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Updated: Jul 15, 2026
A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction
Published on: December 20, 2014
Mesangial function in ureteral obstruction in the rat. Blockade of the efferent limb
Abstract:
The kinetics for mesangial uptake and transport of radiolabeled aggregated human immunoglobulin (Ig)G (AHIgG(125)I) deviated markedly from normal in male Sprague-Dawley rats with ureteral obstruction. Four experimental groups, each containing 25 rats, were used: (a) bilateral ureteral ligation (BUL) with release of one ureter 24 h later; (b) unilateral ureteral ligation with release 24 h later [UUL(R)]; (c) unilateral ureteral ligation without release (unreleased) [UUL(U)]; (d) uremia-control, which consisted of rats with ligated left ureter and a severed right ureter. A similar number of sham-operated rats served as control for each group. AHIgG(125)I (45 mg/100 g body wt) was given intravenously 1 h after release of the ureteral obstruction (25 h after ureteral obstruction or sham surgery). Groups of five control and five experimental animals were sacrificed at 2, 4, 8, 16, and 24 h after injection. At all time intervals, concentrations of AHIgG(125)I in isolated glomeruli from control animals were similar to values obtained from nonobstructed kidneys of UUL(U) and UUL(R) rats: a linear decrease in concentration over a period of 24 h was observed when the logarithm of glomerular AHIgG(125)I concentration was plotted against time. Aberrations in the kinetics were apparent in obstructed kidneys but not in liver, spleen, or blood concentrations of AHIgG(125)I: (a) At 2 h in all obstructed kidneys, glomerular concentration of AHIgG(125)I was markedly reduced. (b) In BUL (released or unreleased), glomerular concentrations of AHIgG(125)I from 4 to 16 h were congruent with 10-fold those in UUL(U) or UUL(R) kidneys. (c) The significant decline in glomerular concentration between 4 and 16 h in control and nonobstructed kidneys was not observed in UUL(R), UUL(U), or BUL (released or unreleased) kidneys; in all obstructed kidneys, a plateau in glomerular concentrations of AHIgG(125)I was observed between 4 and 16 h. (d) After 16 h at a time when the blood level of AHIgG(125)I had decreased to 3% of initial values, there was progressive fall in glomerular AHIgG(125)I. Similar results were obtained in the uremia-control group in rats, which indicated that uremia per se had no measurable effect on mesangial kinetics. These studies demonstrate that ureteral occlusion induces alterations in mesangial uptake (afferent limb) and egress (efferent limb) of macromolecules. Particularly evident is the "blockade" of the efferent limb which is demonstrable at high blood levels of AHIgG(125)I. These alterations in the transit of macromolecules through the mesangium may be mediated in part by the hemodynamic changes that accompany ureteral obstruction.
Insights
Ureteral obstruction significantly alters how the kidneys handle aggregated human immunoglobulin G (AHIgG(125)I), affecting both uptake and transport. This study reveals a "blockade" in the efferent limb of mesangial kinetics, potentially due to hemodynamic changes.
Area of Science:
- Nephrology
- Renal Physiology
- Immunology
Background:
- Mesangial cells play a crucial role in kidney filtration and immune complex handling.
- Ureteral obstruction is a common condition that can lead to significant renal dysfunction.
- Understanding macromolecule transport in the glomerulus is key to diagnosing and treating kidney diseases.
Purpose of the Study:
- To investigate the impact of ureteral obstruction on the kinetics of mesangial uptake and transport of aggregated human immunoglobulin G (AHIgG(125)I).
- To determine if uremia itself affects these kinetic processes.
- To elucidate the specific alterations in the afferent and efferent limbs of mesangial transport.
Main Methods:
- Utilized radiolabeled aggregated human immunoglobulin G (AHIgG(125)I) to track mesangial uptake and transport in Sprague-Dawley rats.
- Established experimental groups with varying degrees of ureteral obstruction (bilateral, unilateral, released, unreleased) and a uremia-control group.
- Quantified glomerular AHIgG(125)I concentrations at multiple time points post-injection in obstructed and control kidneys.
Main Results:
- Ureteral obstruction markedly reduced initial glomerular AHIgG(125)I uptake at 2 hours.
- Obstructed kidneys showed significantly higher glomerular AHIgG(125)I concentrations between 4-16 hours compared to controls.
- A plateau in glomerular AHIgG(125)I was observed in obstructed kidneys from 4-16 hours, indicating impaired egress.
- Uremia alone did not affect mesangial kinetics, isolating the effects to ureteral obstruction.
Conclusions:
- Ureteral obstruction induces significant alterations in mesangial uptake and transport of macromolecules.
- A notable "blockade" of the efferent limb of mesangial transport was observed, particularly at high blood AHIgG(125)I levels.
- Hemodynamic changes associated with ureteral obstruction likely contribute to these observed alterations in macromolecule transit.
