Polycystic Kidney Disease

Polycystic Kidney Diseases (PKD) are among the most common and severe diseases in Pediatric Nephrology and represent one of the most frequent causes of dialysis-requiring end stage renal failure both in children and adults. In polycystic kidney disease, fluid-filled cysts and fibrotic tissue accumulate in the kidney leading to a progressive loss of renal function.

While the autosomal dominant ADPKD usually presents clinically in adults, the more severe autosomal recessive PKD (ARPKD) is usually seen in children. ADPKD is caused by mutations in the genes PKD1, PKD2, GANAB and DNAJB11. ARPKD is mainly caused by mutations in the PKHD1 gene, encoding the protein fibrocystin. Fibrocstin is a large transmembrane protein of poorly understood function. Recently, mutations in DZIP1L and PMM2 have been described as causes of ARPKD.

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 pediatric patients with PKD.

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 pediatric PKD 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 (www.aregpkd.org). 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 biobank ARegPKD may also open novel options for translational research.
Following a similar approach and in a close collaboration with Prof. D. Mekahli from Leuven, we have also established the pediatric ADPKD registry ADPedKD (www.adpedkd.org). ADPedKD aims to identify early markers for rapid progression in ADPKD as a basis for a potential therapeutic intervention in ADPKD during childhood and adolescence.

The Team

Priv.-Doz. Dr. Max Christoph Liebau, leader
E-Mail: max.liebau@uk-koeln.de

Dr. Kathrin Burgmaier
Dr. nat. med. Claudia Dafinger
Sophie Haumann
Dr. Stefan Kohl
Büsra Yildirim

Abdelaziz Akarkach
Giulia Berger
Joy Brandt
Leonie Brinker
Dominica Labus
Nora Liekenbrock
Amrei Mandel


Selected Publications Max Christoph Liebau

  1. Burgmaier K, Brandt J, Shroff R, Witters P, Weber LT, Dötsch J, Schaefer F, Mekahli D, Liebau MC. “Gastrostomy tube insertion in pediatric patients with autosomal recessive polycystic kidney disease (ARPKD): current practice.”; Frontiers in Pediatrics (accepted for publication)

  2. Dafinger C, Rinschen MM, Borgal L, Ehrenberg C, Basten SG, Franke M, Höhne M, Rauh M, Göbel H, Wunderlich FT, Peters DJM, Tasche D, Mishra T, Habbig S, Dötsch J, Müller RU, Brüning JC, Persigehl T, Giles RH, Benzing T, Schermer B, Liebau MC. “Targeted deletion of the AAA-ATPase Ruvbl1 in mice disrupts ciliary integrity and causes renal disease and hydrocephalus”; Experimental Molecular Medicine (in press)

  3. Burgmaier K, Kunzmann K, Ariceta G, Bergmann C, Buescher AK, Burgmaier M, Dursun I, Duzova A, Eid L, Feldkoetter M, Gessner M, Gokce I, Haffner D, Hooman N, Hoppe B, Jankauskiene A, Klaus G, König J, Litwin M, Massella L, Mekahli D, Melek E, Mir S, Pape L, Prikhodina L, Ranchin B, Schild R, Seeman T, Sever L, Shroff R, Soliman NA, Stabouli S, Stanczyk M, Tabel Y, Taranta-Janusz K, Testa S, Thumfart J, Topaloglu R, Weber LT, Wicher D, Wühl E, Wygoda S, Yilmaz A, Zachwieja K, Zagozdzon I, Zerres K, ESCAPE Study Group, GPN Study Group, Dötsch J, Schaefer F, Liebau MC for the ARegPKD consortium. “Risk Factors for Early Dialysis Dependency in ARPKD”; Journal of Pediatrics 2018 May 9. pii: S0022-3476(18)30424-4. doi: 10.1016/j.jpeds.2018.03.052. [Epub ahead of print]

  4. Höhne M, Frese CK, Grahammer F, Dafinger C, Ciarimboli G, Butt L, Binz J, Hackl MJ, Rahmatollahi M, Kann M, Schneider S, Altintas MM, Schermer B, Reinheckel T, Göbel H, Reiser J, Huber TB, Kramann R, Seeger-Nukpezah T, Liebau MC, Beck BB, Benzing T, Beyer A, Rinschen MM. “Individual nephron proteomes connect morphology and function in proteinuric kidney disease”; Kidney Int. 2018 Mar 9. pii: S0085-2538(18)30056-5. doi: 10.1016/j.kint.2017.12.012. [Epub ahead of print]

  5. Gimpel C, Avni FE, Bergmann C, Cetiner M, Habbig S, Haffner D, König J, Konrad M, Liebau MC, Pape L, Rellensmann G, Titieni A, von Kaisenberg C, Weber S, Winyard PJD, Schaefer F. “Perinatal Diagnosis, Management, and Follow-up of Cystic Renal Diseases: A Clinical Practice Recommendation With Systematic Literature Reviews.”; JAMA Pediatrics. 2018 Jan 1;172(1):74-86.

  6. Eich G, Bartosova M, Tischer C, Wlodkowski TT, Schaefer B, Pichl S, Kraewer N, Ranchin B, Vondrak K, Liebau MC, Hackert T, Schmitt CP. „Bicarbonate buffered peritoneal dialysis fluid upregulates angiopoietin-1 and promotes vessel maturation“; PLoS One. 2017 Dec 18;12(12):e0189903.

  7. Hackl A, Becker JU, Körner LM, Ehren R, Habbig S, Nüsken E, Nüsken KD, Ebner K, Liebau MC, Müller C, Pohl M, Weber LT. “Mycophenolate mofetil following glucocorticoid treatment in Henoch-Schönlein purpura nephritis: the role of early initiation and therapeutic drug monitoring”; Pediatric Nephrology (2017). doi.org/10.1007/s00467-017-3846-6 (Epub ahead of print)

  8. Ebner K, Liebau MC. “No general treatment recommendation for nephrectomy in prenatal suspicion of ARPKD”; Der Urologe, 2017 Nov;56,(11), 1465–1466

  9. DeRechter S, Kringen J, Janssens P, Liebau MC, Devriendt K, Levtchenko E, Bergmann C, Jouret F, Bammens B, Borry P, Schaefer F, Mekahli D. “Clinicians' attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease”; PLoS One. 2017 Sep 29;12(9):e0185779.

  10. Ebner K, Dafinger C, Ortiz-Bruechle N, Koerber F, Schermer B, Benzing T, Dötsch J, Zerres K, Weber LT, Beck B, Liebau MC. “Challenges in establishing genotype-phenotype correlations in ARPKD: Case report on a toddler with two severe PKHD1 mutations”; Pediatric Nephrology 2017 Jul;32(7):1269-1273.

  11. Ebner K, Reintjes N, Feldkötter M, Körber F, Nagel M, Dötsch J, Hoppe B, Weber LT, Beck B, Liebau MC. „A case report on the exceptional conincidence of two inherited renal disorders: ADPKD and Alport syndrome”; Clinical Nephrology 2017 Jul;88(1):45-51.

  12. Loos S, Aulbert W, Hoppe B, Ahlenstiel T, Kranz B, Wahl C, Staude H, Humberg A, Benz K, Krause M, Pohl M, Liebau MC, Lemke J, Beringer O, Müller D, Härtel C, Wigger M, Vester U, Konrad M, Haffner D, Pape L, Oh J, Kemper MJ. “Intermediate Follow-up of Pediatric Patients with Hemolytic Uremic Syndrome during the 2011 Outbreak Caused by E. coli O104:H4”; Clinical Infectious Diseases 2017 Jun 15;64(12):1637-1643.

  13. Hackl A, Mehler K, Gottschalk I, Vierzig A, Eydam M, Liebau MC, Ensenauer R, Weber LT, Habbig S. “Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease – different clinical entities with comparable perinatal renal abnormalities”; Pediatric Nephrology 2017 May;32(5):791-800.

  14. Ebner K, Schaefer F, Liebau MC, The ARegPKD consortium. “Recent Progress of the ARegPKD Registry Study on Autosomal Recessive Polycystic Kidney Disease”; Frontiers in Pediatrics. 2017 Feb 16;5:18.

  15. Taylan C, Goebel H, Beck BB, Dötsch J, Nuesken KD, Hoppe B, Weber LT, Liebau MC. „Anuria on the second day following kidney transplantation“; American Journal of Kidney Disease. 2016 Dec;68(6):A18-A21

  16. Hackl A, Cseprekál O, Geßner M, Liebau MC, Habbig S, Ehren R, Müller C, Taylan C, Dötsch J, Weber LT. “Mycophenolate-mofetil therapy in children with idiopathic nephrotic syndrome. Does therapeutic drug monitoring make a difference?”; Therapeutic Drug Monitoring. 2016 Apr;38(2):274-9.

  17. Weber S, Büscher AK, Hagmann H, Liebau MC, Heberle C, Ludwig M, Rath S, Alberer M, Beissert A, Zenker M, Hoyer PF, Konrad M, Klein HG, Hoefele J. “Dealing with the incidental finding of secondary variants by the example of SRNS patients undergoing targeted next-generation sequencing”; Pediatric Nephrology. 2016 Jan;31(1):73-81.

  18. Ebner K, Feldkötter M, Ariceta G, Bergmann C, Büttner R, Doyon A, Duzova A, Göbel H, Haffner D, Hero B, Hoppe B, Illig T, Jankauskiene A, Klopp N, König J, Litwin M, Mekahli D, Ranchin B, Sander A, Testa S, Weber LT, Wicher D, Yuzbasioglu A, Zerres K, Dötsch J, Schaefer F, Liebau MC for The ESCAPE Study Group, The GPN Study Group. “Rationale, design and objectives of ARegPKD, a European ARPKD registry study”; BMC Nephrology 2015, 16:22

  19. Guay-Woodford LM, Bissler JJ, Braun MC, Bockenhauer D, Cadnapaphornchai MA, Dell KM, Kerecuk L, Liebau MC, Alonso-Peclet MH, Shneider B, Emre S, Heller T, Kamath BM, Murray KF, Moise K, Eichenwald EE, Evans J, Keller RL, Wilkins-Haug L, Bergmann C, Gunay-Aygun M, Hooper SR, Hardy KK, Hartung EA, Streisand R, Perrone R, and Moxey-Mims M. “Consensus Expert Recommendations for the Diagnosis and Management of Autosomal Recessive Polycystic Kidney Disease: Report of an International Conference.”; The Journal of Pediatrics. 2014 Sep;165(3):611-7.

  20. Dettmar A, Binder E, Greiner F, Liebau MC, Kurschat C, Jungraithmayr T, Saleem M, Schmitt CP, Feifel E, Orth-Hoeller D, Kemper M, Pepys M, Würzner R, Oh J. “Protection of human podocytes from Shiga toxin 2-induced phosphorylation of mitogen-activated protein kinases and apoptosis by human serum amyloid P component“; Infection and Immunity. 2014 May;82(5):1872-9.

  21. Liebau MC*, Braun F*, Höpker K, Weitbrecht C, Bartels V, Müller RU, Brodesser S, Saleem MA, Benzing T, Schermer B, Cybulla M, Kurschat CE. (* - geteilte Erstautorenschaft) “Dysregulated autophagy contributes to podocyte damage in Fabry's disease”; PLoS One. 2013 May 17;8(5):e63506.

  22. Bartram MP, Höhne M, Dafinger C, Völker LA, Göbel H, Brönneke H, Burst V, Liebau MC, Benzing T, Schermer B, Müller RU. "Conditional loss of kidney microRNAs results in congenital anomalies of the kidney and urinary tract (CAKUT)"; Journal Molecular Medicine (Berl). 2013 Jun;91(6):739-48.

  23. Höpker K, Hagmann H, Khurshid S, Chen S, Hasskamp P, Seeger-Nukpezah T, Schilberg K, Heukamp L, Lamkemeyer T, Sos ML, Thomas RK, Lowery D, Roels F, Fischer M, Liebau MC, Resch U, Kisner T, Röther F, Bartram MP, Müller RU, Fabretti F, Kurschat P, Schumacher B, Gaestel M, Medema RH, Yaffe MB, Schermer B, Reinhardt HC, Benzing T. “AATF/Che1 acts as a phosphorylation-dependent molecular modulator to repress p53-driven apoptosis”; EMBO Journal. 2012 Oct 17;31(20):3961-75.

  24. Chaki M, Airik R, Ghosh AK, Giles RH, Chen R, Slaats GG, Wang H, Hurd TW, Zhou W, Cluckey A, Gee HY, Ramaswami G, Hong CJ, Hamilton BA, Cervenka I, Ganji RS, Bryja V, Arts HH, van Reeuwijk J, Oud MM, Letteboer SJ, Roepman R, Husson H, Ibraghimov-Beskrovnaya O, Yasunaga T, Walz G, Eley L, Sayer JA, Schermer B, Liebau MC, Benzing T, Le Corre S, Drummond I, Janssen S, Allen SJ, Natarajan S, O'Toole JF, Attanasio M, Saunier S, Antignac C, Koenekoop RK, Ren H, Lopez I, Nayir A, Stoetzel C, Dollfus H, Massoudi R, Gleeson JG, Andreoli SP, Doherty DG, Lindstrad A, Golzio C, Katsanis N, Pape L, Abboud EB, Al-Rajhi AA, Lewis RA, Omran H, Lee EY, Wang S, Sekiguchi JM, Saunders R, Johnson CA, Garner E, Vanselow K, Andersen JS, Shlomai J, Nurnberg G, Nurnberg P, Levy S, Smogorzewska A, Otto EA, Hildebrandt F. “Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signalling”; Cell. 2012 Aug 3;150(3):533-48.

  25. Seeger-Nukpezah T, Liebau MC, Hoepker K, Lamkemeyer T, Benzing T, Golemis EA, Schermer B. “The centrosomal kinase Plk1 localizes to the transition zone of primary cilia and induces phosphorylation of Nephrocystin-1”; PLoS One. 2012;7(6):e38838.

  26. Borgal L, Habbig S, Hatzold J, Liebau MC, Dafinger C, Saracea I, Hammerschmidt M, Benzing T, Schermer B. “The ciliary protein NPHP4 translocates the canonical Wnt-regulator Jade-1 to the nucleus to negatively regulate beta-catenin signaling”; Journal of Biological Chemistry. 2012 Jul 20;287(30):25370-80.

  27. Dafinger C*, Liebau MC*, Elsayed SM*, Hellenbroich Y, Boltshauser E, Korenke GC, Fabretti F, Janecke AR, Ebermann I, Nürnberg G, Nürnberg P, Koerber F, Addicks K, Elsobky E, Benzing T, Schermer B, Bolz HJ. (* - geteilte Erstautorenschaft) “Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubular dynamics”; Journal of Clinical Investigation, 2011 Jul 1;121(7):2662-7.

  28. Habbig S, Bartram MP, Müller RU, Schwarz R, Andriopoulos N, Hoehne M, Burst V, Liebau MC, Reinhardt HV, Benzing T and Schermer B. “NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway”; Journal of Cell Biology, 2011 May 16;193(4):633-42.

  29. Liebau MC*, Höpker K*, Müller RU*, Schmedding I, Zank S, Schairer B, Fabretti F, Höhne M, Bartram MP, Dafinger C, Hackl M, Burst V, Habbig S, Zentgraf H, Blaukat A, Walz G, Benzing T, Schermer B. (* - geteilte Erstautorenschaft) “Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of Nephrocystin-1 to control targeting to monocilia”; Journal of Biological Chemistry, 2011 Apr 22;286(16):14237-45.

  30. Ebermann I*, Phillips JB*, Liebau MC*, Koenekoop RK, Schermer B, Lopez I, Schäfer E, Roux AF, Dafinger C, Bernd A, Zrenner E, Claustres M, Blanco B, Nürnberg G, Nürnberg P, Ruland R, Westerfield M, Benzing T, Bolz HJ.  (* - geteilte Erstautorenschaft) “PDZD7 modifies the retinal phenotype in Usher syndrome and contributes to digenic disease”; Journal of Clinical Investigation 2010;120(6):1812–1823.

  31. Höpker K*, Liebau MC*, Friederichsohn C, Waldherr R, Benzing T. (* - geteilte Erstautoren-schaft) „Atypical Alport syndrome associated with a novel COL4A5 mutation”; Clinical Nephrology 2009 Mar; 71(3): 321-325.

  32. Liebau MC, Grünert S, Kayser C, Raedecke J, Greiner P, Schwab KO. „Bauchschmerzen, Erbrechen und Diarrhö“; Monatsschrift Kinderheilkunde 2009 Feb; 157(2): 108-112.

  33. Liebau MC, Gal A, Superti-Furga A, Omran H, Pohl M. „L1CAM mutation in a male with hydrocephalus and duplex kidneys”; Pediatric Nephrology 2007 Jul; 22(7): 1058-61.

  34. Pache G, Schafer C, Wiesemann S, Springer E, Liebau M, Reinhardt HC, August C, Pavenstadt H, Bek MJ. „Upregulation of Id-1 via BMP-2 receptors induces reactive oxygen species in podocytes.” American Journal of Physiology Renal Physiology 2006 Sep; 291(3):F654-62.

  35. Liebau MC, Lang D, Böhm J, Endlich N, Bek MJ, Witherden I, Mathieson P, Saleem MA, Pavenstädt H, Fischer KG. „Functional Expression of the Renin Angiotensin System in Human Podocytes.” American Journal of Physiology Renal Physiology 2006 Mar; 290(3):F710-9.


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