Cardioneral ve Hepatorenal Syndromes

1. Cardiorenal ve
Hepatorenal Syndromes
Dr. Türkay Akbaş
Düzce Üniversity, School of Medicine
Dep. of Internal Medicine, Division of ICU
No Conflict of Interest to Declare

2. Cardiorenal Syndromes
• Acute or chronic dysfunction in one organ induces
acute or chronic dysfunction of the other
Acute/Chronic
• Kidney Heart
Ronco C. Intensive Care Med. 2008; 34:957–962

3. Classification
McCullough PA. Contrib Nephrol. 2013;2:82-98

4. Acute Cardiorenal Syndrome(Type 1)
• Acute hearth disease-worsening of renal
function (WRF)
(Cret ≥ 0.3 mg/dl 48 hr, cret > %50
increase/7 days)
• Patients with AHF/ACS: % 19-45 had
acute kidney injury (AKI)/ WRF
• Mortality predictor (short or long term)
• LOS, chronic kidney disease, readmission, cost↑
• Renal dysfunction severity correlates with mortality, ESRD
Ronco C. Eur Heart J. 2010;31:703-11

5. Acute Cardiorenal Syndrome(Type 1)
Etiology: Acute decompensated heart failure
• Acute coronary syndrome
• Postcardiotomy low cardiac output
• Valve diseases and PE
Risk factors: DM, HT, CKD (%60), elderly
• Admission with AHF, AMI
• Severe cardiac dysfunction (EF↓, pul. edema,
arrhytmia
• High dose diuretic (furosemide > 100mg/day)
• Vasodilator /contrast material use

6. Type-1 - Pathophysiology
3 mechanisms
i. Low cardiac output, %20
ii. Venous congestion: Renal congestion due to increased
renal venous pressure determines the risk.
iii. RAAS and SSS activation: Decreased cardiac output and
renal blood flow: SVR increase
• Villi ischemia → local LPS production and endotoxemia
• Active inflammation

7. Virzi GM. Crit Care. 2014;18:201.

8. Ronco D. Heart Failure Clin. 2014;10: 251–280
Cruz DN. Adv Chr Kid Dis. 2013;20:56-66
Decreased cardiac output
Increased venous press.
Catheterisation and contrast
Furosemide, ACE-I, ..
Benefit from loop
diuretics, vasodilators
(nitrate)

9. Acute Cardiorenal Syndrome(Type 1)
• Clinic: Decrease in furosemide response and then increase
in creatinine
• Sympathetic nervous system and RAAS activation secondary
furosemide → creatinine increase
• Hyponatremia: ↑ neurohormonal activation. Poor
prognosis
• ↑ natriuretic peptide, ↑ CVP / right atrial pressure and
pulm. congestion are risk factors for Type I CRS

10. Chronic Cardiorenal Syndrome(Type 1)
• Chronic heart disease → progressive CKD
Stage 3-5 CKD (GFR < 60 ml/min): % 45- 63
• Difficult to differentiate Type2-4
• Definition: CHF + CRF and
CHF underlies occurance or
progression of CKD
Ronco C. Eur Heart J. 2010;31:703-11

11. Chronic Cardiorenal Syndrome (Type 1)
• Congenital HF: renal dysfunction in %50, GFR < 60 ml/min in
%9 (3 x mortality)
• ACS → Left vent dysfunction → onset or progression of CKD
• CRS 2 CRS 1
• All and CV mortality high
• Readmission due to HF is predictor for mortality and CKD
Dimopoulos K. Circulation. 2008;117:2320–2328

12. McCullough PA. Contrib Nephrol . 2013;2:82-98

13. Acute Renocardiac Syndrome (Type 3)
• AKI: causing heart injury or dysfunction
progressing heart disease
• Insidance ? How many AKI patients will
have myocard injury?
• The time between AKI and heart injury?
• Rarely effects normal heart
• Myocard injury becomes obvious in patients with
subclinical heart disease when AKI develops
Ronco C. Eur Heart J. 2010;31:703-11

14. Acute Renocardiac Syndrome (Type 3)
• ECG: Changes in QRS, PQ
waves
• ECHO: Left ventricular dilation/
hypertrophy, EF, relaxation
abnormalities…
Ronco D. Heart Failure Clin. 2014; 10: 251–280
Prototypical Condition
. Major surgery
. Postinflammatory GN
. Rhabdomyolysis
. Acute pyelonephritis
. Postobstructive uropaty
. Contrast induced AKI
. Drug induced AKI

15. Acute Renocardiac Syndrome (Type 3)
• Mechanism? AKI may directly (inflammation) or
indirectly (acidosis, uremia…) produce an acute
heart event
• Experimental (animal) AKI studies (48 hours):
Systemic inflammation, increased leukocyte
infiltration and cytokine expression in heart,
increased myocardial apoptosis and vasoconstriction
Clementi A. Oxidative Medicine and Cellular Longevity,
2015, http://dx.doi.org/10.1155/2015/148082

16. Virzi GM. Crit Care. 2014;18:201.

17. Chronic Renocardiac Syndrome (Type 4)
• CKD: causing heart injury, disease or
dysfunction.
• Cardiac mortality 10-20 times more,
50 % of all death due to CVD
• As CKD stage increases, all and CV mortality increases
• Histopathology: Left ventricular hypertrophy, cardiac
fibrosis (collagen-1, fibronectin, vimentin increment),
decreased capillary density, increased tissue calcification
Ronco C. Eur Heart J. 2010;31:703-11

18. Chronic Renocardiac Syndrome (Type 4)
Clinic: Systolic/diastolic dysfunction, chronic edema,
hosptalisation due HF, death (pump failure, sudden)
Microischemia due to increased left ventricular hypertropy
in contrast to decreased capillary density
Chest pain: correlates with ACS, HF and hospitalisation
ESRD + RRT: Cellular activation (T cells, heart macrophages)
and cytokine expression→ myocyte apoptosis + fibrosis

19. McCullough PA. Contrib Nephrol . 2013;2:82-98

20. Secondary Cardiorenal Syndrome (Tip 5)
• Involvement of two organs in
systemic diseases
• Acute/chronic
• Examples: Sepsis, DM, SLE,
sarcoidosis, amyloidosis,
Wegener granulomatosis,
cirrhosis
Ronco C. Eur Heart J. 2010;31:703-11

21. Sepsis - Cirrhosis
• Acute: Sepsis. Developes in hours to a few days
• Chronic: Cirrhosis. Takes weeks to months to develop.
Precipitating events (bleeding, infection…) can transition
to an acute deterioration in heart and kidney.
• Mechanism: Inflammation, RAAS, autonomic SS
dysfunction, HPA activation, maldistribution, endothelial
dysfunction
• Both organs have cellular, molecular and functional
changes.

22. Secondary Cardiorenal Syndrome (Tip 5)
• Sepsis: 11-64 % had AKI, 30-80 % had elevated
Troponin, ventricular dysfunction (septic
cardiomyopathy)
• Both are mortality predictors
• In AKI patients, the rate of heart involvement? Or
in septic cardiomyopathy, AKI rate ?
• ABY Cardiac dysfunction

23. Cirrhotic Cardiomyopathy
• Cardiac dysfunction in patients with cirrhosis characterized by
impaired contractile responsiveness to stress, diastolic
dysfunction and electrophysiological abnormalities in the
absence of known cardiac disease
• Diastolic dysfun. → Systolic dysfun.→ left ventricular failure
• Chronotropic incompetence, prolonged QT
• Histopathology: Cardiac hypertrophy, fibrosis, subendotelial
edema
• More insidious onset. Dysfunction develops slowly until a
crucial point is reached and full decompensation occurs
(infection, bleeding..)

24. Moller S. Dig Dis Sci. June 2015
DOI 10.1007/s10620-015-3752-3

25. Ronco D. Heart Failure Clin. 2014;10: 251–280
Enfeksiyon (SBP),
kanama, parasentez

26. HRS - CRS
• As the disease progresses, hyperdynamic cirrhotic heart can not
provide enough cardiac output (CO) to fill vascular beds:
Hypovolemia → WRF
• Cardiac dysfunction is the main determinant of HRS development
• Patients with suppressed cardiac function have more HRS
• Lower CO in patients with cirrhosis who developed renal failure
during a course of spontaneous bacterial peritonitis compared to
those without renal failure. After resolution of the infection,
patients with renal failure have lower CO.
• Data supporting the association between cardiac dysfunction and
renal failure in cirrhosis, the so-called cardio-renal syndrome
Fede G. Ann Gastroenterol. 2015;28 (1):31-40
Ronco D. Heart Failure Clin. 10 (2014) 251–280
Ruiz-del-Arbol L. Hepatology. 2003;38:1210-1218

27. HRS Diagnostic Criteria
1. Cirrhosis with ascites
2. Serum creatinine > 1.5 mg/dl
3. No improvement of serum creatinine (≤ 1.5 mg/dl )after at
least 2 days with diuretic withdrawal and volume expansion
with albumin (1 gr/kg, maximum 100 gr)
4. Absence of shock or nephrotoxic drug use
5. Absence of parenchymal kidney disease (proteinuria > 500
mg/day, >50 rbc/hpf, abnormal renal USG)
• HRS is a subtype of AKI in cirrhotic patients. A functional
abnormality and severe intrarenal vasoconstriction exist.
• CO: low, normal, high. Shortly does not fill a need.
Salerno F. Gut. 2007;56:1310-1318
Wong F. Gut. 2011;60:702-709

28. CRS – Preventive Steps
• Avoid contrast use
– < 30 ml for diagnosis, <100 ml catheterisation
• Avoid NSAID, thiozoldinedione, biguanide use
• Use isotonic fluids instead of colloid fluids
• Hydration (contrast material and cardiac surgery)
• Avoid hypotension
• Be careful when starting ACE-I in early phase of treat.
• Correct electrolyte and acid-base disturbances
• Exclude coronary diseases
• Treat the precipitating disease (Sepsis, cirrhosis, DM)

29. Treatment - Type 1 CRS
• Loop diuretic, ultrafiltration
• Hypotension: Norepineprine, left ventricular assist device
• Inotropic agents: Dobutamine, levosimendan
• Vasodilators: Dopamine, dobutamine, phosphodiesterase
inhibitor
• Vasopressin antagonist
• Do not forget that excessive diuretic use cause AKI
• The same true for ACE-I and spironolactone
• Avoid hypotension during the first 48 hours of treatment

30. Treatment - Type 2 CRS
• ACE-I, ARB, β blocker, aldosterone: Decrease mortality
• Digoxin and loop diuretics: decrease symptoms, no effect
on mortality
• Defibrillator : EF < %30 , long QRS, cardiac arrest, VT
• RRT
• Heart transplantation
• Worsening of renal function with treatment: Over
diuresis, nephrotoxic drug use, persistent hypotension,
renovascular diseases

31. Treatment - Type 3, 4 CRS
• Type 3: Treat underlying disease
– Avoid hypervolemia
– Correct electrolyte disorders
– Correct acid-base disturbances
– Hydration before and after contrast use
• Type 4: HT, DM and HL treatment, avoiding from
hypervolemia, anemia treatment, Ca-P control
revascularization

32. Treatment - Type 5
• Treat underlying disease
• SBP: Albumin (1.5 gr/kg-first day (maximum:150 gr), 1 mg/kg
(maximum:100gr) 3th day
• HRS Tip 1: a-Terlipressin (0.5-2 mg/4-6 hour) + albumin (1 gr/kg
first day, then 20-40 gr/day). Continue until the day of 15.
• b- Midodrine + octreotide + albumin
• c- Noradrenaline (0.5-3 mg/hour) + albumin
• d- TIPS
• Liver transplantation . Medical and TIPS increase waiting time
for transplantation