Kaposi's sarcoma in renal transplant recipients--the impact of proliferation signal inhibitors.
The incidence of Kaposi's sarcoma (KS) is greatly increased in renal transplant recipients compared with the general population, with particular prevalence in certain ethnic groups where it can occur in up to 5% of transplant recipients. The increased incidence of disease in transplant populations may, in part, be attributed to the choice of immunosuppressive regimen, with calcineurin inhibitor (CNI)-based immunosuppression being associated with the development of the tumour. A number of small studies have recently demonstrated that conversion to proliferation signal inhibitors (PSIs) along with the concomitant withdrawal of CNIs leads to a rapid resolution of both cutaneous and visceral Kaposi's lesions. In agreement with these data the abrupt onset of KS has been observed following the withdrawal of PSIs. Histological examination of lesions from patients with KS supports data from animal models which suggests that PSIs inhibit tumour angiogenesis through impaired vascular endothelium growth factor production, a key element in the development of the tumour. Previously unpublished data on renal transplant recipients from a number of European and Australian centres have been pooled to provide further insight into the use of PSIs in the management of post-transplant KS. Both members of the PSI class, everolimus and sirolimus, along with CNI withdrawal lead to regression of KS lesions in 11 out of 12 patients. Conversion to PSIs was generally well tolerated with stable renal function maintained in most patients and no episodes of acute rejection recorded. PSIs provide a potential treatment option in the management of post-transplant KS and should be considered for use in renal transplant recipients who develop the disease.
Campistol
Josep M
JM
Department of Nephrology, Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain. jmcampis@clinic.ub.es
Schena
Francesco P
FP
D065095:Calcineurin Inhibitors; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D011494:Protein Kinases / Q000187:drug effects*; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus