CARDIORENAL SYNDROME

SINA RAISSI, M.D., F.A.S.N.

CASE
Mrs. E.C. is a 81 year-old lady with CAD,
paroxysmal atrial fibrillation, chronic systolic
CHF (EF < 25%), severe pulmonary HTN (RV
pressure of 80 mmHg), progressive CKD
(currently at stage 4).
Admitted to hospital with worsening dyspnea
and edema, accompanied by a rise in serum
Cr from 2.2. to 3.0 mg/dL.

CASE
She is started on intravenous furosemide at
120 mg TID, and dobutamine drip.

Improvement in dyspnea, and edema is

associated with an initial decline in serum Cr
to 2.3 followed by a rise to 2.7 mg/dL, at
which point she was discharged.

CARDIORENAL SYNDROME

CARDIORENAL SYNDROME
Type 1: Acute heart failure
Type 2: Chronic HF
Type 3: AKI
Type 4: CKD

Type 5:
Systemic insult

AKI
CKD

Adverse cardiac events

Adverse cardiac events

Cardiac and Renal events

CARDIORENAL SYNDROME
TYPE 1

Acute

Acute

CARDIORENAL SYNDROME
Over one million patients are admitted every
year for either de novo acute HF or acute
decompensation of chronic HF.

CARDIORENAL SYNDROME
Over one million patients are admitted every
year for either de novo acute HF or acute
decompensation of chronic HF.
These admission are frequently complicated
by AKI.

CARDIORENAL SYNDROME
Over one million patients are admitted every
year for either de novo acute HF or acute
decompensation of chronic HF.
These admission are frequently complicated
by AKI.
AKI seems to be more common in patients
with impaired LV function than those with
preserved LV function (>70% of patients with
cardiogenic shock).

Time course of development of increasing serum Cr of various

extents in patients with HF
Gottlieb S, et al: J Card Fail 2002; 8:136-141

CARDIORENAL SYNDROME
A rise as small as 0.3 mg/dL in serum Cr is an
independent risk factor for in-hospital and
1-year mortality in patients with acute HF,
STEMI, and after revascularization. (Goldberg A, etal,
Am Heart J 2005;150:330-7. Lassnigg A, et al, Crit Care Med 2008;36:1129-37)

WRF=increase in SCr by 0.2

Relationship of combined adjusted all-cause mortality and worsening renal function

Damman K, et al, J Card Fail 2007;13:599-608

WRF=increase in SCr by 0.2

All-cause mortality by type of patient

Damman K, et al, J Card Fail 2007;13:599-608

All-cause mortality and WRF based on the degree of rise in SCr

Damman K, et al, J Card Fail 2007;13:599-608

Relationship between baseline renal function and risk of WRF

Damman K, et al, J Card Fail 2007;13:599-608

OR

Odds Ratio of WRF on future admissions after WRF at index admission

Testani J, et al: Am Heart J 2011;161:944-949

CRS 1

Ronco C, et all, JACC 52, No 19, 2008

CRS 1

Ronco C, et all, JACC 52, No 19, 2008

CRS 1

Ronco C, et all, JACC 52, No 19, 2008

CRS 1

Ronco C, et all, JACC 52, No 19, 2008

CRS 1

Ronco C, et all, JACC 52, No 19, 2008

CRS 1

Ronco C, et all, JACC 52, No 19, 2008

CRS 1

Ronco C, et all, JACC 52, No 19, 2008

CRS 1
CVP

CI

SBP

PCWP

Possibility of WRF during admission based on admission variables

Mullens, W, et al: JACC 2009;53:589-596

ROC curves for CVP and CI on admission for development of WRF

Mullens, W, et al: JACC 2009;53:589-596

Relative contributions of CVP and CI to GFR at time of PAC removal

Mullens, W, et al: JACC 2009;53:589-596

Solid line: CI < 2.5 l/min/m2

Dashed: CI 2.5-3.2 l/min/m2
Dotted: CI>3.2 l/min/m2

Relationship between CVP and eGFR based on different CI values

Baseline serum creatinine level and Intra-abdominal pressure

Mullens W, et al: JACC 2008;51:300306

Changes in renal
parameters and
changes in IAP

Mullens W, et al: JACC 2008;51:300306

FALL IN INTRABDOMINAL PRESSURE WITH PARACENTESIS

Mullens, W, et al. J Card. Fail. 2008;14:508-514

EFFECT OF PARACENTESIS ON GFR

Notice the initial rise in serum Cr and IAP with medical therapy
Mullens, W, et al. J Card. Fail. 2008;14:508-514

Decompensated CHF

Na and H2O Retention

Decreased Renal Blood

Flow

Na and H2O Retention

Vasoconstriction and
venous congestion

PREVENTION of TYPE 1 CRS

Assess for signs of impending decompensated
CHF

PREVENTION of TYPE 1 CRS

Assess for signs of impending decompensated
CHF
Restrict Na intake to less than 2000 mg a day.

PREVENTION of TYPE 1 CRS

Assess for signs of impending decompensated
CHF
Restrict Na intake to less than 2000 mg a day.
Restrict fluid intake if hyponatremic.

PREVENTION of TYPE 1 CRS

Assess for signs of impending decompensated
CHF
Restrict Na intake to less than 2000 mg a day.
Restrict fluid intake if hyponatremic.
Avoid NSAIDs, and other nephrotoxic agents.

PREVENTION of TYPE 1 CRS

Assess for signs of impending decompensated
CHF
Restrict Na intake to less than 2000 mg a day.
Restrict fluid intake if hyponatremic.
Avoid NSAIDs, and other nephrotoxic agents.
Avoid HYPOTENSION

TREATMENT of Type 1 CRS

Intravenous Diuretics: Start with a high dose
of a loop diuretic (2 times the home dose)

TREATMENT of Type 1 CRS

Intravenous Diuretics: Start with a high dose
of a loop diuretic (2 times the home dose)

Dose the diuretic BID or TID.

TREATMENT of Type 1 CRS

Intravenous Diuretics: Start with a high dose
of a loop diuretic (2 times the home dose)

Dose the diuretic BID or TID.

Titrate the dose to effect or side effect

TREATMENT of Type 1 CRS

Intravenous Diuretics: Start with a high dose
of a loop diuretic (2 times the home dose)
Dose the diuretic BID or TID.
Titrate the dose to effect or side effect
Consider adding a thiazide in resistant cases

TREATMENT of Type 1 CRS

Caution with the use of RAS Blockers during
the period of aggressive diuresis and in
patients with hypotension.

TREATMENT of Type 1 CRS

Caution with the use of RAS Blockers during
the period of aggressive diuresis and in
patients with hypotension.
Consider Mineralocorticoid Antagonists

CARDIORENAL SYNDROME
TYPE 2

Chronic

Chronic

CRS 2
Prevalence of renal dysfunction in chronic CHF
is approximately 25%.

CRS 2
Prevalence of renal dysfunction in chronic CHF
is approximately 25%.
Risk factors: Old age, Hypertension, Diabetes
mellitus, and Acute coronary syndrome.

CRS 2
Prevalence of renal dysfunction in chronic CHF
is approximately 25%.
Risk factors: Old age, Hypertension, Diabetes
mellitus, and Acute coronary syndrome.
No significant difference between HF with
reduced or preserved LV function.

CRS 2

Ronco C, et all, JACC 52, No 19, 2008

CRS 2

Ronco C, et all, JACC 52, No 19, 2008

CRS 2

Ronco C, et all, JACC 52, No 19, 2008

CRS 2

Ronco C, et all, JACC 52, No 19, 2008

CRS Type 2 Treatment

CRS Type 2 Treatment

Prevention of acute decompensation.

CRS Type 2 Treatment

Prevention of acute decompensation.
Renin-Angiotensin System Blockers.

CRS Type 2 Treatment

Prevention of acute decompensation.
Renin-Angiotensin System Blockers.
Beta-blockers.

CRS Type 2 Treatment

Prevention of acute decompensation.

Renin-Angiotensin System Blockers.
Beta-blockers.
Loop diuretics.

CRS Type 2 Treatment

Prevention of acute decompensation.

Renin-Angiotensin System Blockers.
Beta-blockers.
Loop diuretics.
Avoiding NSAIDs and other nephrotoxic
agents.

CARDIORENAL SYNDROME
TYPE 3

Acute

Acute
Heart failure
Arrhythmia
ACS

CRS 3
AKI is present in 9% of all hospital admissions
and 35% of admissions to critical care unit.

CRS 3
AKI is present in 9% of all hospital admissions
and 35% of admissions to critical care unit.

Fluid overload, electrolyte abnormalities,

acidemia, uremia, bilateral renal artery
stenosis are potential mediators of adverse
cardiac events.

CRS 3

Ronco C, et all, JACC 52, No 19, 2008

CRS 3

Ronco C, et all, JACC 52, No 19, 2008

CRS 3

Ronco C, et all, JACC 52, No 19, 2008

CRS 3

Ronco C, et all, JACC 52, No 19, 2008

CRS 3

Ronco C, et all, JACC 52, No 19, 2008

CRS Type 3 treatment

Control hypertension
Correct electrolyte abnormalities
Control acidemia
Avoid fluid overload
Monitor patients closely for signs and
symptoms of cardiac complications

CARDIORENAL SYNDROME
TYPE 4

Chronic

Chronic

CRS Type 4
Up to 11% of US adult population has some
degree of CKD.

CRS Type 4
Up to 11% of US adult population has some
degree of CKD.

Patients with CKD have 10-20 fold higher risk

of cardiac death compared to age/gender
matched patients without CKD.

CRS Type 4
Up to 11% of US adult population has some
degree of CKD.
Patients with CKD have 10-20 fold higher risk of
cardiac death compared to age/gender matched
patients without CKD.
Two year mortality after MI in CKD 5 is 50%.
10 year mortality after MI in general population is
25%.

CRS 4

Ronco C, et all, JACC 52, No 19, 2008

CRS 4

Ronco C, et all, JACC 52, No 19, 2008

CRS 4

Ronco C, et all, JACC 52, No 19, 2008

CRS 4

Ronco C, et all, JACC 52, No 19, 2008

CRS Type 4 Treatment

Adequate blood pressure control

CRS Type 4 Treatment

Adequate blood pressure control
Adequate volume control

CRS Type 4 Treatment

Adequate blood pressure control
Adequate volume control
Use of RAS blockers, statins, aspirin

CRS Type 4 Treatment

Adequate blood pressure control
Adequate volume control
Use of RAS blockers, statins, aspirin
Avoiding therapeutic nihilism

CARDIORENAL SYNDROME
TYPE 5

SYSTEMIC CONDITION

CRS 5

Ronco C, et all, JACC 52, No 19, 2008

SUMMARY
Heart and kidney disease share similar
predisposing risk factors.

There is a bidirectional metabolic and

neurohormonal interaction between the 2
organs that leads to combined organ
dysfucntion when either one suffers acute or
chronic injury.

SUMMARY
The most important aspect of care is
prevention of injury, by managing risk factors,
establish an early diagnosis of organ injury,
and timely intervention.
A deeper understanding of pathophysiology of
cardiorenal syndrome, improves care and
outcome.

SUMMARY
A multi-disciplinary approach that includes the
nephrologist, cardiologist, and intensive care
specialist is preferred.

FUTURE
The role of biomarkers for kidney injury such
as Neutrophil gelatinase-associated lipocalin
(NGAL), Cystatin C, Kidney injury molecule 1
(KIM 1) in early diagnosis of AKI.
Role of biomarkers for early cardiac injury
such as Myeloperoxidase, Troponins, BNP, IL-6,
and IL-1.

FUTURE
Conducting cardiovascular studies in patients
with CKD to further clarify outcomes, optimal
therapeutic regimens, and goals.

THANK YOU