ABSTRACT
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 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.
Subject(s)
Angiotensin II/biosynthesis , Kidney/physiopathology , Liver Cirrhosis/physiopathology , Adult , Aged , Aged, 80 and over , Angiotensin II/blood , Angiotensinogen/blood , Blood Volume , Case-Control Studies , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Liver/physiopathology , Liver Cirrhosis/blood , Liver Cirrhosis/metabolism , Male , Middle Aged , Peptidyl-Dipeptidase A/blood , Prospective Studies , Renal Circulation , Renin/blood , Survival AnalysisABSTRACT
BACKGROUND/AIMS: The role of angiotensin II (AT-II) type I receptor antagonists in the treatment of portal hypertension remains controversial. We tested the efficacy of Irbesartan (Irb) vs. Propranolol (Pro) in reducing portal pressure and evaluated its systemic haemodynamic effects. METHODS: Thirty-four patients were randomly assigned to receive either Irb 300 mg/day (19 patients) or Pro 40-120 mg/day (15 patients) for 2 months. RESULTS: Irb was discontinued in five patients (26%). No major side effect occurred in the Pro group. On an average, the portal pressure gradient decreased significantly more in the Pro than in the Irb group (median -19.5%, range -11/-31% vs. -4.8%, +2.5/-10%, P<0.001). A clinically significant decrease was seen in one (7%) of the patients given Irb vs. five (33%) given Pro (P<0.02). The fall in mean arterial pressure was significantly higher with Irb than with Pro (median -29%, range -15/-45% vs. -4.9%, +8/-19%, P<0.02). Irb significantly modified the blood creatinine clearance (median -29 ml/m, range +9/-61 ml/m, -30, -24/-35% P<0.0001 vs. basal). CONCLUSIONS: Irb offers no advantage over Pro in the control of portal hypertension. Moreover, its therapeutic profile is limited by important side effects.
Subject(s)
Antihypertensive Agents/administration & dosage , Biphenyl Compounds/administration & dosage , Hypertension, Portal/drug therapy , Liver Cirrhosis/complications , Propranolol/administration & dosage , Tetrazoles/administration & dosage , Adult , Aged , Angiotensin Receptor Antagonists , Antihypertensive Agents/adverse effects , Biphenyl Compounds/adverse effects , Blood Pressure/drug effects , Female , Humans , Hypertension, Portal/etiology , Hypotension/chemically induced , Irbesartan , Kidney/physiology , Male , Middle Aged , Tetrazoles/adverse effectsABSTRACT
The use of angiotensin II antagonists in the treatment of portal hypertension remains controversial. Our aims were to assess the effect of Irbesartan on portal pressure and to evaluate its safety in cirrhotic patients with portal hypertension. Twenty-five cirrhotic patients were treated in a pilot study with Irbesartan 300 mg orally once daily for 60 days. Hemodynamic evaluations and biochemical tests were performed before therapy and after two months of treatment. Three patients (12%) discontinued treatment for symptomatic arterial hypotension (mean arterial pressure -26.% +/- 3.1 versus basal). In the 18 responders, the hepatic venous pressure gradient diminished by a mean of 18.1% +/- 10.5 from baseline (p = 0.02); the gradient decreased by 20% or more in only 5 patients (23%). The mean arterial pressure decreased significantly during therapy (92 +/- 7 vs 109 +/- 25 mm Hg, P < 0.001). In conclusions, Irbesartan induced a marginal reduction in portal pressure and its safety was limited by the pronounced effects on arterial pressure.
