Renal function in compensated hepatic cirrhosis: effects of an amino acid infusion and relationship with nitric acid.
OBJECTIVE
In order to assess the possible participation of nitric oxide (NO) in renal function during compensated hepatic cirrhosis, we studied renal function, the plasma and urinary levels of cGMP and the concentration of nitrates and nitrites, as markers of NO synthesis in blood and urine, in 10 patients with Child A hepatic cirrhosis as compared with 10 control subjects, both under basal conditions and during stimulation (amino acid-induced glomerular hyperfiltration).


METHODS
To study renal function, the glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal functional reserve (RFR), renal venous resistance (RVR) and the filtration fraction (FF) were measured. Renin and aldosterone levels were determined to assess the possible involvement of these compounds in the renin-angiotensin-aldosterone axis.


RESULTS
GFR and ERPF were significantly lower in the patients with cirrhosis than in the controls (mean GFR: 82+/-12.3 vs. 105+/-15 ml/min, p = 0. 01; ERPF 452+/-86 vs. 543+/-56 ml/min, p = 0.002). The RFR value was similar in both groups. In the basal situation cGMP levels were higher in plasma and urine in patients with cirrhosis than in the controls (plasma cGMP in cirrhosis 8.4+/-2.4 vs. 4.2+/-3.5 pmol/ml; urine cGMP in cirrhosis 1.2+/-2.1 vs. 0.68+/-0.1 pmol/ml). The NO levels were also higher in plasma and urine in patients with cirrhosis vs. controls (plasma NO in cirrhosis 45.5+/-9.2 vs. 30. 3+/-1.2 micromol/l; urinary NO in cirrhosis 6.2+/-1.3 vs. 3.1+/-2.3 micromol/ml). In both groups the amino acid perfusion increased GFR, ERPF, cGMP and NO levels in plasma and urine. In the patients with cirrhosis the RVR decreased significantly during perfusion and no noteworthy changes in FF were observed. The GFR values observed during amino acid perfusion were similar in patients with cirrhosis and portal hypertension to those observed in the controls (27.2+/-12 vs. 25.3+/-16%). However, the changes induced the ERPF were more marked in patients with cirrhosis (cirrhosis 35.3+/-15 vs. 22. 2+/-13%, p = 0.02).


CONCLUSIONS
The present findings point to certain alterations in renal function in patients with hepatic cirrhosis and portal hypertension without ascitis, a clear difference being visible between the ERPF and GFR following amino acid-induced stimulation. The significant elevation in cGMP and NO levels in plasma and urine implies a maintained vasodilatory action that may at least partly compensate the vasoconstrictor effects of angiotensin II.
Rodriquez
A
A
Departmento de Medicina, Hospital Clinico Universitario, Salamanca, España.
Martin
A
A
Oterino
J A
JA
Blanco
I
I
Jimenez
M
M
Perez
A
A
Novoa
J M
JM
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006157:Guanosine Monophosphate / Q000032:analysis*; D006801:Humans; D007262:Infusions, Intravenous; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011336:Probability; D012016:Reference Values; D017596:Renal Plasma Flow, Effective / Q000187:drug effects*; D012720:Severity of Illness Index
D000596:Amino Acids; D009569:Nitric Oxide; D006157:Guanosine Monophosphate