Serum and urinary nitrate levels in liver cirrhosis: endotoxemia, renal function and hyperdynamic circulation

Background/Aims: The relationship between nitric oxide production, endotoxemia, renal function and hyperdynamic circulatory syndrome has not been yet investigated in patients with cirrhosis. Methods: Serum and urine nitrate, endotoxemia and cardiac index were measured in 59 patients with cirrhosis. Results: Patients with a tense ascites had higher serum nitrate levels than health control subjects (39±7 vs 19±4 μmol/l, p<0.01). Patients with mild ascites and without ascites had normal values of nitrate levels. In the group of patients not treated with diuretics (n=38), creatinine and nitrate clearances were lower in ascitic patients than in nonascitic patients (respectively 0.82±0.12 vs 1.48±0.32 ml/s, p<0.02 and 0.30±0.07 vs 2.89±2.04 ml/s, p<0.05). Endotoxin levels were higher in patients with cirrhosis than in control subjects and paralleled the severity of liver failure (Child A/B/C vs control subjects: 0.056±0.014/0.064±0.005/0.090±0.008 vs 0.027±0.005 Endotoxin Units/ml, p<0.001). Serum nitrate levels did not correlate with endotoxemia (r=0.110). On the other hand, levels of orosomucoid, a protein synthesized by the liver in response to a stimulation by cytokines correlated with those of nitrate (respectively r=0.343, p<0.01). Hemoglobin levels were negatively correlated with serum nitrate levels (r=−0.328 p<0.02). Cardiac index was higher in patients than in control subjects and paralleled the degree of liver failure (Child A/B/C vs control subjects: 3.60±0.25/4.10±0.19/4.47±0.25 vs 3.15±0.12 l•min•m2, p<0.001). Cardiac index did not correlate with serum nitrate levels, urine nitrate excretion and endotoxemia. Conclusions: Renal impairment accounts for the increased levels of serum nitrate in ascitic patients. A stimulation of nitric oxide production by cytokines may occur but endotoxemia is not involved in such a mechanism. Anemia has a role in nitric oxide activity. Nitric oxide generation assessed by nitrate in serum and urine does not seem to participate in the hyperdynamic circulatory syndrome in patients with cirrhosis.