Effect of Citrate Infusion on Urinary Aluminium Excretion in the Rat

Abstract

1. Seven pairs of rats received 1 mmol/l aluminium citrate in their drinking water 5 days before the experiments. Five additional rats were treated identically. Six rats received the same food but drank distilled water. 2. After a 6 h fast, the animal was anaesthetized, the jugular vein and femoral artery were cannulated and the bladder was catheterized, after which an intravenous infusion of Hartmann's solution containing [14C]inulin was begun. The urine was collected at 20 min intervals and 1 ml of arterial blood was obtained before the end of each collection. After at least two basal collections, the infusion was modified to contain, in addition, 5 mmol/l NaHCO3 (control) or 5 mmol/l sodium citrate (experimental). The infusion rate, constant in each pair, differed between pairs across the range 60–125 μmol/min. 3. A total of eight collections was made per animal and urine flow, glomerular filtration rate, plasma and urinary aluminium and citrate were measured. 4. Control and experimental rats had a higher mean basal plasma aluminium level (0.39 ± 0.21 μmol/l) than the six rats receiving distilled water (0.16 ± 0.14 mmol/l, P < 0.001). The corresponding urinary aluminium excretion rates were similar (46 ± 31 and 47 ± 23 pmol/min, respectively). There was no significant difference between the basal values of any variable in the control and experimental rats. No significant change was observed in any variable during the infusion of NaHCO3 (controls). Among the experimental rats, there was no significant change in urine flow, glomerular filtration rate or plasma aluminium level. However, the plasma citrate level rose rapidly with the infusion to approach a plateau value in each case, and there were slower rises in urinary citrate and aluminium excretion rates. A renal threshold for citrate appeared to occur at a plasma level of approximately 0.25 mmol/l. The aluminium excretion rate was directly related to the citrate excretion rate (P < 0.01) and the increase in urinary aluminium excretion rate above the basal state was even more closely related (P < 0.001). 5. In the five additional animals pretreated with aluminium, the median ultrafiltrable aluminium was 20% (range 17–24%) of the total plasma level and no change was produced by citrate infused at the maximal rate. The plasma protein concentration also remained unchanged despite the fluid load. 6. We conclude that increased urinary citrate excretion is directly associated with an increase in aluminium excretion in aluminium-loaded animals. The data suggest that this increased excretion is independent of filtered load of aluminium and may therefore be the result of changes in handling of the metal within the kidney.