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Updated: May 25, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Rapamycin induced ultrastructural and molecular alterations in glomerular podocytes in healthy mice
Kostas Stylianou1, Ioannis Petrakis, Vasiliki Mavroeidi
1Department of Nephrology, Heraklion University Hospital, Crete, Greece. kstylianu@gmail.com
Background:
In the normal kidney, rapamycin is considered to be non-nephrotoxic. In the present study, we investigated whether rapamycin is indeed non-nephrotoxic by examining the ultrastructural and molecular alterations of podocytes in healthy mice.
Methods:
Balb/c mice were given three different intraperitoneal doses of rapamycin for 1 week (dose model)-low-dose group: 1 mg/kg/day, intermediate-dose (ID) group: 1.5 mg/kg/day and high-dose (HD) group: 3 mg/kg/day; four mice in each group. An ID of rapamycin was also given for three different periods (time model): 1, 4 and 8 weeks; four mice were in each group. Mice treated with dimethyl sulphoxide served as controls. Body weight was measured weekly. Renal function was assessed by serum creatinine at the time of sacrifice. For estimation of albuminuria, 24-h urine collections were performed before treatment and weekly thereafter. Glomerular content of nephrin, podocin, Akt and Ser473-phospho-Akt was estimated by western blot and immunofluorescence. Nephrin and podocin messenger RNA (mRNA) were measured by real-time polymerase chain reaction. Mean podocyte foot process width (FPW) was measured by electron microscopy.
Results:
Urine albumin levels increased in the HD and 4-week groups. Renal function was modestly deteriorated in the HD group. The mean FPW increased in a dose-dependant manner at Week 1, further deteriorated at Week 4 and finally improved at Week 8. Nephrin and podocin mRNA levels showed a significant decrease at Week 1 and were restored at Week 4 and 8. Nephrin and podocin protein levels were reduced at Week 4 and recovered at Week 8. Ser473-phospho-Akt significantly increased in all rapamycin-treated groups.
Conclusions:
Rapamycin induced significant ultrastructural and molecular alterations in podocytes in association with albuminuria. These alterations happened early during treatment and they tended to improve over an 8-week treatment period.
Insights
Rapamycin causes early kidney podocyte damage, indicated by albuminuria and altered foot processes, though these effects may improve over time. This study examines rapamycin
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Rapamycin is generally considered non-nephrotoxic in healthy kidneys.
- This study investigates potential nephrotoxicity of rapamycin at the ultrastructural and molecular levels of podocytes.
Purpose of the Study:
- To examine the ultrastructural and molecular effects of rapamycin on podocytes in healthy mice.
- To determine if rapamycin induces nephrotoxicity in a dose- and time-dependent manner.
Main Methods:
- Balb/c mice received varying doses or durations of intraperitoneal rapamycin.
- Renal function, albuminuria, podocyte structure (foot process width), and molecular markers (nephrin, podocin, Akt) were assessed.
- Real-time PCR and western blotting were used to measure mRNA and protein levels.
Main Results:
- Albuminuria and modest renal function decline occurred in high-dose and prolonged treatment groups.
- Podocyte foot process width increased with rapamycin dose and duration, but improved by week 8.
- Key podocyte markers (nephrin, podocin) mRNA and protein levels decreased early but recovered by week 8; phospho-Akt increased.
Conclusions:
- Rapamycin induces early ultrastructural and molecular changes in podocytes, leading to albuminuria.
- These rapamycin-induced podocyte alterations show a trend towards improvement over an 8-week treatment period.
