Parenteral aluminum administration in the dog: I. Plasma kinetics, tissue levels, calcium metabolism, and parathyroid hormone

Parenteral aluminum administration in the dog: I. Plasma kinetics, tissue levels, calcium metabolism, and parathyroid hormone. Aluminum (Al) may cause both osteomalacia and encephalopathy in dialysis patients. Little is known about the biology of Al. This study examined the initial distribution kinetics of Al and its biological effects after injections of 1 mg/kg/day into dogs for 3 to 5 weeks. Following one intravenous dose, the plasma half-life (x ±SE) was 276 ± 51.8 min, with an apparent volume of distribution of 1.30 ± 0.17 liters or 5.90 ± 0.30% body wt; 10 to 21% of administered Al was excreted in the urine over 150 min, and the renal contribution to plasma clearance of Al correlated with GFR (r = 0.77, P < 0.05). The total plasma clearance of Al (4.43 ± 2.83 ml/min) exceeded the renal contribution to plasma clearance (1.94 ± 0.36 ml/min) in each dog, and in only two instances did the renal contribution reach 50% of total plasma clearance. Serum calcium rose from 9.4 ± 0.2 to 11.1 ± 0.3 mg/dl and immunoreactive parathyroid hormone (iPTH) fell by 27 ± 4% following one Al injection. With repeated Al injections, serum calcium increased from baseline levels of 10.2 ± 0.07 mg/dl to 11.1 ± 0.22 and 11.3 ± 0.46 mg/dl after 1 and 2 weeks, respectively. Renal function declined in all dogs, and serum creatinine exceeded 3.5 mg/dl in four; over the 5 weeks of study, serum calcium correlated with serum creatinine (r = 0.91, P < 0.001). Liver, kidney, and spleen showed the highest tissue content of Al, and there was substantial uptake by bone; the parathyroid content of Al was modest. Serum iPTH levels were normal or elevated, and the response of serum iPTH to EDTA-induced hypocalcemia was not reduced by Al treatment. These data show substantial tissue retention of Al with repeated Al injections. The renal excretion of Al was limited, probably due to extensive plasma protein and tissue binding. Parenteral Al caused marked disturbances in calcium metabolism and renal function, but the PTH response to hypocalcemia was not impaired. Administration parentérale d'aluminium chez le chien: I. Cinétique plasmatique, niveaux tissulaires, le métabolisme calcique, et l'hormone parathyroidienne. L'aluminium (Al) peut entraîner une ostéomalacie et une encéphalopathie chez des hémodialysés. On sait peu de choses sur la biologie de l'Al. Cette étude a examiné la cinétique de distribution initiale de l'Al et ses effets biologiques après des injections de 1 mg/kg/jour à des chien