CARDIORENAL SYNDROMEs

ByDr.R.AMIRTHA LAKSHMI

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) .

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)

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

Epidemiology and Outcomes in CombinedCardiorenal 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.

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.

• 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.

• 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.

Mechanisms in CRS

• RAAS

• INCREASED SNA

• REACTIVE OXYGEN SPECIES

• INFLAMMATION

• ENDOTHELIN EFFECT

• ARGININE VASOPRESSIN EFFECTS

• BNP EFFECTS

Biomarkers in the diagnosis of AKI Biomarker Assosciated injuryCystatin C Proximal tubule injuryKIM 1 Ischemia and nephrotoxinsNGAL Ischemia and nephrotoxinsNHE3 Ischemia,prerenal ,postrenal AKI

GST Proximal tubule injury ,acute rejection

GST Distal tubule injury,acute rejection

L-FABP Ischemia and nephrotoxinsCyr 6 1 Ischemic ATNNETRIN 1 Ischemia and nephrotoxins,sepsis

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.

CRS Type 1

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

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.

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.

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

CRS Type 2

Management

• Diuretics – volume expanded state

• ACEI

• ARBs block RAAS ---decrease LVH, proteinuria,

decrease progression of CKD .

• Vasodilators may also be useful.

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.

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

CRS Type 3

Management

• Rx of accelerated HTN, hyperkalemia, metabolic

acidosis.

• Hemodialysis.

• CRRT

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.

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

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

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.

CRS Type 5

Management

• Treatment of underlying cause.

• Vasopressors

• Inotropes

• Diuretics

• Intensive renal replacement therapy in sepsis.

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.

Thank you