Advertisement

ResearchIn-Press PreviewGeneticsNephrology Open Access | 10.1172/JCI157782

Synuclein α accumulation mediates podocyte injury in Fabry nephropathy

Fabian Braun,1 Ahmed Abed,2 Dominik Sellung,2 Manuel Rogg,3 Mathias Woidy,4 Oysten Eikrem,5 Nicola Wanner,6 Jessica Gambardella,7 Sandra D. Laufer,1 Fabian Haas,1 Milagros N. Wong,1 Bernhard Dumoulin,1 Paula Rischke,1 Anne K. Mühlig,1 Wiebke Sachs,8 Katharina von Cossel,9 Kristina Schulz,1 Nicole Muschol,9 Sören W. Gersting,4 Ania C. Muntau,11 Oliver Kretz,1 Oliver Hahn,12 Markus M. Rinschen,1 Michael Mauer,13 Tillmann Bork,2 Florian Grahammer,1 Wei Liang,2 Thorsten Eierhoff,15 Winfried Römer,16 Arne Hansen,17 Catherine Meyer-Schwesinger,8 Guido Iaccarino,7 Camilla Tøndel,5 Hans-Peter Marti,5 Behzad Najafian,19 Victor G. Puelles,1 Christoph Schell,2 and Tobias B. Huber1

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Braun, F. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Abed, A. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Sellung, D. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Rogg, M. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Woidy, M. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Eikrem, O. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Wanner, N. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Gambardella, J. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Laufer, S. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Haas, F. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Wong, M. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Dumoulin, B. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Rischke, P. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Mühlig, A. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Sachs, W. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by von Cossel, K. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Schulz, K. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Muschol, N. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Gersting, S. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Muntau, A. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Kretz, O. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Hahn, O. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Rinschen, M. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Mauer, M. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Bork, T. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Grahammer, F. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Liang, W. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Eierhoff, T. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Römer, W. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Hansen, A. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Meyer-Schwesinger, C. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Iaccarino, G. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Tøndel, C. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Marti, H. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Najafian, B. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Puelles, V. in: JCI | PubMed | Google Scholar |

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Schell, C. in: JCI | PubMed | Google Scholar

1III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Department of Medicine IV, Medical Center, University of Freiburg, Hamburg, Germany

3Institute of Surgical Pathology, Medical Center, University of Freiburg, Hamburg, Germany

4University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Clinical Medicine, University of Bergen, Bergen, Norway

6Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Freiburg, Germany

7Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

8Institute of Cellular and Integrative Physiology, Center for Experimental M, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

9Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10University Children's Hospital, University Medical Center Hamburg-Eppendorf, Eppendorf, Germany

11University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany

12Department of Biomedicine, Aarhus University, Aarhus, Denmark

13Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, United States of America

14Department of Medicine IV, Medical Center, University of Freiburg, Freiburg, Germany

15Department of Vascular and Endovascular Surgery, University Hospital of Münster, Münster, Germany

16Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany

17Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

19Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States of America

Find articles by Huber, T. in: JCI | PubMed | Google Scholar |

Published April 4, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI157782.
Copyright © 2023, Braun et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 4, 2023 - Version history
View PDF
Abstract

Current therapies for Fabry disease are based on reversing intra-cellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosome dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kidney disease remains unclear. First, ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Then, a CRISPR/CAS9-mediated α-Galactosidase knockout podocyte cell line confirmed ERT-mediated reversal of Gb3 accumulation without resolution of lysosomal dysfunction. Transcriptome-based connectivity mapping and SILAC-based quantitative proteomics identified alpha-synuclein (SNCA) accumulation as a key event mediating podocyte injury. Genetic and pharmacological inhibition of SNCA improved lysosomal structure and function in Fabry podocytes, exceeding the benefits of ERT. Together, this work reconceptualizes Fabry-associated cell injury beyond Gb3 accumulation, and introduces SNCA modulation as a potential intervention, especially for patients with Fabry nephropathy.

Graphical Abstract
graphical abstract
Supplemental material

View Supplemental Table S1

View Supplemental Table S2

View Supplemental Figures

View Supplemental File - all uncropped blots

Version history
  • Version 1 (April 4, 2023): In-Press Preview
  • Version 2 (June 1, 2023): Electronic publication
Advertisement
Advertisement