Posttransplant Kaposi Sarcoma and Risk for Deep Venous Thrombosis: A Case-Control Study

Abstract

Kaposi sarcoma (KS) is a vascular tumor of the skin, subcutaneous tissues, or gastrointestinal tract arising from endothelial cells in immunocompromised, human herpesvirus-8 (HHV8)-positive patients. In addition to human immunodeficiency virus (HIV) infection, immunosuppressive medication, for example, after solid-organ transplantation, may lead to reactivation of a latent HHV8 infection and KS formation. Although a regular dermatological check up is mandatory for solid-organ transplant recipients to exclude frequent epithelial tumors (1), diagnosis of posttransplant KS may be delayed because of less awareness for this entity in nonendemic areas such as Germany. Differences in host defense and complex subcellular regulations may sign responsible for a great variation in KS incidence (2, 3). Mammalian target of rapamycin inhibitors such as everolimus or sirolimus are the mainstay of KS therapy through its vascular endothelial growth factor inhibitory action (4, 5). Evidence from registry studies with HIV-positive and AIDS patients showed that 23% of HIV/AIDS patients with incident deep venous thrombosis (DVT) had KS as exclusive tumor comorbidity (6). For posttransplant KS, it is unclear whether DVT risk is increased. In a case report, posttransplant KS developed at a skin site where DVT occurred before suggesting the possibility of KS being promoted by DVT through a yet unclear mechanism (7). Alternatively, KS lesions may impede venous blood flow directly or by KS-associated lymphedema (8), thereby promoting DVT in the absence of classic DVT risk factors. At a kidney transplant unit of a University clinic in Germany, a case-control study was conducted to determine the incidence of DVT in kidney transplant recipients with and without histologically proven posttransplant KS. Four HHV8-positive kidney transplant recipients or 0.4% of all kidney transplant recipients were diagnosed with posttransplant KS at the Hospital of the Johann-Wolfgang-Goethe University, Frankfurt am Main, Germany, between 1991 and 2006. As case-control study, each kidney transplant recipient with posttransplant KS matched by a control. Control patients received a kidney transplant 3 months before or after kidney transplantation of the index patient. They had the same transplant modality (living-donor or deceased-donor kidney transplantation), the same gender, and a comparable allograft survival. If more than one patient fulfilled these criteria, the patient with the closest age match was chosen. Based on hospital and outpatient-care records, the incidence of DVT was determined for both posttransplant KS and control patients between 1991 and 2006. Time from transplantation to occurrence of posttransplant KS was 1112±990 days. KS patients and control patients had similar immunosuppression regimens. DVT was not reported before kidney transplant in neither group (Table 1). However, DVT occurred in three of four KS patients at 889±713 days after kidney transplantation, whereas none of the control patients developed DVT after kidney transplant (P=0.02). DVT diagnosis preceded KS diagnosis by 851 and 578 days in two posttransplant KS patients or occurred 674 days after KS diagnosis in one patient.TABLE 1: Patient characteristics of kidney transplant recipients with (cases) or without (controls) incident posttransplant Kaposi sarcoma between 1991 and 2006In all KS patients, calcineurin inhibitor was switched to mammalian target of rapamycin inhibitor therapy, while steroid and mycophenolate mofetil therapy was maintained. One posttransplant KS patient received an empiric interferon therapy. Because of side effects, two patients had to be switched back to a low-dose calcineurin inhibitor regimen. No KS patient lost kidney transplant function or died by the end of the observation period. However, one KS patient unexpectedly died from acute aortoiliac thrombosis, acute Leriche syndrome, 593 days after DVT or 1.5 year after the end of the study period. Control patients had no change of immunosuppression drug class by the end of the study period. One control patient lost kidney transplant function 14.9 years after transplantation and had to resume intermittent hemodialysis therapy. No control patient died during the study period or during a 2-year follow-up period. Taken together, this single-center, case-control study found a significantly increased occurrence of DVT in kidney transplant recipients with KS when compared with age-matched KS-free counterparts. However, because of the small number of KS cases and the relatively long time elapsed between DVT and KS diagnosis of up to 2.4 years, the occurrence of both KS and DVT may be a coincidental finding. However, from the data of this small case-control study, a further investigation for a possible association between KS and DVT seems to be justified. Rainer U. Pliquett1,2 Helmut Schöfer3 Aida Asbe-Vollkopf1 Ingeborg A. Hauser1 Ernst H. Scheuermann4 Heinz-Georg Kachel4 1 Department of Nephrology University Hospital Johann Wolfgang Goethe University Frankfurt/Main, Germany 2 Currently, Department of Nephrology University of Halle Halle/S, Germany 3 Clinic for Dermatology, Venereology, and Allergology University Hospital Johann Wolfgang Goethe—University Frankfurt am Main, Germany 4 KFH Nierenzentrum/Renal Unit Frankfurt am Main, Germany