Historia

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

review article
Medical Progress

Renal Failure in Cirrhosis
enal failure is a challenging complication of cirrhosis1,2 and is one of the most important risk factors when liver transplantation is being considered. Patients with cirrhosis and renal failure are at high risk for death while awaiting transplantation and have anincreased frequency of complications and reduced survival after transplantation, as compared with those without renal failure.3,4 In 2002, the Model for End-Stage Liver Disease (MELD) score — derived from measurements of serum bilirubin, the international normalized ratio of prothrombin time, and serum creatinine to evaluate pretransplantation renal function — was introduced as an aid to organallocation among candidates for liver transplantation. Use of this scoring system has increased the number of patients with renal failure who receive a liver transplant5-7 and has reduced mortality among patients awaiting liver transplantation. In recent years, substantial progress has been made toward understanding the pathogenesis and natural history of renal failure in cirrhosis. Moreover, newlyidentified clinical interventions may assist in the prevention and management of this complication.

R

Pere Ginès, M.D., and Robert W. Schrier, M.D.
From the Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, and Institut d’Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Catalonia, Spain(P.G.); and the Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, Aurora (R.W.S.). Address reprint requests to Dr. Schrier at the University of Colorado Health Sciences Center, 12700 E. 19th Ave., C281, Denver, CO 80045, or at robert.schrier@uchsc.edu. N Engl J Med 2009;361:1279-90.
Copyright © 2009 Massachusetts Medical Society.

Pathoph ysiol o gyof R ena l Fa ilur e
There is considerable evidence that renal failure in patients with cirrhosis is primarily related to disturbances in circulatory function — mainly, a reduction in systemic vascular resistance due to primary arterial vasodilatation in the splanchnic circulation, triggered by portal hypertension.1,8-10 The cause of this arterial vasodilatation is increased production oractivity of vasodilator factors — particularly nitric oxide, carbon monoxide, and endogenous cannabinoids — mainly in the splanchnic circulation.8-12 In the early stages of cirrhosis, when portal hypertension is moderate, increased cardiac output compensates for a modest reduction in systemic vascular resistance, permitting the arterial pressure and effective arterial blood volume to remain withinnormal limits8,9 (Fig. 1). In advanced stages of cirrhosis, systemic vascular resistance is markedly reduced, and additional increases in cardiac output cannot compensate, leading to underfilling of the arterial circulation.8 Moreover, there is evidence that cardiac output decreases as cirrhosis progresses.13 In advanced cirrhosis, arterial pressure must be maintained through the activation ofvasoconstrictor systems, including the renin–angiotensin system, the sympathetic nervous system, and, in late stages, nonosmotic hypersecretion of arginine vasopressin (antidiuretic hormone). These compensatory mechanisms help maintain effective arterial blood volume and relatively normal arterial pressure but have important effects on kidney function, particularly sodium and solute-free water retention,that may eventually lead to ascites and edema and to renal failure by causing intrarenal vasoconstriction and hypoperfusion.8,9 Indeed, renal failure rarely occurs in cirrhosis without ascites and is very frequent in advanced cirrhosis with ascites and edema. Studies in both laboratory animals and patients with cirrhosis suggest that bacte1279

n engl j med 361;13

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