ABSTRACTS from 16th International COnference on ... - CRRT Online

E05
Liver and the Kidney 1: Principles of Hepatic Dysfunction
Heather Patton MD
4:00-5:30
Tuesday, February 14
Educational Objectives:
1. Understand the genesis of hyperdynamic circulation that occurs with portal hypertension
2. Describe how renal response to the hyperdynamic circulation and relative cardiac dysfunction contribute to
acute kidney injury in cirrhosis
3. Apply understanding of mechanisms of functional renal failure in end stage liver disease to current therapeutic
strategies
Content Description:
Hepatorenal syndrome (HRS), first described by Flint in 1963 (Am J Med Sci 1963;45:306-39), is a functional
renal failure caused by severe intra-renal vasoconstriction. This occurs in the setting of circulatory dysfunction
with increased plasma rennin activity, over-activity of the sympathetic nervous system, and increased anti-diuretic
hormone. The ability of the kidneys to excrete sodium and free water is severely diminished and presentation
with dilutional hyponatremia is common. Extra-renal arterial vasodilatation occurs mainly in the splanchnic vascular
bed, whereas other vascular beds, such as those that supply the brain and the liver, may be vasoconstricted.
These vascular derangements may contribute to the development of hepatic encephalopathy and decline in hepatocellular
function observed in HRS. Cardiac output in HRS may be low, normal, or high but is insufficient
because of reduced peripheral vascular resistance. The contribution of diminished cardiac output to hepatorenal
physiology is a more recent concept in this syndrome. It is hypothesized that a hyperdynamic circulation is
essential to maintenance of central blood volume and renal perfusion in cirrhosis. When cardiac output decreases,
effective hypovolemia occurs, leading to renal hypoperfusion and HRS. The mechanism(s) leading to
impaired or insufficient cardiac output in patients developing HRS is unknown. HRS can be triggered by a number
of events including infection, bleeding, and large volume paracentesis (LVP) without administration of IV
albumin. The most common trigger for HRS is bacterial infection, particularly spontaneous bacterial peritonitis
(SBP). Type-1 HRS occurs in about 25% of patients with SBP despite rapid resolution of the infection with
administration of non-nephrotoxic antibiotics. The annual incidence among patients with cirrhosis and ascites is
estimated at 8% and is associated with poor prognosis. Patients with the rapidly progressive Type-1 HRS have a
median survival of 2 weeks and a hospital survival of less than 10% whereas patients with the more insidious
Type-2 HRS have a median survival of 6 months. Kidney function can be improved with prompt medical treatment
in patients with HRS and is associated with improved survival. Treatment of HRS is designed to increase
the central blood volume by simultaneously increasing total plasma volume and reducing intense peripheral
vasodilatation.
Suggested Reading:
1. Gines, P. and R.W. Schrier, Renal failure in cirrhosis. N Engl J Med, 2009. 361(13): p. 1279-90.
2. Wong, F., Nadim, M.K., Kellum, J.A., Salerno, F, Bellomo, R., Gerbes, A., Angeli, P, Moreau, R., Davenport,
A., Jalan, R., Ronco, C., Genyk, Y., and Arroyo, V. Working party proposal for a revised classification system of
renal dysfunction in patients with cirrhosis. Gut 2011;60:702-709.
3. Jalan R, Forrest EH, Redhead DN, Dillon JF, Hayes PC. Reduction in renal blood flow following acute
increase in the portal pressure: evidence for the existence of a hepatorenal reflex in man? Gut 1997;40(5):664-
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4. Stadlbauer V, Wright GA, Banaji M, Mukhopadhya A, Mookerjee RP, Moore K, Jalan R. Relationship
between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis.
Gastroenterology 2008;134(1):111-9.
5. Helmy A, Jalan R, Newby DE, Hayes PC, Webb DJ. Role of angiotensin II in regulation of basal and sympathetically
stimulated vascular tone in early and advanced cirrhosis. Gastroenterology. 2000;118(3):565-72
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