Robert M. Friedler

Acute renal failure due to nontraumatic rhabdomyolysis.

Twenty-one patients developed acute renal failure in association with nontraumatic rhabdomyolysis and myoglobinuria. The illness followed an overdose of ethanol, heroin, or other depressant drug in 18 patients. Lethargy or coma was present in 17 patients and muscle swelling in 11. Evidence of rhabdomyolysis included markedly elevated creatine phosphokinase, myoglobinuria, and aldolase in blood. Initial biochemical findings were similar to those of acute renal failure due to other causes, but the abnormalities were exaggerated. There was a disproportionate rise in serum creatinine concentration in relation to serum urea nitrogen concentration. Profound hyperuricemia was present in most patients. Transient hypercalcemia developed during the diuretic phase in 5 patients. One patient died. We conclude that nontraumatic myoglobinuria with acute renal failure is not infrequent and may occur after an overdose of ethanol or heroin. The disease has good prognosis despite severe hypercatbolism and untreated profound hyperuricemia.

The effects of combined renal vasodilatation and pressor agents on renal hemodynamics and the tubular reabsorption of sodium.

Combination of renal vasodilation and angiotensin infusion effect large changes in renal hemodynamics, excretion and reabsorption of sodium in anesthetized hydropenic dogs

Factors affecting sodium reabsorption by the proximal tubule as determined during blockade of distal sodium reabsorption.

Changes in the tubular reabsorption of sodium independent of aldosterone activity may play an important role in determining sodium excretion. Several studies in the dog employing clearance techniques have demonstrated that infusions of isotonic saline (1-5) or plasma-like solutions (1, 2) result in a depression of the overall net tubular reabsorption of sodium as the excretion of sodium increases. Dirks, Cirksena, and Berliner have demonstrated by micropuncture studies in the dog that this depression of tubular reabsorption during the infusion of saline occurs specifically in the proximal tubule (6). These same authors reported that acute constriction of the thoracic inferior vena cava, a maneuver known to inhibit sodium excretion and to lead to chronic sodium retention and the formation of ascites (7), prevents this depression of proximal reabsorption during saline infusion (8). Such studies indicate that nonaldosterone factors determining the rate of sodium reabsorption by the proximal tubule could play a major role in the normal physiologic regulation of sodium balance and also may be involved in the pathogenesis of sodium retention in disorders characterized by the accumulation of as-cites and edema. Although the factors that determine the rate of proximal tubular reabsorption are unknown, recent studies from our laboratory have demonstrated that renal vascular resistance and perfusion pressure may affect the overall tubular reabsorp-tion of sodium (9). Extension of these studies in dogs with caval constriction has indicated that increased arterial pressure in the presence of reduced renal vascular resistance decreases the net tubular reabsorption of sodium and may completely overcome the impaired response to saline infusion resulting from both acute and chronic constriction of the thoracic inferior vena cava (10). Such studies employing clearance techniques have not revealed whether these hemo-dynamically induced changes in the reabsorption of sodium occur in the proximal nephron, the site at which micropuncture studies indicate a depression in reabsorption in response to extracellular volume expansion, and an increased reabsorption in the presence of acute constriction of the thoracic inferior vena cava. In the present series of studies we have attempted to examine some of the factors that may affect the reabsorption of sodium in the proximal tubule. In the presence of complete, or nearly complete, interference with sodium reabsorption in the distal nephron by natriuretic agents which appear to have little or no effect on the proximal reabsorption of sodium, it should be possible to observe the effects of other maneuvers that independently …

Studies on the mechanism of natriuresis accompanying increased renal blood flow and its role in the renal response to extracellular volume expansion.

Effect of unilateral renal vasodilatation on sodium excretion by infusing acetylcholine into renal artery of dogs

Changes in Renal Blood Flow and Possibly the Intrarenal Distribution of Blood during the Natriuresis Accompanying Saline Loading in the Dog

ing limb of Henles loop, resulting in the delivery of a larger volume of fluid of lower sodium concentration to the transport sites of the ascending limb of the loop. The present studies were undertaken to determine if a relationship could be demonstrated between changes in the tubular reabsorption of sodium and changes in renal blood flow. It was observed that the increased excretion of sodium during isotonic expansion of the extracellular volume was uniformly associated with increased renal blood flow, independent of spontaneous changes in glomerular filtration rate. Furthermore, changes in the net tubular reabsorption of sodium, which were demonstrated both spontaneously during the course of saline loading and during controlled unilateral reductions of renal blood flow, were associated with inverse changes in that portion of renal plasma flow from which p-amino

Studies on Mechanisms of Hypocalcemia of Magnesium Depletion

Studies were carried out to evaluate the mechanism of hypocalcemia in magnesium depletion. Day old chicks fed a magnesium deficient diet developed marked hypocalcemia, with a direct relation between serum calcium (y) and magnesium (x): y = 2.68 x + 4.24, r = 0.84 (both in mg/100 ml). Injections of parathyroid extract that increased serum calcium 2-3 mg/100 ml in normals had no effect in Mg-depleted birds. Very large dietary supplements of calcium or vitamin D(3) increased mean serum calcium only from 5.3 to 7.7 and 7.8 mg/100 ml, respectively, while a normal magnesium diet for 3 days increased calcium from 5.3 to 9.9 mg/100 ml despite absence of dietary calcium. Intestinal calcium transport, studied in vitro, and the calcium concentration of the carcass was significantly increased in magnesium-depleted chicks, making it unlikely that reduced intestinal absorption of calcium caused the hypocalcemia. In magnesium-deficient chicks, the bone content of magnesium was decreased by 74%, the calcium content was unchanged, and the cortical thickness of bone was markedly increased. After 3 days of magnesium-repletion, cortical thickness was reduced with increased endosteal resorption. There was an increase in unmineralized osteoid tissue in the magnesium-depleted chicks. Parathyroid gland size and histology did not differ in magnesium-depleted and control birds. The results suggest that hypocalcemia develops due to altered equilibrium of calcium between extracellular fluid and bone, favoring increased net movement into the latter. Failure of parathyroid gland function could also exist, and unresponsiveness to parathyroid hormone (PTH) may also contribute to the hypocalcemia. However, failure of PTH action is probably due to the presence of excess osteoid tissue rather than a primary event leading to hypocalcemia.

Observations on the Mechanism of Decreased Tubular Reabsorption of Sodium and Water during Saline Loading

Boston, Mass.) It has been demonstrated by several recent studies that the regulation of sodium excretion involves factors other than the total filtered load of sodium and the renal tubular effects of mineralocorticoids. Contrary to earlier suggestions that an increase in the filtered load of sodium may be sufficient to account for the natriuresis of saline loading in the dog, de Wardener, Mills, Chapman, and Hayter (1) reported that the administration of saline to dogs receiving an exogenous mineralocorticoid results in an increased excretion of so

Effect of Renal Denervation and a-Adrenergic Blockade on Sodium Excretion in Dogs with Chronic Ligation of the Common Bile Duct

Summary Chronic ligation of the common bile duct (CBDL) is dogs causes sodium retention and a blunted natriuretic response to extracellular volume expansion (ECVE). Since increased sympatho-adrenal activity plays an important role in other sodium retaining states, the present study was undertaken to evaluate the role of renal denervation and a-adrenergic blockade on the renal handling of sodium in dogs with CBDL. Both renal denervation and the infusion of dibenzyline into the renal artery produced a slight but significant increment in urinary sodium excretion, but these changes were not different from those observed after renal denervation in normal animals. Also, these procedures did not improve the response to saline infusion in dogs with CBDL. These data indicate that the sympatho-adrenal activity does not play an important role in the salt retaining state that follows chronic ligation of the common bile duct. Anne Harrington and Miriam Bick provided technical help and Mrs. Catherine Hoyt provided secretarial assistance.

Spontaneous variations in electrolyte excretion in the awake dog.

Summary The daytime pattern of renal excretion of electrolytes in normal and thyroparathyroidectomized dogs is similar. Marked changes in the excretion of phosphorus were observed with dissociation from the patterns of excretion of sodium and calcium. The fractional excretion of phosphorus varied from 0.01 to 0.35 independent of parathyroid hormone or changes in serum phosphorus. Technical assistance was provided by John Steppe, Ernest Tallos, and Sandy Howard. Mrs. Catherine Hoyt provided valuable secretarial assistance and Nicholas Bolotine prepared the illustrations.