Cyclosporine formulation and Kaposi's sarcoma after renal transplantation.
BACKGROUND
Transplantation enhances the risk of malignancies, due to the chronic use of antirejection medication. In the case of Kaposi's sarcoma (KS) the permissive effect of immunosuppression has been extensively studied, and cyclosporine (CsA) appears to play a key role. Here we have compared the incidence of KS in transplant patients receiving Neoral or Sandimmune as a part of their immunosuppressive therapy.


METHODS
In all, 668 kidney transplant recipient followed at our Nephrology Unit from 1970 to 2003 entered this retrospective analysis; 300 were on CsA Sandimmune-based and 308 on CsA Neoral-based therapy. The primary endpoint was the occurrence of KS.


RESULTS
KS was diagnosed in 20 out of 608 patients given CsA with an incidence rate of 4.7 per 1000 patients per year. No episodes of KS was found in the preCsA era. Among patients on CsA, those treated with Neoral had fourfold higher incidence rate of KS than in the Sandimmune group (10.7 vs. 2.3 per 1000 patients per year). Kaplan-Meier analysis shows that patients on Neoral had lower cumulative KS-free probability than those on Sandimmune. Cox's analysis documented that Neoral was a positive predictor of KS development as compared to Sandimmune (hazard ratio: 2.237). Among patients on Neoral, those who developed KS had higher daily exposure to the drug assessed by pharmacokinetic studies.


CONCLUSIONS
In recipients of kidney transplant CsA Neoral increases the risk of KS as compared to the Sandimmune formulation, possibly due to enhanced drug bioavailability and ultimately patients daily CsA exposure.
Cattaneo
Dario
D
Department of Medicine and Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Gotti
Eliana
E
Perico
Norberto
N
Bertolini
Guido
G
Kainer
Gad
G
Remuzzi
Giuseppe
G
D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D012189:Retrospective Studies; D012514:Sarcoma, Kaposi / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology; D015996:Survival Rate; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine