Saquinavir in steroid-dependent and -resistant nephrotic syndrome: a pilot study.

Rosanna Coppo, Roberta Camilla, Maria Gabriella Porcellini, Licia Peruzzi, Bruno Gianoglio, Alessandro Amore, Valentina Daprà, Elisa Loiacono, Valentina Fonsato, Antonio Dal Canton, Ciro Esposito, Pasquale Esposito, Pier Angelo Tovo

Research output: Contribution to journalArticle

Abstract

Some difficult cases of idiopathic nephrotic syndrome (NS) have been treated with a HIV protease inhibitor provided with proteasome-inhibiting activity. The objective of this study was to limit nuclear factor κB (NF-κB) activation which is up-regulated in these patients, aiming at decreasing proteinuria and prednisone need. Ten cases with long-lasting (up to 15 years) history of NS with steroid dependence (six cases, of which three with secondary steroid resistance) or resistance to steroids (four cases) unsuccessfully treated with multiple immunosuppressive drugs, accepted a treatment with the protease inhibitor saquinavir. p50/p65 NF-κB nuclear localization and immunoproteasome/proteasome messenger RNA (mRNA) were monitored in peripheral blood mononuclear cells (PBMCs). The effects of saquinavir on NF-κB nuclear localization in cultured PBMCs and in immortalized human podocytes were assessed. After a median follow-up of 14.7 months (6-68.7), 1/4 primary steroid-resistant NS (SRNS) and 5/6 steroid-dependent NS or secondary SRNS became infrequent (5) or frequent (1) relapsers, with 63% prednisone reduction (from 25.3 to 8.4 mg/kg/month, P = 0.015). Saquinavir was effective in association with low doses of calcineurin inhibitors (cyclosporine 2 mg/kg/day or tacrolimus 0.01-0.06 mg/kg/day). No side effects were observed apart from transitory mild diarrhoea. In PBMCs, NF-κB was down-regulated, while MECL-1 immunoproteasome/beta2 proteasome mRNA ratio was reversed to normal values. In culture, saquinavir blunted NF-κB activation in human podocytes and in PBMCs. In this pilot study, a HIV antiprotease drug reduced proteinuria and had a steroid-sparing effect in some multidrug-resistant/-dependent NS. This observation warrants further investigation.

Original languageEnglish
Pages (from-to)1902-1910
Number of pages9
JournalNephrology Dialysis Transplantation
Volume27
Issue number5
Publication statusPublished - May 2012

ASJC Scopus subject areas

  • Medicine(all)

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    Coppo, R., Camilla, R., Porcellini, M. G., Peruzzi, L., Gianoglio, B., Amore, A., Daprà, V., Loiacono, E., Fonsato, V., Dal Canton, A., Esposito, C., Esposito, P., & Tovo, P. A. (2012). Saquinavir in steroid-dependent and -resistant nephrotic syndrome: a pilot study. Nephrology Dialysis Transplantation, 27(5), 1902-1910.