On the Mechanism of Hyposthenuria in Hypercalcemia*

Abstract

The renal concentrating defect associated with hypercalcemia was studied in vitamin D-intoxicated rats and hamsters by clearance and micro-puncture methods simultaneously. During brisk mannitol diuresis, the osmolality of early distal tubular fluid was as hypotonic to plasma in the hypercalcemic rats as in the normal controls. No evidence was found of excessive loss of Na in the urine, whether Na excretion was compared at the same absolute rates of osmolar clearance or osmolar clearance per intact nephron (COsm/100 ml GFR). These observations thus failed to demonstrate any localized or generalized impairment of Na transport by the tubules. The osmolality of collecting duct fluid from the papilla of hypercalcemic hamsters with a severe concentrating defect was approximately the same as that of fluid from adjacent loops of Henle and vasa recta. This finding indicates that the concentrating defect in hypercalcemia need not be accompanied by a selective impermeability of the collecting ducts to water. The total amount of Na delivered to the medulla per unit time was much less in the hypercalcemic rats than in the controls because of a marked reduction in GFR (glomerular filtration-rate) and unimpaired reabsorption of the glomerular filtrate by the proximal tubules. We assume this to be an important factor in the concentrating defect. The observations are compatible with the view that the total number of functioning nephrons is reduced due to blockage of tubules by casts, whereas the ability to transfer Na and water remains essentially intact in the remaining nephrons. It is postulated that a higher osmotic load per intact nephron could account for the fall in Umax under hydropenic conditions and the excretion of normal amounts of Na during mannitol diuresis in spite of the large reduction in filtered Na.