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Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: A pilot study. Background. We sought to assess the safety and efficacy of enzyme replacement therapy (ERT) with recombinant human-α-galactosidase A (rh-α-Gal A) in kidney transplant recipients with Fabry disease, a previously unstudied population. Methods. Three male kidney transplant recipients with biochemically, genetically, and histologically confirmed Fabry disease and documented Fabry myocardiopathy received the rh-α-Gal A, agalsidase beta, 1 mg/kg of body weight every 2 weeks by intravenous infusion and were monitored biochemically, clinically, and electrocardiographically and echocardiographically for 18 months. Results. Patients showed biochemical, clinical/functional, and morphologic response to ERT. Plasma globotriaosylceramide decreased 23% to 50%. Extremity pain resolved within 2 months in the patient with this manifestation. On echocardiography, left ventricular mass, end diastolic diameter (EDD), and cardiac contractility, shown by ejection fraction (EF), improved in 2 of the 3 patients receiving essentially all planned infusions. EDD and EF remained basically stable, but cardiac morphologic abnormalities progressed in the other patient, who had a 5-month interruption in ERT after the initial month. Mild mitral insufficiency persisted in all patients, as did atrial fibrillation in the affected individual. After a combined total of 116 infusions, no treatment-related adverse event, intolerance, or seroconversion was seen. Renal function remained stable and the immunosuppression regimen unchanged in all patients. Conclusion. Our pilot study provides preliminary evidence that ERT with agalsidase beta, 1 mg/kg every 2 weeks, is safe and often effective against extra-renal manifestations in kidney transplant patients with Fabry disease. Studies with longer courses of this and higher doses of ERT are merited in this population. [ABSTRACT FROM AUTHOR]

Effects of 1,25(OH)2D3 in experimental mesangial proliferative nephritis in rats. Background. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D3, is a potent immunomodulatory agent on several cell types such as monocytes and mesangial cells. Recruitment of inflammatory cells, as well as stimulation of resident cells and mesangial matrix accumulation are key features of various experimental and human glomerular diseases. Here we show that 1,25(OH)2D3 attenuates the morphologic and functional alterations in anti-Thy-1.1. nephritis, an experimental model of mesangial proliferative glomerulonephritis. Methods. The anti-Thy-1.1 group (group I) comprised 24 rats that at day 0 received 0.5 mL of saline containing 400 μg of monoclonal antibodies (mAb) anti-Thy-1.1 IgG. The anti-Thy-1.1 treated with 1,25(OH)2D3 group (group II) were 24 rats given 1,25(OH)2D3 at the dose of 25 ng/100 g body wt/day, from day -3 to day 14. At day 0, the rats received 400 μg of anti-Thy-1.1 monoclonal IgG. The control group (group III) comprised 12 rats injected with vehicle alone; the control group treated with 1,25(OH)2D3 (group IV)—12 rats were given 1,25(OH)2D3 as in group II without mAb administration. Proteinuria and urinary interleukin-6 excretion were measured daily. Blood urea nitrogen and creatinine, creatinine clearance, calcium, and phosphate were measured at days 0, 4, 7, and 14. In addition to conventional periodic acid-Schiff staining, binding of anti-Thy-1.1 IgG and C3b complement fraction, His48- and ED1–positive cells were studied by immunofluorescence. Mesangial proliferation was studied by the proliferating cell nuclear antigen (PCNA) technique. Apoptosis was evaluated by the TUNEL assay. Results. The anti-Thy-1.1 treated with 1,25(OH)2D3 group versus the anti-Thy-1.1 alone group showed a significant reduction in urinary protein (at day 7, 424 ± 228 vs. 66 ± 30 mg/mg urinary creatinine, P = 0.02) and interleukin-6 excretion (at day 3, 537 ± 360 pg/mL vs. 110 ± 34 pg/mg urinary creatinine, P = 0.015), reduced glomerular diameters (at day 7, 283 ± 38 vs. 261 ± 48 μm, P < 0.01), decreased neutrophil (at day 4, 20 ± 12 His48-positive cells/glomerulus vs. 3.7 ± 1.3 His48-positive cells/glomerulus, P < 0.001), and monocyte accumulation (day 7, 4.9 ± 2.9 ED1-positive cells/glomerulus vs. 2.8 ± 2.9 ED1-positive cells/glomerulus, P < 0.05), and attenuated glomerular cells proliferation (day 7, 13 ± 3.2 PCNA-positive cells/glomerulus vs. 9.4 ± 3 PCNA-positive cells/glomerulus, P < 0.01). Apoptosis showed a biphasic behavior with an early peak at day 4 in the anti-Thy-1.1 group (2.3 ± 2.2 TUNEL-positive cells/glom) related to cellular lysis and a late peak at day 14 related to the recovery phase. Conclusions. 1,25(OH)2D3 can reduce glomerular hypercellularity, inflammatory infiltration in anti-Thy-1.1 nephritis, preserving the apoptotic response of the reparative phase. [ABSTRACT FROM AUTHOR]