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

BACKGROUND: Early detection of renal dysfunction in cirrhosis is important and several renal biomarkers have been put forward. NGAL and Cystatin C are markers of renal dysfunction, but relations to splanchnic and systemic hemodynamics and kinetics are sparsely studied in cirrhosis.

AIMS: 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.

METHODS: 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.

RESULTS: 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 GFR (r = -0.56, p < 0.0001), and HVPG (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 SVR (r = -0.48, p < 0.05). Plasma Cystatin C correlated with HVPG (r = 0.45, p < 0.005), blood pressure (-0.40, p < 0.01), and GFR (r = 0.98, p < 0.000).

CONCLUSIONS: 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.