2. Kidney in CV disease
Cardiorenal overlap
CKD is important independent predictor of mortality
in patients with CAD (BERRY trial)
Even in absence of CV risk factors, pts with renal
insufficiency have elevated risk of CV disease
Mild elevation in CR(>1.5mg/dl) are associated with
development of CV events
Microalbuminuria is independent risk factor for CV
events, with RR higher than serum Cr ( 1.59 vs. 1.40)
Hall Wo et al Am J Med Sci ,1999
Mann JF et al, Ann Intern Med 2001
3. Kidney in CV disease
Acute Renal failure
Contrast induced nephropathy(CIN)
Postbypass ARF
CIN is now the 3rd leading cause of in-hospital ARF*
CIN in patients with PCI
Poor procedural success
Longer hospital stay and increased mortality
* Nash et al , Am J kidney Dis ,2002;39:930
7. Contrast Pharmacology
Contrast sole function is to attenuate X-ray
Radio-opacification achieved by given volume of
contrast is function of iodine concentration
Rough estimate : 125 ml contrast = 500ml of plasma
volume expansion
Excreted by kidney exclusively
Anticoagulant and antiplatelet effect of CM has no
clinical relevance
8. Side effects of contrast
Allergic reaction
Non IgE mediated
Ionic>Nonionic,(0.27%, SCAI registry)
Ioxoglate (Hexabrix) significantly higher allergic reaction as
compared to Iopamidol (Isovue) *
Cardiovascular
Electrophysiological
Heart blocks
Arrhythmias
Hemodynamic
Vasodilatation (hypotension)
Increased volume overload
* Gertz et al, JACC,1992;19:899-906
10. Contrast Media Induce Medullary Hypoxia
A temporary increase in renal transport work
in the thick ascending limb of Henle's loop
( in oxygen consumption)
+
Constriction of medullary capillaries ( in medullary oxygen delivery)
LEAD TO
MEDULLARY ANGINA
Solomon, et al. Kidney Int 1998; 230-242
11. CI-AKI or CIN
Definition:
New onset acute kidney injury (absolute Cr rise 0.5 mg- 1
mg/dl or relative, 25%-50% from baseline) after contrast
administration and in the absence of other etiology
Time course of CI-AKI:
Occurs after 24-48 hrs of contrast
Cr peaks in 3-5days and normalizes in 7-10 days(70%)
In 30%, 3 weeks to return baseline or progress to CKD
Predominantly non-oliguric AKI and with mild proteinuria
12. Epidemiological Issues
Small numbers – not mega RCT
Varying treatments used
Differing hydration regimens
Varying definitions
Outcomes vary by definitions
How much of CIN is due to contrast?
Atheroembolism, hemodynamics
Cause and effect???
16. Incidence
Incidence ranges from 1%-35%
Low risk population incidence is 1.5%
Mayo retrospective series evaluated 7852 pts. who had
undergone cath /PCI found an incidence of 3.3% *
ARF defined as 0.5 mg/dl
Baseline Cr was predictor
* Rihal CS et al, Circulation 2002
17. RISK FACTORS
Non modifiable Modifiable
CKD Volume depletion
DM Volume of contrast
Age(>75yr) Multiple injection of contrast
Class IV CHF within 72 hrs
Renal tx Intraarterial vs. intravenous ?
High osmolal contrast (Not
used anymore)
18. CIN and High risk groups
Baseline Cr < 2.0 mg/dl, diabetic patients had higher
risk of ARF than nondiabetic pts
Cr < 1.1(risk 3.7 % vs 2.0%, p=0.05)
Cr 1.2-1.9(risk 4.5% vs 1.9%, p<0.001)
Baseline Cr > 2.0 mg/dl, risk high regardless of
diabetes status
Cr. 2.0-2.9 mg/dl, risk 22.4%
Cr > 3 mg/dl, risk 30.6%
19. Predictors of ARF requiring dialysis
after PCI
Mean contrast vol
250cc,(Cath+ PCI)
Mean age 65yrs
Predictors of CIN Crcl >DM> contrast dose
21. CIN & Mortality
Retrospective case control
study of 16,248 hospitalized
patients who received
contrast
Cases with CIN(n=183)
matched with controls(n=174)
Matched for baseline
creatinine
APACHE score
Levy EM,JAMA 1995
22. CIN after PCI & Mortality
Derivation-validation
method in 1800 patiens
Incidence of CIN 14% and
ARF requiring HD was
7.7%
Multivariate predictors:
CrCl, diabetes and contrast
dose
No case of CIN in patients
with contrast dose of <
100ml
McCullough PA et al, Am J Med,1997
23. Clinical outcomes of CIN patients
requiring HD after PCI
Long-term outcome
Gruberg L et al Cath Cardiovasc Interv, 2001
24. Long term outcome of CIN
Mayo retrospective series
evaluated 7852 pts. who had
undergone cath /PCI found
an incidence of 3.3%
ARF defined as 0.5 mg/dl
CIN was related to baseline
serum Cr and diabetes
Rihal CS et al Circ 2002
25. Prognostic implications of CIN
following PCI in pts with CKD
439 pts with baseline serum cr. > 1.8
All well hydrated, all received non ionic dye
161 pts(37%) had increase in serum cr > 25%
and 278(63%) did not
26. CIN prognosis after PCI in CKD
In hospital outcome One year outcome
No Cr Rise 25% Cr No Cr Rise 25% Cr
P<0.001 P<0.001 28.7%
30% 50% P<0.001
40% 37.7% P=NS
20% 15.9%
P=NS
14.9% 30% 23.6%
21.4%
19.4%
20% 13.4%
10% 12.4%
4.9%
10%
0% 0%
Death Non-Q MI Death MI TLR
Gruberg et al JACC, 2000
28. Predicting CIN
Developmental data
set(n=8752)
Validation data
set(n=2786)
Multivariate logistic
regression to identify
variables, p<0.0001
C statistics 0.67
Mehran et al JACC,2000
36. Hydration Regimen
Hydration started at 8
am on the day of
elective cath and
continued for another
12 hrs (1ml/kg) after
cath.
Pts encouraged to
drink fluids
Mueller et al Arch intern med ,2002
39. Prevention of CIN with sodium
bicarbonate
Baseline Cr >1.8mg/dl
Iopamidol contrast used
Regimen N=137
3ml/kg bolus for 1hr
before & 1ml/kg 6hr after
Sodium chloride Sodium bicarbonate
N=68 N=69
Primary Endpoint was increase in serum Cr
>25%
Merten et al, JAMA2004
42. N-Acetylcysteine (NAC)
Prospective RCT
83 high risk pts
Cr Cl <50ml/min
Diabetes 33%
IV contrast CT (low
osmolal,75ml)
NAC 600mg BID X 2 days
Hydration 0.45 saline at
1ml/kg
Tepel, NEJM 2000
43. NAC & PCI
N=79
Mean Cr 2.3mg/dl *APART trial n=45
All received hydration Mean Cr 1.6mg/dl
NAC 600mg q12 x4 doses, before NAC IV before PCI and 3 doses BID
PCI after PCI
P=NS
Caputo Am j kidney Dis, 2000 * Diaz-Sandoval et al Am J Cardiol 2002
44. NAC & relative risk
META-ANALYSIS of 7 RCT
Birke et al., Lancet 2003
45. Does type of contrast matter?
Patients with diabetes and CKD
(1.5-3.5 mg/dl)
NEPHRIC STUDY Undergoing coronary
angiography/Aortofemoral
angiography
Iso-Osmolol, Nonionic
Low Osmolar, Nonionic
Iodixanol N=64
Iohexinol N=65
Mean contrast vol. 163 ml
Mean contrast vol.162 ml
PCI
Randomized control trial
Primary endpoint was CIN
Serum Cr at 72 hrs after Cath
Aspelin ,NEJM 2003
47. Renal failure in pts undergoing coronary procedures using Iso-
Osmolar or Low Osmolar CM
Swedish coronary angiography
and angioplasty registry
Swedish hospital discharge
registry
Only included diabetic and CKD
pts
Only pts receiving PCI
Also patients receiving iohexol
fr0m 1999-2003
Mean contrast volume:
iodixanol: 138±89 ml vs.
ioxaglate: 147±105 ml
Liss et al., kidney International 2006
52. Take home points
Contrast-Induced Nephropathy is a common
complication in higher-risk patients
Even with chemical resolution of CIN and a return of
serum creatinine towards baseline, the 1-year mortality
remains over 25%, making prevention mandatory in
higher-risk patients
High-risk characteristics include renal insufficiency
(Cr > 1.5 mg/dL) diabetes and contrast dose
Pathophysiology of CIN seems to involve contrast-
induced renal medullary ischemia
Rct have not founf thesehematoligical effects due to cocncomitant use of antiplatelet and anticoaugs
Osmoality dependent lead to release of adenosine
To compare similar degrees of injury regardless of the baseline serum level, the relative change in serum creatinine is a preferable metric (Table 2b). With a relative change definition, all patients lose the same percentage of renal function regardless of the level of renal function at baseline. There is still a bias, however, for a smaller absolute loss of GFR to satisfy the definition of CIN when there is a lower GFR at baseline. Finally, it follows from the above discussion that in patients with milder degrees of renal insufficiency (creatinine less than 2 mg/dl), the incidence of CIN will always be less when a 0.5 mg/dl absolute increase is used as a definition compared to a 25% increase in serum creatinine. A greater loss of GFR is necessary to satisfy the definition of CIN when the absolute change in serum creatinine is used (Table 2a vs b).Which definition, absolute or relative increase in serum creatinine, reflects outcomes the best? Gruberget al.1 correlated outcomes following contrast exposure in patients who underwent cardiac catheterization. A worse outcome (at 1 year) was found in those
Peterm Mc cullough
There is no question that ccin lead to increased mortalityThis is the data from aretropective study of more than 16k pts who received contrast for any radiological procedure Odds of dying was 5 times high if cinoccured
How about CIN after PCI Ina study by peter mccollough the risk of inhospital mortality wasignificanlty higher in pts who had arf after pci and it was higher if they needed dialysis comapred to very low risk with no CIN
Based on risk score you see that there is linear and exponential increase in the incidenc of CINFrom 7.5 to 14 to 16 and 57
They also found that this score predicted need for inhospital dialysis and higher score were significantly associated with need for hd
Prognostic significance of the score and higher score had higher one yr mortality
I am not good at drawing
This is alist of ailed therapies thathave been tried and they should no longer be used infact some of these therapies can cause harmHypothesis discusss
Interestingly you see that pts with 0.9 hydration had less cin as compared to .45When you can hydrate the pt.
Trial terminated earlierHad not presecified the the P and P0.02Alpha errorNonetheless it was positive trial and a s you know law of nature is for every pos trail there is one negative trial
Study in pts not undergoing cath or pci
Barrettecarlisle radiology1993
To convert into a dichotomous variable they used mrcd ratioAsmrcd is a continous variable and can’t comape
