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Presenter: Delawir, Kahn, Cape Town, South Africa
Authors: Kahn D., Spearman W., Tyler M., Mall A., Lotz Z.
CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY
D. Kahn, W. Spearman, A. Mall, M. Tyler, Z. Lotz
, University of Cape Town, Cape Town/SOUTH AFRICA
Body: In transplantation, the renal allograft is susceptible to both a cold and warm ischaemic injury. In response to this injury the renal tubules undergo regeneration. Several interventions in theperi-transplant period may influence regeneration of the renal tubules. The aim of this study was to investigate the effect of cyclosporine and tacrolimus on regeneration of the renal tubules.
Long Evans rats weighing 250-300g were subjected to a midline laparotomy under anaesthesia, and the right kidney mobilized and the predicle clampled for 45 min. The animals were randomized to receiveeither saline (Group 1), cyclosporine (5mg/kg twice daily) (Group 2) or tacrolimus (0.1mg/kg twice daily) (Group 3) by oral gavage. Groups of animals (n = 10) were sacrificed at 0, 24, 48, 72 and 96hours post-unclamping of the right renal pedicle, and both kidneys removed for histological examination. The mitotic index (MI) and Ki67 labelling index in the cortex and medulla in both kidneys weremeasured.
In all three groups, the MI and the Ki67 increased significantly at 24 hours, reached a peak at 48 hours, and then declined thereafter. At 48 hours the MI in the right kidney was highest in Group 1(saline) and lowest in Group 3 (tacrolimus) (11 vs 10 vs 6; p < 0,05). The pattern was similar in both the cortex and the medulla of the kidney. In contrast at 48 hours, the Ki67 in the rightkidney was highest in Group 2 (cyclosporine) and lowest in Group 3 (tacrolimus) (33 vs 26 vs 19; p < 0.05). Interestingly there was a small but significant increase in MI and Ki67 in the left(non-ischaemic) kidney.
In conclusion, tacrolimus significantly inhibits the regeneration of the renal tubules after an ischaemic injury to the kidney. There is evidence that cyclosporine may potentiate the regenerationresponse in the renal tubules. The presence of regeneration in the left (non-ischaemic) kidney supports an endocrine effect of the growth factors.
Disclosure: All authors have declared no conflicts of interest.
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