Charles R. Kleeman

Diuretic-Induced Hyponatremia

Abstract Severe hyponatremia (serum Na, 91 to 120 mEq/liter) secondary to the use of diuretics was observed in 25 nonedematous patients with clinically normal hydration and creatinine clearances; i...

Skeletal Resistance to Parathyroid Hormone in Renal Failure: Studies in 105 Human Subjects

Abstract The effects of an infusion of parathyroid extract on serum calcium and urinary phosphate levels were evaluated in 105 individuals—normal persons, patients with renal failure, patients trea...

EFFECT OF VARIATIONS IN SODIUM INTAKE ON CALCIUM EXCRETION IN NORMAL HUMANS.

Summary The effect of variations in excretion of sodium on calcium excretion and clearance has been studied in 6 normal humans. The excretion of sodium was altered by varying the salt content of the diet. A direct relationship between calcium excretion and clearance and the simultaneous sodium excretion was demonstrated. These studies emphasize the importance of measuring sodium excretion in any investigation of the regulation of calcium excretion.

THE INFLUENCE OF BODILY HYDRATION ON THE RENAL CONCENTRATING PROCESS

Although the ability of the kidneys to produce a concentrated urine is widely used in the clinic as a measure of renal function, there have been few systematic studies of factors affecting maximum urinary concentration in normal persons. It is clear that a major influence on renal reabsorption of water is exerted by the antidiuretic hormone of the posterior pituitary (ADH); however, Shannon pointed out that, even in the absence of exogenous or endogenous Pitressin®, dogs with diabetes insipidus could elaborate a concentrated urine when they were severely dehydrated (1). It has been observed repeatedly that injecting large amounts of posterior pituitary substance into hydrated normal subjects does not produce as concentrated a urine as does prolonged dehydration (2-6). The present experiments were designed to explore some of the effects of bodily hydration in altering the response of normal kidneys to maximumdoses of ADH. The results indicate that chronic underhydration as well as prolonged forcing of fluids drastically modify the ability of the kidneys to reabsorb water and to concentrate solutes in the urine.

The influence of extracellular volume expansion on renal phosphate reabsorption in the dog

Extracellular volume expansion (ECVE) was produced, by normal saline infusion, in five normal and six thyroparathyroidectomized anesthetized dogs while glomerular filtration rate was reduced by the inflation of an intra-aortic balloon located above the renal arteries. The effect of ECVE on the maximum renal tubular reabsorptive capacity of phosphate (phosphate Tm) was also evaluated in five additional dogs. During ECVE, phosphate excretion increased both in normal and thyroparathyroidectomized dogs, and a direct and significant correlation was found between the fractional excretion of phosphate and sodium. Despite a substantial decrease in filtered phosphate which is produced by the acute reduction in glomerular filtration rate, phosphate excretion, during ECVE, exceeded control values. ECVE was associated with a reduction in phosphate Tm. The results demonstrate that ECVE increases phosphate excretion independent of changes in glomerular filtration rate and parathyroid gland activity. The data indicate that ECVE produced by saline infusion decreases the renal tubular reabsorption of phosphate.

Evidence for suppression of parathyroid gland activity by hypermagnesemia

The effect of hypermagnesemia, produced by MgCl(2) infusion, on the activity of parathyroid glands, as assessed by changes in levels of serum calcium (S(Ca)) and in the fraction of filtered phosphate excreted (C(P)/C(Cr)), was studied in 11 intact and 4 thyroparathyroidectomized (T-PTX) dogs. To exclude the effect of diurnal variation in C(P)/C(Cr) on the results, studies were initiated in both morning and afternoon hours and each study with MgCl(2) infusion was paired with a control experiment in the same dog not receiving MgCl(2). During MgCl(2) infusion, serum phosphorus rose progressively. Despite this rise, the levels of C(P)/C(Cr) fell in all experiments and were significantly different from values observed at the same time of the day in the paired control experiments. The concentrations of total S(Ca) fell by 1.0-2.4 mg/100 ml with a proportional decrease in the levels of the diffusible and ionized fractions. The pattern of the fall in C(P)/C(Cr) during MgCl(2) resembled that observed after CaCl(2) infusion (seven dogs) and that which acutely followed thyroparathyroidectomy (seven dogs). When parathyroid extract was given to dogs receiving MgCl(2) infusion both C(P)/C(Cr) and S(Ca) rose, and MgCl(2) infusion did not affect C(P)/C(Cr) and S(Ca) in T-PTX dogs. These results indicate that hypermagnesemia suppresses the activity of the parathyroid glands, probably, by inhibiting production and (or) release of the hormone, without interfering with end-organ response. An increase in serum magnesium of 1.7-2.0 mg/100 ml was capable of producing the suppressive effect. Evaluation of the effect of simultaneous modest hypocalcemia and hypermagnesemia suggests that a decrease in the level of serum calcium is more potent than an increase in the concentration of serum magnesium in the regulation of parathyroid activity.

Mechanisms of Impaired Water Excretion in Adrenal and Pituitary Insufficiency. IV. Antidiuretic Hormone in Primary and Secondary Adrenal Insufficiency

The exact mechanism (s) responsible for the impaired water diuresis of primary and secondary adrenal cortical insufficiency is still unknown. Previous studies from this (1-3) and other laboratories (4-6) have suggested that this defect is due in part to the loss of a permissive effect of cortisol-like steroids on the diluting segments of the nephron, i.e., a normal amount of glucocorticoid is essential to allow maximal impermeability to water to develop in these segments in the absence of circulating antidiuretic hormone (ADH). This concept implies that the release, metabolism, and action of ADHare normal in the adrenal-insufficient patient (1-3). Others (7-12), however, imply that adrenal glucocorticoids directly affect the release and metabolism of ADH. This implies that the impaired water diuresis of adrenal insufficiency is due to the altered ADHphysiology or its unopposed activity. These conflicting points of view have in general developed from experiments in which the release, metabolism, and action of ADH were studied indirectly rather than by direct measurement of the hormone in biologic

Vascular Calcification and Peripheral Necrosis in a Renal Transplant Recipient Reversal of Lesions Following Subtotal Parathyroidectomy

In the patient described progressive vascular calcification and digital necrosis developed after successful renal transplantation. The development of these lesions was associated with hypercalcemia and evidence of secondary hyperparathyroidism, and occurred in the face of a low calcium-phosphorus product. After the removal of three and a half hyperplastic parathyroid glands, the cutaneous lesions healed, and there was a marked reduction in the degree of vascular calcification. It is suggested that these lesions developed as a result of secondary hyperparathyroidism, and they may represent a form of calciphylaxis in man.

Hypocalcemia in magnesium-depleted dogs: Evidence for reduced responsiveness to parathyroid hormone and relative failure of parathyroid gland function

The effect of magnesium depletion on serum calcium and magnesium and on the response to the infusion of parathyroid extract (PTE) was evaluated in nine adult mongrel dogs during a control period, magnesium depletion, and following magnesium repletion. Magnesium depletion was associated with a fall in serum magnesium and calcium, and both returned to normal with magnesium repletion. There was a significant direct correlation between the serum concentration of calcium and magnesium in the magnesium-deficient state. During magnesium depletion, there were significant calcemic and phosphaturic responses to PTE, but these effects were reduced; the impaired responsiveness of the skeleton and the kidney to PTE returned to normal after magnesium repletion. Serum levels of immunoreactive parathyroid hormone, measured in two animals during the control and magnesium depletion state, remained stable during magnesium depletion, despite the hypocalcemia present. These results indicate that both impaired responsiveness of the skeleton to parathyroid hormone and reduced secretion of the hormone in response to hypocalcemia exist in dogs with magnesium depletion. Each of these factors probably contributes to a reduced level of serum calcium in magnesium depletion, and they may compound each other and hence aggravate the degree of hypocalcemia.

Antidiuretic Principle in Tuberculous Lung Tissue of a Patient with Pulmonary Tuberculosis and Hyponatremia

Abstract A 51-year-old white man had advanced pulmonary tuberculosis without renal or adrenal involvement, hyponatremia, and high urinary osmolality. The tuberculous lung tissue and the urine from ...