• Rosanna Coppo.
• Nephrology Dialysis and Transplantation, City of Health and Science of Turin, Regina Margherita Children's Hospital, Turin, Italy. rosanna.coppo@unito.it
• Contrib Nephrol. 2013 Jan 1; 181: 84-90.

AbstractVarious drugs have been used for the treatment of focal segmental glomerular sclerosis (FSGS) or minimal change disease (idiopathic nephrotic syndrome, INS) including methylprednisolone pulses, alkylating agents and calcineurin inhibitors, often without a strong rationale. For some drugs the rationale has been recently provided by the identification of mechanisms regulating proteinuria. The characterization of molecules acting as permeability factors, including hemopexin, soluble urokinase receptor and cardiotrophin-like cytokine-1, supports plasma exchange in severe cases of INS, particularly in patients at high risk of recurrence of FSGS after transplantation. The collaboration of B and T cells for the production of permeability factors has provided a rationale for targeting B cells using rituximab. Several studies in children and adults, mostly in steroid-dependent cases, or after recurrence in grafted kidneys, have reported improved outcomes after rituximab. Podocyte actin cytoskeleton is a new target for therapy. Calcineurin inhibitors block the dephosphorylation of the cytoskeleton component synaptopodin, and steroids increase actin polymerization and stability. High doses of methylprednisolone and cyclosporine proved to be beneficial in patients with a high risk of FSGS recurrence. An interesting new target for blunting the INS pathogenetical mechanisms is the transcription factor nuclear factor-κB (NF-κB) which was reported to be activated in circulating mononuclear cells of these patients. NF-κB is regulated by the proteasome and saquinavir, a HIV protease inhibitor, is provided with antiproteasome activity. Using saquinavir associated with small doses of calcineurin inhibitors, we treated a small series of very difficult cases of INS with insufficient response to steroid therapy and multiple immunosuppressive drugs. Saquinavir allowed a significant reduction of steroid cumulative doses and disappearance of features of steroid toxicity. In conclusion, recent reports have allowed a new insight into the pathogenetical mechanism regulating proteinuria in INS, offering new targets for treating severe cases.Copyright © 2013 S. Karger AG, Basel.

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