Tacrolimus Improves the Proteinuria Remission in Patients with Refractory IgA Nephropathy
American Journal of Nephrology, 03/29/2012  Clinical Article

Zhang 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• Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline.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.