Fol. Biol. 2010, 56, 72-77
Leflunomide Derivate FK 778 in Accelerated Renal Injury in Transgenic Rat
Renal ischaemia/reperfusion (I/R) injury and hypertension represent major alloantigen-independent risk factors contributing to the development of chronic allograft nephropathy. In a model of accelerated major histocompatibility complex-independent renal injury, we evaluated the effect of leflunomide derivate – FK778 – on the progression of accelerated nephropathy. Thirty-six uninephrectomized hypertensive transgenic (m-REN-2)-27 rats received a clip on renal pedicle for 45 minutes. Animals were treated with FK778 3 mg/kg/day (I/R 3 mg, N = 12), 10 mg/kg/day (I/R 10 mg, N = 12) or placebo (N = 12) via gavage for 16 weeks. Eighteen animals were sham-operated and treated with FK778 3 mg/kg/day (sham 3 mg, N = 6), 10 mg/kg/day (sham 10 mg, N = 6) or were untreated (sham, N = 6). Proteinuria and blood pressure were evaluated throughout and the kidneys were harvested for morphological and immunohistochemical analysis at the end of the experiment. At week 16, rats with I/R injury and FK778 treatment had lower proteinuria compared with placebo-treated rats (I/R 3 mg: 48.42 ± 26.16, I/R 10 mg 27.28 ± 21.86 vs. Placebo: 70.13 ± 50.19 mg/day, P < 0.05). The untreated sham group exhibited lower proteinuria compared with FK778-treated sham groups (Sham 3 mg: 24.23 ± 10.89; Sham 10 mg: 17.37 ± 4.13; Sham: 14.23 ± 1.18) There was no difference in glomerulosclerosis and interstitial fibrosis among the treated groups. In the untreated animals the rate of interstitial fibrosis decline reached statistical significance (Placebo vs. Sham: 1.125 ± 0.641 % vs. 0.250 ± 0.500 %, P < 0.05). There was higher CD5+ leukocyte infiltration in the placebotreated group. FK778-treated rats displayed amelioration of some changes induced by the I/R injury. Our observation also suggests potential nephrotoxicity of FK778.
Keywords
ischaemia/reperfusion injury, FK 778, leflunomide, transgenic rat, chronic allograft nephropathy, hypertension.
Funding
The study was supported by the Institute for Clinical and Experimental Medicine (M20 00023001).
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.
