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Updated: Oct 3, 2026

A Mouse Model to Evaluate the Long-Term Structural and Functional Outcomes after the Reversal of Prolonged Unilateral Ureteric Obstruction
Published on: July 18, 2025
Long-term effect of partial nephrectomy on biological parameters, kidney histology, and guanidino compound levels in
M Al Banchaabouchi1, B Marescau, E Van Marck
1Laboratory of Neurochemistry and Behaviour, Born-Bunge Foundation, University of Antwerp, Antwerp, Belgium.
Abstract:
The long-term adverse consequences of early renal mass reduction in mice have not yet been investigated. The effects of partial surgical nephrectomy (NX) in 2-month-old mice on some biological parameters, on histopathologic and morphometric features of the kidney, and on urea and guanidino compound (GC) levels in plasma, urine, and brain were examined at 10 days, and 1, 2, 4, and 12 months postsurgery. Body weight, urinary volume, and plasma urea were most affected at 10 days and 12 months post-NX. NX-induced changes in the remaining renal tissue (including hypertrophy, glomerular mesangial expansion, and presence of protein casts) increased with age. As in human renal insufficiency, NX mice showed significantly higher plasma guanidinosuccinic acid (GSA) and creatinine (CTN) levels at all studied periods. The same tendency could be seen for most other plasma GCs examined, except for arginine (Arg), guanidinoacetic acid (GAA), and homoarginine (HA). As seen in human pathobiochemistry, the latter 2 compounds tended to be lower in NX mice in our follow-up study. Remarkably, and also similar to humans, NX mice excreted less GAA and more GSA than controls during the entire follow-up study. During the follow-up, excretion levels of GAA were unchanged in NX and sham-operated mice. In brain, GAA and gamma-guanidinobutyric acid (GBA) levels were always higher in NX mice with a tendency to respectively increase or decrease over time in NX as well as sham-operated mice. Although urea and GC metabolism were influenced by time post-NX and aging, the model was confirmed to display a mild stable chronic impairment of renal function. Histopathologic and morphometric changes of the kidney increased with age.
Insights
Early partial nephrectomy (NX) in mice leads to long-term kidney impairment and altered urea and guanidino compound (GC) levels. These changes, including kidney tissue alterations and specific GC variations, mimic aspects of human renal insufficiency.
Area of Science:
- Nephrology
- Experimental Medicine
- Biochemistry
Background:
- Long-term effects of early renal mass reduction are not well understood.
- Partial surgical nephrectomy (NX) is a model for studying chronic kidney disease.
- Investigating the consequences of reduced renal mass is crucial for understanding kidney disease progression.
Purpose of the Study:
- To investigate the long-term adverse consequences of early partial nephrectomy (NX) in mice.
- To examine the effects of NX on biological parameters, kidney histology, and urea and guanidino compound (GC) levels.
- To establish a mouse model for mild, stable chronic renal impairment.
Main Methods:
- Partial surgical nephrectomy (NX) performed on 2-month-old mice.
- Assessment of biological parameters, kidney histopathology, and morphometry at multiple time points (10 days to 12 months).
- Measurement of urea and various guanidino compounds (GCs) in plasma, urine, and brain tissue.
Main Results:
- Body weight, urinary volume, and plasma urea were significantly affected post-NX, particularly at early and late time points.
- NX induced progressive histopathologic and morphometric changes in the remaining kidney tissue with age.
- NX mice exhibited altered plasma and urinary levels of GCs, including increased guanidinosuccinic acid (GSA) and decreased guanidinoacetic acid (GAA), mirroring human renal insufficiency.
Conclusions:
- Early partial nephrectomy in mice results in a mild, stable chronic impairment of renal function.
- The study successfully established a mouse model that replicates key aspects of human renal insufficiency.
- Age-dependent changes in kidney tissue and GC metabolism highlight the long-term impact of reduced renal mass.

