On the Mechanism of Impairment of Renal Concentrating Ability in Hypercalcemia*

Abstract

A decrease in the ability of the kidneys to concentrate the urine is characteristic of many varieties of experimental and clinical hypercalcemia, hypercalciuria and nephrocalcinosis (1). Vitamin D intoxication in rats (2) and large doses of parathyroid extract in dogs (3, 4), in addition to producing hyposthenuria, have been shown to cause morphological changes which are most marked in the epithelial cells lining the collecting ducts but are also present in the distal convoluted tubules and the loops of Henle. Such lesions might impair renal concentrating capacity by interfering with the accumulation and concentration of sodium in the interstitial fluids of the medulla and papilla, or by impairing the back-diffusion of water from the lumen of the collecting duct into a hypertonic interstitium (5).In the present studies the composition of renal cortex, medulla and papilla was compared with that of plasma and urine in hydropenic rats in which hypercalcemia had been induced by large doses of vitamin D. The results indicate that the hyposthenuria observed in such animals results at least in part from a diminished concentration of sodium in renal medulla and papilla. MATERIALS AND METHODSWhite male Sprague-Dawley rats weighing 150 to 200 g were fed a synthetic diet containing liberal amounts of sodium and potassium (6).

Effects of Colchicine and Vinblastine on the Cellular Action of Vasopressin in Mammalian Kidney A POSSIBLE ROLE OF MICROTUBULES

“…-It is unlikely that the alkaloids damaged the renal tubules since the excretion of sodium, potassium, and creatinine was unaffected and no glucosuriaor proteinuria was detected. Hypercalcemia can inhibit the response to vasopressin (24). In our control experiment, no changes in serum calcium were observed in colchicine-treated rats; Henneman, Montierth, and Nichols reported that colchicine caused hypocalcemia in rats (13).…”

On the Mechanism of Hyposthenuria in Hypercalcemia*

“…On the basis of experimental observations in animals (2-5) and man (6)(7)(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)(4)(5)(6)(7)(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).…”

“…The abnormality proposed most often is that the collecting ducts become relatively impermeable to water (3)(4)(5)(6)(7)(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.…”

A tribute to Franklin H. Epstein

“…I was attracted to Yale partly because of Frank's research, and he invited me to lunch at a nearby restaurant that day. He talked about his new studies on the effects of water diuresis on susceptibility to pyelonephritis (1) and his previous JCI papers on the mechanism of impaired concentrating ability in hypokalemia and hypercalcemia (2,3). I was struck by Frank's clarity and intellectual rigor, his capacity to probe complex renal and electrolyte disorders, and his sheer brilliance.…”