Inappropriately low angiotensin II generation: a factor determining reduced kidney function and survival in patients with decompensated cirrhosis

Background/Aims: Angiotensin II contributes to the post-glomerular arteriolar vasoconstriction which maintains the glomerular filtration rate (GFR) in renal hypoperfusion. To explore whether depressed angiotensin II generation, due to reduced angiotensinogen production or low angiotensin-converting enzyme (ACE) levels, could impair kidney function in advanced cirrhosis. Methods: We studied and prospectively followed up 21 diuretic-free ascitic cirrhotic patients, through these determinations: plasma levels of active renin (AR), renin activity (PRA), angiotensin II, ACE and aldosterone; renal clearances of sodium, inulin and para-aminohippurate; antipyrine clearance. Fifteen healthy subjects were also studied. Results: GFR distribution was bimodal, 10 patients had low GFR values (l-GFR group) and 11 had normal-GFR values (n-GFR group) (below and above 105 ml/min per 1.73 m2 body surface area). Antipyrine clearance and Child-Pugh score did not differ in the two patient groups. l-GFR group had higher AR and PRA values, lower ACE levels and a significantly higher AR/Angiotensin II ratio than n-GFR group (all P<0.01). All 21 patients showed increased values of the AR/PRA ratio, i.e. subnormal angiotensinogen levels (P<0.03). The 18-month survival rates of l-GFR and n-GFR groups were 20 and 81% (P<0.02). Conclusions: Low-GFR cirrhotic patients had a worse survival rate associated with more severe contraction of the effective arterial blood volume, higher AR/Angiotensin II ratio and lower ACE levels.