Kidney Week

Abstract: PUB216

Enzyme Replacement Therapy and Fabry Nephropathy

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Gueiros, Ana Paula, Instituto de Medicina Integral Professor Fernando Figueira, Recife, Pernambuco, Brazil

Ana Paula Gueiros,

• Gueiros, Jose Edevanilson, Instituto de Medicina Integral Professor Fernando Figueira, Recife, Pernambuco, Brazil

Jose Edevanilson Gueiros,

• Santos, Andréa De melo, Instituto de Medicina Integral Professor Fernando Figueira, Recife, Pernambuco, Brazil

Andréa De melo Santos,

• Antunes, Natália Soares, Instituto de Medicina Integral Professor Fernando Figueira, Recife, Pernambuco, Brazil

Natália Soares Antunes,

• Siqueira, Ana cecília Menezes, Instituto de Medicina Integral Professor Fernando Figueira, Recife, Pernambuco, Brazil

Ana cecília Menezes Siqueira,

Introduction

In Fabry nephropathy (FN), alpha-galactosidase deficiency leads to accumulation of glycosphingolipidis in all kidney cell types, proteinuria and progressive loss of kidney function. The aim of this study was to assess the clinical course of FN in two women with pathogenic mutations undergoing treatment with agalsidase beta (Fabrazyme^®; Sanofi Genzyme, Cambridge, MA, USA) during a 6-year period.

Case Description

Case 1– AMSL, aged 61. Symptoms first appeared when the patient was aged 51, when she complained of myalgia, arthralgia, asthenia, dyspnea on exertion, tinnitus, abdominal pain and constipation. One year later, she was diagnosed with proteinuria and heart disease. She performed a kidney biopsy, which under light microscopy suggested deposit disease. No electron microscopy was performed. Genetic analysis demonstrated a mutation in exon 5 - p.K237X. At the time, she presented with creatinine (Cr) of 0.9 mg/dL and proteinuria of 1.2 g/day and an echocardiogram with a left ventricular mass (LV) of 392 g and LV mass index 238 g/m². In January 2012, she initiated enzyme replacement therapy (ERT) with agalsidase beta, 1.0 mg/Kg body weight once every 2 weeks, and conversion enzyme inhibitor. Currently, Cr is 1.0 mg/dL and proteinuria 0.3 g/day. During the follow-up period, there were no major cardiovascular and/or central nervous system events.
Case 2– DCBT, aged 60. The patient was diagnosed with cornea verticillata aged 13. Twelve years ago, she presented clinical signs of hypohidrosis, arthralgia, bradycardia and proteinuria. Genotyping revealed a C142R mutation. In 2012, after presenting a transient ischemic attack, she was commenced on ERT with agalsidase beta (1.0 mg/kg once every 2 weeks). At the time, she presented Cr 0.9 mg/dL and proteinuria 0.3 g/day. During the follow-up period, she presented three episodes of atrial fibrillation, which motivated treatment with propafenone and rivaroxaban. Currently, Cr is 0.8 mg/dL and proteinuria 0.17 g/day.

Discussion

This 6-year study has documented the effectiveness of agalsidase beta in patients with FN, despite delayed initiation of ERT.