Martina Gaggl1, Marlene Hofer2, Stefanie Weidner2, Julia Kleinert2, Günter Fauler3, Manfred Wallner4, Peter Kotanko5, Eduard Paschke6, Gere Sunder-Plassmann2. 1. Department of Medicine III, Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria. martina.gaggl@meduniwien.ac.at. 2. Department of Medicine III, Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria. 3. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria. 4. Department of Internal Medicine IV, Section of Nephrology, Klinikum Wels-Grieskirchen, Wels, Austria. 5. Renal Research Institute, New York, NY, USA. 6. Department of Pediatrics, Medical University Graz, Graz, Austria.
Abstract
INTRODUCTION: Globotriaosylceramide (Gb3, CD77) represents a pivotal part of the cell membrane. Measuring the urinary Gb3 content can be used to screen patients with chronic kidney disease (CKD) for Fabry disease, a disorder caused by hampered Gb3 degradation. However, little is known about factors influencing urinary Gb3 excretion other than Fabry disease. The aim of the present study was to identify routine diagnostic parameters as predictors of urinary Gb3 excretion in patients with CKD. METHODS: Our study included 609 subjects with CKD stage I-V. We analyzed the influence of age, gender, renal function, urinary cell content and chemical characteristics on urinary Gb3 concentrations (total Gb3, Gb3-24 isoform, and Gb3-24:18 isoform ratio), determined by direct electrospray ionization mass spectrometry. RESULTS: In 609 subjects the median total urinary Gb3 was 233 ng/mg and the Gb3-24:18 isoform ratio was 1.2. Twenty-one patients, none of whom had Fabry disease, had a Gb3-24:18 isoform ratio ≥2.3. Females excreted a higher total amount of Gb3, but the Gb3-24:18 isoform ratio was comparable to males. Renal function and age had no influence on total Gb3, Gb3 isoforms or the ratio. Only a distinct load of bacteria and leukocytes was associated with an increased Gb3 excretion. Urinary leukocytes, erythrocytes, bacteria, or protein content did not affect the Gb3-24:18 isoform ratio. CONCLUSION: The Gb3-24:18 isoform ratio is unaffected by several potential influencing variables and may thus be applied for screening for Fabry disease in unselected cohorts of patients presenting with CKD.
INTRODUCTION:Globotriaosylceramide (Gb3, CD77) represents a pivotal part of the cell membrane. Measuring the urinary Gb3 content can be used to screen patients with chronic kidney disease (CKD) for Fabry disease, a disorder caused by hampered Gb3 degradation. However, little is known about factors influencing urinary Gb3 excretion other than Fabry disease. The aim of the present study was to identify routine diagnostic parameters as predictors of urinary Gb3 excretion in patients with CKD. METHODS: Our study included 609 subjects with CKD stage I-V. We analyzed the influence of age, gender, renal function, urinary cell content and chemical characteristics on urinary Gb3 concentrations (total Gb3, Gb3-24 isoform, and Gb3-24:18 isoform ratio), determined by direct electrospray ionization mass spectrometry. RESULTS: In 609 subjects the median total urinary Gb3 was 233 ng/mg and the Gb3-24:18 isoform ratio was 1.2. Twenty-one patients, none of whom had Fabry disease, had a Gb3-24:18 isoform ratio ≥2.3. Females excreted a higher total amount of Gb3, but the Gb3-24:18 isoform ratio was comparable to males. Renal function and age had no influence on total Gb3, Gb3 isoforms or the ratio. Only a distinct load of bacteria and leukocytes was associated with an increased Gb3 excretion. Urinary leukocytes, erythrocytes, bacteria, or protein content did not affect the Gb3-24:18 isoform ratio. CONCLUSION: The Gb3-24:18 isoform ratio is unaffected by several potential influencing variables and may thus be applied for screening for Fabry disease in unselected cohorts of patients presenting with CKD.
Authors: Eduard Paschke; Guenter Fauler; Heimo Winkler; Axel Schlagenhauf; Barbara Plecko; Wolfgang Erwa; Frank Breunig; Wolfgang Urban; Bojan Vujkovac; Gere Sunder-Plassmann; Peter Kotanko Journal: Am J Kidney Dis Date: 2010-12-24 Impact factor: 8.860
Authors: Raphael Schiffmann; Sabrina Forni; Caren Swift; Nastry Brignol; Xiaoyang Wu; David J Lockhart; Derek Blankenship; Xuan Wang; Paul A Grayburn; Matthew R G Taylor; Brian D Lowes; Maria Fuller; Elfrida R Benjamin; Lawrence Sweetman Journal: J Am Heart Assoc Date: 2014-02-04 Impact factor: 5.501
Authors: Martina Gaggl; Natalija Lajic; Georg Heinze; Till Voigtländer; Raute Sunder-Plassmann; Eduard Paschke; Günter Fauler; Gere Sunder-Plassmann; Gerald Mundigler Journal: Int J Med Sci Date: 2016-04-26 Impact factor: 3.738