On the Mechanism of Hyposthenuria in Hypercalcemia * NORMAN BANK t AND HAGOP

Loss of renal concentrating ability is a wellknown consequence of hypercalcemia (1). On the basis of experimental observations in animals (2-5) and man (6-8), it has been suggested that one or more specific functional abnormalities of the renal tubules underlie the concentrating defect. The abnormality proposed most often is that the collecting ducts become relatively impermeable to water (3-8). It has also been suggested that sodium transport is impaired at some site in the tubule which contributes to creating and maintaining high concentrations of sodium in the interstitial fluids of the medulla and papilla (4). Aside from these specific transport abnormalities, the possibility exists that obstruction of tubules by intraluminal casts (9) and the consequent decrease in number of functioning nephrons may play an important role in the hyposthenuria. In the present study, hypercalcemic nephropathy was studied in vitamin D-intoxicated rats and hamsters by utilizing clearance and micropuncture methods simultaneously. The data failed to reveal any evidence of either impaired sodium transport by the tubules or impermeability of the collecting ducts to water. The total amount of sodium delivered to the medulla per unit time was markedly diminished since glomerular filtration rate (GFR) was reduced and reabsorption of the glomerular filtrate by the proximal tubules was unimpaired. It is postulated