Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis.

Autor:	Veys KRP; Division of Pediatric Nephrology, Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.; Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium., Elmonem MA; Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt., Van Dyck M; Division of Pediatric Nephrology, Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium., Janssen MC; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Cornelissen EAM; Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., Hohenfellner K; Department of Pediatrics, Children's Hospital of Rosenheim, Rosenheim, Germany., Prencipe G; Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Gesù Children's Hospital, Rome, Italy., van den Heuvel LP; Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.; Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., Levtchenko E; Division of Pediatric Nephrology, Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium elena.levtchenko@uzleuven.be.; Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2020 May; Vol. 31 (5), pp. 1092-1106. Date of Electronic Publication: 2020 Apr 09.
DOI:	10.1681/ASN.2019080774
Abstrakt:	Background: Nephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. White blood cell cystine concentration is the current gold standard for therapeutic monitoring, but the assay is technically demanding and is available only on a limited basis. Because macrophage-mediated inflammation plays an important role in the pathogenesis of cystinosis, biomarkers of macrophage activation could have potential for the therapeutic monitoring of cystinosis. Methods: We conducted a 2-year prospective, longitudinal study in which 61 patients with cystinosis who were receiving cysteamine therapy were recruited from three European reference centers. Each regular care visit included measuring four biomarkers of macrophage activation: IL-1 β , IL-6, IL-18, and chitotriosidase enzyme activity. Results: A multivariate linear regression analysis of the longitudinal data for 57 analyzable patients found chitotriosidase enzyme activity and IL-6 to be significant independent predictors for white blood cell cystine levels in patients of all ages with cystinosis; a receiver operating characteristic analysis ranked chitotriosidase as superior to IL-6 in distinguishing good from poor therapeutic control (on the basis of white blood cell cystine levels of <2 nmol 1/2 cystine/mg protein or ≥2 nmol 1/2 cystine/mg protein, respectively). Moreover, in patients with at least one extrarenal complication, chitotriosidase significantly correlated with the number of extrarenal complications and was superior to white blood cell cystine levels in predicting the presence of multiple extrarenal complications. Conclusions: Chitotriosidase enzyme activity holds promise as a biomarker for use in therapeutic monitoring of nephropathic cystinosis. (Copyright © 2020 by the American Society of Nephrology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu