Anderson-Fabry disease: a case-finding study among male kidney transplant recipients in Austria.

The diagnosis of Anderson-Fabry disease is often delayed or even missed. As severe renal manifestations are a hallmark of alfa-galactosidase A (AGAL) deficiency, we tested the hypothesis that Anderson-Fabry disease is under-recognized among male kidney transplant recipients. This nation-wide study in Austria enrolled 1306 patients (ca 65% of all kidney transplanted males) from 30 kidney centers. AGAL activity was determined from filter paper dried blood spots by a fluorescence assay. A positive screening test was defined by an AGAL activity below 1.5 nmol/h/ml. In patients with a positive blood spot-screening test, AGAL activity was re-examined in peripheral blood leukocytes. Genetic testing for mutations in the GLA gene was performed by sequencing to confirm the diagnosis of Anderson-Fabry disease. Two previously not recognized cases with Anderson-Fabry disease were identified. Our study is the first showing that a diagnosis of Anderson-Fabry disease can be missed even in patients who undergo kidney transplantation. Case-finding strategies may be considered a useful tool for diagnosis of this rare disease that may be somewhat more prevalent among kidney transplant recipients compared with dialysis populations.

Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation: 2 year follow-up results.

BACKGROUND: Comparison studies of calcineurin inhibitors as cornerstone immunosuppressants in renal transplantation have demonstrated that tacrolimus consistently reduces acute rejection rates and, in some studies, also improves long-term renal outcome in comparison to cyclosporin A (CsA). The aim of the present 2 year follow-up of the European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was to investigate long-term clinical outcome in terms of rate of acute rejection, graft and patient survival and graft function. METHODS: The European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was a randomized, comparative 6 month trial of the calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine and steroids. The intent-to-treat population (ITT) consisted of 286 patients in the tacrolimus arm and 271 in the CsA microemulsion (CsA-ME) arm. Whereas whole blood level targets were 10-20 and 5-15 ng/ml for tacrolimus and 100-400 and 100-200 ng/ml for CsA during months 0-3 and 4-6, respectively, during the investigator-driven follow-up after termination of the main study (months 7-24) no specific calcineurin inhibitor target levels were required. Follow-up data were collected at 2 years post-transplantation from 237 (82.9% of the ITT population) patients who received tacrolimus and 222 (81.9% of the ITT population) patients who received CsA-ME. RESULTS: Calculated on ITT populations, mortality (2.0% vs 3.3%; P<0.05 in Kaplan-Meier analysis) was lower, but rate of graft loss (9.3% vs 11.2%; P = 0.12 in Kaplan-Meier analysis) was not significantly different after 2 years with tacrolimus- vs CsA-ME-based immunosuppression. Biopsy-proven acute rejection was significantly lower (19.6%) with tacrolimus than with CsA-ME (37.3%) during months 0-6 (P<0.0001), but was not significantly different during months 7-12 and 13-24 of follow-up (1.7% and 0.8% with tacrolimus and 4.7% and 0.9% with CsA-ME, respectively). A composite endpoint consisting of graft loss, patient death and biopsy-proven acute rejection occurred significantly more frequently in CsA-ME patients than in tacrolimus patients (42.8% vs 25.9%; P<0.001) during 24 months follow-up. Renal function 2 years post-transplant, measured by serum creatinine concentrations, was significantly better in tacrolimus-based compared with CsA-ME-based immunosuppression (136.9 vs 161.6 micromol/l; P<0.01). Cornerstone immunosuppression remained unchanged in 82.5% and 66.2% of patients treated with tacrolimus and CsA-ME, respectively. At 2 years, more patients in the tacrolimus arm were off steroids and received calcineurin inhibitor monotherapy, and fewer tacrolimus patients remained on a triple immunosuppressive regimen. The cardiovascular risk profile was affected favourably in the tacrolimus arm, with lower cholesterol and triglyceride concentrations (despite less use of cholesterol-lowering drugs); no significant difference in requirement for antidiabetic medication was noted. CONCLUSIONS: The 2 year study results confirm that tacrolimus is a highly efficacious cornerstone immunosuppressant in kidney transplantation. Tacrolimus-based immunosuppression may induce long-term benefits with regard to graft function and graft survival. The overall side-effect profile is considered to be favourable.