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. 1981 Sep;68(3):760–767. doi: 10.1172/JCI110312

Functional Profile of the Isolated Uremic Nephron

EVIDENCE OF PROXIMAL TUBULAR “MEMORY” IN EXPERIMENTAL RENAL DISEASE

Walter Trizna 1, Norimoto Yanagawa 1, Yaacov Bar-Khayim 1, Barbara Houston 1, Leon G Fine 1
PMCID: PMC370858  PMID: 7276170

Abstract

In experimental models of glomerular and nonglomerular renal disease, single nephron filtration rate and proximal tubular reabsorption of fluid decrease or increase in parallel in the same nephron. To assess whether intrinsic adaptations in proximal tubular function, i.e., changes that are independent of the peritubular or humoral milieu, contribute to this phenomenon, segments of rabbit late superficial proximal convoluted tubules (PCT) were studied by in vitro perfusion. PCT were obtained from normal kidneys, from remnant kidneys, and from kidneys embolized with microspheres. Single nephron filtration rates are increased in the remnant and decreased in the embolized kidneys. Whereas the embolized-kidney rabbits were nonazotemic (the contralateral kidney was left in situ), the remnant-kidney animals were uremic. In order to study a nonazotemic model of increased single nephron filtration rate, PCT were also obtained from uninephrectomized rabbits.

Significant compensatory hypertrophy occurred in the PCT of the remnant kidney. Net fluid reabsorption (Jv) per unit length was increased by ∼60%; Jv per unit luminal surface area was the same as in the normal PCT. Transepithelial potential difference (PD) was significantly greater than normal. This was associated with a reversal of the normal permselective properties (PCl > PNa) of the late superficial PCT so that PNa exceeded PCl. The changes could not be ascribed to some undetermined effect of the uremic state in vivo, since increases in tubule size, Jv per unit length, and PD also occurred in PCT from nonazotemic uninephrectomized rabbits.

In contrast, Jv, per unit length or per unit luminal surface area, was decreased by ∼50% in PCT from embolized kidneys and PD was also reduced. In these tubules, the normal permselective properties were also reversed. Tubule size, however, was not significantly different from normal.

The increases or decreases in Jv that occurred in the different disease models were not dependent on tubular fluid flow rate or the uremic milieu in vitro.

These studies indicate that intrinsic proximal tubular function is modified by the disease state in vivo and that the “memory” of this adaptation is expressed in the in vitro situation. The changes in Jv observed in vitro parallel the increases or decreases in single nephron filtration rates that occur in vivo. Compensatory hypertrophy, with an attendant increase in luminal surface area, could explain the increased Jv per millimeter in the remnant kidneys, but the adaptation observed in the embolized kidneys cannot be ascribed to changes in tubule size.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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