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Medium-term cyclosporin renal dysfunction and its reversibility in rats
M Sabbatini1, L De Nicola, F Uccello
1Department of Nephrology, First Faculty of Medicine, University of Naples, Italy.
The American Journal of Physiology
|June 1, 1991
Summary
Cyclosporin A (CsA) impairs kidney function and glomerular dynamics in rats, causing reversible changes. Withdrawal of CsA leads to recovery of kidney function and glomerular parameters.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Cyclosporin A (CsA) is a widely used immunosuppressant.
- Understanding CsA's impact on renal function is crucial for patient management.
- Medium-term effects of CsA on renal dynamics and morphology require detailed investigation.
Purpose of the Study:
- To investigate the effects of medium-term cyclosporin A administration on renal dynamics and morphology in a rat model.
- To assess the reversibility of CsA-induced renal changes after drug withdrawal.
Main Methods:
- Metabolic studies, renal micropuncture (RM), and electron microscopy (EM) were employed.
- 50 female rats were treated with CsA (40 mg/kg) for 10, 20, or 30 days.
- Control rats received olive oil; post-treatment recovery was assessed after CsA withdrawal.
Main Results:
- CsA administration progressively decreased glomerular filtration rate (GFR) and single-nephron GFR (SNGFR).
- Impaired SNGFR was linked to reduced glomerular capillary pressure, increased afferent arteriole resistance, and decreased glomerular plasma flow.
- Electron microscopy revealed progressive vacuolation in proximal and distal tubular cells.
- Renal function and dynamics normalized 30 days after CsA withdrawal.
Conclusions:
- Medium-term CsA administration induces reversible changes in glomerular dynamics.
- CsA treatment results in only mild histological lesions, primarily tubular cell vacuolation.
- The observed renal effects of CsA are reversible upon drug cessation.