Enhanced Enteric Excretion of Urate in Rats with Chronic Renal Failure

Abstract

1. The potential contribution of enteric pathways to the extra-renal excretion of uric acid in chronic renal failure was evaluated by measuring [14C]-urate and 36Cl− transport in isolated, short-circuited segments of jejunum, ileum and distal colon from normal rats and rats with chronic renal failure (five-sixths nephrectomized) 6 weeks after surgery. Plasma and urine creatinine and urate concentrations were also determined to establish urate status in chronic renal failure. 2. A 40% reduction in creatinine clearance was observed in the group with chronic renal failure, resulting in a two-fold increase in plasma creatinine concentration (0.064 ± 0.001 mmol/l, n = 9, to 0.120 ± 0.008 mmol/l, n = 14). In contrast, there was no change in plasma urate concentration, despite a 75% reduction in urate clearance. 3. The transport studies demonstrated alterations in intestinal urate transport in rats with chronic renal failure compared with normal rats. Net absorption of urate was observed in the distal colon of control rats, whereas a significant secretory flux was observed in rats with chronic renal failure (from 0.88 ± 0.16 to −1.62 ± 0.81 nmol h−1 cm−2, n = 12). Urate secretion was induced in the jejunum of the group with chronic renal failure (−0.15 ± 0.25 in control and −1.67 ± 0.35 nmol h−1 cm−2 in chronic renal failure, n = 11). Urate transport across the ileum was not altered in chronic renal failure and there was no net flux of urate in either the normal group or the group with chronic renal failure. Net Cl− absorption, which was observed in all segments of the control animals, was reversed to net secretion in chronic renal failure. 4. These studies indicate that urate homoeostasis is maintained in chronic renal failure and both the jejunum and colon may be actively involved in the extra-renal excretion of urate. These studies do not exclude the possibility that urate metabolic pathways are involved in urate homoeostasis in chronic renal failure.