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Cardiorenal Syndrome
Samira Tabiban MD
Rajaie Cardiovascular medical and research
center
Cardiorenal syndrom
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•
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Definition
Classification
Pathophysiology
Treatment
Definition Of CRS
The CRS can generally be defined as a
pathophysiological disorder of the heart and
kidneys whereby acute or chronic dysfunction
in one organ may induce acute or chronic
dysfunction in the other organ.
The cardiorenal syndrome (CRS)
Definition
Heart failure with…
Worsening renal function (> 25-30% increase in
creatinine or BUN during treatment for acute
decompensation)
High Prevalence of Renal Dysfunction and Its Impact
on Outcome in 118,465 Patients Hospitalized With
Acute Decompensated Heart Failure: A Report From
the ADHERE Database
J. Thomas Heywood MD et al J Card Failure Sept 2007
65%
Have at least
Moderate renal
dysfunction
Inpatient mortality from ADHERE Registry
Based on admission BUN, creatinine and BP
<

BUN 43
(n=32220)
2.88%
(n=24469)
<

<
2.31%
(n=20820)
15.30%
(n-1863)
SBP 115
(n=2,702)
5.67%
(n=3882)
8.35%
(n=67640)
<
13.23%
(n-1270)
SBP 115
(n=6697)
Cr 2.75
(n-1862)


5.63%
(n-4834)
19.76%
(n-592)
Analysis of patients in the National Acute Decompensated Heart Failure National Registry (ADHERE)
BUN=blood urea nitrogen, Cr=serum creatinine, SBP-systolic blood pressure
Fonarow GC et al. J Cardiac Fail 2003;9(suppl 1):S79.
Why is renal function
abnormal
in patients with heart failure?
Role of the kidney in congestive heart failure:
Relationship of CI to kidney function
RBF, p<.05 with Group A
500
Renal
Blood
Flow
400
Renovascular
200
Resistance
100
RVR, p<.01 with Group A
300
0
Renal BF
RV Resistance
A, CI> 2
B, CI>1.5
<2.0
C, CI <1.5
Ljungman, Cody Drugs 1990;39 Suppl 4:10-21
Role of the kidney in congestive heart failure:
Relationship of CI to kidney function
CI, p<.001 with Group A
70
BUN, p<.01 with Group A
60
GFR / BUN
50
40
GFR
BUN
30
20
10
0
A, CI> 2
B, CI>1.5 <2.0
C, CI <1.5
Creatinine was not different between the groups. BUN better indicated
low CI and GFR than creatinine
Ljungman, Cody Drugs 1990;39 Suppl 4:10-21
`
Am J Cardiol 2006:97:1759
Effect of increasing central venous pressure on
GFR in dogs, constant BP
1.4
Raised Venous
Pressure: A
direct cause of
renal sodium
retention
P< .05
GFR 1.1
Ml/min
P< .05
0.8
Firth et al Lancet
5/7/88
High CVP significantly
impairs GFR
0.5
0
6.25
12 18.75
25
mm Hg
0
Central Venous Pressure
Effect of Increased Renal Venous Pressure
on Renal Function
Doty J et al J of Trauma: Injury, Infection and Critical Care 1999 47:1000-1005
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Swine where anesthetized, instrumented and a unilateral nephrectomy preformed.
In the remaining kidney the renal vein was constricted in half the animals to obtain a renal
venous pressure of 30, the other animals served as controls
30
P <.05 between groups
25
20
15
Control
RV Constric
10
5
0
RA Blood
flow Index
GFR
Aldosterone
Renin
Activity
Renal Decapsulation in the Prevention of
Post-Ischemic Oliguria
Stone HJ Annals of Surgery 1977:343-355
•
15 rhesus monkeys, 1 hour suprarenal aortic clamping to produce ATN, after which
the renal capsule was stripped from one kidney. The ureters of each kidneys were
catheterized to collect urine for creatinine, urea and free water.
7
6
P <.01
5
4
Decapsuled
Control
3
2
1
0
Cr Cl
Urea Cl
Free Water
Prevalence of Worsening Renal Function During Hospitalization
According to Categories of Admission CVP, CI, SBP, and PCWP
Mullens, W. et al. J Am Coll Cardiol 2009;53:589-596
Treatment of the Cardiorenal
Syndrome
5 important questions…
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•
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What is the fluid status?
Is the blood pressure adequate for renal perfusion?
What is the cardiac output?
Is there evidence of high central venous pressure?
Is there intrinsic renal disease?
Hypovolemic Cardiorenal Syndrome
Too Dry!!!
• Overdiuresed or intercurrent illness results in volume loss and
renal dysfunction
• Give fluids, stop diuretics and IV vasodilators
• Often a reluctance to give fluids to HF patients but it may be
critical in this situation and time is of the essence to avoid
irreversible renal damage
CRS due to high central venous pressure
Too Wet!!!
• Poor renal perfusion due to high central venous pressure
• Usually CVP > 15-20 mm Hg coupled with reduced blood
pressure
• Diuretics often held because of worsening renal function and
misguided idea of “ intravascular volume depletion”
• Continue diuretics to reduce central venous pressure
• Ultrafiltration
CRS with vasoconstriction
Clamped
Down!!!
• Low CO and hence renal hypoperfusion due to HF mediated
vasoconstriction (Ang II, endothelin induced increased afterload)
• CO is low and SVR high, often over 1800-2000
• ACEI and vasodilators very useful since CO can increase significantly if
afterload normalized. Actual improvement in renal function may be seen
• May need temporary inotropic support if systolic BP <80 as vasodilators
are added
(J Am Coll Cardiol 2014;63:853–71)
“Although there is no serum creatinine level per se that
contraindicates ACE inhibitor therapy, greater increases in
serum creatinine occur more frequently when ACE
inhibitors are used in patients with underlying
chronic renal insufficiency.”
ACEI play a complex role in renal function in HF
• May improve CO in some patient and hence increase effective
renal perfusion
• ACEI may lower BP to the point where effective renal
perfusion is impaired
• With chronic renal disease, there is hyperfiltration in the
remaining nephrons. ACEI decreases efferent arteriole
constriction and hence decreases glomerular capillary pressure
which may preserve renal function longterm
• This may result in a 10-20% increase in creatinine, but over
the long term renal function is preserved
CRS
with vasodilation
“Vasodilated!!”
• Renal hypoperfusion due to low perfusion; CO may be normal
but SVR and BP low
• Vasodilators worsen BP and hence renal perfusion
• Stop of ACEI, especially if SVR is low
• Rule out sepsis
• Pressors, Inotropes, ? Vasopressin
• Consider transplant or ventricular assist device if renal
dysfunction is felt to be reversible
CRS with normal CO and SVR
“It’s the
Kidneys,
Not the
Heart!!!!””
• Consider intrinsic renal disease (IRD) or diuretic resistance syndrome,
renal artery stenosis
• Probable IRD when long hx of HTN and/or diabetes, look for proteinuria,
renal artery stenosis
• Trial of loop diuretic infusion, combination with distal tubular diuretic
• Add nesiritide
• Consider ultrafiltration
Invasive hemodynamic monitoring
should be considered in a patient:
•
who is refractory to initial therapy,
•
whose volume status and cardiac filling pressures are unclear,
•
who has clinically significant hypotension (typically SBP !80 mm Hg) or
worsening renal function during therapy,
Or
• who is being considered for cardiac transplant
and needs assessment of degree and reversibility of pulmonary hypertension,
Or
in whom documentation of an adequate hemodynamic response to the inotropic agent
is necessary when chronic outpatient infusion is being considered. (Strength of
Evidence 5 C)
Profiles of the Cardiorenal Syndrome
CRS due to:
Fluid
Status
CO
CI
SVR
Proteinuria
Too Dry!!!
Dry
Low
Nml or high
None
Fluids, stop diuretics
Too Wet!!!
(high CVP)
Wet
Nml
Nml
None
Continuous diuretic
infusion, distal tubular
diuretic, ultrafiltration
Too Clamped
Down!!!
Wet or
Nml
Low
High
None
ACEI, Nitroprusside,
Nesiritide, Relaxin
Nml or
high
Low
None
Vasodilated!!!
Nml or
wet
Stop ACEI,
Pressors, Vasopressin
Inotropes, VAD
Low
Nml
None
No Pump!!!
Wet or
Nml
Inotropes,
Vasopressors
Balloon Pump
LVAD
Wet
Nml
Nml
None
Continuous diuretic
infusion, distal tubular
diuretic, ultrafiltration
Intrinsic Renal
Disease/Diureti
c Resistance
Treatment
Volume Management
Concept of Plasma Refill Rate in
ADHF
Diuretics to increase
sodium loss and decrease
venous pressures
Redefining the Therapeutic Objective in
Decompensated Heart Failure: Hemoconcentration
as a Surrogate for Plasma Refill Rate Boyle and Sbotka J Card Failure May 2006
Concept of Plasma Refill
Rate in ADHF
Diuretics to increase sodium loss and
decrease venous pressures
Hemodynamic
Changes
No
Hemoconcentration
Hemoconcentration
P value
RA pressure
-2.8±5.6
-5.4±
0.031
Pulm Art Sys Pres
-9.0±12.4
-14.4±10.8
0.124
Wedge Pressure
-6.2±8.3
-12.6±9.6
0.015
Hemoconcentration
No Hemoconcentration
Secondary Endpoints:
Low vs. High Intensification
Low
High
P value
Dyspnea VAS AUC at 72 hours
4478
4668
0.041
% free from congestion at 72 hrs
11%
18%
0.091
-5.3 lbs
-8.2 lbs
0.011
3575 mL
4899 mL
<0.001
% Treatment failure
37%
40%
0.56
% with Cr increase > 0.3 mg/dL
at 72 hrs
14%
23%
0.041
6
5
0.55
Change in weight at 72 hrs
Net volume loss at 72 hrs
Length of stay, days (median)
Changes in Creatinine over Time *:
High vs. Low
1.8
p = 0.34
1.75
Low
High
p = 0.59
1.7
Creatinine (mg/dL)
p = 0.85
1.65
p = 0.07
p = 0.81
p = 0.28
1.6
1.55
1.5
1.45
0
1
2
3
4
7
Time (days)
* P values are for change in creatinine from baseline
60
Proportion with Worsening Renal Function:
High vs. Low
25%
Low
% with Δ Cr > 0.3 mg/dL
20%
High
15%
10%
5%
0%
0
1
2
3
Time (days)
4
7
60