The natural history and management of hepatorenal disorders: from pre-ascites to hepatorenal syndrome

Abstract

-In cirrhosis, the natural history of hepatorenal disorders starts with a pre-ascitic stage and is followed by the development of ascites; hepatorenal syndrome (HRS ) begins with compensated renal sodium retention, or preascites. In pre-ascites, the renal sodium retaining tendency leads to 'overfilling' of total blood volume, with increased glomerular filtration rates (GFR), overcoming the renal sodium retaining tendency possibly due to renal accumulation of angiotensin II. IntroductionThe most severe hepatorenal disorders, refractory ascites and hepatorenal syndrome (HRS), account for more than 30% of referrals of cirrhotic patients for transplantation. 1 It is therefore important to understand the pathogenesis of the natural history of this complication of cirrhosis, and if possible prevent its development. Pre-ascites (Fig 1a)In patients with compensated cirrhosis which is free of ascites, it is possible to demonstrate abnormal renal handling of sodium. For example, when preascitic cirrhotic patients are given a challenge of a 200 mmol sodium, high-salt diet for one week, they fail to achieve a sodium balance within that time, remaining in positive sodium balance, whereas normal healthy controls achieve a sodium balance within three to four days. 2 We found this the most physiological way of defining pre-ascites. In fact, if this high-salt diet is maintained, pre-ascitic patients do eventually achieve sodium balance after three to four weeks, along with a significant gain in weight, and without ultrasound evidence of ascites. 3 The current theory explaining sodium retention in cirrhosis is known as the peripheral vasodilatation theory. 4 This states that splanchnic vasodilatation, secondary to vasodilators such as nitric oxide, results in increased pooling of blood from the increased total blood volume within the splanchnic vascular bed. This results in hyperkinetic circulation with a decreased effective arterial blood volume, increased cardiac output, decreased systemic vascular resistance, decreasing renal blood flow (RBF), and glomerular filtration rate (GFR), with activation of the sodium-retaining systems, renin-angiotensinaldosterone system (RAAS), and sympathetic nerve activity (SNA) initiating sodium retention. Although this explanation is clearly appropriate for the more advanced stages of ascites, does it explain pre-ascites, and the many patients with early ascites? In the upright position, pre-ascitic patients have no evidence of hyperkinetic circulation, but may have mild elevation of serum aldosterone levels and sodium retention. 5 In contrast, when these patients The natural history and management of hepatorenal disorders: from pre-ascites to hepatorenal syndrome Laurie Blendis and Florence Wong Key PointsIn compensated cirrhosis, pre-ascites may be defined as failure to reach sodium balance on a 200 mmol sodium diet within seven daysIn pre-ascites, vasodilatation and hyperkinesis appear to be secondary to compensated sodium retention secondary to portal hypertensionThe development of...

Portal Hypertension and Its Complications

“…Refractory ascites (Table 1) is associated with increasing systemic vasodilation, decreased effective circulating volume, and renal perfusion. 140 Repeated LVP or total paracentesis are the most commonly used modalities for the treatment of refractory ascites. Although they immediately relieve ascites, they are associated with ascites recurrence in most subjects and do not improve survival.…”

Oxidative stress, NOx/ l -arginine ratio and glutathione/glutathione S-transferase ratio as predictors of ‘sterile inflammation’ in patients with alcoholic cirrhosis and hepatorenal syndrome type II

“…In patients with HRS, liver disease progression and transition to the decompensated stage of the disease due to the development of mild-to refractory ascites aggravate renal retention of sodium [ 41 , 42 ]. In patients with HRS contributing factors for renal failure, GFR reduction may also include the loss of renal blood flow autoregulation, the contraction of mesangial cells stimulated by endothelin, the activation of inflammatory markers leukotriene and thromboxane A, followed by a reduction of NO synthesis in liver and reduced sensitivity of the receptors on glomerular endothelial cells to NO [ 4 , 43 ].…”

“…Renal failure may develop rapidly with a serum creatinine level >220 μmol/l and is associated with type I HRS, or it may develop slowly with a serum creatinine level greater than 130 μmol/l, being associated with type II HRS. These two types of HRS are two different clinical patterns of renal failure manifestation [ 4 , 5 ].…”

Misapplications of Commonly Used Kidney Equations

“…Estimating equations therefore may be imprecise in patients with chronic illness or HIV infection (10). Similarly, estimating equations may not be accurate in patients with ascites, congestive heart failure, or nephrotic syndrome because of abnormalities in muscle mass, volume of distribution, or renal hemodynamics (11)(12)(13). Race and gender are important determinants of muscle mass.…”