Kidney, lower limb and whole-body uptake and release of catecholamines in alcoholic liver disease

Abstract

Regional (kidney, lower limb) and whole-body kinetics of endogenous noradrenaline (NA) and tritium-labelled L-noradrenaline (3H-NA) were determined in patients with alcoholic liver disease (one alcoholic hepatitis, 12 cirrhosis) and in control subjects (n = 6) in order to get information on the sympatho-adrenal system in liver disease. Arterial NA was significantly elevated in ascitic patients (median 2.5 nmol/l, n = 9, P less than 0.05) as compared to non-ascitic patients (1.6 nmol/l) and controls (1.7) nmol/l). NA spillover per unit NA inflow was increased in the kidney in patients with ascites (0.69 vs. 0.45 pmol/min.g per pmol/min.g in controls, P less than 0.005) but not in the lower limb (0.23 vs. 0.49 in controls, P less than 0.01). In patients with ascites the spillover rate of NA from the kidney into plasma (1.9 pmol/min.g) was significantly increased (P less than 0.02) compared to controls and non-ascitic patients (1.2 and 1.0 pmol/min.g, respectively. Patients and control kidneys and limbs extracted almost the same fraction of 3H-NA (0.34 vs. 0.32 NS and 0.34 vs. 0.37 NS, respectively). Whole-body clearance of 3H-NA was not significantly different in cirrhotics and controls (median 0.89 vs. 0.91 l/min.m2), indicating that the raised NA in decompensated cirrhosis reflects enhanced sympatho-adrenal activity rather than decreased metabolism of this amine. Our results do not point towards a uniform sympatho-adrenal overactivity in decompensated cirrhosis, but rather indicate regional differences with different order of NA spillover. The renal sympathetic overactivity, as indicated by the increased renal NA overflow, is likely to be important to the decreased renal perfusion and increased salt-water retention characteristic of this clinical condition.