Relative role of bone and kidney in the hypercalcaemia associated with the rat Walker carcinosarcoma 256

The rat Walker carcinosarcoma 256 is an animal model for humoral hypercalcaemia of malignancy (HHM). In this model, the relative contribution of bone and kidney in the hypercalcaemia of tumour-bearing rats was investigated. Daily administration of pamidronate, a bone resorption inhibitor, for 2 days prevented the increased fasting Ca2+ excretion observed in the hypercalcaemic rats, although serum Ca2+ remained high. However, the high serum Ca2+ normalised after the acute injection of ethiofos, an inhibitor of renal Ca2+ reabsorption, which was associated with a marked increase of Ca2+ excretion. Changes in Ca2+ were accompanied by similar changes in Mg2+. The results indicate that altered renal Ca2+ handling has a key role in the hypercalcaemia associated with this HHM model.