Abstract: SA-PO609
Macrophage Enzyme Chitotriosidase Reflects Long-Term Cystine Accumulation in Cystinosis
Session Information
- Noncystic Mendelian Diseases
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Genetic Diseases of the Kidney
- 802 Non-Cystic Mendelian Diseases
Authors
- Elmonem, Mohamed A., University Hospital Leuven, KU Leuven, Leuven, Belgium
- Veys, Koenraad, University Hospitals Leuven, Leuven, Belgium
- Van dyck, Maria, university hospitals Leuven, Leuven, Belgium
- Janssen, Mirian Ch, Radboudumc university Medical centre, NIJMEGEN, Netherlands
- Cornelissen, Elisabeth A.M., Radboud University Medical Centre, Nijmegen, Netherlands
- Levtchenko, Elena N., University Hospitals Leuven, Leuven, Belgium
Background
Cystinosis is an autosomal recessive lysosomal storage disorder characterized by early renal damage. Strict compliance to the cystine depleting agent cysteamine is necessary for more efficient treatment. Leucocyte cystine is the current therapeutic monitor. Although highly specific, its use is hindered by many technical difficulties and its availability in only few laboratories. Recent evidence suggests that inflammatory cells play a major role in the pathogenesis of cystinosis and its rapid progression to ESRD. Macrophage activation markers, such as chitotriosidase and several cytokines have been linked to disease severity and response to cysteamine therapy in cross-sectional studies. We aim to assess the longitudinal clinical value of these markers as potential therapeutic monitors in a large cohort of cystinosis patients.
Methods
Fifty four patients (19 children and 35 adults) were recruited from the cystinosis clinics in Leuven (Belgium), Nijmegen (Netherlands) and Traunstein (Germany). Patients were followed-up for two years during which, clinical and laboratory data were regularly collected from hospital records. Every three months, plasma samples were obtained to analyze chitotriosidase and other cytokines. These markers were correlated with leucocyte cystine concentration and with other parameters of renal disease such as, serum creatinine and urinary albumin/creatinine ratio.
Results
Cystinosis patients showed large variation in compliance/response to cysteamine therapy. Average leucocyte cystine concentrations over two years ranged from 0.65 to 5.8 nmol ½ cystine/mg protein. During the first year of the study, plasma chitotriosidase activities ranged from 2 to 834 nmol/ml plasma/h in cystinosis patients (reference range <55 nmol/ml plasma/h). Chitotriosidase activities correlated with individual cystine measurements (r=0.432, P=0.002). More importantly, the correlation was stronger with the average cystine values (r=0.582, P<0.001).
Conclusion
Chitotriosidase activity correlates with long-term cystine concentrations and can be used for the therapeutic monitoring of cysteamine therapy in nephropathic cystinosis.
Funding
- Commercial Support – Raptor pharmaceuticals