Renal Function in Compensated Hepatic Cirrhosis: Effects of an Amino Acid Infusion and Relationship with Nitric Acid

Abstract

Aims: 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 μmol/l; urinary NO in cirrhosis 6.2±1.3 vs. 3.1±2.3 μmol/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.

Non-Invasive Predictors of Portal Hypertension in Patients with Hepatitis C Virus Related Hepatocellular Carcinoma

“…Others (Zaman et al, 1999;Choi et al, 2003) found no relation between Doppler parameters and HVPG due to significant variability in portosystemic collateral patterns (Merkel et al, 1998). The significant differences were between groups as to splenic vein diameter, splenic vein cross sectional area, splenic vein mean flow velocity and splenic vein congestion index agreed with others (Rodriquez et al, 1999;El Zeiny et al, 2002;Kayacetin et al, 2004), but differed due to lower sample sizes (De Bem et al, 2006) or due to liver disease with bleeding varices (Choi et al, 2003).…”

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

“…In hypertensive patients with an activated renin-ANG system, unopposed activity of ANG II was not involved in the L-NAME-induced pressor response and renal vasoconstrictor response, whereas the L-NAME-induced decrease in GFR was enhanced, indicating a greater dependence of GFR on NO-mediated vasodilator tone during sodium depletion ( Van der Linde et al, 2003). In patients with hepatic cirrhosis and portal hypertension, GFR and effective renal plasma flow were lower than in the control subjects, and, under basal conditions, cyclic GMP and NO levels in plasma and urine were higher; the renal plasma flow change was more marked in the patient group and the GFR values were similar in both groups (Rodriquez et al, 1999). It was concluded that the increased cyclic GMP and NO levels in plasma and urine imply a maintained vasodilatory action that may at least partly compensate for the vasoconstrictor effect of ANG II in patients with hepatic cirrhosis and portal hypertension.…”

Nitric oxide and cirrhosis of the liver

“…98 Some authors described in patients with liver disease that this state of renal hyperfiltration is accompanied by a lack of response to an amino acid stimulus. 98 This lack of response was not observed in other studies 99,100 in which cirrhotic patients showed a response to amino acid infusion similar to that of controls.…”