Československý transplantační kongres
Konferenční abstrakta 2006
Abstrakta posterů – sekce lékařů
EFFECT OF A NEW IMMUNOSUPPRESSANT FK778 IN A MODEL OF ACCELERATED RENAL INJURY IN HYPERTENSIVE RATS
Bloudickova S.1, Rajnoch J.1, Lodererova A.2, Honsova E.2, Viklicky O.1
1Department of Nephrology, Transplant Center, 2Department of Pathology, IKEM, Prague
Renal ischemia/reperfusion injury (I/R) and hypertension represent major alloantigen-independent risk factors contributing to the development of chronic allograft nephropathy. In a model of accelerated MHC independent renal injury we evaluated the effect of FK778 on the progression of accelerated nephropathy.
27 uninephrectomized hypertensive transgenic (m-REN-2)-27 rats (TGR) received a clip on renal pedicle for 45 minutes. Animals were treated with FK778 3 mg/kg/day (I/R 3 mg, n=8), 10 mg/kg/day (I/R 10 mg, n=11) or placebo (I/R PLAC, n=8) via gavage for 16 weeks. 12 animals were sham operated and treated with FK778 3mg/kg/day (SHAM 3 mg, n=4), 10 mg/kg/day (SHAM 10 mg, n=4) or were no treated (SHAM, n=4). Proteinuria and blood pressure were evaluated throughout and kidneys were harvested for morphological and immunohistochemical analysis at the end of experiment.
At week 16, operated and FK778-treated rats had lower proteinuria compared to operated and placebo-treated group (I/R 3 mg vs I/R PLAC: 48.42±26.16 vs 70.13±50.19; I/R 10 mg vs I/R PLAC: 27.28±21.86 vs 70.13±50.19, p<0.05). Sham-operated untreated rats developed lower proteinuria than sham-operated rats treated either with FK778 3 mg/kg/day or 10 mg/kg/day (SHAM 3 mg/kg/day – 24.23±10.89; SHAM 10 mg/kg/day – 17.37±4.13; SHAM – 14.23±1.18). I/R FK778-treated rat had reduced extent of glomerulosclerosis in comparison to placebo-treated rats (I/R 3 mg vs I/R PLAC:12.51±8.40 vs 14.90±7.09; I/R 10 mg vs I/R PLAC: 7.99±5.94 vs 14.90±7.09, p<0.05). There were no differences in extent of glomerulosclerosis among sham-operated groups.
FK778 treatment ameliorated changes induced by I/R. Our observation also supports the hypothesis about the nephrotoxicity of FK778.