1. The metabolic clearance rate of arginine vasopressin was determined using a constant infusion technique in normal subjects and patients with chronic renal failure immediately before commencing dialysis. Endogenous arginine vasopressin was suppressed in all subjects before the infusion with a water load.
2. Plasma arginine vasopressin concentrations were determined using a sensitive and specific radioimmunoassay after Florisil extraction. The detection limit of the assay was 0.3 pmol/l, and intra- and inter-assay coefficients of variation at 2 pmol/l were 9.7% and 15.3%, respectively.
3. In normal subjects, the metabolic clearance rate was determined at two infusion rates producing steady-state concentrations of arginine vasopressin of 1.3 and 4.4 pmol/l. In the patients with renal failure, a single infusion rate was used, producing a steady-state concentration of 1.5 pmol/l.
4. At comparable plasma arginine vasopressin concentrations, metabolic clearance rate was significantly reduced in patients with renal failure (normal 1168 ± 235 ml/min versus renal failure 584 ± 169 ml/min; means ± sd; P<0.001).
5. Free water clearance was significantly reduced in normal subjects during the arginine vasopressin infusion from 8.19 ± 2.61 to −1.41 ± 0.51 ml/min (P<0.001), but was unchanged in the patients with renal failure after attaining comparable plasma arginine vasopressin concentrations.
6. In normal subjects there was a small but significant fall in metabolic clearance rate at the higher steady-state arginine vasopressin concentration (1168 ± 235 ml/min at 1.3 pmol/l versus 1059 ± 269 ml/min at 4.4 pmol/l; P = 0.016).
7. Our results show that the metabolic clearance rate of arginine vasopressin is reduced by approximately 50% in severe chronic renal failure. This alone may account for the raised plasma concentrations of the hormone seen in this condition.