A case of nephrotic syndrome, showing evidence of response to saquinavir.

Giles Walters,Faisal A Choudhury,Budhima Nanayakkara

doi:10.1155/2015/512549

Giles Walters, Faisal A Choudhury + Show 1 more

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https://doi.org/10.1155/2015/512549

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Abstract

The treatment of primary nephrotic syndrome such as minimal change nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis nephropathy remains challenging. Whilst most cases of idiopathic nephrotic syndrome respond to steroid therapy and experience a limited number of relapses prior to complete remission, some cases suffer from frequent relapses and become steroid dependent or are primarily steroid resistant. Treatment options are limited to immunosuppressive drugs with significant side effect profiles. New modalities targeting novel pathways in the pathogenesis of nephrotic syndrome are actively sought. Here we report the case of a patient with steroid dependent focal segmental glomerulosclerosis (FSGS) nephrotic syndrome with a favourable response to a novel proteasome inhibitor saquinavir.

Highlights

This case study highlights the potential use of saquinavir, a proteasome inhibitor, to treat a difficult case of steroid dependent nephrotic syndrome
The proteasome was implicated in pathogenesis by studies showing that NF-κB is elevated in circulating peripheral blood mononuclear cells in patients with idiopathic nephrotic syndrome [7, 8]
We report an initial response to this regime, adding support to the small number of existing cases regarding the therapeutic efficacy of saquinavir in the treatment of nephrotic syndrome

Summary

Introduction

This case study highlights the potential use of saquinavir, a proteasome inhibitor, to treat a difficult case of steroid dependent nephrotic syndrome. In addition to its HIV protease inhibition, it acts to inhibit the proteasome, a key factor in the regulation of NF-κB activity [4,5,6]. The proteasome was implicated in pathogenesis by studies showing that NF-κB is elevated in circulating peripheral blood mononuclear cells in patients with idiopathic nephrotic syndrome [7, 8]. This was confirmed by T-cell transcriptome analysis [9]. Elevation of NFkappa beta in T cells and its subsequent translocation into the nucleus lead to synthesis of circulating T-cell factors causing podocyte cytoskeleton disorganisation, increased glomerular permeability, and eventual proteinuria [10]

Case Study

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Discussion

Conclusion