Early-onset of disseminated cryptococcal infection in two renal transplant recipients.

Cryptococcosis is the third most common invasive fungal infection in organ transplant recipients after candidiasis and aspergillosis. Newly acquired and reactivation of latent infection are the major causes of infection, with typical later-onset and mainly as disseminated infection. The type and intensity of immunosuppression, diabetes mellitus and other co-morbidities as well as uremia seem to be important determinants on clinical presentation and outcome. Moreover, the diagnosis is not always apparent since it usually presents subacutely, as well as mimicking bacterial infections, which may be responsible for a delay in the diagnosis. Thus, a high degree of suspicion and need of invasive procedures for microbiological and histological evaluation are critical for definitive diagnosis and prompt institution of adequate treatment. We report two cases of disseminated cryptococcosis with different presentations and with an early-onset after renal transplantation.

Rituximab for steroid-dependent nephrotic syndrome.

Minimal change disease (MCD) is characterized by marked sensitivity to glucocorticoid therapy. However, in 40 - 50% of all cases the disease presents with frequent relapses and needs repeated courses of steroids as well as additional immunosuppressive therapy including azathioprine, cyclophosphamide or cyclosporine. Because such regimens are associated with significant toxicity, the therapeutic challenge of this disease is to identify the treatment with the highest probability of producing a sustained remission with the lowest risk of toxicity. There is increasing evidence that rituximab may play an important role in the treatment of idiopathic nephrotic syndrome. Here, we present an adult patient with steroid-sensitive but high-dose steroid-dependent MCD beginning in childhood with a heavy history of multiple immunosuppressive therapy that was brought into 1 year sustained remission of proteinuria with two infusions of rituximab (375 mg/m2).

Relationship between everolimus blood concentration assessed using the Innofluor Certican Fluorescence Polarization Immunoassay and the Architect i System sirolimus chemiluminescent microparticle immunoassay.

Everolimus, an immunosuppressive macrolide derivative of sirolimus, has a narrow therapeutic index and variable bioavailability. Assessment of blood concentration of everolimus is necessary to improve immunosuppressive efficacy without increasing potential adverse effects. Recently, Seradyn, Inc (Indianapolis, Indiana) introduced a fluorescence polarization immunoassay (Innofluor Certican Fluorescent Polarization Immunoassay [FPIA]) for quantitation of everolimus blood concentration. This immunoassay has concentration-dependent cross-reactivity with sirolimus, which must be considered in patients recently treated with that drug. In this short-term study, treatment in 53 renal transplant recipients was converted from a sirolimus-based regimen to an everolimus-based regimen. Patients were followed up for 3 months. We investigated whether cross-reactivity with everolimus also occurred with the Abbott Laboratories (Abbott Park, Illinois) Architect i System, a sirolimus chemiluminescent microparticle immunoassay (CMIA) used to quantify sirolimus blood concentration. Quantification of everolimus blood concentration using both the CMIA and the FPIA demonstrated a linear regression: CMIA = 0.73 FPIA +/- 0.77 (r(2) = 0.80; P < .001). A high degree of correlation between the CMIA and FPIA methods (r = 0.90) was confirmed using the Bland-Altman test. We conclude that the Abbott Architect i System sirolimus CMIA should be considered an alternative method for everolimus drug monitoring. The cross-reactions of both the FPIA and CMIA techniques with both sirolimus and everolimus must be considered when converting therapy from one drug to the other. In these conditions, use of an equivalent dosage is of particular importance.