New clues to the pathophysiology of hepatorenal failure

Abstract

In patients with advanced liver disease, decreases in renal blood flow, glomerular filtration rate, and urinary output are frequently observed. The deterioration in renal function is usually not due to a unique cause but is the result of the concerted action of several mechanisms operating in parallel; decreased plasma protein formation and increased intrahepatic vascular resistance lead to sequestration of blood volume, favoring hypovolemia and reduction in cardiac output. At the same time enhanced formation of nitroxide leads to peripheral vasodilation; bacterial endotoxin escaping clearance by the diseased liver stimulates the expression of a long-acting nitroxide synthase. Furthermore, vasodilating intestinal mediators such as substance P escape inactivation by the liver. In the face of peripheral vasodilation the maintenance of blood pressure requires an increase in cardiac output, which is achieved by activation of sympathetic nervous tone, renal vasoconstriction, enhanced release of renin, angiotensin, aldosterone, and antidiuretic hormone, leading to renal retention of sodium and water. Renal vasoconstriction is opposed by vasodilatatory prostaglandins, and renal failure may be triggered by inhibition of prostaglandin formation. On the other hand, vasoconstrictive eicosanoids, such as thromboxane B2 and leukotriene E2, which escape hepatic inactivation, may contribute to renal vasoconstriction. Beyond these mechanisms disturbed hepatic regulation of renal function may participate in the generation of hepatorenal syndrome. The liver regulates renal function via both a hepatorenal reflex decreasing renal blood flow and a hypothetical liver-borne diuretic factor increasing renal blood flow. Both enhanced hepatorenal reflex activity and decreased formation of the liver-borne diuretic factor could participate in the pathogenesis of hepatorenal syndrome.

Changes in renal artery resistance after meal‐induced splanchnic vasodilatation in cirrhotic patients

“…34 Our study is in agreement with these findings and supports splanchnic vasodilatation as the initial causative factor of functional kidney failure in cirrhotic patients, rather than hepatocellular insufficiency itself, as previously suggested. 20 Our results are also in agreement with many of those reported by Iwao et al, 35 who studied by duplex Doppler sonography the postprandial hemodynamic response in the mesenteric and renal arteries of cirrhotic patients. Iwao et al found a decrease in the SMA pulsatility index and an increase in the renal artery pulsatility index after ingestion of a balanced liquid meal.…”

The creatinine approach to estimate skeletal muscle mass in patients with cirrhosis

“…Owen and coworkers 47 tion. 43,44 Regarding the high prevalence of renal dysfunction in advanced liver disease, 45,46 it is tempting to speculate that found a decreased plasma creatinine concentration in eight patients with alcoholic cirrhosis when compared with 10 norrenal insufficiency contributes significantly to the malnutrition of these patients. mal subjects, which was taken as evidence for a decreased creatinine production in chronic liver disease.…”

Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion

“…The second theory suggests that renal hypoperfusion is not related to the disturbed systemic hemodynamics, and has a direct pathogenic relationship with the diseased liver. 27,28 A putative renal vasodilator factor, of which hepatic synthesis would be reduced in cirrhotic patients with HRS, is the proposed link between liver failure and renal vasoconstriction. 27 The results of the current study, showing that a maneuver that combines arterial vasoconstriction with plasma volume expansion to increase effective arterial blood volume, are associated with a normalization of the increased activity of vasoconstrictor systems, and the reversal of HRS provides strong support of the arterial vasodilation theory.…”