Effect of osmotic diuresis on intrarenal solutes in diabetes insipidus and hydropenia

Abstract

Changes in composition of renal solutes were studied in normal and in diabetes insipidus (D.I.) dogs subjected to varying degrees of solute (mannitol) loading. In both D.I. and hydropenic states, solute loading induced decreases in concentration of medullary solutes, and consequently decreases in corticomedullary gradients of solute concentration. The maximal level of papillary osmolality was associated with excretion of maximally hypertonic urine (nonloaded hydropenic states). The minimal level of papillary osmolality was not associated with excretion of hypotonic urine (D.I. states), but with excretion of slightly hypertonic urine during massive solute loading in normal hydropenic states. Hypertonicity of renal papillae (with respect to systemic plasma) even during excretion of hypotonic urine, together with a 7.6% vol of distribution of PAH in the papillae, indicates that final urine occupies only a small fraction of the renal papillary mass. Except for differences in location of peak concentrations, profiles of sodium and urea roughly paralleled those of total solute under all conditions. Decreases in papillary concentrations of sodium, induced by solute loading, paralleled those of osmolality in all cases. Decreases in papillary urea paralleled those of total solute (and Na) during loading in hydropenic dogs, but not in D.I. dogs. In the latter, concentration of papillary urea remained essentially fixed while those of Na and total solute decreased. In contrast to tissue concentrations of sodium and urea those of potassium increased in going from cortex to papilla under all conditions. The significance of these findings is discussed.

The time course of changes in renal tissue composition during mannitol diuresis in the rat

“…Furthermore, the changes in medullary solute composition are not closely related in time or magnitude to those in urinary solute concentrations (present experiments;Goldberg & Ramirez, 1967). We therefore agree with previous suggestions (Appelboom et al 1965;Goldberg & Ramirez, 1967) that the medullary data primarily express the composition of extratubular fluid. To what extent the statistically significant initial inicrease in water content and the non-significant increase in sodium content and decrease in potassium content in the cortex may be attributed to a higher proportion of intratubular fluid is uncertain.…”

“…Thus, within any one slice level changes in the net composition may result from changes in any of these contributory compartments, for example, in intratubular fluid and blood: conversely, redistribution of a constituent between these compartments does not, per se, affect the over-all slice composition. However, not more than about 5 % of medullary tissue is occupied by urine during anti-diuresis in the rat (Bray, 1960b) and not more than about 8 % in osmotic diuresis in the dog (Appelboom et al 1965;Goldberg & Ramirez, 1967). Furthermore, the changes in medullary solute composition are not closely related in time or magnitude to those in urinary solute concentrations (present experiments;Goldberg & Ramirez, 1967).…”

“…production. The water permeability of the collecting duct would remain high, as indicated by osmotic equilibration between papilla and collecting duct urine during hypertonic mannitol administration (Gottschalk & Mylle, 1959;Appelboom et al 1965) except, perhaps, at very high flow rates in the dog (Goldberg & Ramirez, 1967). In these circumstances, increased flow in the loop of Henle and collecting duct would contribute an increased delivery of water to the medullary interstitium, despite the reduced transtubular osmotic gradient (Goldberg & Ramirez, 1967).…”

Renal Phenotype of UT-A Urea Transporter Knockout Mice

“…In humans, urea production and excretion can amount to several hundred millimoles per day. Such large amounts of any other solute, for example mannitol (1,2), would obligate large amounts of water excretion by causing an osmotic diuresis. A basic model of urea handling was proposed by Berliner et al (3), hypothesizing that an osmotic diuresis does not occur with urea because of the accumulation of urea in the inner medullary interstitium, which osmotically balances the high level of urea in the inner medullary collecting duct (IMCD) and urine.…”

Renal inner medullary prostaglandin synthesis. A calcium-calmodulin-dependent process suppressed by urea.

“…The influence of Ca2" on PG synthesis may be mediated through an action of this cation to stimulate the release of free arachidonate (AA) from tissue lipid stores (1), a step which appears to be rate limiting in the cellular generation of PG (4). In the renal IM, where osmolality ordinarily varies over a wide range under normal physiologic conditions (5), there is evidence that solute concentration is an important local determinant of PG synthesis (1,(6)(7)(8). Earlier studies from our laboratory indicated that effects of solute concentration on immunoreactive PGE (iPGE) synthesis, analogous to those of Ca2+, are mediated through alterations in the release of AA from tissue lipid stores (1).…”