Glomerular Filtration and determinants of glomerular filtration .pptx
CARDIO- RENAL SYNDROME
1. Dr. R. Vishwanath M.R.C.P (U.K)Dr. R. Vishwanath M.R.C.P (U.K)
Department of CardiologyDepartment of Cardiology
Apollo Hospitals, HydergudaApollo Hospitals, Hyderguda
HyderabadHyderabad
THE CARDIORENALTHE CARDIORENAL
SYNDROME – A GLIMPSESYNDROME – A GLIMPSE
3. Topics for Consideration….Topics for Consideration….
1. Definition of CRS.
2. Classification - subtypes of CRS.
3. Incidence of CRS.
4. Proposed pathogenesis of CRS.
5. Biomarkers in CRS.
6. Early recognition of CRS.
7. Management strategies.
8. Long term prognostic outcomes.
4. Definition of CRSDefinition of CRS
• Pathophysiological disorder of thePathophysiological disorder of the
heart and kidneys, whereby acute orheart and kidneys, whereby acute or
chronic dysfunction in one organ maychronic dysfunction in one organ may
induce acute or chronic dysfunction ininduce acute or chronic dysfunction in
the other organ.the other organ.
BIDIRECTIONALBIDIRECTIONAL
5.
6. Sub types of CRS……..Sub types of CRS……..
• Type I CRS :Type I CRS : (acute CRS) Abrupt(acute CRS) Abrupt
worsening of cardiac function leadingworsening of cardiac function leading
to Acute Kidney Injury.to Acute Kidney Injury.
7.
8. Subtypes of CRS…..Subtypes of CRS…..
• Type II CRS (Chronic CRS):Type II CRS (Chronic CRS): ChronicChronic
abnormalities in cardiac functionabnormalities in cardiac function
causing progressive and permanentcausing progressive and permanent
chronic kidney diseasechronic kidney disease
9.
10. Sub types of CRS…..Sub types of CRS…..
• Type III CRS ( Acute renocardiacType III CRS ( Acute renocardiac
syndrome):syndrome): Abrupt worsening of renalAbrupt worsening of renal
function leading to acute cardiacfunction leading to acute cardiac
disorder (e.g. heart failure, arrhythmia,disorder (e.g. heart failure, arrhythmia,
ischaemia)ischaemia)
11.
12. Sub types of CRS……Sub types of CRS……
• Type IV CRS (Chronic renocardiacType IV CRS (Chronic renocardiac
syndrome):syndrome): Chronic Kidney DiseaseChronic Kidney Disease
contributing to decreased cardiaccontributing to decreased cardiac
function, cardiac hypertrophy and/orfunction, cardiac hypertrophy and/or
increased risk of adverse cardiovascularincreased risk of adverse cardiovascular
eventsevents
13.
14. Subtypes of CRS……Subtypes of CRS……
• Type V CRS (Secondary CRS):Type V CRS (Secondary CRS):
Systemic condition (DM, Sepsis)Systemic condition (DM, Sepsis)
causing both cardiac and renalcausing both cardiac and renal
dysfunctiondysfunction
17. CRS – OMINOUS CO-EXISTENCECRS – OMINOUS CO-EXISTENCE
2 Year mortality % 2 Year Incidence of
ESRD%
No Anaemia/ CHF/ CKI 7.7 0.1
Anaemia 16.6 0.1
CHF 26.1 0.2
CHF & Anaemia 34.6 0.3
CKI 16.4 2.6
CKI & Anaemia 27.3 5.4
CHF & CKI 38.4 3.5
CHF, CKI & Anaemia 45.6 5.9
2-year mortality and incidence of ESRD in a 5%
sample of Medicare patients from the USA (1.1
million patients)
Gilbertson D. J Am Soc Nephrol 2002;13:SA848
18. Predictors of All-Cause MortalityPredictors of All-Cause Mortality
to 7 Years BARI Trial + Registryto 7 Years BARI Trial + Registry
Szczech L. et al.,Szczech L. et al., CirculationCirculation 2002; 105:2253-8.2002; 105:2253-8.
19. Early detection --- New BiomarkersEarly detection --- New Biomarkers
Biomarker Associated Injury
Cystatin Cs Proximal tubule injury
KIM-1 Ischemia and nephrotoxins
NGAL (lipocalin) Ischemia and nephrotoxins
NHE3 Ischemia, pre-renal, post-renal AKI
Cytokines (IL-6, IL-8, IL-18) Toxic, delayed graft function
Actin-actin depolymerizing F Ischemia and delayed graft function
α-GST Proximal T injury, acute rejection
π-GST Distal tubule injury, acute rejection
L-FABP Ischemia and nephrotoxins
Netrin-1 Ischemia and nephrotoxins, sepsis
Keratin-derived chemokine Ischemia and delayed graft function
21. Management Strategies…Management Strategies…
• DiureticsDiuretics
• Diuretic Resistance.Diuretic Resistance.
• Role of ACE-I / ARBRole of ACE-I / ARB
• Role of Beta Blockers.Role of Beta Blockers.
• Ionotropic agents.Ionotropic agents.
• Ultra filtrationUltra filtration
• Role of Nesiritide.Role of Nesiritide.
• Vasopressin and Adenosine antagonists.Vasopressin and Adenosine antagonists.
• Palliative CarePalliative Care
23. Conclusions…Conclusions…
1.Recent studies have identified and characterized
several novel biomarkers for CRSs
2.It is anticipated that these biomarkers will help
make an earlier diagnosis of CRSs as well as
identify its specific type and potentially its
pathophysiology
24. It remains to be seen whether or not effective
prevention and treatment of CRSs will improve
hard renal and cardiac outcomes including
SCD,ESRD, hospitalizations, and death
Conclusions….Conclusions….
25. Longitudinal care……Longitudinal care……
• Palliative Care has a more stronger rolePalliative Care has a more stronger role
now than in the past as people are livingnow than in the past as people are living
longer due to better diagnostic andlonger due to better diagnostic and
therapeutic modalities……..therapeutic modalities……..
26.
27. Contrast Induced NephropathyContrast Induced Nephropathy
Cardiac InterventionCardiac Intervention
Department of CardiologyDepartment of Cardiology
Apollo Hospitals, HydergudaApollo Hospitals, Hyderguda
HyderabadHyderabad
Dr. R. Vishwanath MRCP(UK)
28. ControversialControversial
• Thousands of literature and papers.
• Hundreds of meta-analysis of the published papers.
DENIAL RESPONSE !!!
Experience Vs Evidence based practice
Many contradictory results
29. Renal Function TestsRenal Function Tests
1. Serum Creatinine
• Calibration and Estimation
• Many variables – Age, Race, Sex .…
A normal Serum Creatinine is not indicative of
a normal renal function.
GFR
30. How to Assess Renal Function?How to Assess Renal Function?
Abbreviated Modification of Diet in Renal Disease
equations (MDRD) equation:
eGFR, ml/min/1.73 m2
= 186 x (Serum Creatinine [mg/dL]) -1.154 x
(Age-0.203x (0.742 if female) x (1.210 if African American)
(140- age) x Body Weight [kg]*
Creatinine Clearance, ml/min =
* Multiple by 0.8 in female
Cockcroft-Gault equation:
Serum Creatinine mg/dL] x 72
31. Definition of CINDefinition of CIN
CIN ↑ in Serum Creatinine
concentration
0.5 mg/dL (44 mol/L) or
25% above baseline within
48 hours after contrast
administration
32. • Non-oliguricNon-oliguric
• ↓↓ renal function post-contrast in the absencerenal function post-contrast in the absence
of other causes.of other causes.
• Recovery usually occurs within 5 to 14 days.Recovery usually occurs within 5 to 14 days.
However the long term outcome on renalHowever the long term outcome on renal
dysfunction is unclear.dysfunction is unclear.
DefinitionDefinition
33. INCIDENCE OF CININCIDENCE OF CIN ::
Marked variation in the reported incidence of CIN
0 to >50%
Causative Factors for the wide variation of CIN:
Consensus on what is Renal dysfunction .
Variability of risk factors
Various types of contrast and variable procedures.
Radiologic procedure.
34. Risk Factors for CINRisk Factors for CIN
Patient-related Risk FactorsPatient-related Risk Factors
• Renal insufficiencyRenal insufficiency
• Diabetes mellitus withDiabetes mellitus with
renal insufficiencyrenal insufficiency
• AgeAge
• Volume depletionVolume depletion
• HypotensionHypotension
• Low cardiac outputLow cardiac output
• Class IV CHFClass IV CHF
• Other nephrotoxinsOther nephrotoxins
• Renal transplantRenal transplant
• Hypoalbuminemia (<35 g/l)Hypoalbuminemia (<35 g/l)
Procedure-related Risk FactorsProcedure-related Risk Factors
• Multiple contrast mediaMultiple contrast media
injection within 72 hrsinjection within 72 hrs
• Intra-arterial injection siteIntra-arterial injection site
• High volume of contrast mediaHigh volume of contrast media
• High osmolality of contrastHigh osmolality of contrast
mediamedia
35. RiskRisk
ScoreScore
RiskRisk
of CINof CIN
Risk ofRisk of
DialysisDialysis
≤≤ 55 7.5%7.5% 0.04%0.04%
6 to 106 to 10 14.0%14.0% 0.12%0.12%
11 to11 to
1616
26.1%26.1% 1.09%1.09%
≥≥ 1616 57.3%57.3% 12.6%12.6%
Mehran et al. JACC 2004;44:1393-1399.
Hypotension
IABP
CHF
Age >75 years
Anemia
Diabetes
Contrast media volume
Risk Factors
5
5
5
4
3
3
Integer Score
1 for each 100 cc3
Scheme to Define CIN Risk ScoreScheme to Define CIN Risk Score
Serum creatinine > 1.5mg/dl 4
eGFR <60ml/min/1.73 m2
2 for 40 – 60
4 for 20 – 40
6 for < 20
eGFR < 60ml/min/1.73 m2
=
186 x (SCr)-1.154
x (Age)-0.203
X (0.742 if female) x (1.210
if African American)
Calculate
OR
36. Prognostic significance of the proposed risk score for CIN extended to
prediction of 1-year mortality. (Red bars = development dataset; blue bars =
validation dataset.)
CIN Risk Score & 1-year MortalityCIN Risk Score & 1-year Mortality
31.2 33.3
15.5
5.5
1.9 2.0
5.7
13.5
0
5
10
15
20
25
30
35
Low Moderate High Very High
1-yearmortality
Risk Groups:
Risk Score: ≤5 6 to 10 11 to 15 ≥16
Mehran et al. JACC 2004;44:1393-1399.
37. Proposed PathogenesisProposed Pathogenesis
Following exposure to contrast :
• Renal GFR ↓ due to ↓ renal vasoconstriction.
• Resultant Ischemia in the deeper portion of the outer
medulla.
• High Oxygen requirement and remote from the Vasa
recta from which it’s blood supply is derived.
Exact Mechanisms of CIN – Not fully known
Present Proposed Etiology:
Direct toxic affects of renal tubular cells, causing
vacuolization, altered mitochondrial function
and apoptosis
40. Physicochemical Properties of ContrastPhysicochemical Properties of Contrast
AgentsAgents
Table 1. Properties of Commonly Used Radiocontrast Media.
41. Renal Failure in Patients Undergoing CoronaryRenal Failure in Patients Undergoing Coronary
Procedures using Iso-osmolar or Low-osmolarProcedures using Iso-osmolar or Low-osmolar
Contrast MediaContrast Media
ContrastContrast
media (CM)media (CM) CM propertiesCM properties NN Time periodTime period
IodixanolIodixanol iso-osmolar, nonionic,iso-osmolar, nonionic, 45 48545 485 2000-20032000-2003
IoxaglateIoxaglate low-osmolar, nonionic,low-osmolar, nonionic, 12 44012 440 2000-20032000-2003
Liss et al. Kidney International 2006
• Swedish Coronary Angiography and Angioplasty Registry
• Swedish Hospital Discharge Registry
43. • 0.45% Saline0.45% Saline
• ↑↑ Free water excretion & thus dilute CM in tubuleFree water excretion & thus dilute CM in tubule
• 0.9% Saline0.9% Saline
• ↑↑ Na+ at the DCT, thus ↓ stimulation of reninNa+ at the DCT, thus ↓ stimulation of renin
angiotensin system.angiotensin system.
• NaHCO3- (isotonic)NaHCO3- (isotonic)
• Protection against free radical injuryProtection against free radical injury
FluidsFluids
44. • IV infusion vs Oral hydrationIV infusion vs Oral hydration
• IV infusion vs IV bolusIV infusion vs IV bolus
FluidsFluids
48. Optimal Hydration RegimenOptimal Hydration Regimen
Mueller et alMueller et al Arch Intern MedArch Intern Med 20022002
1937 Patients Screened
317 Ineligible or
No Consent
685 for Primary End Point
Analysis
698 for Primary End Point
Analysis
1620 Randomized
809 Received 0.9% Saline
124 Excluded From Primary
End Point Analysis
Repeat Catheterization (n=78)
Incomplete Data (n=46)
811 Received 0.45%
Sodium Chloride
113 Excluded From Primary
End Point Analysis
Repeat Catheterization (n=59)
Incomplete Data (n=53)
Bypass Grafting (n=1)
49. Optimal HydrationOptimal Hydration
0.9% NS vs 0.45% NS0.9% NS vs 0.45% NS
P=.35P=.35
0
1
2
3
CN Mortality Vascular
Incidence,%
0.9% Saline
0.45% Sodium Chloride
P=.93P=.93
P=.04P=.04
Mueller et alMueller et al Arch Intern MedArch Intern Med 20022002
50. Prevention of CIN withPrevention of CIN with
Sodium BicarbonateSodium Bicarbonate
Merten GJ et al.Merten GJ et al. JAMAJAMA, 2004;291:2328-2334, 2004;291:2328-2334
Patients With Baseline Serum Creatinine >1.8 mg/dlPatients With Baseline Serum Creatinine >1.8 mg/dl
who Underwent Contrast Exposure (Iopamidol in All)who Underwent Contrast Exposure (Iopamidol in All)
N=137N=137
Sodium ChlorideSodium Chloride
Hydration (154 mEq/L ofHydration (154 mEq/L of
Sodium Chloride)Sodium Chloride)
N=68N=68
Sodium BicarbonateSodium Bicarbonate
Hydration (154 mEq/L ofHydration (154 mEq/L of
Sodium Bicarbonate)Sodium Bicarbonate)
N=69N=69
Primary endpoint: increase in serum creatinine ≥25%Primary endpoint: increase in serum creatinine ≥25%
within 2 days post-exposurewithin 2 days post-exposure
51. Prevention of CIN with SodiumPrevention of CIN with Sodium
Bicarbonate: ResultsBicarbonate: Results
EndpointsEndpoints
SodiumSodium
ChlorideChloride
N=59N=59
SodiumSodium
BicarbonateBicarbonate
N=60N=60
PP
valuevalue
Incidence of CIN (%)Incidence of CIN (%) 13.6%13.6% 1.7%1.7% 0.020.02
Incidence of CINIncidence of CIN
(↑SCr 0.5 mg/dL)(↑SCr 0.5 mg/dL)
11.9%11.9% 1.7%1.7% 0.030.03
Merten GJ et al.Merten GJ et al. JAMA,JAMA, 2004;291:2328-23342004;291:2328-2334
52. REMEDIAL TrialREMEDIAL Trial
Saline + NACSaline + NAC
N=118N=118
Bicarbonate + NACBicarbonate + NAC
N=117N=117
Saline+AA+NACSaline+AA+NAC
N=116N=116
7 excluded7 excluded
Pts with eGFR<40Pts with eGFR<40
N=393N=393
Randomized N=351Randomized N=351
Excluded N=42Excluded N=42
NAC =NAC = NN-acetylcysteine, AA = ascorbic acid-acetylcysteine, AA = ascorbic acid
9 excluded9 excluded9 excluded9 excluded
107 included107 included
into analysisinto analysis
108 included108 included
into analysisinto analysis
111 included111 included
into analysisinto analysis
Briguorio C. et al,Briguorio C. et al, CirculationCirculation 20072007
53. REMEDIAL Trial: ResultsREMEDIAL Trial: Results
Saline + NAC
Bicarbonate +
NAC
Saline +
Ascorbic Acid
+ NAC
P Value
N=111 N=108 N=107
Serum creatinine
increase by ≥25%
11 (9.9%) 2 (1.9%)* 10 (10.3%) 0.010
Serum creatinine
increase by ≥0.5 mg/dL
12 (10.8%) 1 (0.9%)† 12 (11.2%) 0.026
eGFR decrease by
≥25%
10 (9.2%) 1 (0.9%)† 10 (10.3%) 0.018
*P=0.019P=0.019, †P<0.01P<0.01 vs. saline + NAC group
Briguorio C. et al,Briguorio C. et al, CirculationCirculation 20072007
54. MEENAMEENA
DesignDesign
• DESIGN: Prospective,
randomized, parallel-group,
single-center clinical evaluation
of two hydration strategies for
patients undergoing coronary
angiography
• OBJECTIVE: To compare the
incidence of CIN between
periprocedural hydration with
sodium bicarbonate vs. sodium
chloride (0.9%, normal saline)
• PRIMARY ENDPOINT:
Decrease in estimated GFR by ≥
25% within 4 days of coronary
angiography
353 patients enrolled between January 2006
and January 2007
353 patients enrolled between January 2006
and January 2007
236 patients
assigned to sodium
chloride
236 patients
assigned to sodium
chloride
178 patients
assigned to sodium
bicarbonate
178 patients
assigned to sodium
bicarbonate
156 evaluable
patient
156 evaluable
patient
Brar, S et. al., i2/ACC 2007
147 evaluable
patient
147 evaluable
patient
22
excluded
22
excluded
28
excluded
28
excluded
Hydration ProtocolHydration Protocol
•3 mL/kg for 1 hr before the procedure
•1.5 mL/kg during and for 4hrs post-
procedure
Hydration ProtocolHydration Protocol
•3 mL/kg for 1 hr before the procedure
•1.5 mL/kg during and for 4hrs post-
procedure
58. CIN: Effect of n-AcetylcysteineCIN: Effect of n-Acetylcysteine
• Prospective, randomizedProspective, randomized
• 83 high risk patients83 high risk patients
CrCl < 50 ml/minCrCl < 50 ml/min
Diabetes 33%Diabetes 33%
• IV CONTRAST for CT (75IV CONTRAST for CT (75
ml of Low Osmolar CM)ml of Low Osmolar CM)
• n-AC 600 bid x 2 days pre-n-AC 600 bid x 2 days pre-
• CIN definition: creatinineCIN definition: creatinine
increase of 0.5 mg/dlincrease of 0.5 mg/dl
• Hydration with 0.45% @ 1Hydration with 0.45% @ 1
ml/kg/h x 24 hml/kg/h x 24 h
21%
2%
0%
5%
10%
15%
20%
25%
Control (42) AC (41)
CIM(%)
TepelTepel NEJMNEJM 20002000
p= 0.01p= 0.01
59. Zagler et al. Am Heart J 2006;151:140-145.
Relative Risk for Developing CIN after NACRelative Risk for Developing CIN after NAC
Risk Ratio (Random)Risk Ratio (Random)
95% Cl95% Cl
0.10.1 11 1010
Favors treatmentFavors treatment Favors controlFavors control
0.20.2 0.50.5 22 55
RR (Random)RR (Random)
95% Cl95% Cl
ControlControl
n/Nn/N
NACNAC
n/Nn/N
Study orStudy or
substurysubstury
Review:Review: Acetylcysteine and CINAcetylcysteine and CIN
Comparison:Comparison: 01 NAC on CIN01 NAC on CIN
Outcome:Outcome: 01 CIN01 CIN
Total events:Total events: 124 (NAC), 162 (Control)124 (NAC), 162 (Control)
Test for heterogenety:Test for heterogenety: Ch=27.54 (P0.005), 1Ch=27.54 (P0.005), 122
=56.4%=56.4%
Test for overall effect:Test for overall effect: Z=1.88 (Z=1.88 (P=0.05P=0.05))
Allaqaband et al 8/45 6/40 1.19 (0.45, 3.12)
Briguori et al 6/92 10/91 0.59 (0.23, 1.57)
Diaz-Sandoval et al 2/25 13/29 0.18 (0.04, 0.72)
Durham et al 10/38 9/41 1.20 (0.55, 2.63)
Goldenberg et al 4/41 3/39 1.27 (0.30, 5.31)
Gomes et al 8/78 8/78 1.00 (0.40, 2.53)
Kay et al 4/102 12/98 0.32 (0.11, 0.96)
Nguyen-Ho et al 9/95 19/85 0.42 (0.20, 0.89)
Oldemeyer 4/49 3/47 1.28 (0.30, 5.41)
Pate et al 57/238 50/239 1.14 (0.82, 1.60)
RAPIDO 2/41 8/39 0.24 (0.05, 1.05)
Shyu 2/60 15/61 0.14 (0.03, 0.57)
Fung et al 8/46 6/45 1.30 (0.49, 3.46)
Total: (95% Cl)Total: (95% Cl) 950950 932932 0.68 (0.46, 1.02)0.68 (0.46, 1.02)
60. Meta-analysis: High vs.Meta-analysis: High vs.
Low Osm Contrast MediaLow Osm Contrast Media
1.0
0.61
0.0
0.2
0.4
0.6
0.8
1.0
1.2
High Osm Low Osm
RelativeRiskofCIN
• 39 Trials - 5146 patients39 Trials - 5146 patients
• CIN > 0.5 mg/dlCIN > 0.5 mg/dl
• CIN in 7% of all patientsCIN in 7% of all patients
• CIN in 30% of CRICIN in 30% of CRI
patientspatients
• For CRI, NNT=8 (treat 8 toFor CRI, NNT=8 (treat 8 to
prevent 1 CIN case)prevent 1 CIN case)
• Low osmolal groupLow osmolal group
included Ioxaglateincluded Ioxaglate
(Hexabrix); Iodixanol(Hexabrix); Iodixanol
(Visipaque) not studied(Visipaque) not studied
Barrett and CarlisleBarrett and Carlisle J Am Soc NephrolJ Am Soc Nephrol 92;92;
61. The NEPHRIC StudyThe NEPHRIC Study
Nephrotoxicity in High-risk PatientsNephrotoxicity in High-risk Patients
a Double Blind Randomized Multicentrea Double Blind Randomized Multicentre
Study of Iso-osmolar and Low-osmolarStudy of Iso-osmolar and Low-osmolar
Non-ionic Contrast MediaNon-ionic Contrast Media
62. NEPHRICNEPHRIC Study: ProtocolStudy: Protocol
• Randomized, double blind, prospective, multicenterRandomized, double blind, prospective, multicenter
• Primary endpoint: peak increase in serum creatininePrimary endpoint: peak increase in serum creatinine
concentration @ 3 days after angiographyconcentration @ 3 days after angiography
Patients with diabetes and serum creatinine 1.5-3.5 mg/dl whoPatients with diabetes and serum creatinine 1.5-3.5 mg/dl who
underwent coronary or aortofemoral angiographyunderwent coronary or aortofemoral angiography
Iso-osmolar, non-ionicIso-osmolar, non-ionic
Iodixanol [Visipaque]Iodixanol [Visipaque]
N=64N=64
Mean Contrast Volume = 163 mlMean Contrast Volume = 163 ml
PTCA – 17%PTCA – 17%
Low-osmolar, non-ionicLow-osmolar, non-ionic
Iohexol [Omnipaque]Iohexol [Omnipaque]
N=65N=65
Mean Contrast Volume =Mean Contrast Volume = 162 ml162 ml
PTCA – 25%PTCA – 25%
Aspelin P et al,Aspelin P et al, NEJMNEJM, 2003; 348: 491-499, 2003; 348: 491-499
63. Primary Endpoint –Primary Endpoint –
Peak Increase in Scr from Baseline to Day 3Peak Increase in Scr from Baseline to Day 3
IodixanolIodixanol
(Visipaque)
IohexolIohexol
(Omnipaque)
n=62n=62 n=64n=64
MeanMean 11.2 ±19.711.2 ±19.7 41.5 ± 68.641.5 ± 68.6
MinimumMinimum - 19.0- 19.0 - 21.0- 21.0
MaxMax 74.074.0 331.0331.0
(µmol/l)(µmol/l) p=0.002p=0.002
64. RECOVER Trial – Renal Toxicity Evaluation and ComparisonRECOVER Trial – Renal Toxicity Evaluation and Comparison
Between Visipaque and Hexabrix in Patients With RenalBetween Visipaque and Hexabrix in Patients With Renal
Insufficiency Undergoing Coronary AngiographyInsufficiency Undergoing Coronary Angiography
Jo et al. JACC 2006; 48:924-30
Prospective, randomized trialProspective, randomized trial
300 patients
with CrCl ≤ 60 ml/min
149 pts. (135 pts. included
in primary analysis)
ioxaglate
151 pts. (140 pts. included
in primary analysis)
iodixanol
Primary endpoint – Incidence of CIN
Increase in SCr ≥ 25% or ≥ 0.5 mg/dl
65. RECOVER Trial – Incidence of CINRECOVER Trial – Incidence of CIN
17.0%
7.9%
0.0%
10.0%
20.0%
CIN
ioxaglate
iodixanol
Jo et al. JACC 2006; 48:924-30
P=0.021P=0.021
N=300
66. ICONICON TTrialrial
24.2%
16.2%
0%
10%
20%
30%
Ioxaglate Iodixanol
PatientsPatients wwithith cchronichronic rrenalenal iinsufficiencynsufficiency
uundergondergoinging PCIPCI wwith atith at lleast 150cc ofeast 150cc of ccontrastontrast vvolumeolume
PatientsPatients wwithith cchronichronic rrenalenal iinsufficiencynsufficiency
uundergondergoinging PCIPCI wwith atith at lleast 150cc ofeast 150cc of ccontrastontrast vvolumeolume
IoxaglateIoxaglate
N=74N=74
IoxaglateIoxaglate
N=74N=74
IodixanolIodixanol
N=71N=71
IodixanolIodixanol
N=71N=71
NN=130=130
P=0.26P=0.26
Incidence of CIN
Mehran R. et al, Transcatheter Cardiovascular Therapeutics.
2006.
67. Rehospitalization with Renal Failure as aRehospitalization with Renal Failure as a
Primary DiagnosisPrimary Diagnosis
0.02% 0.03%
0.10%
0.07%
0.20%
0.30%
0.00%
0.10%
0.20%
0.30%
0.40%
Within 1 week Within 1 month Within 3
months
Ioxaglate
Iodixanol
Liss et al. Kidney International 2006
P<0.001P<0.001
P<0.001P<0.001
P=0.022P=0.022
68. Start of Dialysis after CoronaryStart of Dialysis after Coronary
Angiography or PCIAngiography or PCI
0.00%
0.02%
0.10%
0.02%
0.10%
0.20%
0.00%
0.05%
0.10%
0.15%
0.20%
0.25%
Within 1 week Within 1 month Within 3 months
Ioxaglate
Iodixanol
Liss et al. Kidney International 2006
P=0.098P=0.098
P=0.010P=0.010
P=0.009P=0.009
69. 1-year Follow-up1-year Follow-up
CMCM N of ptsN of pts
iodixanoliodixanol 54 61654 616
ioxaglateioxaglate 24 47924 479
** iohexoliohexol 6 8546 854
Liss et al. Kidney International 2006
* Groups differ in
time period !
Renal failureRenal failure
Iodixanol
Iohexol
Ioxaglate
f
Time (years)
%
6
5
4
3
2
1
0
0 1 2 3 4 5 6 7 8 9 10 11 12
70. CARECARE
DesignDesign
• DESIGN: Prospective,
randomized, double-blind,
parallel-group, multi-center
clinical evaluation ipamidol-370
and iodixanol-320
• OBJECTIVE: To compare the
incidence of CIN between
iopamidol-370 and iodixanol-320
• PRIMARY ENDPOINT:
Increase in SCr ≥ 0.5 mg/dL from
baseline to 45 to 120 hours after
administration
482 patients enrolled between July 2005 and
June 2006 in 25 clinical site in North
America
482 patients enrolled between July 2005 and
June 2006 in 25 clinical site in North
America
14 patients withdrew
consent
14 patients withdrew
consent
468 assigned to a treatment arm468 assigned to a treatment arm
236 patients
assigned to
Iodixanol-320
236 patients
assigned to
Iodixanol-320
230 patients
assigned to
Iopamidol-370
230 patients
assigned to
Iopamidol-370
204 evaluable
patient
204 evaluable
patient
Solomon, RJ et. al., Circulation 115, 3189 (2007)
210 evaluable
patient
210 evaluable
patient
26
excluded
26
excluded
26
excluded
26
excluded
72. CARECARE
p = 0.11p = 0.11 p = 0.37p = 0.37 p = 0.20p = 0.20
Diabetic SubgroupDiabetic Subgroup
73. Figure. Strategy for Management of Patients With Risk Factors for Contrast-Induced
Nephropathy *See Box for listing of risk factors for contrast-induced nephropathy.
Pannu, N. et al. JAMA 2006;295:2765-2779
74. Conclusions (1)Conclusions (1)
• CRI is one of the most important independentCRI is one of the most important independent
predictors of poor outcome post PCIpredictors of poor outcome post PCI
• CIN remains a frequent source of acute renalCIN remains a frequent source of acute renal
failure and is associated with increased morbidityfailure and is associated with increased morbidity
and mortality, and higher resource utilizationand mortality, and higher resource utilization
• Several factors predispose patients to CINSeveral factors predispose patients to CIN
• Preventive measures pre procedure, as well asPreventive measures pre procedure, as well as
careful post procedure management should becareful post procedure management should be
routine in all patientsroutine in all patients
75. Conclusions (2)Conclusions (2)
• Hydration pre-PCI (12 hours recommended)Hydration pre-PCI (12 hours recommended)
• Avoid nephrotoxic drugs (NSAIDS, antibiotics, metformin etc)Avoid nephrotoxic drugs (NSAIDS, antibiotics, metformin etc)
• Role of n-acetylcysteine is disputableRole of n-acetylcysteine is disputable
• No Role for IV FenoldopamNo Role for IV Fenoldopam
• Sodium bicarbonate may be useful, but need more definitiveSodium bicarbonate may be useful, but need more definitive
datadata
• Limit contrast agent volumeLimit contrast agent volume
• Low-osmolar agents are better than high-osmolarLow-osmolar agents are better than high-osmolar
Within non-ionic contrast, the data are contradictoryWithin non-ionic contrast, the data are contradictory
Allow time before repeat procedures / staged procedures.Allow time before repeat procedures / staged procedures.
• Role of local drug delivery for prevention of CIN requiresRole of local drug delivery for prevention of CIN requires
further investigationfurther investigation
• Role of Cooling Therapy is being examined: COOL CIN StudyRole of Cooling Therapy is being examined: COOL CIN Study
Notes de l'éditeur
There is a strong bidirectional association between cardiac diseases and renal insufficiency.
In multiple clinical trials and analyses, and you see just one of them, CKD represented the most significant independent predictor of long-term mortality.
Risk factors for CIN maybe divided into patient-related and procedure-related. Patient-related factors include Renal insufficiency Diabetes mellitus with renal insufficiency Age Volume depletion Hypotension Low cardiac output Class IV CHF Other nephrotoxins Renal transplant Hypoalbuminemia (<35 g/l) And procedure-related factors include Multiple contrast media injection within 72 hrs Intra-arterial injection site High volume of contrast media High osmolality of contrast media
Recently, CIN risk score was developed and validated based on the analysis of large prospectively created database. You may see that risk of CIN may be as high as 57% and risk of dialysis maybe as high as 12% in pts with multiple risk factors.
We also found a strong relationship between 1-year mortality and risk score of CIN.
A prospective randomized trial utilizing the oxygen radical scavenger, acetylcysteine, explored the role of oxidative injury in contrast induced nephropathy. Patients undergoing a contrast CT scan were randomized to usual care or pretreatment with 600 mg bid of acetylcysteine starting 24 hours before the contrast exposure and continuing for 24 hours after the exposure. A marked decrease in the incidence of contrast induced nephropathy (CIN) was noted. Although the study is very exciting, a number of limitations are worth noting. First, the low dose of contrast and the route of administration (intravenous) make it difficult to extrapolate the positive results to patients receiving 2-3 times as much contrast intraarterially. Second, the marked reduction in the incidence of CIN was associated with an actual decrease in serum creatinine in many patient, a finding difficult to explain based on the presumed mechanism of action of acetylcysteine. Finally, a number of other experiments involving animal models of renal injury have failed to produce such dramatic results using other free oxygen radical scavengers. This may simply mean that animal models don’t mimic human pathophysiology accurately. In any case, until additional studies in other clinical situations confirm the dramatic results found here, it should not be assumed that acetylcysteine is a magic bullet.
Solomon A meta-analysis of 39 clinical trials involving more than 5000 patients found that there were no significant benefits of low osmolar media compared to high osmolar media in low risk patients. However, in high risk patients (for example, those with baseline renal insufficiency), low osmolar media reduced the risk of contrast-induced nephropathy by 39%. Based upon the expected incidence of contrast-induced nephropathy, only a small number of high risk patients would need to be treated to prevent a single case of contrast-induced nephropathy. Since contrast-induced nephropathy is associated with significant morbidity, a cost-benefit analysis favors the use of low osmolar media in high risk patients.
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