Hepatorenal syndrome: a disease mediated by the intrarenal action of renin.

The functional renal failure accompanying advanced liver disease is characterized by azotemia, a urine of very low sodium concentration and systemic hypotension with decreased renal perfusion and high renal vascular resistance. Patients with this disorder have a markedly reduced ability to excrete free water and develop hyponatremia, ascites and edema. It is postulated that this renal dysfunction is due to hepatic failure to make renin substrate. Renin released from the kidney is thus unable to exert its pressor effect. The resultant hypotension and renal hypoperfusion continue to stimulate excessive synthesis and release of renin. It is postulated that the overdriven renal renin system increases renovascular resistance at the level of the glomerular arterioles. This causes decreased renal blood flow and decreased glomerular filtration rate leading to salt and water retention and azotemia. Since no renin substrate is available for human infusion, this hypothesis could be tested either by infusion of angiotensin II to restore systemic blood pressure and renal perfusion or by beta adrenergic blockade with propranolol to attempt to decrease the intrarenal effects of renin, restore glomerular blood flow and filtration and thus return of renal function.