Related Experiment Video
Updated: Aug 12, 2026
The Mouse Isolated Perfused Kidney Technique
Published on: November 17, 2016
Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney
J R Saunders1, A Aminian, J L McRae
1Department of Nephrology, St. Vincent's Hospital, Melbourne, Victoria, Australia.
Insights
Clusterin, a plasma protein, protects against complement-induced kidney injury. Depleting clusterin in plasma significantly increased glomerular damage in a rat nephritis model.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Clusterin is a plasma protein involved in complement regulation.
- It is found in glomerular immune deposits in nephritis.
- Its role in protecting against complement-mediated glomerular injury is unclear.
Purpose of the Study:
- To investigate the role of clusterin in preventing complement-induced glomerular injury.
- To assess the effect of clusterin depletion on nephritis development in a rat kidney model.
Main Methods:
- Used an isolated perfused rat kidney model of passive Heymann nephritis.
- Perfused kidneys with clusterin-depleted human plasma or control plasma.
- Initiated glomerular injury using specific antibodies and complement components.
Main Results:
- Kidneys perfused with clusterin-depleted plasma showed significantly higher proteinuria.
- Antibody binding and C3 deposition were similar between groups.
- Terminal complement component deposition was higher in the clusterin-depleted group.
Conclusions:
- Clusterin may play a protective role in vivo against complement-induced glomerular injury.
- These findings suggest clusterin as a potential therapeutic target for nephritis.
Abstract:
Clusterin is a normal plasma protein, shown to be an inhibitor of reactive complement hemolysis and a component of the fluid phase SC5b-9 terminal complement complexes. It is a component of glomerular immune deposits in human and experimental glomerulonephritis. Using the complement-dependent isolated perfused rat kidney model of autologous phase passive Heymann nephritis, we have studied the effect of clusterin depletion of perfused plasma on the development of glomerular injury. Kidneys with planted glomerular sheep anti-rat Fx1A antibody were perfused with human plasma either depleted of clusterin to < or = 30%, or control plasma depleted of plasma fibronectin. Glomerular injury was then initiated by the addition of guinea pig anti-sheep immunoglobulins to the perfusate. Kidneys perfused with clusterin depleted plasma developed significantly greater proteinuria at all time points when compared to control kidneys. Glomerular antibody binding and C3 deposition were similar in the two groups, but terminal complement components were deposited in larger amounts in the clusterin depleted group. These data support a possible role for clusterin in vivo in the protection of complement-induced glomerular injury.
