Luminal hypotonicity: a driving force for fluid absorption from the proximal tubule

The ability of rat proximal tubules to generate a hypotonic luminal fluid was investigated. Simultaneous perfusion of tubules and peritubular capillaries was performed with simple solutions. When tubules were perfused at 10 nl X min-1 and NaCl was the perfusate for tubules and capillaries, solute and fluid (0.41 nl X min-1 X mm-1) were transported and the luminal fluid became hypotonic (delta osmol = -1.7 mosmol X kg-1). When the same solutions were used but the tubule was perfused at 45 nl X min-1, more fluid (0.89 nl X min-1 X mm-1) was reabsorbed and the fluid became more hypotonic (delta osmol = -3.9 mosmol X kg-1). Bicarbonate in the peritubular capillaries increased the fluid reabsorption (1.21 nl X min-1 X mm-1) but did not generate cryoscopically hypotonic fluid. Cyanide abolished all net movement of fluid and solute. It is concluded that the tubule can generate a hypotonic fluid, that the hydraulic conductivity for proximal tubular epithelium is 3,200-3,400 microns X s-1, and that the reflection coefficient for NaHCO3 is slightly higher than for NaCl.

Download Full-text

Expanding the Pathologic Spectrum of Immunoglobulin Light Chain Proximal Tubulopathy

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-1368-etpsoi ◽

2007 ◽

Vol 131 (9) ◽

pp. 1368-1372 ◽

Cited By ~ 1

Author(s):

Umesh Kapur ◽

Kevin Barton ◽

Raoul Fresco ◽

David J. Leehy ◽

Maria M. Picken

Keyword(s):

Plasma Cell ◽

Light Chain ◽

Proximal Tubules ◽

Plasma Cell Dyscrasia ◽

Tubular Epithelium ◽

Light Chain Restriction ◽

Proximal Tubular ◽

Proximal Tubulopathy ◽

Light Chain Proximal Tubulopathy ◽

Proximal Tubular Epithelium

Abstract Context.—In plasma cell dyscrasias, involvement of the distal tubules is frequent and well characterized. In contrast, proximal tubules have only rarely been reported to show diagnostic pathology such as intracytoplasmic crystals. Objective.—To look for additional morphologic features that might be helpful in the diagnosis of proximal tubulopathy associated with an underlying plasma cell dyscrasia. Design.—We examined patients presenting with nonspecific renal symptoms who were found to have light chain restriction limited to proximal tubular epithelium by immunofluorescence. We correlated these results with light microscopy, electron microscopy, and the clinical findings. Results.—By immunofluorescence, 5 patients had light chain restriction in proximal tubular epithelium. By light microscopy, only 1 patient had focal rhomboid crystals in the proximal tubular epithelium; all other biopsies failed to show any discernible pathology within the proximal tubules or elsewhere in the kidney. By electron microscopy, proximal tubules from 2 patients showed crystals with a latticelike structure, whereas the remaining 3 patients had only prominent phagolysosomes. However, by immunoelectron microscopy, the lysosomal content showed light chain restriction (in 2 cases studied). Post–kidney biopsy, all patients were diagnosed with multiple myeloma or plasma cell dyscrasia. One patient developed renal failure and had recurrence of crystals in the allograft. Conclusions.—Light chain proximal tubulopathy may be associated with the presence of crystals or with the presence of phagolysosomes with light chain restriction as the sole abnormality. Both κ and λ light chains may be involved. The prognosis is variable and the pathology may recur in transplants.

Download Full-text

Osmotic forces driving water reabsorption in the proximal tubule of the rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.4.f669 ◽

1989 ◽

Vol 257 (4) ◽

pp. F669-F675 ◽

Cited By ~ 2

Author(s):

R. Green ◽

G. Giebisch

Keyword(s):

Reflection Coefficient ◽

Water Permeability ◽

Rat Kidney ◽

Proximal Tubules ◽

Osmotic Gradient ◽

Water Reabsorption ◽

Fluid Flux ◽

Fluid Reabsorption ◽

Ionic Fluxes ◽

Peritubular Capillaries

Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to measure reabsorption of fluid in response to an imposed osmotic gradient. The tubular fluid was isotonic and the peritubular capillaries were made hypertonic with NaCl or NaHCO3. Mean gradients and ionic fluxes were measured. When no gradient was imposed tubular fluid became hypotonic and rate of fluid reabsorption was 0.700 nl.mm-1.min-1. Imposition of a 25 mM NaCl gradient increased fluid flux to 3.887 nl.mm-1.min-1, whereas 25 mM NaHCO3 stimulated 5.226 ml/mm fluid reabsorption. This gave a relative reflection coefficient of NaCl:NaHCO3 of 0.73. Apparent water permeability varied with highest values for the smallest gradients. This suggests the possibility of a compartment in the epithelium that is hypertonic to the peritubular capillaries. The hypertonicity required to account for fluid movement was 6-16 mosmol/kg.

Download Full-text

Luminal hypotonicity in proximal tubules of aquaporin-1-knockout mice

AJP Renal Physiology ◽

10.1152/ajprenal.2000.278.6.f1030 ◽

2000 ◽

Vol 278 (6) ◽

pp. F1030-F1033 ◽

Cited By ~ 56

Author(s):

V. Vallon ◽

A. S. Verkman ◽

J. Schnermann

Keyword(s):

Knockout Mice ◽

Chloride Concentration ◽

Plasma Osmolality ◽

Proximal Tubules ◽

Fluid Absorption ◽

Wild Type ◽

Fluid Reabsorption ◽

Aquaporin 1 ◽

Proximal Tubular

To examine the role of aquaporin-1 (AQP1) in near-isosmolar fluid reabsorption in the proximal tubule, we compared osmolalities in micropuncture samples of late proximal tubular fluid and plasma in wild-type (+/+) and AQP1-knockout (−/−) mice. Compared with matched wild-type mice, the −/− animals produce a relatively hypotonic urine (607 ± 42 vs. 1,856 ± 101 mosmol/kgH2O) and have a higher plasma osmolality under micropuncture conditions (346 ± 11 vs. 318 ± 5 mosmol/kgH2O; P < 0.05). Measurements of tubular fluid osmolality were done in three groups of mice, +/+, −/−, and hydrated −/− mice in which plasma osmolality was reduced to 323 ± 1 mosmol/kgH2O. Late proximal tubular fluid osmolalities were 309 ± 5 (+/+, n= 21), 309 ± 4 (−/−, n = 24), and 284 ± 3 mosmol/kgH2O (hydrated −/−, n = 19). Tubular fluid chloride concentration averaged 152 ± 1 (+/+), 154 ± 1 (−/−), and 140 ± 1 mM (hydrated −/−). Transtubular osmotic gradients in untreated and hydrated AQP1 −/− mice were 39 ± 4 ( n = 25) and 39 ± 3 mosmol/kgH2O ( n = 19), values significantly higher than in +/+ mice (12 ± 2 mosmol/kgH2O; n = 24; both P < 0.001). AQP1 deficiency in mice generates marked luminal hypotonicity in proximal tubules, resulting from the retrieval of a hypertonic absorbate and indicating that near-isosmolar fluid absorption requires functional AQP1.

Download Full-text

Transfer of Na transport inhibition in proximal tubules from saline volume-expanded to nonexpanded rats

AJP Renal Physiology ◽

10.1152/ajprenal.1991.260.1.f69 ◽

1991 ◽

Vol 260 (1) ◽

pp. F69-F74

Author(s):

S. Reddy ◽

A. Z. Gyory ◽

T. Bostrom ◽

C. Cochineas

Keyword(s):

Proximal Tubules ◽

Tubular Epithelium ◽

Volume Flux ◽

Na Transport ◽

Transport Inhibitor ◽

Transport Inhibition ◽

Proximal Tubular ◽

Physical Forces ◽

Proximal Tubular Epithelium ◽

Drop Technique

In dual micropuncture experiments the shrinking drop technique was used to measure volume flux with artificial tubular fluid (AF) alternating with harvested tubular fluid (HTF) during saline volume-expanded (VE) and nonexpanded (NE) periods. In VE rats, volume flux (Jv) (nl.mm-1.min-1) with AF was 1.78 +/- 0.08 (means +/- SE) during NE and was reduced to 1.39 +/- 0.09 (P = 0.01) during subsequent VE, whereas with randomly alternating HTF during VE it was 1.07 +/- 0.08 (P less than 0.0001 and less than 0.03, respectively). Jv with HTF from NE rats tested in the VE rats was 1.20 +/- 0.06, which is significantly higher than that measured with their own HTF (Wilcoxon rank, P = 0.05). In NE rats Jv was 1.65 +/- 0.10 and 1.69 +/- 0.10 with AF and HTF and was 1.28 +/- 0.07 (P less than 0.001 from both) with HTF obtained from VE rats. Elemental analysis of reaspirated tubular fluids showed no significant differences in Na or Cl concentrations among any of the fluids. It is concluded that during VE, a transferable Na transport inhibitor appears in proximal tubular fluid, which, together with a changed proximal tubular epithelium, possibly due to physical forces, accounts for proximal tubular Na transport inhibition during VE.

Download Full-text

Effective luminal hypotonicity: the driving force for isotonic proximal tubular fluid absorption

AJP Renal Physiology ◽

10.1152/ajprenal.1979.236.2.f89 ◽

1979 ◽

Vol 236 (2) ◽

pp. F89-F96 ◽

Cited By ~ 2

Author(s):

T. E. Andreoli ◽

J. A. Schafer

Keyword(s):

Driving Force ◽

Fluid Transport ◽

Driving Forces ◽

Proximal Tubules ◽

Diffusion Resistance ◽

Fluid Absorption ◽

Isotonic Fluid ◽

Lateral Intercellular Spaces ◽

Proximal Tubular ◽

Editorial Review

This Editorial Review summarizes certain considerations relevant to the mechanism(s) of isotonic fluid absorption by the mammalian proximal nephron. Recent evidence indicates that the paracellular pathway in this epithelium has a low diffusion resistance. Therefore it is possible that lateral intercellular spaces are in diffusion equilibrium with the peritubular medium. For such a circumstance, the driving forces for isotonic fluid absorption may reside in external solutions. But since the hydraulic conductance of mammalian proximal tubules is remarkably high, the effective osmotic pressure gradient between luminal and pertibular solutions required to drive isotonic fluid transport is relatively small. In the mammalian proximal nephron, effective luminal hypotonicity may provide the driving force for isotonic fluid transport. At least two mechanisms could account for the development of effective luminal hypotonicity. First, preferential absorption of bicarbonate results in a rise of luminal Cl- concentration. And because proximal tubules are more permeable to Cl- than to HCO3-, there develops a driving force for isotonic fluid transport. Second, trivial degrees of luminal hypotonicity may develop attendant on active Na+ absorption. We provide evidence that, of these two mechanisms, axial anion asymmetry is the dominant force for isotonic fluid transport.

Download Full-text

In vitro nephrotoxicity testing: Polarized approach of proximal tubular epithelium

Toxicology Letters ◽

10.1016/s0378-4274(98)80669-3 ◽

1998 ◽

Vol 95 ◽

pp. 167

Author(s):

I. Genestie ◽

V. Keravec ◽

J.P. Morin ◽

J.P. Fillastre

Keyword(s):

Tubular Epithelium ◽

Proximal Tubular ◽

Proximal Tubular Epithelium

Download Full-text

Molecular Mechanisms of Receptor-Mediated Endocytosis in the Renal Proximal Tubular Epithelium

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/403272 ◽

2010 ◽

Vol 2010 ◽

pp. 1-7 ◽

Cited By ~ 42

Author(s):

Akihiko Saito ◽

Hiroyoshi Sato ◽

Noriaki Iino ◽

Tetsuro Takeda

Keyword(s):

Molecular Mechanisms ◽

Adaptor Proteins ◽

Risk Marker ◽

Tubular Epithelium ◽

Coated Pits ◽

Receptor Mediated Endocytosis ◽

Other Substances ◽

Proximal Tubular ◽

Renal Proximal Tubular ◽

Proximal Tubular Epithelium

Receptor-mediated endocytosis is a pivotal function of renal proximal tubule epithelial cells (PTECs) to reabsorb and metabolize substantial amounts of proteins and other substances in glomerular filtrates. The function accounts for the conservation of nutrients, including carrier-bound vitamins and trace elements, filtered by glomeruli. Impairment of the process results in a loss of such substances and development of proteinuria, an important clinical sign of kidney disease and a risk marker for cardiovascular disease. Megalin is a multiligand endocytic receptor expressed at clathrin-coated pits of PTEC, playing a central role in the process. Megalin cooperates with various membrane molecules and interacts with many intracellular adaptor proteins for endocytic trafficking. Megalin is also involved in signaling pathways in the cells. Megalin-mediated endocytic overload leads to damage of PTEC. Further studies are needed to elucidate the mechanism of megalin-mediated endocytosis and develop strategies for preventing the damage of PTEC.

Download Full-text

Transcellular Diffusion of Non-Electrolytes across the Renal Tubular Epithelium

The Journal of General Physiology ◽

10.1085/jgp.45.4.643 ◽

1962 ◽

Vol 45 (4) ◽

pp. 643-649 ◽

Cited By ~ 3

Author(s):

José Carlos Peña ◽

Richard L. Malvin

Keyword(s):

Tubular Epithelium ◽

Permeability Characteristics ◽

Molecular Weights ◽

Renal Tubular Epithelium ◽

Significant Movement ◽

Proximal Tubular ◽

Renal Tubular ◽

Proximal Tubular Epithelium ◽

Stop Flow ◽

Transcellular Diffusion

The stop flow technique was used to investigate the permeability characteristics of the dog nephron to various C14-labeled non-electrolytes. 12 minutes after clamping the ureter, creatinine, PAH, and C14 compound were injected intravenously. 2 minutes later, urine samples were collected. Urea and glycerol were able to enter the tubular urine along the entire nephron at rates which were commensurate with their molecular weights. No significant movement of larger molecules (D-arabinose, D-glucose, and mannitol) could be detected. However, after administration of twenty units of pitressin, D-arabinose was able to diffuse across the distal and proximal tubular epithelium.

Download Full-text