Long-term administration of isosorbide-5-mononitrate does not impair renal function in cirrhotic patients.
Isosorbide-5-mononitrate (Is-5-Mn), alone or combined with beta-blockers, has been proposed for prophylaxis of variceal bleeding in cirrhosis. However, renal insufficiency, might be an important undesirable effect of this therapy, especially in patients with ascites. We assessed the changes in renal function induced in 26 cirrhotic patients by acute or chronic administration of Is-5-Mn. The acute administration of 20 mg of Is-5-Mn to 21 patients reduced mean blood pressure (83.4 +/- 2.4 vs. 92.8 +/- 3.4 mm Hg, P < .001), urine volume (5.5 +/- 0.8 vs. 8.7 +/- 1.1 mL/min, P < .05), urine sodium excretion (114 +/- 19 vs. 244 +/- 41 muEq/min, p < .001), urine potassium excretion (41 +/- 3.4 vs. 67 +/- 8.5 muEq/min, P < .001), and atrial natriuretic factor (74 +/- 10 vs. 98 +/- 12 pg/mL, P < .005). The glomerular filtration rate was decreased in the 11 patients with ascites (57 +/- 9 vs. 68 +/- 12 mL/min, P < .05), and plasma renin activity was increased in 4 ascitics. Twenty-one patients (16 from the acute study + 5 other patients) were given Is-5-Mn for 3 months at the dose of 80 mg/d. This did not affect blood pressure and renal function in patients without ascites, but reduced mean blood pressure (91.9 +/- 3.4 vs. 89.6 +/- 3 mm Hg, P < .05), urine volume (5.8 +/- 1.1 vs. 3.4 +/- 0.9 mL/min, P < .05), and urine sodium excretion (205 +/- 38 vs. 99 +/- 16 muEq/min, P < .01) in those with ascites. There were no changes in glomerular filtration rate and renal plasma flow, while plasma renin activity increased in only 3 patients with ascites and 1 without. Systemic hemodynamics and renal function of cirrhotic patients, especially those with ascites, are affected adversely by acute administration of Is-5-Mn. Long-term administration of the drug is well tolerated by compensated patients and does not affect renal plasma flow nor glomerular filtration rate, but can induce hypotension and sodium retention in patients with ascites.
Salerno
F
F
Istituto di Medicina Interna, Università degli Studi di Milano, Italy.
Borroni
G
G
Lorenzano
E
E
Solenghi
D
D
Cazzaniga
M
M
Bissoli
F
F
Ceriani
R
R
deFranchis
R
R
D001201:Ascites / Q000209:etiology; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D017595:Renal Plasma Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*
D014665:Vasodilator Agents; D009320:Atrial Natriuretic Factor; D012083:Renin; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D011188:Potassium