Cardiorenal syndrome (CRS) refers to conditions where acute or chronic dysfunction of the heart or kidneys induces dysfunction of the other organ. CRS is classified into 5 subtypes depending on whether cardiac or renal dysfunction occurs first, and whether it is acute or chronic. Type 1 involves acute cardiac dysfunction leading to acute kidney injury. Type 2 involves chronic cardiac dysfunction resulting in worsening chronic kidney disease. Type 3 involves acute kidney injury leading to cardiac issues. Type 4 involves chronic kidney disease contributing to cardiac problems. Type 5 involves secondary cardiac and renal dysfunction due to another systemic condition. Early diagnosis and treatment individualized to the CRS subtype is important for improving survival.

1. CARDIORENAL
SYNDROMEs
By
Dr.R.AMIRTHA LAKSHMI

2. Introduction
• Cardiac and renal diseases are common and frequently
coexist to significantly increase mortality, morbidity, and
the complexity and cost of care.
• Primary disorders of 1 of these 2 organs often result in
secondary dysfunction or injury to the other. Such
interactions represent the pathophysiological basis for a
clinical entity called cardiorenal syndrome (CRS) .

3. Definition
CRS can be generally defined as a patho physiologic
disorder of the heart and kidneys whereby acute or chronic
dysfunction of one organ may induce acute or chronic
dysfunction of the other.
- European Heart Journal (2010)

4. CLASSIFICATION
• World congress of nephrology classified cardiorenal syndromes into 5
subtypes based on patho-physiology:
• CRS type 1 : acute cardio-renal syndrome
• CRS type 2 : chronic cardio-renal syndrome
• CRS type 3 : acute reno-cardiac syndrome
• CRS type 4 : chronic reno-cardiac syndrome
• CRS type 5 : secondary cardio-renal syndrome

5. Epidemiology and Outcomes in Combined
Cardiorenal Disease
• Prevalence of Renal Disease in Patients With HF
• In the Acute Decompensated Heart Failure National
Registry (ADHERE) of 1,05,000 individuals admitted
for acute decompensated HF, 30% had a history of
renal insufficiency, 21% had serum creatinine
concentrations >2.0 mg/dL, and 9% had creatinine
concentrations >3.0 mg/dL.

6. Impact of Renal Disease on Clinical
Outcomes in Patients With HF
• Renal dysfunction is one of the most important
independent risk factors for poor outcomes and all-cause
mortality in patients with HF.
• Baseline glomerular filtration rate (GFR) appears to be a
stronger predictor of mortality in patients with HF than left
ventricular ejection fraction or NYHA functional class.
• Both elevated serum creatinine on admission and
worsening creatinine during hospitalization predict
prolonged hospitalization, rehospitalization, and death.

7. • HF Outcomes in Patients With Renal Disease
• Patients with chronic renal insufficiency are at
strikingly higher risk for myocardial infarction, HF
with systolic dysfunction, HF with preserved left
ventricular ejection fraction, and death resulting from
cardiac causes compared with individuals with normal
GFR.

8. • Age adjusted CVD mortality is about 30 times higher in CKD
than in general population.
• Risk of dying because of cardiovascular causes in patients
with ESRD – 65 times higher in pts with 45-54 yrs, 500
times higher than general population in young cohort.
• 1/3 of patients with mild renal impairment –h/o overt CVD.

9. Mechanisms in CRS
• RAAS
• INCREASED SNA
• REACTIVE OXYGEN SPECIES
• INFLAMMATION
• ENDOTHELIN EFFECT
• ARGININE VASOPRESSIN EFFECTS
• BNP EFFECTS

11. Biomarkers in the diagnosis of AKI
Biomarker Assosciated injury
Cystatin C Proximal tubule injury
KIM 1 Ischemia and nephrotoxins
NGAL Ischemia and nephrotoxins
NHE3 Ischemia,prerenal ,postrenal AKI
 GST Proximal tubule injury ,acute rejection
 GST Distal tubule injury,acute rejection
L-FABP Ischemia and nephrotoxins
Cyr 6 1 Ischemic ATN
NETRIN 1 Ischemia and nephrotoxins,sepsis

12. CRS type 1
• CRS type 1 (acute CRS)--is characterized by a rapid worsening of
cardiac function, leading to acute kidney injury (AKI).
• Acute heart failure (HF) may be divided into 4 subtypes:
• Hypertensive pulmonary edema with preserved left ventricular
(LV) systolic function,
• Acutely decompensated chronic HF,
• Cardiogenic shock, and
• Predominant right ventricular failure.

13. CRS Type 1

14. Management of CRS 1
• Diuretics –useful in volume overloaded non hypotensive patients.
• Loop diuretics ,thiazides--Overzealous use → worsening renal function
• Exacerbates neuro hormonal activity , activates RAAS , Increase
SVR ,worsens LVF .
• Inotropes --dopamine,dobutamine,milirinone
• Vasodialtors – nesiritide
• Ultrafiltration(aquapheresis)
• Arginine vasopressin receptor antagonists—tolvaptan

15. CRS type 2
• CRS type 2 (chronic CRS) is characterized by chronic abnormalities in
cardiac function (e.g., chronic congestive HF) causing progressive CKD.
Worsening renal function in the context of HF is associated with
adverse outcomes and prolonged hospitalizations.
• The prevalence of renal dysfunction in chronic HF has been reported to
be approximately 25%. Even slight decreases in estimated glomerular
filtration rate (GFR) significantly increase mortality risk and are
considered a marker of severity of vascular disease.

16. Pathophysiology
• Low cardiac output--- activation of RAAS –SNS ---
subclinical inflammation ---endothelial dysfunction—
increased renal vascular resistance—accelerated
atherosclerosis.
• Relative or absolute erythropoietin deficiency.
• Activation of the receptor of erythropoietin in heart
may protect it from apoptosis , inflammation and
fibrosis.

17. Ronco, C. et al. J Am Coll Cardiol 2008;52:1527-1539
CRS Type 2

18. Management
• Diuretics – volume expanded state
• ACEI
• ARBs block RAAS ---decrease LVH, proteinuria,
decrease progression of CKD .
• Vasodilators may also be useful.

19. CRS TYPE 3
• CRS type 3 (acute renocardiac syndrome)- is characterized
by an abrupt and primary worsening of kidney function
(e.g., AKI, ischemia, or glomerulonephritis), leading to acute
cardiac dysfunction (e.g., HF, arrhythmia, ischemia).
• Type 3 CRS appears less common than type 1 CRS, but this
may only be due to the fact that, unlike type 1 CRS, it has
not been systematically studied.

20. Ronco, C. et al. J Am Coll Cardiol 2008;52:1527-1539
CRS Type 3

21. Management
• Rx of accelerated HTN, hyperkalemia, metabolic
acidosis.
• Hemodialysis.
• CRRT

22. CRS TYPE 4
• CRS type 4 (chronic renocardiac syndrome)- is
characterized by a condition of primary CKD (e.g., chronic
glomerular disease) contributing to decreased cardiac
function, ventricular hypertrophy, diastolic dysfunction,
and/or increased risk of adverse cardiovascular events.

23. Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.
Ronco, C. et al. J Am Coll Cardiol 2008;52:1527-1539
CRS Type 4

24. Management
• Cessation of smoking, control of diabetes, HTN.
• Correction of anemia –iron supplements and erythropoietin
• Hb 11-12 gm % hct >36%
• Loop diuretics ,ACEI, ARB s, Beta blockers
• Calcium-phosphate ionic product to be kept below 50 mg2/m2
• Sevelamer .
• Statins
• Vitamin E

26. CRS TYPE 5
• CRS type 5 (secondary CRS)- is characterized by the presence of
combined cardiac and renal dysfunction due to acute or chronic
systemic disorders.
• Several acute and chronic diseases can affect both organs
simultaneously and that the disease induced in one can affect the
other and vice versa. Examples include sepsis, diabetes,
amyloidosis, systemic lupus erythematosus, and sarcoidosis.
• Several chronic conditions such as diabetes and hypertension
may contribute to type 2 and 4 CRS.

27. CRS Type 5

28. Management
• Treatment of underlying cause.
• Vasopressors
• Inotropes
• Diuretics
• Intensive renal replacement therapy in sepsis.

29. Take home message
• CRS is a pathophysiological condition.
• Treatment is to be individualized based on the etiology.
• Early diagnosis is important for better survival.
• Early novel biomarkers are to be used in diagnosis.
• Each patient with either CKD,CVD to be assessed with risk
factors and followed up.

30. Thank you