Abstract
541 Aims: BUF/Mna rats develop spontaneously FSGS (Nakamura et al., Nephron, 1986). To investigate the relevance of this syndrome as a animal model of human idiopathic nephrotic syndrome (INS), we have analysed its sensitivity to immunosuppressive drugs and its possible relapse on kidney transplantation. Methods: BUF/Mna rats (5 per group) received either Methylprednisolone (MP, 1mg/kg/day-IP), Cyclosporin A (CsA, 10mg/kg/day-PO), association of MP-CsA or cyclophosphamide (50mg/kg/week-IV) for 61 days. Saline or olive oil were given as controls. In addition, six proteinuric BUF/Mna rats (RT1u) of 4.5-month old, received a kidney from healthy and MHC compatible LEW.1W rat after induction of specific tolerance (DST). Control group was of 4 Wistar Furth rats receving LEW.1 kidneys. For all experiments, proteinuria was measured by calculating the ratio [urinary proteins]/[urinary creatinine] (g/mmol). Results: A significant decrease in proteinuria was observed for all the treatments, 40 to 60% decreased after 21 days under treatment while the renal function remains stable. In contrast, whatever the control vehicle, the proteinuria remained stable or increased. In transplanted rats, recurrence of proteinuria appeared around 48 days after kidney transplantation in 5/6 of the animals. This proteinuria increased to become massive (2.12±0.68 g/mmol) and blood creatinine levels were increased (175±61 μmol/l) on day 122. Light and electron microscopy revealed significant focal sclerotic glomeruli compared to control. The histological pattern was similar to that observed in aged BUF/Mna rats (> 18 months). There is no sign of acute/chronic rejection. Conclusion: Proteinuria of BUF/Mna rats is partially sensitive to several immunosuppressive drugs usually given in the INS. Our preliminary observation of the transplanted animals, supports the possibility that the initial disease recurs on a normal kidney when a tolerance regimen is administred. This observation could improves our understanding of the mecanisms of INS lesion and suggest the presence of circulating proteinuria inducing factor in these animals.
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