Inappropriately low angiotensin II generation: a factor determining reduced kidney function and survival in patients with decompensated cirrhosis.
OBJECTIVE
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 m(2) 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.
Sansoé
Giovanni
G
Gastroenterology Unit, Gradenigo Hospital, C.so Regina Margherita 10, 10153 Torino, Italy. giovannisan@iol.it
Silvano
Stefano
S
Mengozzi
Giulio
G
Todros
Luca
L
Smedile
Antonina
A
Touscoz
Giovanni
G
Rosina
Floriano
F
Rizzetto
Mario
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000096:biosynthesis* / Q000097:blood; D000808:Angiotensinogen / Q000097:blood; D001810:Blood Volume; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011446:Prospective Studies; D012079:Renal Circulation; D012083:Renin / Q000097:blood; D016019:Survival Analysis
D000808:Angiotensinogen; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin