ESPN 50th Annual Meeting

ESPN 2017


 
The role of macrophage activation markers in the therapeutic monitoring of nephropathic cystinosis: a multicenter longitudinal study
MOHAMED IBRAHIM 1 KOENRAAD VEYS 1 MIRIAN JANSSEN 2 KATHARINA HOHENFELLNER 3 GIUSI PRENCIPE 4 LAMBERTUS VAN DEN HEUVEL 1 ELENA LEVTCHENKO 1

1- KU LEUVEN
2- RADBOUD UNIVERSITY MEDICAL CENTER
3- KLINIKUM TRAUNSTEIN
4- OSPEDALE PEDIATRICO BAMBINO GESU
 
Introduction:

Cystinosis is an autosomal recessive lysosomal storage disorder characterized by cystine accumulation and 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 all over the world. Recent evidence suggests that inflammatory cells play an important 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.

Material and 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 macrophage activation markers including chitotriosidase. 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 during the previous two years ranged from 0.65 to 5.8 nmol ½ cystine/mg protein. During the first year, 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).

Conclusions:

Chitotriosidase activity seems to correlate with long-term cystine accumulation and can be a candidate for the therapeutic monitoring of cysteamine therapy in nephropathic cystinosis.