Hepatorenal syndrome

Chapter 12 Hepatorenal syndrome



Mónica Guevara, MD, PhD, Juan Rodés, MD, FRCP



Key Points



1 Hepatorenal syndrome (HRS) is a severe complication of patients with cirrhosis and ascites.

2 The annual incidence of HRS in patients with ascites is approximately 8%.

3 The diagnosis of HRS is associated with a poor prognosis and very short survival.

4 Liver transplantation is the treatment of choice for HRS.


Overview



1. The term hepatorenal syndrome (HRS) was initially applied to many different disorders involving the liver and the kidney.

2. During the 1960s and the 1970s, nephrologists in the United States popularized the term to define renal failure in cirrhosis.

3. In 1996, the International Ascites Club delineated the first diagnostic criteria to define HRS.

4. In 2007, these criteria were revisited and changed (Table 12.1).

TABLE 12.1 Diagnostic criteria for hepatorenal syndrome















1. Cirrhosis with ascites
2. Serum creatinine level greater than 133 μmol/L (1.5 mg/dL)
3. Lack of improvement in serum creatinine level (i.e., lack of a decrease to a level of ≤ 133 μmol/L) after ≥2 days following diuretic withdrawal and volume expansion with albumin; recommended dose of albumin: 1 g/kg of body weight per day up to a maximum of 100 g/day
4. Absence of shock
5. Lack of current or recent treatment with nephrotoxic drugs
6. Absence of parenchymal kidney disease as indicated by proteinuria >500 mg/day, microhematuria (>50 red blood cells/high-power field), and/or abnormal renal ultrasonography


Definition



1. Renal failure, estimated by a level of serum creatinine greater than 1.5 mg/dL, occurring in a patient with advanced liver disease and portal hypertension

2. HRS characterized by
image A marked decrease in glomerular filtration rate (GFR) and renal plasma flow (RPF) in the absence of other identifiable causes of renal failure

image Marked abnormalities in systemic hemodynamics

image Activation of endogenous vasoactive systems


Pathogenesis



1. The pathogenesis of HRS is not completely understood.

2. Several mechanisms have been implicated (Fig. 12.1):
image Disturbance in systemic hemodynamics

image Increased activity of vasoconstrictor systems

image Reduced or insufficiently increased activity of vasodilator factors

3. Systemic hemodynamics
image Hemodynamic alteration results from severe arterial vasodilation located mainly in the splanchnic territory.

image The hemodynamic profile is characterized by hypervolemia, low arterial pressure, and low systemic vascular resistance.

image In the setting of increased activity of vasoconstrictor systems, marked renal vasoconstriction develops.

image Vasoconstriction occurs not only in renal circulation but also in brachial, femoral, and cerebral blood flow, probably as a compensatory mechanism to counteract splanchnic vasodilation.

image HRS has been traditionally assumed to develop in the setting of progression of the hyperdynamic circulation with high cardiac output; however, in few studies assessing cardiovascular function in patients with HRS or refractory ascites, cardiac output was found to be significantly reduced compared with patients without HRS.

4. Vasoconstrictor systems
a. Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS)
image RAAS and SNS activity are increased in most cirrhotic patients with ascites.

image These systems are particularly activated in patients with HRS.

image The activity of both systems, RAAS and SNS, correlates inversely with renal blood flow.

image Experimental studies have demonstrated the compensatory nature of the increased vasoconstrictor activity.

image Pharmacologic blockage of the effectors of these systems induces reduction in systemic vascular resistance and arterial hypotension, findings suggesting that their increased activation is crucial to maintain systemic hemodynamics.

b. Antidiuretic hormone arginine vasopressin [AVP]
image This hormone contributes to water retention and dilutional hyponatremia.

c. Endothelin (ET)
image This endothelial-derived peptide is also increased in cirrhosis.

image The most important effect of ET is renal vasoconstriction, which can decrease RBF and GFR.

image Among patients with cirrhosis, those with HRS show the highest levels of ET.

image The role of ET in the pathogenesis of HRS remains to be clarified.

d. Others: adenosine, leukotrienes, and isoprostanes

5. Vasodilatory factors
a. Renal prostaglandins (PGs)
image PGs are the most important intrarenal vasodilators.

image PGs contribute to maintain renal perfusion in cirrhotic patients.

image Inhibition of synthesis of PGs induces a profound derangement of RPF and GFR.

image Cirrhotic patients with HRS have reduced production of renal PGs.

image Renal vasoconstriction results from the imbalance between renal vasoconstrictors and vasodilators.

b. Nitric oxide (NO)
image NO is locally synthesized within the kidney.

image Under normal conditions, NO plays a role in the regulation of glomerular microcirculation, sodium excretion, and renin release.

image Inhibition of NO does not induce renal vasoconstriction as a result of the compensatory increase of renal PGs.

image Inhibition of both NO and PGs induces renal vasoconstriction in patients with cirrhosis and ascites.

image NO interacts with PGs to maintain renal perfusion in cirrhotic patients with ascites.

c. Natriuretic peptides
image These vasodilators are involved in the maintenance of renal perfusion.

image Atrial natriuretic peptide (ANP) is the major natriuretic hormone.

image ANP is elevated in decompensated cirrhosis, and patients with HRS have the highest levels.

image Increased ANP may act as a homeostatic mechanism to counteract the effect of vasoconstrictor systems.

image

Fig. 12.1

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Jun 4, 2016 | Posted by in GASTROENTEROLOGY | Comments Off on Hepatorenal syndrome

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