Tacrolimus Improves the Proteinuria Remission in Patients with Refractory IgA Nephropathy
American Journal of Nephrology, 03/29/2012Zhang Q et al.
Tacrolimus showed a rapid proteinuria remission in refractory IgA nephropathy patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression.
14 refractory IgAN patients were enrolled.
The patients received tacrolimus (0.05–0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months.
Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy.
A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission.
Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline.
In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month.
In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy.
In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased.
After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered.
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