, Kline-Rogers E, Share D, O’Donnell MJ, et al.Statin therapy reduces contrast-induced nephropathy: an analysis ofcontemporary percutaneous interventions. Am J Med. 2005;118(8):843–9.248. Kini AA, Sharma SK. Managing the high-risk patient: experience withfenoldopam, a selective dopamine receptor agonist, in prevention ofradiocontrast nephropathy during percutaneous coronary intervention. RevCardiovasc Med. 2001;2(Suppl 1):S19–25.249. Kolonko A, Wiecek A, Kokot F. The nonselective adenosine antagonisttheophylline does prevent renal dysfunction induced by radiographiccontrast agents. J Nephrol. 1998;11(3):151–6.250. Kramer BK, Preuner J, Ebenburger A, Kaiser M, Bergner U, Eilles C, et al. Lackof renoprotective effect of theophylline during aortocoronary bypasssurgery. Nephrol Dial Transplant. 2002;17(5):910–5.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 16 of 18251. Krasuski RA, Beard BM, Geoghagan JD, Thompson CM, Guidera SA. Optimaltiming of hydration to erase contrast-associated nephropathy: the OTHERCAN study. J Invasive Cardiol. 2003;15(12):699–702.252. Kristeller JL, Zavorsky GS, Prior JE, Keating DA, Brady MA, Romaldini TA, et al.Lack of effectiveness of sodium bicarbonate in preventing kidney injury inpatients undergoing cardiac surgery: a randomized controlled trial.Pharmacotherapy. 2013;33(7):710–7.253. Lassnigg A, Donner E, Grubhofer G, Presterl E, Druml W, Hiesmayr M. Lack ofrenoprotective effects of dopamine and furosemide during cardiac surgery.J Am Soc Nephrol. 2000;11(1):97–104.254. Lee PT, Chou KJ, Liu CP, Mar GY, Chen CL, Hsu CY, et al. Renal protection forcoronary angiography in advanced renal failure patients by prophylactichemodialysis. A randomized controlled trial. J Am Coll Cardiol. 2007;50(11):1015–20.255. Majumdar SR, Kjellstrand CM, Tymchak WJ, Hervas-Malo M, Taylor DA, Teo KK.Forced euvolemic diuresis with mannitol and furosemide for prevention ofcontrast-induced nephropathy in patients with CKD undergoing coronaryangiography: a randomized controlled trial. Am J Kidney Dis. 2009;54(4):602–9.256. Marenzi G, Bartorelli AL, Lauri G, Assanelli E, Grazi M, Campodonico J, et al.Continuous veno-venous hemofiltration for the treatment of contrast-induced acute renal failure after percutaneous coronary interventions.Catheter Cardiovasc Interv. 2003;58(1):59–64.257. Miller HI, Dascalu A, Rassin TA, Wollman Y, Chernichowsky T, Iaina A. Effectsof an acute dose of L-arginine during coronary angiography in patientswith chronic renal failure: a randomized, parallel, double-blind clinical trial.Am J Nephrol. 2003;23(2):91–5.258. Mueller C, Buerkle G, Buettner HJ, Petersen J, Perruchoud AP, Eriksson U, etal. Prevention of contrast media-associated nephropathy: randomizedcomparison of 2 hydration regimens in 1620 patients undergoing coronaryangioplasty. Arch Intern Med. 2002;162(3):329–36.259. Neumayer HH, Junge W, Kufner A, Wenning A. Prevention of radiocontrast-media-induced nephrotoxicity by the calcium channel blocker nitrendipine: aprospective randomised clinical trial. Nephrol Dial Transplant. 1989;4(12):1030–6.260. Recio-Mayoral A, Chaparro M, Prado B, Cozar R, Mendez I, Banerjee D, et al.The Reno-protective effect of hydration with sodium bicarbonate plus N-acetylcysteine in patients undergoing emergency percutaneous coronaryintervention: the RENO Study. J Am Coll Cardiol. 2007;49(12):1283–8.261. Rosenstock JL, Bruno R, Kim JK, Lubarsky L, Schaller R, Panagopoulos G, etal. The effect of withdrawal of ACE inhibitors or angiotensin receptorblockers prior to coronary angiography on the incidence of contrast-induced nephropathy. Int Urol Nephrol. 2008;40(3):749–55.262. Schwab SJ, Hlatky MA, Pieper KS, Davidson CJ, Morris KG, Skelton TN, et al.Contrast nephrotoxicity: a randomized controlled trial of a nonionic and anionic radiographic contrast agent. N Engl J Med. 1989;320(3):149–53.263. Shavit L, Korenfeld R, Lifschitz M, Butnaru A, Slotki I. Sodium bicarbonateversus sodium chloride and oral N-acetylcysteine for the prevention ofcontrast-induced nephropathy in advanced chronic kidney disease. J IntervCardiol. 2009;22(6):556–63.264. Shemirani H. Pourrmoghaddas M. a randomized trial of saline hydration toprevent contrast-induced nephropathy in patients on regular captopril orfurosemide therapy undergoing percutaneous coronary intervention. SaudiJ Kidney Dis Transpl. 2012;23(2):280–5.265. Shin DH, Choi DJ, Youn TJ, Yoon CH, Suh JW, Kim KI, et al. Comparison of contrast-induced nephrotoxicity of iodixanol and iopromide in patients with renalinsufficiency undergoing coronary angiography. Am J Cardiol. 2011;108(2):189–94.266. Sochman J, Krizova B. Prevention of contrast agent-induced renalimpairment in patients with chronic renal insufficiency and heart disease byhigh-dose intravenous N-acetylcysteine: a pilot-ministudy. Kardiol Pol. 2006;64(6):559–64 discussion 65-6.267. Spangberg-Viklund B, Berglund J, Nikonoff T, Nyberg P, Skau T, Larsson R.Does prophylactic treatment with felodipine, a calcium antagonist, preventlow-osmolar contrast-induced renal dysfunction in hydrated diabetic andnondiabetic patients with normal or moderately reduced renal function?Scand J Urol Nephrol. 1996;30(1):63–8.268. Staniloae CS, Doucet S, Sharma SK, Katholi RE, Mody KR, Coppola JT, et al.N-acetylcysteine added to volume expansion with sodium bicarbonatedoes not further prevent contrast-induced nephropathy: results from thecardiac angiography in renally impaired patients study. J Interv Cardiol.2009;22(3):261–5.269. Stegmayr BG, Brannstrom M, Bucht S, Crougneau V, Dimeny E, Ekspong A, et al.Low-dose atorvastatin in severe chronic kidney disease patients: a randomized,controlled endpoint study. Scand J Urol Nephrol. 2005;39(6):489–97.270. Sterner G, Frennby B, Kurkus J, Nyman U. Does post-angiographichemodialysis reduce the risk of contrast-medium nephropathy? Scand JUrol Nephrol. 2000;34(5):323–6.271. Stevens MA, McCullough PA, Tobin KJ, Speck JP, Westveer DC, Guido-AllenDA, et al. A prospective randomized trial of prevention measures in patientsat high risk for contrast nephropathy: results of the PRINCE StudyPrevention of Radiocontrast Induced Nephropathy Clinical Evaluation. J AmColl Cardiol. 1999;33(2):403–11.272. Tamai N, Ito S, Nakasuka K, Morimoto K, Miyata K, Inomata M, et al. Sodiumbicarbonate for the prevention of contrast-induced nephropathy: theefficacy of high concentration solution. J Invasive Cardiol. 2012;24(9):439–42.273. Taylor AJ, Hotchkiss D, Morse RW, McCabe JPREPARED. Preparation forangiography in renal dysfunction: a randomized trial of inpatient vsoutpatient hydration protocols for cardiac catheterization in mild-to-moderate renal dysfunction. Chest. 1998;114(6):1570–4.274. Torigoe K, Tamura A, Watanabe T, Kadota J. 20-hour preproceduralhydration is not superior to 5-hour preprocedural hydration in theprevention of contrast-induced increases in serum creatinine and cystatin C.Int J Cardiol. 2013;167(5):2200–3.275. Ueda H, Yamada T, Masuda M, Okuyama Y, Morita T, Furukawa Y, et al.Prevention of contrast-induced nephropathy by bolus injection of sodiumbicarbonate in patients with chronic kidney disease undergoing emergentcoronary procedures. Am J Cardiol. 2011;107(8):1163–7.276. Weinstein JM, Heyman S, Brezis M. Potential deleterious effect offurosemide in radiocontrast nephropathy. Nephron. 1992;62(4):413–5.277. Xinwei J, Xianghua F, Jing Z, Xinshun G, Ling X, Weize F, et al. Comparison ofusefulness of simvastatin 20 mg versus 80 mg in preventing contrast-inducednephropathy in patients with acute coronary syndrome undergoingpercutaneous coronary intervention. Am J Cardiol. 2009;104(4):519–24.278. Carraro M, Stacul F, Collari P, Toson D, Zucconi F, Torre R, et al. Contrastmedia nephrotoxicity: urinary protein and enzyme pattern in patients withor without saline infusion during digital subtracting angiography. ContribNephrol. 1993;101:251–4.279. Shakeryan F, Sanati H, Fathi H, Firouzi A, Zahedmehr A, Valizadeh G, et al.Evaluation of combination therapy with vitamin C and pentoxifylline onpreventing kidney failure secondary to intravenous contrast material incoronary angioplasty. Iranian Heart J. 2013:17–21.280. Berger ED, Bader BD, Bosker J, Risler T, Erley CM. Contrast media-inducedkidney failure cannot be prevented by hemodialysis. Dtsch MedWochenschr. 2001;126(7):162–6.281. Koch JA, Sketch M, Brinker J, Bernink PJ. Prostaglandin E1 for prevention ofcontrast medium-induced kidney dysfunction. Rofo. 1999;170(6):557–63.282. Cao S, Wang P, Cui K, Zhang L, Hou Y. Atorvastatin prevents contrastagent-induced renal injury in patients undergoing coronaryangiography by inhibiting oxidative stress. Nan Fang Yi Ke Da Xue XueBao. 2012;32(11):1600–2.283. Chen GL, Su JZ. Atorvastatin attenuated contrast induced renal functiondamage. Zhonghua Xin Xue Guan Bing Za Zhi. 2009;37(5):389–93.284. Hui H, Li K, Li Z, Wang J, Gao M, Han X. Protective effect of amlodipineagainst contrast agent-induced renal injury in elderly patients with coronaryheart disease. Nan Fang Yi Ke Da Xue Xue Bao. 2012;32(11):1580–3.285. Wang ZL, Liu M, Zhang YQ. The prevention of denhong injection oncontrast-induced renal impairment after percutaneous coronaryintervention. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2011;31(12):1611–4.286. Yin L, Li GP, Liu T, Liu HM, Chen X, He M, et al. Role of probucol inpreventing contrast induced acute kidney injury after coronaryinterventional procedure: a randomized trial. Zhonghua Xin Xue Guan BingZa Zhi. 2009;37(5):385–8.287. Zhou X, Jin YZ, Wang Q, Min R, Zhang XY. Efficacy of high dose atorvastatin onpreventing contrast induced nephropathy in patients underwent coronaryangiography. Zhonghua Xin Xue Guan Bing Za Zhi. 2009;37(5):394–6.288. Diez T, Bagilet D, Ramos M, Jolly H, Diab M, Marcucci R, et al. Evaluation oftwo methods to avoid the nephropathy associated with radiologic contrast.Medicina (B Aires). 1999;59(1):55–8.289. El Mahmoud R, Le Feuvre C, Le Quan Sang KH, Helft G, Beygui F, Batisse JP,et al. Absence of nephro-protective effect of acetylcysteine in patients withchronic renal failure investigated by coronary angiography. Arch Mal CoeurVaiss. 2003;96(12):1157–61.290. Toprak O, Cirit M, Bayata S, Yesil M, Aslan SL. The effect of pre-proceduralcaptopril on contrast-induced nephropathy in patients who underwentcoronary angiography. Anadolu Kardiyol Derg. 2003;3(2):98–103.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 17 of 18291. Vallero A, Cesano G, Pozzato M, Garbo R, Minelli M, Quarello F, et al. Contrastnephropathy in cardiac procedures: no advantages with prophylactic use of N-acetylcysteine (NAC). G Ital Nefrol. 2002;19(5):529–33.292. Chen H, Wu H, He Q, Chen H, Mao Y. Comparison of sodium bicarbonateand sodium chloride as strategies for preventing contrast nephropathy[abstract no: SU-PO1046]. J Am Soc Nephrol : JASN. 2007:817A–8A.293. Grygier M, Janus M, Araszkiewicz A, Kowal J, Mularek-Kubzdela T, Olasinska-Wisniewska A, et al. Combined treatment with ascorbic acid and N-acetylcysteine prevents contrast-induced nephropathy in high-risk patientswith acute myocardial infarction undergoing percutaneous coronaryintervention. Eur heart J. 2011:954–5.294. Habib M, Hillis A, Hamad A. Low dose of N-acetylcysteine plus ascorbic acidversus hydration with (saline 0.9%) for prevention of contrast-inducednephropathy in patients undergoing coronary angiography. Int J Cardiol.2013:S81–S.295. Lin M, Sabeti M, Iskandar E, Malhotra N, Pham PT, Pham PC. Prevention ofcontrast nephropathy with sodium bicarbonate [abstract no: PUB591]. J AmSoc Nephrol : JASN. 2007:959a–60a.296. Lukas R, Eren A, Keller F, Jehle P. Prevention of contrast nephropathy (cnp)with hydratation and furosemide (fs) [abstract]. Nephrol Dial Transplant.1999:A73–A.297. Moreyra A, Natarajan MK, Doucet S, Sharma SK, Staniloae CS, Katholi RE.Contrast nephropathy in patients with chronic kidney disease undergoingeither diagnostic or interventional procedures [abstract no:TCT-313]. Am JCardiol. 2007:124L–L.298. Ray DS, Srinivas V. Role of n-acetyl cysteine in prevention of contrastnephropathy in patients of diabetic renal failure: a prospective study[abstract]. Nephrol Dial Transplant. 2003:664.299. Saidin R, Zainudin S, Kong NCT, Maskon O, Saaidin NF, Shah SA. Intravenoussodium bicarbonate versus normal saline infusion as prophylaxis againstcontrast nephropathy in patients with chronic kidney disease undergoingcoronary angiography or angioplasty [abstract no: F-SA-DS911]. Journal ofthe American Society of Nephrology : JASN. 2006:766A–A.300. Andrew Lewington RM, Hoefield R, Sutton A, Smith D, Downes M.Prevention of Contrast Induced Acute Kidney Injury (CI-AKI). In: Adult.Patients. The Renal Association, British Cardiovascular Intervention Societyand The Royal College of Radiologists; 2013.301. Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. Evidencesynthesis for decision making 4: inconsistency in networks of evidencebased on randomized controlled trials. Med Decis Mak. 2013;33(5):641–56.302. Zhang JZ, Kang XJ, Gao Y, Zheng YY, Wu TT, Li L, et al. Efficacy of alprostadilfor preventing of contrast-induced nephropathy: a meta-analysis. Sci Rep.2017;7(1):1045.303. Feldkamp T, Baumgart D, Elsner M, Herget-Rosenthal S, Pietruck F, Erbel R,et al. Nephrotoxicity of iso-osmolar versus low-osmolar contrast media isequal in low risk patients. Clin Nephrol. 2006;66(5):322–30.304. Subramaniam RM, Suarez-Cuervo C, Wilson RF, Turban S, Zhang A, Sherrod C,et al. Effectiveness of prevention strategies for contrast-induced nephropathy:a systematic review and meta-analysis. Ann Intern Med. 2016;164(6):406–16.Ahmed et al. BMC Nephrology          (2018) 19:323 Page 18 of 18


Citation Scheme:


Citations by CSL (citeproc-js)

Usage Statistics



Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            async >
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:


Related Items