Neutrophil gelatinase-associated lipocalin and cystatin C in cirrhosis and portal hypertension: Relations to organ extraction and dysfunction.

Abstract

Early detection of renal dysfunction in cirrhosis is important, and several renal biomarkers have been put forward. Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C are markers of renal dysfunction, but relations to splanchnic and systemic hemodynamics and kinetics are sparsely studied in cirrhosis. In patients with cirrhosis and portal hypertension, we studied plasma levels and renal, hepatic, and peripheral extraction of NGAL and cystatin C and relations to patients characteristics, liver dysfunction, and hemodynamics. Forty-five cirrhotic patients (Child class A/B/C:15/15/15) and 15 controls were evaluated with a full clinical, biochemical, and hemodynamic assessment. Urine and regional plasma concentrations of NGAL and cystatin C were measured. There was no significant difference in circulating or hepatic NGAL or cystatin C between all patients and controls but a trend towards increased levels with increasing Child class. In addition, there was a significant renal but no hepatic or systemic extraction of both NGAL and cystatin C (P < 0.001). Plasma NGAL correlated with glomerular filtration rate (r = -0.56, P < 0.0001), and hepatic venous pressure gradient (r = 0.34,P = 0.02) and urinary NGAL correlated with heart rate (r = 0.58, P= 0.007), blood pressure (r = -0.46, P < 0.05), cardiac output (r = 0.45, P < 0.05), and systemic vascular resistance (SVR) (r = -0.48, p < 0.05). Plasma cystatin C correlated with hepatic venous pressure gradient (r = 0.45, P < 0.005), blood pressure (-0.40, P < 0.01), and glomerular filtration rate (r = 0.98, P < 0.000). Extractions of NGAL and cystatin C levels seem largely unaffected by the severity of liver disease in cirrhosis with a renal extraction. These biomarkers therefore have the potential of being both valuable in diagnosing renal failure and reflecting the degree of portal hypertension and systemic haemodynamic changes.