Possible pathophysiological mechanisms are as follows: (1) Circulatory disturbance caused by liver dysfunction and portal hypertension can lead to renal hypoperfusion; (2) an afferent arterial vasoconstriction caused by inadequate effective circulatory volume and renin–angiotensin–aldosterone activation; and (3) the formation of intratubular bile casts and the direct bilirubin tubular toxicity (37). This evidence concerns the gene REN and portal hypertension.