Combined heart and kidney transplantation in a patient with Fabry disease in the enzyme replacement therapy era.

Fabry disease (FD) is an X-linked genetic disease, resulting from the deficiency of alpha-galactosidase A, a lysosomal enzyme responsible for the cleavage of glycosphingolipids. In absence of enzyme replacement therapy (ERT), globotriaosylceramide (Gb3) accumulates in tissue, leading to progressive organ damage with severe renal, cardiac and central nervous system complications. We herein describe the first case of successful combined and simultaneous heart and kidney transplantation in a young male patient with FD complicated by end-stage renal disease and severe heart failure not responding to late-onset ERT. Combined heart and kidney transplantation can be recommended for Fabry patients with end-stage renal disease and overt hypertrophic cardiomyopathy, severe ischemic or valvular heart disease.

Intracranial Nocardia recurrence during fluorinated quinolones therapy.

Nocardia infection is a well-recognized complication in renal transplant recipients and other immunocompromised hosts. It is mostly a primary pulmonary infection, which can disseminate to other organs in half of the cases. Nocardiosis is a life-threatening infection. Therefore, an efficient long-lasting treatment must be rapidly administered. We report 1 case of disseminated nocardiosis with pulmonary involvement, brain lesions, and bone lesions in a renal transplant patient, who was treated with stereotactic aspiration in association with high dose of trimethoprim/sulfamethoxazole (TMP/SMX) and imipenem, changed, after 3 weeks to moxifloxacin. First, clinical manifestations decreased after surgical drainage and combination therapy with the 2 antimicrobial agents, but later the patient developed a recurrence of brain lesions during treatment with quinolones. Consequently, the patient was again treated with TMP/SMX and imipenem, after which the patient recovered. It is surprising that moxifloxacin was efficient in vitro and the antimicrobial concentration in the central nervous system was high, yet the nocardial abscess recurred under this therapy.

[The benefits of new immunosuppressive treatments in adult kidney transplantation]. / Apport des nouvelles thérapeutiques immunosuppressives en transplantation rénale adulte.

NEW KNOWLEDGE: Over the last few years, improved knowledge of the immunological mechanisms underlying transplant rejection have resulted in the development of new immunosuppressive agents capable of selectively blocking various steps of the immune response. NEW MOLECULES: The review focuses on new immunosuppressive drugs that have been developed for clinical use in renal transplantation and mechanism of action, advantages and side effects will be discussed for each of them. Neoral is a cyclosporin microemulsion, characterized by more consistent absorption. Tacrolimus shares with cyclosporin an ability to inhibit calcineurin but presents some differences. Mycophenolate mofetyl selectively inhibits purine synthesis and lymphocyte proliferation; it is easy to use and has been found effective in large clinical trials. Rapamycin and RAD are two related molecules that inhibit signal transduction by cytokines to T-cells, their use in transplant therapy remains to be determined. Anti-interleukin-2 receptor antibodies are also reviewed; they are easy to use and have been found effective. NEW STRATEGIES: These new immunosuppressive drugs provide new approaches in transplant therapy to improve their efficacy and safety.

Renal transplantation in a patient with hypocomplementemic urticarial vasculitis syndrome.

We describe a 36-year-old man who presented with hypocomplementemic urticarial vasculitis syndrome (HUVS) with severe renal involvement. Despite steroid therapy, the patient developed end-stage renal disease (ESRD) leading to chronic hemodialysis therapy. Renal transplantation was performed after hemodialysis therapy (secondary), and the patient developed a typical HUVS relapse 9 months after transplantation despite conventional immunosuppressive therapy that was successfully treated with plasma exchange. This case shows for the first time that HUVS can induce severe renal involvement responsible for ESRD and that HUVS can relapse after renal transplantation. It also suggests that plasma exchange therapy may be of value for rapidly controlling the clinical symptoms.

[Recent immunologic aspects]. / Aspects immunologiques actuels.

Three main aspects of rejection are described in kidney transplantation: hyperacute graft rejection mediated by cytotoxic antibodies, acute rejection initiated by lymphocytes T CD4+ activated after direct or indirect pathways of allopeptides recognition, and chronic rejection (graft chronic dysfunction). Immunologic and non-immunologic factors have been implicated in the development of chronic rejection but there is no evidence for a unique physiopathological pathway. The various steps of immune response in acute rejection have been better defined in the past years. The development of new immunosuppressive drugs and their combination have led to drastic decrease of acute graft rejection occurrence. On the other hand, highly HLA sensitized recipients, chronic graft rejection and toxicity of immunosuppressive drugs should support active research but the final goal is the induction of a specific tolerance.

[Results of 25 years of kidney transplantation]. / Résultats de 25 ans de transplantation rénale.

Between 1975 and 2000, 1008 renal transplantations were performed in 935 recipients at Henri Mondor hospital. The mean objective of this study is to analyse patient and graft survivals at long term. For kidney transplantations performed respectively before and after 1985, ten years patient survival was 74.3% +/- 0.03 and 85.7% +/- 0.01, p = 0.03 and ten years graft survival was 39.5% +/- 0.04 and 71.9% +/- 0.02 after 1985, p = 0.001. Since 1985, an enhancement in graft actuarial survival still improved (one year survival 86.1% +/- 0.01 versus 90.8% +/- 0.02, three years survival 78.5% +/- 0.02 versus 85.5% +/- 0.02, five years survival 71.7% +/- 0.02 versus 78.8% +/- 0.04, for the years 1985-1994 versus 1995-2000, p < or = 0.05). Immunosuppressive drugs may contribute to results enhancement in kidney transplantation while other non immunologic factors are becoming more predominant.

[Use of mycophenolate mofetil (MMF) in kidney transplantation: results of a single center trial]. / Utilisation du mycophénolate mofétil (MMF) en transplantation rénale: résultats d'une expérience monocentrique.

Mycophenolate Mofetil (MMF) is a new immunosuppressant demonstrated to be effective at the dose of 2 to 3 g/day. The objective of this study was to determine whether MMF could be used at a lower dose with the same efficacy. Two patient groups were studied: 334 patients treated with azathioprine (AZA) and 60 patients treated MMF (at the dose of 750 mg/day, for patients receiving triple combination therapy or 1.5 g/day for those receiving two-agent combination therapy). The rest of the treatment was identical for the 2 groups. The main endpoint was the incidence of acute rejection at 3 months, which was 16% in the MMF group and 35% in the AZA group (p = 0.003). Multivariate analysis confirmed the impact of the type of purine synthesis inhibitor used (AZA or MMF, p = 0.007) on the acute rejection rate at 3 months. This study confirms the value of MMF, even at doses lower than those recommended in the international literature, with improved safety. MMF has now replaced azathioprine in our immunosuppressant protocols.