ContrastContrast NephropathyNephropathy

Neil R Neil R CollingeCollinge MDMDGreyGrey’’s Hospital, PMBs Hospital, PMB

15 Aug 200715 Aug 2007

Presentation GoalsPresentation Goals

Understand pathogenesis of contrast induced Understand pathogenesis of contrast induced nephropathy (CIN)nephropathy (CIN)Clinical presentation, diagnosis and risk of Clinical presentation, diagnosis and risk of developing ESRD developing ESRD Assess risk factors for development of CINAssess risk factors for development of CINBecome acquainted with prevention of CINBecome acquainted with prevention of CINTreatment of CINTreatment of CINDiscussion of Cholesterol Discussion of Cholesterol AtheroembolicAtheroembolicKidney DiseaseKidney Disease

IntroductionIntroduction

Administration of Administration of radiocontrastradiocontrast media can lead media can lead to usually reversible ARF soon after the contrast to usually reversible ARF soon after the contrast in administered.in administered.Many important issues remain unresolved Many important issues remain unresolved including pathogenesis of the disorder, efficacies including pathogenesis of the disorder, efficacies of various prophylactic strategies and the relative of various prophylactic strategies and the relative nephrotoxicitynephrotoxicity of different iodinated of different iodinated radiocontrastradiocontrast agentsagents

PathogenesisPathogenesis

Some studies show evidence of ATN, Some studies show evidence of ATN, mechanism poorly understoodmechanism poorly understoodRenal vasoconstriction resulting in Renal vasoconstriction resulting in medullarymedullaryhypoxemia, possibly mediated by alterations in hypoxemia, possibly mediated by alterations in nitric oxide, nitric oxide, endotheinendothein &/or adenosine&/or adenosineDirect Direct cytotoxiccytotoxic effects of contrast agentseffects of contrast agentsRecovery from CIN typically much faster than Recovery from CIN typically much faster than usually associated with ATNusually associated with ATN

Renal VasoconstrictionRenal Vasoconstriction

Mediated by contrastMediated by contrast--induced release of induced release of endothelinendothelin and and adenosine and by high adenosine and by high osmolalityosmolality of agentof agentReductions in Reductions in medullarymedullary blood due to effects of blood due to effects of viscosityviscosityRenal vasoconstriction and reduced Renal vasoconstriction and reduced medullarymedullary blood blood flow result in hypoxemic conditions flow result in hypoxemic conditions facillitatingfacillitating renal renal injuryinjuryDiabetes and heart failure associated w/ impaired nitric Diabetes and heart failure associated w/ impaired nitric oxide generation, contributing to susceptibility to CINoxide generation, contributing to susceptibility to CIN

Tubular InjuryTubular Injury

Direct Direct cytotoxiccytotoxic effectseffectsGeneration of oxygen free radicalsGeneration of oxygen free radicalsMay act in concert with renal May act in concert with renal asoconstrictionasoconstriction

IncidenceIncidence

Incidence is negligible w/ normal renal functionIncidence is negligible w/ normal renal function44--11% w/ mild11% w/ mild--moderate renal impairment (moderate renal impairment (SCrSCr132 to 352umol/L)132 to 352umol/L)99--38% w/ mod renal impairment and DM38% w/ mod renal impairment and DM50% or more if 50% or more if SCrSCr >352>352--440umol/L440umol/LRisk is increased w/ marked renal dysfunction, Risk is increased w/ marked renal dysfunction, marked volume depletion, multiple contrast marked volume depletion, multiple contrast studies within a 72hr periodstudies within a 72hr period

PercutaneousPercutaneous Coronary InterventionCoronary Intervention

Review of 7500 PCI patientsReview of 7500 PCI patientsCIN occurrence in 3.3% overallCIN occurrence in 3.3% overall25% in individuals w/ 25% in individuals w/ SCrSCr >177umol/L>177umol/LARF assoc w/ significant increase in mortality ARF assoc w/ significant increase in mortality inin--hospital (22 v 1.4% without renal failure). hospital (22 v 1.4% without renal failure). However these studies. However, these studies However these studies. However, these studies fail to establish cause of renal failure in the fail to establish cause of renal failure in the setting of PCI.setting of PCI.

DialysisDialysis

Incidence of CIN requiring dialysis appears very Incidence of CIN requiring dialysis appears very low.low.Retrospective review of 58,000 coronary Retrospective review of 58,000 coronary procedures: 10 and 49 patients required dialysis procedures: 10 and 49 patients required dialysis @ one week and one month (@ one week and one month (i.ei.e <0.1%)<0.1%)

RadiocontrastRadiocontrast AgentsAgents

High High osmololalosmololal, first generation contrast agents , first generation contrast agents ((osmolalityosmolality 14001400--1800mosmol/kg) associated 1800mosmol/kg) associated w/ higher risk of CINw/ higher risk of CINNewer agents, Newer agents, iohexoliohexol (500(500--850mosmol/kg) and 850mosmol/kg) and iodixanoliodixanol (290 (290 mosmolmosmol/kg) appear to have less /kg) appear to have less nephrotoxicnephrotoxic propertiespropertiesLower doses also associated with decreased Lower doses also associated with decreased incidence of CINincidence of CIN

Clinical Clinical CharacterisiticsCharacterisitics

12 to 24 hrs post contrast12 to 24 hrs post contrastTypically Typically nonoliguricnonoliguric in vast majority of patientsin vast majority of patientsAlmost all cases, renal impairment is mild and Almost all cases, renal impairment is mild and transient, with recovery in 3 to 5 daystransient, with recovery in 3 to 5 daysPersistent renal failure has been primarily Persistent renal failure has been primarily described in patients w/ preexisting advanced described in patients w/ preexisting advanced underlying disease, particularly diabetics.underlying disease, particularly diabetics.2 year survival in group requiring dialysis is only 2 year survival in group requiring dialysis is only 19%19%

DiagnosisDiagnosis

Diagnosis based on characteristic rise in plasma Diagnosis based on characteristic rise in plasma creatininecreatinine 12 to 24 hours after contrast dose12 to 24 hours after contrast doseDifferential includes ischemic ATN, acute Differential includes ischemic ATN, acute interstitial nephritis and renal interstitial nephritis and renal atheroemboliatheroemboliParticularly in angiography among those w/ Particularly in angiography among those w/ diffuse atherosclerosis, contrast nephropathy diffuse atherosclerosis, contrast nephropathy must be distinguished from must be distinguished from atheroemboliatheroemboli

TreatmentTreatment

No specific treatmentNo specific treatmentMaintain Maintain fludflud and electrolyte balanceand electrolyte balanceBest treatment is preventionBest treatment is prevention

PreventionPrevention

Use Use ultrasonographyultrasonography, MRI or non, MRI or non--contrast CT contrast CT in high risk patients, if clinically possiblein high risk patients, if clinically possibleLower doses of contrast, avoid repetitive studiesLower doses of contrast, avoid repetitive studiesAvoid volume depletion or NSAIDSAvoid volume depletion or NSAIDSAdmin of IV saline or possibly Sodium Admin of IV saline or possibly Sodium BicarbBicarbAdministration of antioxidants, Administration of antioxidants, acetylcyseineacetylcyseineUse of low or Use of low or isoiso--osmololalosmololal contrast agents contrast agents

Carbon DioxideCarbon Dioxide

Alternative contrast agentAlternative contrast agentNo or little No or little nephrotoxicitynephrotoxicitySatisfactory imaging, particularly with digital Satisfactory imaging, particularly with digital subtraction angiographysubtraction angiographyRisk is Risk is neurotoxicityneurotoxicity when injected close to when injected close to cerebral circulation or if there is a rightcerebral circulation or if there is a right--toto--left left cardiac shuntcardiac shuntUse should be limited to imaging below Use should be limited to imaging below diaphragmdiaphragm

HydrationHydration

Prospective randomized trial, 1620 pts, isotonic Prospective randomized trial, 1620 pts, isotonic v onev one--half isotonic saline. Significant benefit to half isotonic saline. Significant benefit to those given isotonic saline, 0.7 versus 2.0% those given isotonic saline, 0.7 versus 2.0% incidence. Diabetics (0 versus 5.5%)incidence. Diabetics (0 versus 5.5%)119 pts, 119 pts, bicarbbicarb or saline pre and post contrast, or saline pre and post contrast, incidence was 1.7 versus 13.6% in favor of incidence was 1.7 versus 13.6% in favor of bicarbbicarb infusion.infusion.

DiureticsDiuretics

Diuretic Diuretic adminstrationadminstration associated with higher associated with higher incidence of renal failureincidence of renal failureDopamine, Dopamine, mannitolmannitol and and atrialatrial natriureticnatriureticpeptide were associated with MUCH higher peptide were associated with MUCH higher incidence of renal failure (75incidence of renal failure (75--83%) in diabetic 83%) in diabetic subjectssubjects

AcetylcysteineAcetylcysteine

Antioxidant and Antioxidant and vasodilatoryvasodilatory propertiespropertiesGreat heterogeneity and conflicting resultsGreat heterogeneity and conflicting resultsOverall direction of data is towards benefitOverall direction of data is towards benefitMetaMeta--analysis of 25 trials, 2195 patients, of oral analysis of 25 trials, 2195 patients, of oral acetylcysteineacetylcysteine –– nonnon--significant 27% reduction significant 27% reduction in CIN (95% CI 0.52 to 1.0)in CIN (95% CI 0.52 to 1.0)Dosing: 600 Dosing: 600 –– 1200mg 1200mg popo 12hourly, 24 hours 12hourly, 24 hours before and after contrast administration.before and after contrast administration.

HaemodialysisHaemodialysis and and HaemofiltrationHaemofiltration

Contrast media is partially removed by HD and Contrast media is partially removed by HD and HFHFStudies to date have failed to demonstrate a Studies to date have failed to demonstrate a benefit of prophylactic HD/HFbenefit of prophylactic HD/HFMay mask CIN by artificially lowering May mask CIN by artificially lowering creatininecreatinine

Inhibition of VasoconstrictionInhibition of Vasoconstriction

2005 meta2005 meta--analysis of analysis of theophyllinetheophylline, 585 patients , 585 patients versus controls, showed versus controls, showed theophyllinetheophylline may may provide some benefit, albeit small.provide some benefit, albeit small.Prospective randomized trial (CONTRAST) Prospective randomized trial (CONTRAST) assessed assessed fenoldapamfenoldapam in 315 patients (one half in 315 patients (one half diabetic) undergoing cardiovascular procedure diabetic) undergoing cardiovascular procedure with CKD. No reduction in incidence of CIN with CKD. No reduction in incidence of CIN in group receiving in group receiving fenoldapamfenoldapam versus placeboversus placebo

MRI with GadoliniumMRI with Gadolinium

Emerging data from animal experiments, case reports Emerging data from animal experiments, case reports and small series that gadoliniumand small series that gadolinium--based contrast media based contrast media can be associated with can be associated with nephrotoxicitynephrotoxicitySome have claimed that Some have claimed that nephrotoxicnephrotoxic profile of profile of gadolinium is similar to diluted iodinated contrast gadolinium is similar to diluted iodinated contrast mediamediaMore importantly, among pts w/ mod to severe renal More importantly, among pts w/ mod to severe renal failure, potentially severe syndrome of failure, potentially severe syndrome of nephrogenicnephrogenicsystemic fibrosis.systemic fibrosis.

RecommendationsRecommendations

Avoid volume depletionAvoid volume depletionUltrasound, MRI w/o gadolinium, CT without Ultrasound, MRI w/o gadolinium, CT without radiocontrastradiocontrast agentsagentsAvoid use of high Avoid use of high osmololalosmololal agentsagentsLower doses of contrastLower doses of contrastIsotonic volume expansion if possibleIsotonic volume expansion if possibleAvoid concomitant use of NSAIDS, diureticsAvoid concomitant use of NSAIDS, diureticsAcetylcysteineAcetylcysteine

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Renal Renal AtheroemboliAtheroemboli

EmbolizationEmbolization of portions of of portions of atheroembolicatheroembolicplaques resulting in occlusion of multiple small plaques resulting in occlusion of multiple small arteries and tissue/organ ischemia.arteries and tissue/organ ischemia.AtheroemboliAtheroemboli (cholesterol crystals) usually affect (cholesterol crystals) usually affect older patients with diffuse erosive older patients with diffuse erosive atherosclerosis.atherosclerosis.

Risk FactorsRisk Factors

Manipulation of aorta and other large arteries Manipulation of aorta and other large arteries during during arteriographyarteriography, angioplasty or surgery., angioplasty or surgery.Some cases are spontaneousSome cases are spontaneous

Clinical CharacteristicsClinical Characteristics

May be associated with May be associated with embolizationembolization to other to other sites including blue toe syndrome, sites including blue toe syndrome, livedolivedoreticularisreticularis and gastrointestinal manifestationsand gastrointestinal manifestations7.1% of 259 patients over age 60 w/ ARF 7.1% of 259 patients over age 60 w/ ARF undergoing biopsy had undergoing biopsy had atheroembolicatheroembolic diseasediseaseProgressive decline in renal function for three to Progressive decline in renal function for three to eight weeks after procedure, starting one to two eight weeks after procedure, starting one to two weeks after procedureweeks after procedure

Often has staggered courseOften has staggered courseRarely patients have stable renal impairment.Rarely patients have stable renal impairment.

Diagnostic FindingsDiagnostic Findings

Benign urineBenign urineRarely with Rarely with proteinuriaproteinuria but may be but may be nephroticnephroticRarely have Rarely have haematuriahaematuria and and redcellredcell castscastsEosinophiliaEosinophilia and and hypocomplementemiahypocomplementemiaEosinophiluriaEosinophiluria may also be presentmay also be presentBiopsy of a skin lesion or kidney may be Biopsy of a skin lesion or kidney may be necessarynecessary

HistopathologyHistopathology

LivedoLivedo ReticularisReticularis

Treatment and PrognosisTreatment and Prognosis

No specific treatmentNo specific treatmentAggressively treat for secondary prevention of Aggressively treat for secondary prevention of cardiovascular diseasecardiovascular diseasePoor overall prognosisPoor overall prognosisProspective study of 95 patients, end stage renal Prospective study of 95 patients, end stage renal disease and death occurred in 24 and 38% of disease and death occurred in 24 and 38% of patients patients respectivelyrespectively

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