The Effects of Adrenal Steroids and Potassium Depletion on the Elaboration of an Osmotically Concentrated Urine*

Abstract

The investigation reported in this paper is concerned with the effects of desoxycorticosterone acetate (DCA), hydrocortisone and dietary potassium depletion on the elaboration of an osmotically concentrated urine in the hydropenic state. Loeb and his associates (1, 2) demonstrated that dogs maintained on large amounts of DCA develop a diabetes insipidus-like picture. Since then, renal function studies in man (3-5), dogs (6) and rats (7,8) have shown that the ability of the kidney to concentrate the urine is markedly reduced in states of adrenal hyperfunction and potassium deficiency. The mechanism by which polyuria is produced under these conditions has not been established. In particular, the role of potassium deficiency is still a matter of controversy. Thus, contrary to Loeb and co-workers (1, 2), who were unable to prevent the development of polyuria in their DCA-treated animals by feeding potassium chloride, some authors maintain (9) that the increased loss of potassium following the administration of adrenal steroids is responsible for the impairment of water conservation. Also, there is no agreement on the sensitivity of the kidney to vasopressin (Pitressin®) during various states of potassium depletion (7, 9).The present study is an attempt to clarify some of these points. We have, in particular, studied the formation of a concentrated urine during osmotic diuresis in the hydropenic state. According to current concepts, an osmotically concentrated urine can be visualized as being made up of an isosmotic portion less the amount of water abstracted from it to produce hypertonicity ( 10, 11 ). * Aided by a grant from the National Heart Institute, Bethesda, Md.t This work was done during the tenure of an Established Investigatorship of the American Heart Association. This latter moiety has been designated TCHEO (10,11) or water economy (12) and direct evidence indicates that the collecting duct system is the site where the process of final water abstraction occurs (13,14). Contrary to findings obtained on control animals in which variations of TCH,0 are fairly small over a wide range of urine flows, our results show that DCA administration produces a significant and progressive reduction of that amount of water as urine flow increases. Also, at higher flow rates the occurrence of marked hypotonicity was a frequent finding, thus indicating that the fluid reaching the site of final water abstraction was not rendered isosmotic during its passage along the distal tubule and collecting duct (13,14). METHODSThirty-eight experiments were performed on nine female mongrel dogs ranging in weight from 17 to 25 Kg.' Anesthesia was induced and maintained by appropriate amounts of sodium pentobarbital given intravenously. In all animals data on osmolality of urine and plasma at low urine flow rates and during osmotic diuresis were obtained before and after treatment with various hormones and diets. Thus, each animal served as its own control. Since, in particular, variations in the protein intake have been shown to influe...

Water Excretion in Potassium-Deficient Man*

“…These data indicate that kaliopenic isosthenuria can not be attributed solely to ADH refractoriness, unless it is assumed that the permissive action of ADH on water diffusion indirectly regulates medullary blood flow and hence solute retention. A reduced solute concentration in the medulla may prevent efficient operation of the countercurrent multiplier system of the loops of Henle and the collecting ducts by reducing the rate of transfer of water across the tubular cell (36)(37)(38)(39).…”

Osmolality of distal tubular fluid in the dog.

“…These findings in rodents have precluded a satisfactory explanation for the observation that man and dog can excrete hypotonic final urine during certain experimental and pathological conditions when antidiuretic hormone activity is presumably adequate (3)(4)(5)(6)(7)(8)(9)(10)(11). These observations have been most apparent at high rates of urine flow and solute excretion.…”

Effects of potassium deficiency on renal function in the dog

“…Chronic potassium deficiency characteristically results in a decrease in urinary concentrating ability (1)(2)(3). The effects of potassium deficiency on other aspects of renal function are less clearly defined.…”

“…The effects of potassium deficiency on other aspects of renal function are less clearly defined. Glomerular filtration rate has been reported to decrease in some studies (1,2), but others have found no consistent change (4). Paraaminohippuric acid (PAH) clearance is often decreased in potassium-depleted patients (2).…”

“…This finding may be due to a defect in the tubular extraction or secretion of PAH rather than a decrease in effective renal plasma flow rate (5). Only limited data are available concerning the effect of potassium deficiency on the maximum renal reabsorptive rate for glucose (1,4).…”