REGRESSION OF KAPOSI’S SARCOMA IN RENAL GRAFT RECIPIENTS AFTER CONVERSION TO SIROLIMUS TREATMENT.

Abstract

P852 Kaposi’s sarcoma (KS) is a rare complication of renal transplantation in Poland (in our center it appeared in 2 out of 1000 renal graft recipients). Substantial proportion of tumor structure consists of newly developed vascular capillaries. Neovascularization is usually promoted by tumor - related vascular endothelial growth factor (t-r-VEGF). Experimental studies provided evidence, that sirolimus (Sir) treatment led to reduction in t-r-VEGF synthesis and inhibited intracellular PI3K-p70S6 kinase signalling pathway, required for VEGF stimulation of endothelial cells. The classic approach to treatment of immunocompromised KS patient is reduction of immunosuppressive therapy (IST), which carries a risk of graft rejection. Here we present clinical data, suggesting that immunosuppressive therapy including Sir, may be associated with KS regression. We report 2 patients diagnosed with KS, maintained initially on standard triple IST. The 58, and 51 year old men underwent cadaveric renal transplantation in 2002. Initial IST consisted of cyclosporine A (CsA), azathioprine (Aza), and prednisone (P). Due to acute rejection in 2-nd patient, since 8-th week after transplantation, IST was switched to tacrolimus (Tac) and mycophenolate mophetil (MMF). The onset of KS symptoms appeared 7 months after engraftment in both patients. The first patient presented with brown – blue polyp – like, and plane lesions on the hard palate. In the 12-th month rapidly growing brownish nodular sheling skin lesions, localized on the internal surface of both calves, over the ankles, were noted. Smaller lesions were spread all over the skin. The second patient presented with nearly the same skin and mucous lesions. In the 1-st patient repeated X-ray films showed increasing shadows in lungs with enlargement of mediastinal lymph nodes. It was associated with increasing respiratory insufficiecy. Bronchoalveolar lavage gave no consistent data. In the 1-st patient graft function deteriorated slightly (serum creatinine raised from 1,55 to 1,85 mg/dl), while in the 2-nd patient it remained nearly stable (creatinine ∼2,0 mg/dl). In both patients skin biopsy proved KS. Since confirmation of the diagnosis. IST had been minimized (Aza, CsA or MMF were withdrawn) and switched to sirolimus (1-2 mg/24h) with prednisone (10 mg/24h). Serum levels of sirolimus were maintained within 5-8 ng/ml range. Within one month the progression of lung and skin disease has stopped, and patients condition began to improve: regression of lung opacities, reduction of the biggest nodular skin lesions and disappearance of smaller ones were noted. In one year observation renal function remained stable. Conclusions: It is difficult to ascertain whether KS regression can be atributted to sirolimus treatment or to immunosuppression reduction. Our observation may suggest, that sirolimus based IST brings the possibility of KS regression with concomitant renal function preservation in renal graft recipients.