Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Polyzystische Nierenerkrankung im Kindesalter und andere Ziliopathien

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is among the most severe diseases in Pediatric Nephrology and represents one of the most frequent causes of dialysis-requiring end stage renal failure. In polycystic kidney disease, fluid-filled cysts and fibrotic tissue accumulate in the renal parenchyma leading to a progressive loss of renal function. The monogenetic ARPKD is caused by mutations in the PKHD1 gene, encoding the protein fibrocystin. Fibrocstin is a large transmembrane protein of poorly understood function.

The overarching aim of our group is to understand the molecular mechanisms underlying cystogenesis and renal fibrosis in PKD as well as to deeply characterize clinical courses and the effect of current therapeutic approaches in ARPKD.

A special focus of our cell biological work is on the role of FC and FC-associated ciliary proteins. Like other gene products affected in cystic kidney disease, fibrocystin localizes to the so-called primary cilia of cells. Cilia are small hairlikemembrane protuberances projecting from nearly every cell of the human body. Cilia seem to act as little antennae sensing the cellular environment and are crucial regulators of multiple intracellular signaling pathways.

Using multiple screening approaches we recently identified various novel candidates for members of the FC protein complex and are currently characterizing these proteins functionally both in vitro and in vivo. In close collaboration with the Nephrology Research Laboratory of the Department II of Internal Medicine this work examines two main aspects of protein dysfunction in PKD and other ciliopathies: impaired trafficking to cilia and defective signal transduction from cilia to the cell resulting e.g. in altered expression of transcriptional cell programs.

In addition to our molecular work a second main project is a deep clinical and phenotypic characterization of ARPKD patients. ARPKD shows major phenotypic variability. The underlying mechanisms remain unclear. Detailed data on long-term courses are rare and current treatment approaches are symptomatic and mainly based on the opinion of experts.

To improve clinical characterization of ARPKD patients, to gather long-term data and to assess current therapeutic approaches, we recently set up an international ARPKD registry study ( With the support of the German Pediatric Nephrology Association (GPN) and the ESCAPE Network (European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients) this registry study pro- and retrospectively collects pseudonimyzed clinical data of ARPKD patients in a web-based data base. This registry study may lay the foundation for first clinical trials on ARPKD. With the associated biobankARegPKD may also open novel options for translational research.

The Team

Priv.-Doz. Dr. Max Christoph Liebau, leader

Dr. nat. med. Claudia Dafinger
Dr. Kathrin Ebner
Sophie Haumann
Cand. Med. Nora Liekenbrock
Cand. Med. Asem Al-Hamad
Cand. Med. Abdelaziz Akarkach
Cand. Med. Björn Birke


"Zystennieren im Kindesalter"

Max C. Liebau, Dieter Haffner
Monatsschrift Kinderheilkunde
; April 2015, Volume 163, Issue 4, pp 343-351

Rationale, design and objectives of ARegPKD, a European ARPKD registry study

Kathrin Ebner, Markus Feldkoetter, Gema Ariceta, Carsten Bergmann, Reinhard Buettner, Anke Doyon, Ali Duzova, Heike Goebel, Dieter Haffner, Barbara Hero, Bernd Hoppe, Thomas Illig, Augustina Jankauskiene, Norman Klopp, Jens König, Mieczyslaw Litwin, Djalila Mekahli, Bruno Ranchin, Anja Sander, Sara Testa, Lutz Weber, Dorota Wicher, Ayse Yuzbasioglu, Klaus Zerres, Jörg Dötsch, Franz Schaefer, Max C. Liebau, ESCAPE Study Group, GPN Study Group
BMC Nephrology
2015, 16:22 (18 February 2015)

“Consensus Expert Recommendations for the Diagnosis and Management of Autosomal Recessive Polycystic Kidney Disease: Report of an International Conference.”
Lisa M. Guay-Woodford, John J. Bissler, Michael C. Braun, Detlef Bockenhauer, Melissa A. Cadnapaphornchai, Katherine M. Dell, Larissa Kerecuk, Max C. Liebau, Maria H. Alonso-Peclet, Benjamin Shneider, SukruEmre, Theo Heller,Binita M. Kamath, Karen F. Murray, Kenneth Moise, Eric E. Eichenwald,Jacquelyn Evans, Roberta L. Keller, Louise Wilkins-Haug, Carsten Bergmann, MeralGunay-Aygun, Stephen R. Hooper, Kristina K. Hardy, Erum A. Hartung, Randi Streisand,Ronald Perrone, and Marva Moxey-Mims
The Journal of Pediatrics. 2014 Sep;165(3):611-7. doi: 10.1016/j.jpeds.2014.06.015. Epub 2014 Jul 9.

“An emerging molecular understanding and novel targeted treatment approaches in pediatric kidney diseases”
Max C. Liebau

Frontiers in Pediatrics, 2:68. doi: 10.3389/fped.2014.00068. Epub 2014 July 1.

„Autosomal rezessive polyzystische Nierenerkrankung - Klinik, therapeutische Optionen und neue Entwicklungen“
Kathrin Ebner, Max C. Liebau
Der Nephrologe 2014 Jul; 4:  312-318;  Epub 2014 May 16

“Protection of human podocytes from Shiga toxin 2-induced phosphorylation of mitogen-activated protein kinases and apoptosis by human serum amyloid P component“
Anne Dettmar, Elisabeth Binder, Friederike Greiner, Max C. Liebau, Christine Kurschat, Therese Jungraithmayr, Moin Saleem, Claus-Peter Schmitt, Elisabeth Feifel, Dorothea Orth-Hoeller, Markus Kemper, Mark Pepys, Reinhard Würzner, Jun Oh
Infection and Immunity. 2014 May;82(5):1872-9. doi: 10.1128/IAI.01591-14. Epub 2014 Feb 24.

„Looking at the (w)hole: Magnet Resonance Imaging in Polycystic Kidney Disease”
Max C. Liebau, Andreas L. Serra
Pediatric Nephrology 2013 Sep;28(9):1771-83. doi: 10.1007/s00467-012-2370-y. Epub 2012 Dec 14.

“Dysregulated autophagy contributes to podocyte damage in Fabry's disease”
Max C. Liebau*, Fabian Braun*, Katja Höpker, Claudia Weitbrecht, Valerie Bartels, Roman-Ulrich Müller, Susanne Brodesser, Moin A. Saleem, Thomas Benzing, Bernhard Schermer, Markus Cybulla, Christine E. Kurschat (* - geteilte Erstautorenschaft)
PLOS ONE 8(5): e63506. doi:10.1371/journal.pone.0063506. Epub 2013 May 17

"Conditional loss of kidney microRNAs results in congenital anomalies of the kidney and urinary tract (CAKUT)"
Malte P. Bartram, Martin Höhne, Claudia Dafinger, Linus A. Völker, Heike Göbel, Hella Brönneke, Volker Burst, Max C. Liebau, Thomas Benzing, Bernhard Schermer, Roman-Ulrich Müller
Journal Molecular Medicine (Berl). 2013 Jun;91(6):739-48. doi: 10.1007/s00109-013-1000-x. Epub 2013 Jan 24.

“AATF/Che1 acts as a phosphorylation-dependent molecular modulator to repress p53-driven apoptosis”
Katja Höpker, Henning Hagmann, Safiya Khurshid, Shuhua Chen, Pia Hasskamp, Tamina Seeger-Nukpezah, Katharina Schilberg, Lukas Heukamp, Tobias Lamkemeyer, Martin Sos, Roman Thomas, Drew Lowery, Matthias Fischer, Frederik Roels, Max C. Liebau, Ulrike Resch, Tülay Kisner, Fabian Röther, Malte Philipp Bartram, Roman Ulrich Müller, Francesca Fabretti, Peter Kurschat, Björn Schumacher, René Medema, Michael Bruce Yaffe, Bernhard Schermer, Hans Christian Reinhardt, Thomas Benzing
EMBO Journal. 2012 Oct 17;31(20):3961-75. doi: 10.1038/emboj.2012.236. Epub 2012 Aug 21.

“Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signalling”
MoumitaChaki, RannarAirik, Amiya K. Ghosh, Rachel H. Giles, Rui Chen, Gisela G. Slaats, Hui Wang, Toby W. Hurd, Weibin Zhou, Andrew Cluckey, Heon Yung Gee, GokulRamaswami, Chen-Jei Hong, Bruce A. Hamilton, Igor Červenka, Ranjani Sri Ganji, VitezslavBryja, Heleen H. Arts, Jeroen van Reeuwijk, Machteld M. Oud, Stef J.F. Letteboer, Ronald Roepman, HervéHusson, OxanaIbraghimov-Beskrovnaya, Takayuki Yasunaga, GerdWalz, Lorraine Eley, John A. Sayer, Bernhard Schermer, Max C. Liebau, Thomas Benzing, Stephanie Le Corre, Iain Drummond, Sabine Janssen, Susan J. Allen, Sivakumar Natarajan, John F. O’Toole, Massimo Attanasio, Sophie Saunier, Corinne Antignac, Robert K. Koenekoop, Huanan Ren, Irma Lopez, Ahmet Nayir, Corinne Stoetzel, Helene Dollfus, Rustin Massoudi, Joseph G. Gleeson, Sharon P. Andreoli, Dan G. Doherty, Anna Lindstrad, ChristelleGolzio, Nicholas Katsanis, Lars Pape, Emad B. Abboud, Ali A. Al-Rajhi, Richard A. Lewis, HeymutOmran, Eva Y.-H.P. Lee, Shaohui Wang, JoAnn M. Sekiguchi, Rudel Saunders, Colin A. Johnson, Elizabeth Garner, Katja Vanselow, Jens S. Andersen, Joseph Shlomai, Gudrun Nurnberg, Peter Nurnberg, Shawn Levy, AgataSmogorzewska, Edgar A. Otto, Friedhelm Hildebrandt
Cell. 2012 Aug 3;150(3):533-48. doi: 10.1016/j.cell.2012.06.028.

“The centrosomal kinase Plk1 localizes to the transition zone of primary cilia and induces phosphorylation of Nephrocystin-1”
Tamina Seeger-Nukpezah, Max C. Liebau, Katja Hoepker, Thomas Benzing, Erica A. Golemis, Bernhard Schermer
PLoS One. 2012;7(6):e38838. doi: 10.1371/journal.pone.0038838. Epub 2012 Jun 11.

“The ciliary protein NPHP4 translocates the canonical Wnt-regulator Jade-1 to the nucleus to negatively regulate beta-catenin signaling”
Lori Borgal, Sandra Habbig, Julia Hatzold, Max C. Liebau, Claudia Dafinger, IlincaSaracea, Matthias Hammerschmidt, Thomas Benzing, Bernhard Schermer
Journal of Biological Chemistry. 2012 Jul 20;287(30):25370-80. Epub 2012 May 31.

“Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubular dynamics”
Claudia Dafinger*, Max C. Liebau*, Solaf Mohamed Elsayed*, Yorck Hellenbroich, Eugen Boltshauser, Georg C. Korenke, Francesca Fabretti, Andreas Robert Janecke, Inga Ebermann, Gudrun Nürnberg, Peter Nürnberg, Friederike Koerber, Klaus Addicks, EzzatElsobky, Thomas Benzing, Bernhard Schermer, Hanno Jörn Bolz
(* - geteilteErstautorenschaft)
Journal of Clinical Investigation, 2011 Jul 1;121(7):2662-7. doi: 10.1172/JCI43639. Epub 2011 June 1.

“NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway”
Sandra Habbig, Malte P. Bartram, Roman U. Müller, Ricarda Schwarz, Nikolaos Andriopoulos, Martin Hoehne, Volker Burst, Max C. Liebau, H. Christian Reinhardt, Thomas
Benzing, and Bernhard Schermer
Journal of Cell Biology, 2011 May 16;193(4):633-42. Epub 2011 May 9.

„Neue Entwicklungen auf dem Gebiet der genetischen Nierenerkrankungen“
Max C. Liebau, Thomas Benzing
Deutsche Medizinische Wochenschrift 2011 May;136(19):1014-1020. Epub 2011 May 3.

“Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of Nephrocystin-1 to control targeting to monocilia”
Max C. Liebau*, Katja Höpker*, Roman U. Müller*,IngolfSchmedding, Sibylle Zank, Benjamin Schairer, Francesca Fabretti, Martin Höhne, Malte P. Bartram, Claudia Dafinger, Matthias Hackl, Volker Burst, Sandra Habbig, HanswalterZentgraf, Andree Blaukat, GerdWalz, Thomas Benzing, Bernhard Schermer
(* - geteilte Erstautorenschaft)
Journal of Biological Chemistry, 2011 Apr 22;286(16):14237-45, Epub 2011 Feb 28

„Pathogenese, Klinik und Therapie des nephrotischen Syndroms“
Max C. Liebau, Thomas Benzing, Volker Burst
Der Nephrologe 2009 Sept; 4(5): 453-467 Epub 2009 Aug 14

“PDZD7 modifies the retinal phenotype in Usher syndrome and contributes to digenic disease”
Inga Ebermann*, Jennifer Phillips*, Max C. Liebau*, Robert K. Koenekoop, Bernhard Schermer, Irma Lopez, Ellen Schäfer, Anne-Francoise Roux, Claudia Dafinger, Antje Bernd, EberhartZrenner, MireilleClaustres, Bernardo Blanco, Gudrun Nürnberg, Peter Nürnberg, Rebecca Ruland, Monte Westerfield, Thomas Benzing, Hanno J. Bolz
(* - geteilteErstautorenschaft)
Journal of Clinical Investigation 2010;120(6):1812–1823. doi:10.1172/JCI39715. Epub 2010 May 3

„AtypicalAlport syndrome associated with a novel COL4A5 mutation”
Katja Höpker*,Max C. Liebau*, Christian Friederichsohn, RüdigerWaldherr, Thomas Benzing    
(* - geteilte Erstautorenschaft)
Clinical Nephrology 2009 Mar; 71(3): 321-325. Epub 2009 Feb 24

„Bauchschmerzen, Erbrechen und Diarrhö“
Max C. Liebau, Sarah Grünert, Carolin Kayser, Jochen Raedecke, Peter Greiner, Karl-Ottfried Schwab
Monatsschrift Kinderheilkunde 2009 Feb; 157(2): 108-112. Epub 2008 Jun 20

„L1CAM mutation in a male with hydrocephalus and duplex kidneys”
Max C. Liebau, Andreas Gal, Andrea Superti-Furga, Heymut Omran, Martin Pohl
Pediatric Nephrology 2007 Jul; 22(7): 1058-61. Epub2007 Feb 10

„Upregulation of Id-1 via BMP-2 receptors induces reactive oxygen species in podocytes.”
Gregor Pache, Christina Schafer, Steffen Wiesemann, Erik Springer, Max C. Liebau, Hans Christian Reinhardt, Christian August, Hermann Pavenstadt, Martin J. Bek
American Journal of Physiology Renal Physiology 2006 Sep; 291(3):F654-62. Epub 2006 Apr 18

„Functional Expression of the Renin Angiotensin System in Human Podocytes.”
Max C. Liebau, Detlev Lang, Joachim Böhm, Nicole Endlich, Martin J. Bek, Ian Witherden, Peter Mathieson, Moin A. Saleem, Hermann Pavenstädt, Karl-Georg Fischer
American Journal of Physiology Renal Physiology 2006 Mar; 290(3):F710-9. Epub 2005 Sep 27.

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