Hepatorenal and cardiorenal

syndrome

DR.C.ANANDABABU, JOPHDC ,JIPMER

 Hepatorenal Syndrome

 Hepatorenal syndrome (HRS) is a reversible and functional renal failure that occurs in patients with
acute or chronic liver disease and portal hypertension.
 Widespread splanchnic and systemic vasodilatation, together with intense renal vasoconstriction, is
the pathophysiological hallmark of HRS.
 Although HRS is associated with an extremely poor prognosis, the histological appearance of the
kidneys is normal, and the kidney function often improves following liver transplantation.
 The reported incidence of HRS in cirrhotic patients with normal renal function is 18% and 39%, at
one and five years respectively, making it a common condition.
 It is also important to bear in mind that HRS is a diagnosis of exclusion, and there is no single gold
standard diagnostic test.
 Pathogenesis

 Onset of portal hypertension and the subsequent development of ascites predate the development of HRS.
 In patients with portal hypertension, bacterial products such as endotoxins or bacterial DNA are not cleared
efficiently and enter the systemic circulation due to portal‐systemic shunting.
 The presence of these agents stimulates increased production of nitric oxide (NO) by both the endothelium
and peritoneal macrophages.
 NO in turn leads tosignificant splanchnic vasodilatation, with a profound reduction in the systemic vascular
resistance and mean arterial pressure (MAP).
 The ongoing vasodilatation stimulates the carotid and renal volume receptors, which leads to
compensatory activation of vasoconstrictor systems,RAAS,SNS,ADH\
 Reduction of renal vasodilators with unopposed action of renal vasoconstrictors is the final event that leads
to the development of HRS.
 Clinical Presentation

HRS is characterized by the following features ;

 A progressive rise in serum creatinine
 Absence of significant haematuria and proteinuria of less than 500mg/day
 A very low rate of sodium excretion (urine sodium concentration )
 HRS is classified into two groups, depending on the severity of presentation:
 Type 1 HRS: Associated with doubling of serum creatinine to greater than 2.5mg/dl (220 μmol/l) or
a 50% reduction in GFR to less than 20ml/min in less than two weeks
 Median survival without treatment is two weeks
 Type 2 HRS: ● Associated with a much less rapid decline in renal function and often presents with
refractory ascites
 Median survival without treatment is four to six months
Type 1 HRS is characterized by a rapid decline in kidney function and is most often observed in
patients suffering from acute liver failure, acute alcoholic hepatitis or acute decompensation on a
background of cirrhosis.
These patients often have multiorgan failure with low blood pressure and hyponatraemia. At times, a
clear precipitating event such as spontaneous bacterial peritonitis, sepsis, gastrointestinal bleeding,
vigorous diuretic therapy, abdominal paracentesis or administration of NSAIDs might be identified.
 Type 2 HRS presents with a more insidious onset.
 Patients usually have refractory ascites and low to normal blood pressure.
 Usually no precipitating cause is identified and the condition reflects the natural course of the
disease.
 The urea cycle occurs in the liver and therefore patients with advanced liver disease have a low
urea generation.
 These patients are also likely to have reduced meat intake and decreased muscle mass, often
leading to a lower than expected serum creatinine level.
 Hence, patients with HRS often have a renal dysfunction that is significantly more severe than is
suggested by the serum urea and creatinine levels
Diagnosis
 Treatment

 The initial treatment for HRS should include improvement of liver function through management of
the underlying condition, such as abstinence in alcoholic hepatitis or treatment of decompensated
hepatitis B with effective antiviral therapy.
 Once the diagnosis of HRS is made, suitable candidates, especially those suffering from HRS type
1, should be placed on the urgent waiting list for cadaveric or living donor liver transplantation.
 Pharmacotherapy with systemic vasoconstrictors is based on the understanding that systemic
vasodilatation, especially in the splanchnic circulation, is responsible for the renal failure in HRS.
 Vasoconstriction increases the effective arterial blood volume and leads to better renal perfusion
and some reversal of the condition
Terlipressin with Albumin :
 Terlipressin is a vasopressin analogue which reverses splanchnic vasodilatation. The
administration of terlipressin and albumin is associated with a significant improvement in GFR,
increase in MAP, and reduction of serum creatinine in 42–77% of cases.
Midodrine, Octreotide, and Albumin :
 In many countries , terlipressin is not available and the combination of midodrine, octreotide, and
albumin is a reasonable alternative.
 Midodrine, by its alpha‐1 adrenergic agonist activity, is a systemic vasoconstrictor,
 whilst octreotide is an inhibitor of endogenous vasodilators.
Norepinephrine with Albumin :
 In patients with HRS who are admitted to the Intensive Care Unit with hypotension, a
norepinephrine infusion (with the aim of raising the MAP by at least 10mmHg) along with
intravenous albumin for at least two days is another option.
 Treatment options for patients who do not respond to one of the medical therapies listed here
include a transjugular intrahepatic portosystemic shunt (TIPS) and dialysis.
 However, many patients with HRS are too ill to undergo TIPS or dialysis.
 It is important to realize that the definitive treatment for HRS is liver transplantation
 CARDIORENAL SYNDROME

 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) .

 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.
 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

 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.
 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.
 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.

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
 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.

 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.
 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.
 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.

 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
 Sevelamer for hyperphospahtemia
 Statins
 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.
 management

 Treatment of underlying cause.

 Vasopressors

 Inotropes

 Diuretics

 Intensive renal replacement therapy in sepsis.