Use of CFTR Modulators for Cystic Fibrosis in a Patient with Liver Transplant and ESRD on Hemodialysis

Abstract

Cystic fibrosis is an autosomal recessive disorder caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most recent therapeutic approach to cystic fibrosis aims to correct structural and functional abnormalities of CFTR protein.
CFTR modulators including ivacaftor-tezacaftor-elexacaftor are used in patients with F508del mutation, with clinical improvement. To date, there are no experiences of CFTR modulator therapy in cystic fibrosis patients with organ transplantation and severe renal impairment.
We report the case of a patient diagnosed with cystic fibrosis with F508del mutation, who underwent liver transplantation at the age of 19 and started hemodialysis at the age of 24 due to end-stage renal disease secondary to membranous glomerulonephritis. She was treated with Kaftrio (ivacaftor-tezacaftor-elexacaftor) with clinical benefits on appetite, improvement of body mass index, and reduction of pulmonary exacerbations. A reduction of dosage to 75% of the standard dose was required due to alterations of the liver function.
Conclusions. Use of CFTR modulators in patient with cystic fibrosis, liver transplant and end-stage renal disease could be considered safe but a clinical and laboratoristic monitoring of hepatic function is needed.

Keywords: CFTR modulators, cystic fibrosis, ESRD, liver transplant

Introduction

Cystic fibrosis (CF) is an inherited disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, expressed on the epithelial cells of many organs, including respiratory tract, pancreas, liver, intestine, reproductive tract.

The main clinical manifestations include chronic productive cough, difficulty in breathing, intolerance to exercise, pancreatic insufficiency, intestinal malabsorption, meconium ileus at birth.

The main burden to quality of life and the major cause of mortality in CF is progressive lung disease secondary to chronic airway obstruction that predisposes to recurrent pulmonary infection.

Classical treatment of CF is focused on the consequences of CFTR dysfunction and it includes respiratory physiotherapy, muco-active agents, aggressive antibiotic therapy, pancreatic enzyme replacement, high-calorie and high-fat diet.

The newest therapy approach to CF aims to correct structural and functional abnormalities of CFTR protein using CFTR modulators.

To date, there is no experience of CFTR modulators use in patients with end-stage renal disease (ESRD) and in patients undergone organ transplantation. 

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