Selective Renal Involvement in the Early Development of Hypercalcemia and Hypophosphatemia in VX-2 Carcinoma-bearing Rabbits: Studies on Serum and Tissues Alkaline Phosphatase and Renal Handling of Phosphorus 1,2

Skeletal, renal, and intestinal effects of VX-2 carcinoma in rabbits were studied in relation to the pathogenesis of a hypercalcemic and hypophosphatemic state induced by the tumor. On the basis of an initial screening, alkaline phosphatase was chosen as a biochemical marker for monitoring any change in the cellular activity of bone, kidney, intestine, and liver in the carcinoma-bearing rabbits. Renal function was also evaluated by measuring the tubular reabsorption of phosphorus. No significant changes in bone, duodenal, or liver alkaline phosphatase levels were detected at any time throughout the experiment. However, kidney cortex alkaline phosphatase activity was markedly depressed on the second week posttransplantadon, coinciding with hypophosphatasia of similar magnitude. No inhibitors of alkaline phosphatase were present in the circulation. Serum acid phosphatase as well as serum acid protease activities were uneffected by the tumor. Moderate hypercalcemia and hypophosphatemia developed on the third week posttransplantation and were associated with a significant depression of renal tubular reabsorption of phosphorus. Weight loss which accompanied the tumor growth was of minor importance in the development of hypophosphatasia and did not affect all the other parameters studied. The reported findings single out the kidney as an initially and primarily affected target organ in the carcinoma-bearing rabbits and indicate parathyroid-like effect of the tumor on renal function, namely, depressed tubular reabsorption of phosphorus. The metabolic consequences of the tumor action on its host in relation to calcium homeostasis are discussed, with special reference to the possibility of parathyroid-like hormone involvement.