Skip to main content
SpringerLink
Log in

Polycystic Kidney Disease: ADPKD and ARPKD

  • Chapter
  • First Online:
Pediatric Kidney Disease

Abstract

Cystic kidney diseases are among the most common causes of end stage renal disease both in children and adults. The two main forms of genetic cystic kidney disorders are Autosomal Dominant and Autosomal Recessive Polycystic Kidney Disease (ADPKD and ARPKD). While ADPKD is a common disorder mainly affecting adult patients, ARPKD is the rare but often severe form of PKD usually presenting in early childhood. Recent cell biological and clinical research approaches have considerably expanded our knowledge on both PKDs. Still, many important questions remain to be solved. This chapter aims to give an overview of the current knowledge of PKD with a special focus on pediatric aspects of the diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Fliegauf M, Benzing T, Omran H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol. 2007;8(11):880–93.

    Article  CAS  PubMed  Google Scholar 

  2. Gerdes JM, Davis EE, Katsanis N. The vertebrate primary cilium in development, homeostasis, and disease. Cell. 2009;137(1):32–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nigg EA, Raff JW. Centrioles, centrosomes, and cilia in health and disease. Cell. 2009;139(4):663–78.

    Article  CAS  PubMed  Google Scholar 

  4. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med. 2011;364(16):1533–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bergmann C. ARPKD and early manifestations of ADPKD: the original polycystic kidney disease and phenocopies. Pediatr Nephrol Berl Ger. 2015;30(1):15–30.

    Article  Google Scholar 

  6. Sweeney Jr WE, Avner ED. Diagnosis and management of childhood polycystic kidney disease. Pediatr Nephrol Berl Ger. 2011;26(5):675–92.

    Article  Google Scholar 

  7. Drenth JPH, Chrispijn M, Bergmann C. Congenital fibrocystic liver diseases. Best Pract Res Clin Gastroenterol. 2010;24(5):573–84.

    Article  CAS  PubMed  Google Scholar 

  8. Bergmann C, Weiskirchen R. It’s not all in the cilium, but on the road to it: genetic interaction network in polycystic kidney and liver diseases and how trafficking and quality control matter. J Hepatol. 2012;56(5):1201–3.

    Article  CAS  PubMed  Google Scholar 

  9. Liebau MC, Serra AL. Looking at the (w)hole: magnet resonance imaging in polycystic kidney disease. Pediatr Nephrol Berl Ger. 2013;28(9):1771–83.

    Article  Google Scholar 

  10. Osathanondh V, Potter EL. Pathogenesis of polycystic kidneys. Type 4 due to urethral obstruction. Arch Pathol. 1964;77:502–9.

    CAS  PubMed  Google Scholar 

  11. McHugh K, Stringer DA, Hebert D, Babiak CA. Simple renal cysts in children: diagnosis and follow-up with US. Radiology. 1991;178(2):383–5.

    Article  CAS  PubMed  Google Scholar 

  12. Ogborn MR. Polycystic kidney disease – a truly pediatric problem. Pediatr Nephrol Berl Ger. 1994;8(6):762–7.

    Article  CAS  Google Scholar 

  13. Bear JC, McManamon P, Morgan J, Payne RH, Lewis H, Gault MH, et al. Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling. Am J Med Genet. 1984;18(1):45–53.

    Article  CAS  PubMed  Google Scholar 

  14. Pei Y, Obaji J, Dupuis A, Paterson AD, Magistroni R, Dicks E, et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol JASN. 2009;20(1):205–12.

    Article  CAS  PubMed  Google Scholar 

  15. Ravine D, Gibson RN, Donlan J, Sheffield LJ. An ultrasound renal cyst prevalence survey: specificity data for inherited renal cystic diseases. Am J Kidney Dis Off J Natl Kidney Found. 1993;22(6):803–7.

    Article  CAS  Google Scholar 

  16. Harris PC, Rossetti S. Determinants of renal disease variability in ADPKD. Adv Chronic Kidney Dis. 2010;17(2):131–9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int. 2009;76(2):149–68.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wilson PD. Polycystic kidney disease. N Engl J Med. 2004;350(2):151–64.

    Article  CAS  PubMed  Google Scholar 

  19. Luciano RL, Dahl NK. Extra-renal manifestations of autosomal dominant polycystic kidney disease (ADPKD): considerations for routine screening and management. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2014;29(2):247–54.

    Google Scholar 

  20. Helal I, Reed B, Schrier RW. Emergent early markers of renal progression in autosomal-dominant polycystic kidney disease patients: implications for prevention and treatment. Am J Nephrol. 2012;36(2):162–7.

    Article  CAS  PubMed  Google Scholar 

  21. Gabow PA, Kimberling WJ, Strain JD, Manco-Johnson ML, Johnson AM. Utility of ultrasonography in the diagnosis of autosomal dominant polycystic kidney disease in children. J Am Soc Nephrol JASN. 1997;8(1):105–10.

    CAS  PubMed  Google Scholar 

  22. Bear JC, Parfrey PS, Morgan JM, Martin CJ, Cramer BC. Autosomal dominant polycystic kidney disease: new information for genetic counselling. Am J Med Genet. 1992;43(3):548–53.

    Article  CAS  PubMed  Google Scholar 

  23. Reed B, Nobakht E, Dadgar S, Bekheirnia MR, Masoumi A, Belibi F, et al. Renal ultrasonographic evaluation in children at risk of autosomal dominant polycystic kidney disease. Am J Kidney Dis Off J Natl Kidney Found. 2010;56(1):50–6.

    Article  Google Scholar 

  24. Chapman AB, Wei W. Imaging approaches to patients with polycystic kidney disease. Semin Nephrol. 2011;31(3):237–44.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Nascimento AB, Mitchell DG, Zhang XM, Kamishima T, Parker L, Holland GA. Rapid MR imaging detection of renal cysts: age-based standards. Radiology. 2001;221(3):628–32.

    Article  CAS  PubMed  Google Scholar 

  26. Laucks Jr SP, McLachlan MS. Aging and simple cysts of the kidney. Br J Radiol. 1981;54(637):12–4.

    Article  PubMed  Google Scholar 

  27. Tada S, Yamagishi J, Kobayashi H, Hata Y, Kobari T. The incidence of simple renal cyst by computed tomography. Clin Radiol. 1983;34(4):437–9.

    Article  CAS  PubMed  Google Scholar 

  28. Boyer O, Gagnadoux M-F, Guest G, Biebuyck N, Charbit M, Salomon R, et al. Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth. Pediatr Nephrol Berl Ger. 2007;22(3):380–8.

    Article  Google Scholar 

  29. Pei Y. Diagnostic approach in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol CJASN. 2006;1(5):1108–14.

    Article  PubMed  Google Scholar 

  30. Rizk D, Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD. Pediatr Nephrol Berl Ger. 2008;23(7):1029–36.

    Article  Google Scholar 

  31. Chapman AB, et al. Autosomal Dominant Polycystic Kidney Disease (ADPKD): report from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference. Kidney Int. 2015;88(1):17–27.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Grantham JJ, Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King Jr BF, et al. Volume progression in polycystic kidney disease. N Engl J Med. 2006;354(20):2122–30.

    Article  CAS  PubMed  Google Scholar 

  33. Bae KT, Tao C, Zhu F, Bost JE, Chapman AB, Grantham JJ, et al. MRI-based kidney volume measurements in ADPKD: reliability and effect of gadolinium enhancement. Clin J Am Soc Nephrol CJASN. 2009;4(4):719–25.

    Article  PubMed  Google Scholar 

  34. Torres VE, King BF, Chapman AB, Brummer ME, Bae KT, Glockner JF, et al. Magnetic resonance measurements of renal blood flow and disease progression in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol CJASN. 2007;2(1):112–20.

    Article  PubMed  Google Scholar 

  35. Chapman AB. Approaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies. Clin J Am Soc Nephrol CJASN. 2008;3(4):1197–204.

    Article  CAS  PubMed  Google Scholar 

  36. Kistler AD, Poster D, Krauer F, Weishaupt D, Raina S, Senn O, et al. Increases in kidney volume in autosomal dominant polycystic kidney disease can be detected within 6 months. Kidney Int. 2009;75(2):235–41.

    Article  PubMed  Google Scholar 

  37. Torres VE, Chapman AB, Perrone RD, Bae KT, Abebe KZ, Bost JE, et al. Analysis of baseline parameters in the HALT polycystic kidney disease trials. Kidney Int. 2012;81(6):577–85.

    Article  CAS  PubMed  Google Scholar 

  38. Cornec-Le Gall E, Audrézet M-P, Chen J-M, Hourmant M, Morin M-P, Perrichot R, et al. Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol JASN. 2013;24(6):1006–13.

    Article  PubMed  CAS  Google Scholar 

  39. Magistroni R, He N, Wang K, Andrew R, Johnson A, Gabow P, et al. Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol JASN. 2003;14(5):1164–74.

    Article  PubMed  Google Scholar 

  40. Paterson AD, Magistroni R, He N, Wang K, Johnson A, Fain PR, et al. Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease. J Am Soc Nephrol JASN. 2005;16(3):755–62.

    Article  PubMed  Google Scholar 

  41. Persu A, Duyme M, Pirson Y, Lens XM, Messiaen T, Breuning MH, et al. Comparison between siblings and twins supports a role for modifier genes in ADPKD. Kidney Int. 2004;66(6):2132–6.

    Article  CAS  PubMed  Google Scholar 

  42. Sedman A, Bell P, Manco-Johnson M, Schrier R, Warady BA, Heard EO, et al. Autosomal dominant polycystic kidney disease in childhood: a longitudinal study. Kidney Int. 1987;31(4):1000–5.

    Article  CAS  PubMed  Google Scholar 

  43. Sweeney Jr WE, Avner ED. Molecular and cellular pathophysiology of autosomal recessive polycystic kidney disease (ARPKD). Cell Tissue Res. 2006;326(3):671–85.

    Article  CAS  PubMed  Google Scholar 

  44. Ulinski T, Lescure S, Beaufils S, Guigonis V, Decramer S, Morin D, et al. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. J Am Soc Nephrol JASN. 2006;17(2):497–503.

    Article  CAS  PubMed  Google Scholar 

  45. Faguer S, Bouissou F, Dumazer P, Guitard J, Bellanné-Chantelot C, Chauveau D. Massively enlarged polycystic kidneys in monozygotic twins with TCF2/HNF-1beta (hepatocyte nuclear factor-1beta) heterozygous whole-gene deletion. Am J Kidney Dis Off J Natl Kidney Found. 2007;50(6):1023–7.

    Article  CAS  Google Scholar 

  46. Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW. Prospective change in renal volume and function in children with ADPKD. Clin J Am Soc Nephrol CJASN. 2009;4(4):820–9.

    Article  CAS  PubMed  Google Scholar 

  47. Fick-Brosnahan GM, Tran ZV, Johnson AM, Strain JD, Gabow PA. Progression of autosomal-dominant polycystic kidney disease in children. Kidney Int. 2001;59(5):1654–62.

    Article  CAS  PubMed  Google Scholar 

  48. Shamshirsaz AA, Shamshirsaz A, Reza Bekheirnia M, Bekheirnia RM, Kamgar M, Johnson AM, et al. Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome. Kidney Int. 2005;68(5):2218–24.

    Article  PubMed  Google Scholar 

  49. Cadnapaphornchai MA, Masoumi A, Strain JD, McFann K, Schrier RW. Magnetic resonance imaging of kidney and cyst volume in children with ADPKD. Clin J Am Soc Nephrol CJASN. 2011;6(2):369–76.

    Article  PubMed  Google Scholar 

  50. Fick-Brosnahan G, Johnson AM, Strain JD, Gabow PA. Renal asymmetry in children with autosomal dominant polycystic kidney disease. Am J Kidney Dis Off J Natl Kidney Found. 1999;34(4):639–45.

    Article  CAS  Google Scholar 

  51. Bergmann C, Zerres K. Autosomal dominant polycystic kidney disease (ADPKD) in children and young adults. In: Turner N, et al., editors. Oxford textbook of clinical nephrology. Oxford University Press; 2015.

    Google Scholar 

  52. Gabow PA, Duley I, Johnson AM. Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease. Am J Kidney Dis Off J Natl Kidney Found. 1992;20(2):140–3.

    Article  CAS  Google Scholar 

  53. Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, et al. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int. 1992;41(5):1311–9.

    Article  CAS  PubMed  Google Scholar 

  54. Johnson AM, Gabow PA. Identification of patients with autosomal dominant polycystic kidney disease at highest risk for end-stage renal disease. J Am Soc Nephrol JASN. 1997;8(10):1560–7.

    CAS  PubMed  Google Scholar 

  55. Gagnadoux MF, Habib R, Levy M, Brunelle F, Broyer M. Cystic renal diseases in children. Adv Nephrol Necker Hosp. 1989;18:33–57.

    CAS  PubMed  Google Scholar 

  56. MacDermot KD, Saggar-Malik AK, Economides DL, Jeffery S. Prenatal diagnosis of autosomal dominant polycystic kidney disease (PKD1) presenting in utero and prognosis for very early onset disease. J Med Genet. 1998;35(1):13–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Avner ED. Childhood ADPKD: answers and more questions. Kidney Int. 2001;59(5):1979–80.

    Article  CAS  PubMed  Google Scholar 

  58. Chapman AB, Schrier RW. Pathogenesis of hypertension in autosomal dominant polycystic kidney disease. Semin Nephrol. 1991;11(6):653–60.

    CAS  PubMed  Google Scholar 

  59. Harrap SB, Davies DL, Macnicol AM, Dominiczak AF, Fraser R, Wright AF, et al. Renal, cardiovascular and hormonal characteristics of young adults with autosomal dominant polycystic kidney disease. Kidney Int. 1991;40(3):501–8.

    Article  CAS  PubMed  Google Scholar 

  60. Schrier RW. Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol JASN. 2009;20(9):1888–93.

    Article  PubMed  Google Scholar 

  61. Tkachenko O, Helal I, Shchekochikhin D, Schrier RW. Renin-Angiotensin-aldosterone system in autosomal dominant polycystic kidney disease. Curr Hypertens Rev. 2013;9(1):12–20.

    Article  CAS  PubMed  Google Scholar 

  62. Gibbs GF, Huston 3rd J, Qian Q, Kubly V, Harris PC, Brown Jr RD, et al. Follow-up of intracranial aneurysms in autosomal-dominant polycystic kidney disease. Kidney Int. 2004;65(5):1621–7.

    Article  PubMed  Google Scholar 

  63. Pirson Y. Extrarenal manifestations of autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):173–80.

    Article  PubMed  Google Scholar 

  64. Pirson Y, Chauveau D, Torres V. Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol JASN. 2002;13(1):269–76.

    PubMed  Google Scholar 

  65. Chapman AB, Rubinstein D, Hughes R, Stears JC, Earnest MP, Johnson AM, et al. Intracranial aneurysms in autosomal dominant polycystic kidney disease. N Engl J Med. 1992;327(13):916–20.

    Article  CAS  PubMed  Google Scholar 

  66. Huston 3rd J, Torres VE, Sulivan PP, Offord KP, Wiebers DO. Value of magnetic resonance angiography for the detection of intracranial aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol JASN. 1993;3(12):1871–7.

    PubMed  Google Scholar 

  67. Ruggieri PM, Poulos N, Masaryk TJ, Ross JS, Obuchowski NA, Awad IA, et al. Occult intracranial aneurysms in polycystic kidney disease: screening with MR angiography. Radiology. 1994;191(1):33–9.

    Article  CAS  PubMed  Google Scholar 

  68. Xu HW, Yu SQ, Mei CL, Li MH. Screening for intracranial aneurysm in 355 patients with autosomal-dominant polycystic kidney disease. Stroke J Cereb Circ. 2011;42(1):204–6.

    Article  CAS  Google Scholar 

  69. Nicholas BA, Vricella GJ, Smith M, Passalacqua M, Gulani V, Ponsky LE. Contrast-induced nephropathy and nephrogenic systemic fibrosis: minimizing the risk. Can J Urol. 2012;19(1):6074–80.

    PubMed  Google Scholar 

  70. Kaufmann TJ, Huston 3rd J, Mandrekar JN, Schleck CD, Thielen KR, Kallmes DF. Complications of diagnostic cerebral angiography: evaluation of 19,826 consecutive patients. Radiology. 2007;243(3):812–9.

    Article  PubMed  Google Scholar 

  71. Belz MM, Hughes RL, Kaehny WD, Johnson AM, Fick-Brosnahan GM, Earnest MP, et al. Familial clustering of ruptured intracranial aneurysms in autosomal dominant polycystic kidney disease. Am J Kidney Dis Off J Natl Kidney Found. 2001;38(4):770–6.

    Article  CAS  Google Scholar 

  72. Chauveau D, Pirson Y, Le Moine A, Franco D, Belghiti J, Grünfeld JP. Extrarenal manifestations in autosomal dominant polycystic kidney disease. Adv Nephrol Necker Hosp. 1997;26:265–89.

    CAS  PubMed  Google Scholar 

  73. Cheung J, Scudamore CH, Yoshida EM. Management of polycystic liver disease. Can J Gastroenterol J Can Gastroenterol. 2004;18(11):666–70.

    Article  Google Scholar 

  74. Mathieu D, Vilgrain V, Mahfouz AE, Anglade MC, Vullierme MP, Denys A. Benign liver tumors. Magn Reson Imaging Clin N Am. 1997;5(2):255–88.

    CAS  PubMed  Google Scholar 

  75. Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM, et al. Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. Clin J Am Soc Nephrol CJASN. 2006;1(1):64–9.

    Article  PubMed  Google Scholar 

  76. Gevers TJG, Drenth JPH. Diagnosis and management of polycystic liver disease. Nat Rev Gastroenterol Hepatol. 2013;10(2):101–8.

    Article  CAS  PubMed  Google Scholar 

  77. Abu-Wasel B, Walsh C, Keough V, Molinari M. Pathophysiology, epidemiology, classification and treatment options for polycystic liver diseases. World J Gastroenterol WJG. 2013;19(35):5775–86.

    Article  PubMed  CAS  Google Scholar 

  78. Davila S, Furu L, Gharavi AG, Tian X, Onoe T, Qian Q, et al. Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nat Genet. 2004;36(6):575–7.

    Article  CAS  PubMed  Google Scholar 

  79. Drenth JPH, te Morsche RHM, Smink R, Bonifacino JS, Jansen JBMJ. Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease. Nat Genet. 2003;33(3):345–7.

    Article  CAS  PubMed  Google Scholar 

  80. Fedeles SV, Tian X, Gallagher A-R, Mitobe M, Nishio S, Lee SH, et al. A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation. Nat Genet. 2011;43(7):639–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Strazzabosco M, Somlo S. Polycystic liver diseases: congenital disorders of cholangiocyte signaling. Gastroenterology. 2011;140(7):1855–9, 1859.e1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Desmet VJ. Ludwig symposium on biliary disorders – part I. Pathogenesis of ductal plate abnormalities. Mayo Clin Proc Mayo Clin. 1998;73(1):80–9.

    Article  CAS  PubMed  Google Scholar 

  83. Lazaridis KN, Strazzabosco M, Larusso NF. The cholangiopathies: disorders of biliary epithelia. Gastroenterology. 2004;127(5):1565–77.

    Article  CAS  PubMed  Google Scholar 

  84. Cobben JM, Breuning MH, Schoots C, ten Kate LP, Zerres K. Congenital hepatic fibrosis in autosomal-dominant polycystic kidney disease. Kidney Int. 1990;38(5):880–5.

    Article  CAS  PubMed  Google Scholar 

  85. Lipschitz B, Berdon WE, Defelice AR, Levy J. Association of congenital hepatic fibrosis with autosomal dominant polycystic kidney disease. Report of a family with review of literature. Pediatr Radiol. 1993;23(2):131–3.

    Article  CAS  PubMed  Google Scholar 

  86. Milutinovic J, Schabel SI, Ainsworth SK. Autosomal dominant polycystic kidney disease with liver and pancreatic involvement in early childhood. Am J Kidney Dis Off J Natl Kidney Found. 1989;13(4):340–4.

    Article  CAS  Google Scholar 

  87. Tamura H, Kato H, Hirose S, Itoyama S, Matsumura O, Nagasawa R, et al. An adult case of polycystic kidney disease associated with congenital hepatic fibrosis. Nihon Jinzo Gakkai Shi. 1994;36(8):962–7.

    CAS  PubMed  Google Scholar 

  88. Everson GT. Hepatic cysts in autosomal dominant polycystic kidney disease. Mayo Clin Proc Mayo Clin. 1990;65(7):1020–5.

    Article  CAS  PubMed  Google Scholar 

  89. Telenti A, Torres VE, Gross Jr JB, Van Scoy RE, Brown ML, Hattery RR. Hepatic cyst infection in autosomal dominant polycystic kidney disease. Mayo Clin Proc Mayo Clin. 1990;65(7):933–42.

    Article  CAS  PubMed  Google Scholar 

  90. Tan YM, Ooi LLPJ, Mack POP. Current status in the surgical management of adult polycystic liver disease. Ann Acad Med Singapore. 2002;31(2):217–22.

    CAS  PubMed  Google Scholar 

  91. Garcea G, Rajesh A, Dennison AR. Surgical management of cystic lesions in the liver. ANZ J Surg. 2013;83(7–8):E3–20.

    Article  PubMed  Google Scholar 

  92. Caroli A, Antiga L, Cafaro M, Fasolini G, Remuzzi A, Remuzzi G, et al. Reducing polycystic liver volume in ADPKD: effects of somatostatin analogue octreotide. Clin J Am Soc Nephrol CJASN. 2010;5(5):783–9.

    Article  CAS  PubMed  Google Scholar 

  93. Chrispijn M, Nevens F, Gevers TJG, Vanslembrouck R, van Oijen MGH, Coudyzer W, et al. The long-term outcome of patients with polycystic liver disease treated with lanreotide. Aliment Pharmacol Ther. 2012;35(2):266–74.

    Article  CAS  PubMed  Google Scholar 

  94. Chrispijn M, Gevers TJG, Hol JC, Monshouwer R, Dekker HM, Drenth JPH. Everolimus does not further reduce polycystic liver volume when added to long acting octreotide: results from a randomized controlled trial. J Hepatol. 2013;59(1):153–9.

    Article  CAS  PubMed  Google Scholar 

  95. Gevers TJG, Chrispijn M, Wetzels JFM, Drenth JPH. Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease. BMC Nephrol. 2012;13:17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Gevers TJG, Inthout J, Caroli A, Ruggenenti P, Hogan MC, Torres VE, et al. Young women with polycystic liver disease respond best to somatostatin analogues: a pooled analysis of individual patient data. Gastroenterology. 2013;145(2):357–65.e1. –2.

    Article  CAS  PubMed  Google Scholar 

  97. Hogan MC, Masyuk TV, Page LJ, Kubly VJ, Bergstralh EJ, Li X, et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J Am Soc Nephrol JASN. 2010;21(6):1052–61.

    Article  CAS  PubMed  Google Scholar 

  98. Hogan MC, Masyuk TV, Page L, Holmes 3rd DR, Li X, Bergstralh EJ, et al. Somatostatin analog therapy for severe polycystic liver disease: results after 2 years. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2012;27(9):3532–9.

    CAS  Google Scholar 

  99. Van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MGH, Hoffmann AL, Dekker HM, et al. Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2009;137(5):1661–8.e1. –2.

    Article  PubMed  CAS  Google Scholar 

  100. Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369(9569):1287–301.

    Article  PubMed  Google Scholar 

  101. Marquardt. Cystennieren, Cystenleber, und Cystenpancreas bei zwei Geschwistern. Universität Tübingen; 1935.

    Google Scholar 

  102. Blyth H, Ockenden BG. Polycystic disease of kidney and liver presenting in childhood. J Med Genet. 1971;8(3):257–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, et al. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet. 1995;10(2):151–60.

    Article  CAS  PubMed  Google Scholar 

  104. Torres VE, Harris PC. Polycystic kidney disease: genes, proteins, animal models, disease mechanisms and therapeutic opportunities. J Intern Med. 2007;261(1):17–31.

    Article  CAS  PubMed  Google Scholar 

  105. Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, et al. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science. 1996;272(5266):1339–42.

    Article  CAS  PubMed  Google Scholar 

  106. Boulter C, Mulroy S, Webb S, Fleming S, Brindle K, Sandford R. Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene. Proc Natl Acad Sci U S A. 2001;98(21):12174–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kim K, Drummond I, Ibraghimov-Beskrovnaya O, Klinger K, Arnaout MA. Polycystin 1 is required for the structural integrity of blood vessels. Proc Natl Acad Sci U S A. 2000;97(4):1731–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Lu W, Peissel B, Babakhanlou H, Pavlova A, Geng L, Fan X, et al. Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Nat Genet. 1997;17(2):179–81.

    Article  CAS  PubMed  Google Scholar 

  109. Lu W, Shen X, Pavlova A, Lakkis M, Ward CJ, Pritchard L, et al. Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum Mol Genet. 2001;10(21):2385–96.

    Article  CAS  PubMed  Google Scholar 

  110. Brasier JL, Henske EP. Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis. J Clin Invest. 1997;99(2):194–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Koptides M, Mean R, Demetriou K, Pierides A, Deltas CC. Genetic evidence for a trans-heterozygous model for cystogenesis in autosomal dominant polycystic kidney disease. Hum Mol Genet. 2000;9(3):447–52.

    Article  CAS  PubMed  Google Scholar 

  112. Qian F, Watnick TJ, Onuchic LF, Germino GG. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell. 1996;87(6):979–87.

    Article  CAS  PubMed  Google Scholar 

  113. Watnick T, He N, Wang K, Liang Y, Parfrey P, Hefferton D, et al. Mutations of PKD1 in ADPKD2 cysts suggest a pathogenic effect of trans-heterozygous mutations. Nat Genet. 2000;25(2):143–4.

    Article  CAS  PubMed  Google Scholar 

  114. Watnick TJ, Torres VE, Gandolph MA, Qian F, Onuchic LF, Klinger KW, et al. Somatic mutation in individual liver cysts supports a two-hit model of cystogenesis in autosomal dominant polycystic kidney disease. Mol Cell. 1998;2(2):247–51.

    Article  CAS  PubMed  Google Scholar 

  115. Pei Y, Paterson AD, Wang KR, He N, Hefferton D, Watnick T, et al. Bilineal disease and trans-heterozygotes in autosomal dominant polycystic kidney disease. Am J Hum Genet. 2001;68(2):355–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Wu G, Tian X, Nishimura S, Markowitz GS, D’Agati V, Park JH, et al. Trans-heterozygous Pkd1 and Pkd2 mutations modify expression of polycystic kidney disease. Hum Mol Genet. 2002;11(16):1845–54.

    Article  CAS  PubMed  Google Scholar 

  117. Thivierge C, Kurbegovic A, Couillard M, Guillaume R, Coté O, Trudel M. Overexpression of PKD1 causes polycystic kidney disease. Mol Cell Biol. 2006;26(4):1538–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Happé H, Peters DJM. Translational research in ADPKD: lessons from animal models. Nat Rev Nephrol. 2014;10(10):587–601.

    Article  PubMed  CAS  Google Scholar 

  119. Lantinga-van Leeuwen IS, Dauwerse JG, Baelde HJ, Leonhard WN, van de Wal A, Ward CJ, et al. Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum Mol Genet. 2004;13(24):3069–77.

    Article  CAS  PubMed  Google Scholar 

  120. Piontek K, Menezes LF, Garcia-Gonzalez MA, Huso DL, Germino GG. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med. 2007;13(12):1490–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Bastos AP, Piontek K, Silva AM, Martini D, Menezes LF, Fonseca JM, et al. Pkd1 haploinsufficiency increases renal damage and induces microcyst formation following ischemia/reperfusion. J Am Soc Nephrol JASN. 2009;20(11):2389–402.

    Article  CAS  PubMed  Google Scholar 

  122. Patel V, Li L, Cobo-Stark P, Shao X, Somlo S, Lin F, et al. Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia. Hum Mol Genet. 2008;17(11):1578–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Takakura A, Contrino L, Zhou X, Bonventre JV, Sun Y, Humphreys BD, et al. Renal injury is a third hit promoting rapid development of adult polycystic kidney disease. Hum Mol Genet. 2009;18(14):2523–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Happé H, Leonhard WN, van der Wal A, van de Water B, Lantinga-van Leeuwen IS, Breuning MH, et al. Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways. Hum Mol Genet. 2009;18(14):2532–42.

    Article  PubMed  CAS  Google Scholar 

  125. Karihaloo A, Koraishy F, Huen SC, Lee Y, Merrick D, Caplan MJ, et al. Macrophages promote cyst growth in polycystic kidney disease. J Am Soc Nephrol JASN. 2011;22(10):1809–14.

    Article  CAS  PubMed  Google Scholar 

  126. Swenson-Fields KI, Vivian CJ, Salah SM, Peda JD, Davis BM, van Rooijen N, et al. Macrophages promote polycystic kidney disease progression. Kidney Int. 2013;83(5):855–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Weimbs T. Third-hit signaling in renal cyst formation. J Am Soc Nephrol JASN. 2011;22(5):793–5.

    Article  PubMed  Google Scholar 

  128. Zhou J. Polycystins and primary cilia: primers for cell cycle progression. Annu Rev Physiol. 2009;71:83–113.

    Article  CAS  PubMed  Google Scholar 

  129. Ibraghimov-Beskrovnaya O, Bukanov N. Polycystic kidney diseases: from molecular discoveries to targeted therapeutic strategies. Cell Mol Life Sci CMLS. 2008;65(4):605–19.

    Article  CAS  PubMed  Google Scholar 

  130. Hofherr A, Köttgen M. TRPP channels and polycystins. Adv Exp Med Biol. 2011;704:287–313.

    Article  CAS  PubMed  Google Scholar 

  131. Hanaoka K, Qian F, Boletta A, Bhunia AK, Piontek K, Tsiokas L, et al. Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature. 2000;408(6815):990–4.

    Article  CAS  PubMed  Google Scholar 

  132. Qian F, Germino FJ, Cai Y, Zhang X, Somlo S, Germino GG. PKD1 interacts with PKD2 through a probable coiled-coil domain. Nat Genet. 1997;16(2):179–83.

    Article  CAS  PubMed  Google Scholar 

  133. Qian F, Boletta A, Bhunia AK, Xu H, Liu L, Ahrabi AK, et al. Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. Proc Natl Acad Sci U S A. 2002;99(26):16981–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Hogan MC, Manganelli L, Woollard JR, Masyuk AI, Masyuk TV, Tammachote R, et al. Characterization of PKD protein-positive exosome-like vesicles. J Am Soc Nephrol JASN. 2009;20(2):278–88.

    Article  CAS  PubMed  Google Scholar 

  135. Yoder BK. Role of primary cilia in the pathogenesis of polycystic kidney disease. J Am Soc Nephrol JASN. 2007;18(5):1381–8.

    Article  CAS  PubMed  Google Scholar 

  136. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003;33(2):129–37.

    Article  CAS  PubMed  Google Scholar 

  137. Praetorius HA, Spring KR. Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol. 2001;184(1):71–9.

    Article  CAS  PubMed  Google Scholar 

  138. Sharif-Naeini R, Folgering JHA, Bichet D, Duprat F, Lauritzen I, Arhatte M, et al. Polycystin-1 and -2 dosage regulates pressure sensing. Cell. 2009;139(3):587–96.

    Article  CAS  PubMed  Google Scholar 

  139. Gallagher AR, Germino GG, Somlo S. Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):118–30.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Rossetti S, Harris PC. Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease. J Am Soc Nephrol JASN. 2007;18(5):1374–80.

    Article  CAS  PubMed  Google Scholar 

  141. Rossetti S, Strmecki L, Gamble V, Burton S, Sneddon V, Peral B, et al. Mutation analysis of the entire PKD1 gene: genetic and diagnostic implications. Am J Hum Genet. 2001;68(1):46–63.

    Article  CAS  PubMed  Google Scholar 

  142. Rossetti S, Torra R, Coto E, Consugar M, Kubly V, Málaga S, et al. A complete mutation screen of PKHD1 in autosomal-recessive polycystic kidney disease (ARPKD) pedigrees. Kidney Int. 2003;64(2):391–403.

    Article  CAS  PubMed  Google Scholar 

  143. Hateboer N, Veldhuisen B, Peters D, Breuning MH, San-Millán JL, Bogdanova N, et al. Location of mutations within the PKD2 gene influences clinical outcome. Kidney Int. 2000;57(4):1444–51.

    Article  CAS  PubMed  Google Scholar 

  144. Rossetti S, Burton S, Strmecki L, Pond GR, San Millán JL, Zerres K, et al. The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease. J Am Soc Nephrol JASN. 2002;13(5):1230–7.

    Article  CAS  PubMed  Google Scholar 

  145. Rossetti S, Chauveau D, Kubly V, Slezak JM, Saggar-Malik AK, Pei Y, et al. Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet. 2003;361(9376):2196–201.

    Article  CAS  PubMed  Google Scholar 

  146. Bergmann C, von Bothmer J, Ortiz Brüchle N, Venghaus A, Frank V, Fehrenbach H, et al. Mutations in multiple PKD genes may explain early and severe polycystic kidney disease. J Am Soc Nephrol JASN. 2011;22(11):2047–56.

    Article  CAS  PubMed  Google Scholar 

  147. Fain PR, McFann KK, Taylor MRG, Tison M, Johnson AM, Reed B, et al. Modifier genes play a significant role in the phenotypic expression of PKD1. Kidney Int. 2005;67(4):1256–67.

    Article  CAS  PubMed  Google Scholar 

  148. Zerres K, Rudnik-Schöneborn S, Deget F. Childhood onset autosomal dominant polycystic kidney disease in sibs: clinical picture and recurrence risk. German Working Group on Paediatric Nephrology (Arbeitsgemeinschaft für Pädiatrische Nephrologie). J Med Genet. 1993;30(7):583–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Kääriäinen H. Polycystic kidney disease in children: a genetic and epidemiological study of 82 Finnish patients. J Med Genet. 1987;24(8):474–81.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Bergmann C, Küpper F, Dornia C, Schneider F, Senderek J, Zerres K. Algorithm for efficient PKHD1 mutation screening in autosomal recessive polycystic kidney disease (ARPKD). Hum Mutat. 2005;25(3):225–31.

    Article  CAS  PubMed  Google Scholar 

  151. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003;111(5 Pt 1):1072–80.

    Article  PubMed  Google Scholar 

  152. Gunay-Aygun M, Avner ED, Bacallao RL, Choyke PL, Flynn JT, Germino GG, et al. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis: summary statement of a first National Institutes of Health/Office of Rare Diseases conference. J Pediatr. 2006;149(2):159–64.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Nakanishi K, Sweeney Jr WE, Zerres K, Guay-Woodford LM, Avner ED. Proximal tubular cysts in fetal human autosomal recessive polycystic kidney disease. J Am Soc Nephrol JASN. 2000;11(4):760–3.

    CAS  PubMed  Google Scholar 

  154. Bergmann C. Autosomal recessive polycystic kidney disease. In: Kenny TD, Beales PL, Herausgeber, editors. Ciliopathies: a reference for clinicians. Oxford University Press; 2014.

    Google Scholar 

  155. Büscher R, Büscher AK, Weber S, Mohr J, Hegen B, Vester U, et al. Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes. Pediatr Nephrol Berl Ger. 2014;29(10):1915–25.

    Article  Google Scholar 

  156. Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman Gerstein M, Piwnica-Worms K, Choyke P, et al. Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. Gastroenterology. 2013;144(1):112–21.e2.

    Article  PubMed  Google Scholar 

  157. Adeva M, El-Youssef M, Rossetti S, Kamath PS, Kubly V, Consugar MB, et al. Clinical and molecular characterization defines a broadened spectrum of autosomal recessive polycystic kidney disease (ARPKD). Medicine (Baltimore). 2006;85(1):1–21.

    Article  Google Scholar 

  158. Guay-Woodford LM, Bissler JJ, Braun MC, Bockenhauer D, Cadnapaphornchai MA, Dell KM, et al. Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an International Conference. J Pediatr. 2014;165(3):611–7.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Cole BR, Conley SB, Stapleton FB. Polycystic kidney disease in the first year of life. J Pediatr. 1987;111(5):693–9.

    Article  CAS  PubMed  Google Scholar 

  160. Kääriäinen H, Koskimies O, Norio R. Dominant and recessive polycystic kidney disease in children: evaluation of clinical features and laboratory data. Pediatr Nephrol Berl Ger. 1988;2(3):296–302.

    Article  Google Scholar 

  161. Kaplan BS, Fay J, Shah V, Dillon MJ, Barratt TM. Autosomal recessive polycystic kidney disease. Pediatr Nephrol Berl Ger. 1989;3(1):43–9.

    Article  CAS  Google Scholar 

  162. Zerres K, Rudnik-Schöneborn S, Deget F, Holtkamp U, Brodehl J, Geisert J, et al. Autosomal recessive polycystic kidney disease in 115 children: clinical presentation, course and influence of gender. Arbeitsgemeinschaft für Pädiatrische Nephrol Acta Paediatr Oslo Nor. 1996;85(4):437–45. 1992.

    CAS  Google Scholar 

  163. Roy S, Dillon MJ, Trompeter RS, Barratt TM. Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors. Pediatr Nephrol Berl Ger. 1997;11(3):302–6.

    Article  CAS  Google Scholar 

  164. Capisonda R, Phan V, Traubuci J, Daneman A, Balfe JW, Guay-Woodford LM. Autosomal recessive polycystic kidney disease: outcomes from a single-center experience. Pediatr Nephrol Berl Ger. 2003;18(2):119–26.

    Google Scholar 

  165. Bergmann C, Senderek J, Windelen E, Küpper F, Middeldorf I, Schneider F, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int. 2005;67(3):829–48.

    Article  CAS  PubMed  Google Scholar 

  166. Bergmann C, Küpper F, Schmitt CP, Vester U, Neuhaus TJ, Senderek J, et al. Multi-exon deletions of the PKHD1 gene cause autosomal recessive polycystic kidney disease (ARPKD). J Med Genet. 2005;42(10):e63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Gunay-Aygun M, Tuchman M, Font-Montgomery E, Lukose L, Edwards H, Garcia A, et al. PKHD1 sequence variations in 78 children and adults with autosomal recessive polycystic kidney disease and congenital hepatic fibrosis. Mol Genet Metab. 2010;99(2):160–73.

    Article  CAS  PubMed  Google Scholar 

  168. Mehler K, Beck BB, Kaul I, Rahimi G, Hoppe B, Kribs A. Respiratory and general outcome in neonates with renal oligohydramnios – a single-centre experience. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2011;26(11):3514–22.

    Google Scholar 

  169. Zurowska AM, Fischbach M, Watson AR, Edefonti A, Stefanidis CJ, European Paediatric Dialysis Working Group. Clinical practice recommendations for the care of infants with stage 5 chronic kidney disease (CKD5). Pediatr Nephrol Berl Ger. 2013;28(9):1739–48.

    Article  Google Scholar 

  170. Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman M, Graf J, Bryant JC, et al. Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease. Clin J Am Soc Nephrol CJASN. 2010;5(6):972–84.

    Article  CAS  PubMed  Google Scholar 

  171. Arbeiter A, Büscher R, Bonzel K-E, Wingen A-M, Vester U, Wohlschläger J, et al. Nephrectomy in an autosomal recessive polycystic kidney disease (ARPKD) patient with rapid kidney enlargement and increased expression of EGFR. Nephrol Dial Transplant. 2008;23(9):3026–9.

    Article  CAS  PubMed  Google Scholar 

  172. Bean SA, Bednarek FJ, Primack WA. Aggressive respiratory support and unilateral nephrectomy for infants with severe perinatal autosomal recessive polycystic kidney disease. J Pediatr. 1995;127(2):311–3.

    Article  CAS  PubMed  Google Scholar 

  173. Beaunoyer M, Snehal M, Li L, Concepcion W, Salvatierra Jr O, Sarwal M. Optimizing outcomes for neonatal ARPKD. Pediatr Transplant. 2007;11(3):267–71.

    Article  PubMed  Google Scholar 

  174. Shukla AR, Kiddoo DA, Canning DA. Unilateral nephrectomy as palliative therapy in an infant with autosomal recessive polycystic kidney disease. J Urol. 2004;172(5 Pt 1):2000–1.

    Article  PubMed  Google Scholar 

  175. Spechtenhauser B, Hochleitner BW, Ellemunter H, Simma B, Hörmann C, Königsrainer A, et al. Bilateral nephrectomy, peritoneal dialysis and subsequent cadaveric renal transplantation for treatment of renal failure due to polycystic kidney disease requiring continuous ventilation. Pediatr Transplant. 1999;3(3):246–8.

    Article  CAS  PubMed  Google Scholar 

  176. Sumfest JM, Burns MW, Mitchell ME. Aggressive surgical and medical management of autosomal recessive polycystic kidney disease. Urology. 1993;42(3):309–12.

    Article  CAS  PubMed  Google Scholar 

  177. Jafar TH, Stark PC, Schmid CH, Strandgaard S, Kamper A-L, Maschio G, et al. The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease. Kidney Int. 2005;67(1):265–71.

    Article  CAS  PubMed  Google Scholar 

  178. Veizis EI, Carlin CR, Cotton CU. Decreased amiloride-sensitive Na+ absorption in collecting duct principal cells isolated from BPK ARPKD mice. Am J Physiol Renal Physiol. 2004;286(2):F244–54.

    Article  CAS  PubMed  Google Scholar 

  179. Goto M, Hoxha N, Osman R, Dell KM. The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease. Pediatr Nephrol Berl Ger. 2010;25(12):2449–57.

    Article  Google Scholar 

  180. Goto M, Hoxha N, Osman R, Wen J, Wells RG, Dell KM. Renin-angiotensin system activation in congenital hepatic fibrosis in the PCK rat model of autosomal recessive polycystic kidney disease. J Pediatr Gastroenterol Nutr. 2010;50(6):639–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Nahm A-M, Henriquez DE, Ritz E. Renal cystic disease (ADPKD and ARPKD). Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2002;17(2):311–4.

    Google Scholar 

  182. Nicolau C, Torra R, Badenas C, Pérez L, Oliver JA, Darnell A, et al. Sonographic pattern of recessive polycystic kidney disease in young adults. Differences from the dominant form. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2000;15(9):1373–8.

    CAS  Google Scholar 

  183. Vester U, Kranz B, Hoyer PF. The diagnostic value of ultrasound in cystic kidney diseases. Pediatr Nephrol Berl Ger. 2010;25(2):231–40.

    Article  Google Scholar 

  184. Srinath A, Shneider BL. Congenital hepatic fibrosis and autosomal recessive polycystic kidney disease. J Pediatr Gastroenterol Nutr. 2012;54(5):580–7.

    Article  PubMed  PubMed Central  Google Scholar 

  185. Kashtan CE, Primack WA, Kainer G, Rosenberg AR, McDonald RA, Warady BA. Recurrent bacteremia with enteric pathogens in recessive polycystic kidney disease. Pediatr Nephrol Berl Ger. 1999;13(8):678–82.

    Article  CAS  Google Scholar 

  186. Gallagher A-R, Esquivel EL, Briere TS, Tian X, Mitobe M, Menezes LF, et al. Biliary and pancreatic dysgenesis in mice harboring a mutation in Pkhd1. Am J Pathol. 2008;172(2):417–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Garcia-Gonzalez MA, Menezes LF, Piontek KB, Kaimori J, Huso DL, Watnick T, et al. Genetic interaction studies link autosomal dominant and recessive polycystic kidney disease in a common pathway. Hum Mol Genet. 2007;16(16):1940–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Moser M, Matthiesen S, Kirfel J, Schorle H, Bergmann C, Senderek J, et al. A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD). Hepatol Baltim Md. 2005;41(5):1113–21.

    Article  CAS  Google Scholar 

  189. Woollard JR, Punyashtiti R, Richardson S, Masyuk TV, Whelan S, Huang BQ, et al. A mouse model of autosomal recessive polycystic kidney disease with biliary duct and proximal tubule dilatation. Kidney Int. 2007;72(3):328–36.

    Article  CAS  PubMed  Google Scholar 

  190. Brinkert F, Lehnhardt A, Montoya C, Helmke K, Schaefer H, Fischer L, et al. Combined liver-kidney transplantation for children with autosomal recessive polycystic kidney disease (ARPKD): indication and outcome. Transpl Int Off J Eur Soc Org Transplant. 2013;26(6):640–50.

    Article  CAS  Google Scholar 

  191. Jalanko H, Pakarinen M. Combined liver and kidney transplantation in children. Pediatr Nephrol Berl Ger. 2014;29(5):805–14; quiz 812.

    Article  Google Scholar 

  192. Telega G, Cronin D, Avner ED. New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications. Pediatr Transplant. 2013;17(4):328–35.

    Article  PubMed  PubMed Central  Google Scholar 

  193. Turkbey B, Ocak I, Daryanani K, Font-Montgomery E, Lukose L, Bryant J, et al. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF). Pediatr Radiol. 2009;39(2):100–11.

    Article  PubMed  Google Scholar 

  194. Chilton SJ, Cremin BJ. The spectrum of polycystic disease in children. Pediatr Radiol. 1981;11(1):9–15.

    Article  CAS  PubMed  Google Scholar 

  195. Deget F, Rudnik-Schöneborn S, Zerres K. Course of autosomal recessive polycystic kidney disease (ARPKD) in siblings: a clinical comparison of 20 sibships. Clin Genet. 1995;47(5):248–53.

    Article  CAS  PubMed  Google Scholar 

  196. Kaplan BS, Kaplan P, de Chadarevian JP, Jequier S, O’Regan S, Russo P. Variable expression of autosomal recessive polycystic kidney disease and congenital hepatic fibrosis within a family. Am J Med Genet. 1988;29(3):639–47.

    Article  CAS  PubMed  Google Scholar 

  197. Zerres K, Völpel MC, Weiss H. Cystic kidneys. Genetics, pathologic anatomy, clinical picture, and prenatal diagnosis. Hum Genet. 1984;68(2):104–35.

    Article  CAS  PubMed  Google Scholar 

  198. Guay-Woodford LM, Muecher G, Hopkins SD, Avner ED, Germino GG, Guillot AP, et al. The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: implications for genetic counseling. Am J Hum Genet. 1995;56(5):1101–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Zerres K, Mücher G, Bachner L, Deschennes G, Eggermann T, Kääriäinen H, et al. Mapping of the gene for autosomal recessive polycystic kidney disease (ARPKD) to chromosome 6p21-cen. Nat Genet. 1994;7(3):429–32.

    Article  CAS  PubMed  Google Scholar 

  200. Onuchic LF, Furu L, Nagasawa Y, Hou X, Eggermann T, Ren Z, et al. PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats. Am J Hum Genet. 2002;70(5):1305–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Ward CJ, Hogan MC, Rossetti S, Walker D, Sneddon T, Wang X, et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet. 2002;30(3):259–69.

    Article  PubMed  Google Scholar 

  202. Nagasawa Y, Matthiesen S, Onuchic LF, Hou X, Bergmann C, Esquivel E, et al. Identification and characterization of Pkhd1, the mouse orthologue of the human ARPKD gene. J Am Soc Nephrol JASN. 2002;13(9):2246–58.

    Article  CAS  PubMed  Google Scholar 

  203. Masyuk TV, Huang BQ, Ward CJ, Masyuk AI, Yuan D, Splinter PL, et al. Defects in cholangiocyte fibrocystin expression and ciliary structure in the PCK rat. Gastroenterology. 2003;125(5):1303–10.

    Article  CAS  PubMed  Google Scholar 

  204. Menezes LFC, Cai Y, Nagasawa Y, Silva AMG, Watkins ML, Da Silva AM, et al. Polyductin, the PKHD1 gene product, comprises isoforms expressed in plasma membrane, primary cilium, and cytoplasm. Kidney Int. 2004;66(4):1345–55.

    Article  CAS  PubMed  Google Scholar 

  205. Wang S, Luo Y, Wilson PD, Witman GB, Zhou J. The autosomal recessive polycystic kidney disease protein is localized to primary cilia, with concentration in the basal body area. J Am Soc Nephrol JASN. 2004;15(3):592–602.

    Article  PubMed  Google Scholar 

  206. Ward CJ, Yuan D, Masyuk TV, Wang X, Punyashthiti R, Whelan S, et al. Cellular and subcellular localization of the ARPKD protein; fibrocystin is expressed on primary cilia. Hum Mol Genet. 2003;12(20):2703–10.

    Article  CAS  PubMed  Google Scholar 

  207. Zhang M-Z, Mai W, Li C, Cho S, Hao C, Moeckel G, et al. PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells. Proc Natl Acad Sci U S A. 2004;101(8):2311–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Follit JA, Li L, Vucica Y, Pazour GJ. The cytoplasmic tail of fibrocystin contains a ciliary targeting sequence. J Cell Biol. 2010;188(1):21–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Hiesberger T, Gourley E, Erickson A, Koulen P, Ward CJ, Masyuk TV, et al. Proteolytic cleavage and nuclear translocation of fibrocystin is regulated by intracellular Ca2+ and activation of protein kinase C. J Biol Chem. 2006;281(45):34357–64.

    Article  CAS  PubMed  Google Scholar 

  210. Kaimori J, Nagasawa Y, Menezes LF, Garcia-Gonzalez MA, Deng J, Imai E, et al. Polyductin undergoes notch-like processing and regulated release from primary cilia. Hum Mol Genet. 2007;16(8):942–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Bergmann C, Senderek J, Sedlacek B, Pegiazoglou I, Puglia P, Eggermann T, et al. Spectrum of mutations in the gene for autosomal recessive polycystic kidney disease (ARPKD/PKHD1). J Am Soc Nephrol JASN. 2003;14(1):76–89.

    Article  CAS  PubMed  Google Scholar 

  212. Bergmann C, Senderek J, Küpper F, Schneider F, Dornia C, Windelen E, et al. PKHD1 mutations in autosomal recessive polycystic kidney disease (ARPKD). Hum Mutat. 2004;23(5):453–63.

    Article  CAS  PubMed  Google Scholar 

  213. Bergmann C, Senderek J, Schneider F, Dornia C, Küpper F, Eggermann T, et al. PKHD1 mutations in families requesting prenatal diagnosis for autosomal recessive polycystic kidney disease (ARPKD). Hum Mutat. 2004;23(5):487–95.

    Article  CAS  PubMed  Google Scholar 

  214. Furu L, Onuchic LF, Gharavi A, Hou X, Esquivel EL, Nagasawa Y, et al. Milder presentation of recessive polycystic kidney disease requires presence of amino acid substitution mutations. J Am Soc Nephrol JASN. 2003;14(8):2004–14.

    Article  CAS  PubMed  Google Scholar 

  215. Losekoot M, Haarloo C, Ruivenkamp C, White SJ, Breuning MH, Peters DJM. Analysis of missense variants in the PKHD1-gene in patients with autosomal recessive polycystic kidney disease (ARPKD). Hum Genet. 2005;118(2):185–206.

    Article  CAS  PubMed  Google Scholar 

  216. Baralle D, Baralle M. Splicing in action: assessing disease causing sequence changes. J Med Genet. 2005;42(10):737–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Bergmann C, Frank V, Küpper F, Schmidt C, Senderek J, Zerres K. Functional analysis of PKHD1 splicing in autosomal recessive polycystic kidney disease. J Hum Genet. 2006;51(9):788–93.

    Article  CAS  PubMed  Google Scholar 

  218. Consugar MB, Anderson SA, Rossetti S, Pankratz VS, Ward CJ, Torra R, et al. Haplotype analysis improves molecular diagnostics of autosomal recessive polycystic kidney disease. Am J Kidney Dis Off J Natl Kidney Found. 2005;45(1):77–87.

    Article  CAS  Google Scholar 

  219. Krall P, Pineda C, Ruiz P, Ejarque L, Vendrell T, Camacho JA, et al. Cost-effective PKHD1 genetic testing for autosomal recessive polycystic kidney disease. Pediatr Nephrol Berl Ger. 2014;29(2):223–34.

    Article  Google Scholar 

  220. Boddu R, Yang C, O’Connor AK, Hendrickson RC, Boone B, Cui X, et al. Intragenic motifs regulate the transcriptional complexity of Pkhd1/PKHD1. J Mol Med Berl Ger. 2014;92(10):1045–56.

    Article  CAS  Google Scholar 

  221. Frank V, Zerres K, Bergmann C. Transcriptional complexity in autosomal recessive polycystic kidney disease. Clin J Am Soc Nephrol CJASN. 2014;9(10):1729–36.

    Article  CAS  PubMed  Google Scholar 

  222. Guay-Woodford LM, Wright CJ, Walz G, Churchill GA. Quantitative trait loci modulate renal cystic disease severity in the mouse bpk model. J Am Soc Nephrol JASN. 2000;11(7):1253–60.

    CAS  PubMed  Google Scholar 

  223. Liebau MC, Benzing T. Recent developments in genetic kidney diseases. Dtsch Med Wochenschr. 2011;136(19):1014–20. 1946.

    Article  CAS  PubMed  Google Scholar 

  224. Sommardahl C, Cottrell M, Wilkinson JE, Woychik RP, Johnson DK. Phenotypic variations of orpk mutation and chromosomal localization of modifiers influencing kidney phenotype. Physiol Genomics. 2001;7(2):127–34.

    Article  CAS  PubMed  Google Scholar 

  225. Zaghloul NA, Katsanis N. Functional modules, mutational load and human genetic disease. Trends Genet TIG. 2010;26(4):168–76.

    Article  CAS  PubMed  Google Scholar 

  226. Modrek B, Lee C. A genomic view of alternative splicing. Nat Genet. 2002;30(1):13–9.

    Article  CAS  PubMed  Google Scholar 

  227. Nissim-Rafinia M, Kerem B. Splicing regulation as a potential genetic modifier. Trends Genet TIG. 2002;18(3):123–7.

    Article  CAS  PubMed  Google Scholar 

  228. Zerres K, Senderek J, Rudnik-Schöneborn S, Eggermann T, Kunze J, Mononen T, et al. New options for prenatal diagnosis in autosomal recessive polycystic kidney disease by mutation analysis of the PKHD1 gene. Clin Genet. 2004;66(1):53–7.

    Article  CAS  PubMed  Google Scholar 

  229. Barr MM, Sternberg PW. A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature. 1999;401(6751):386–9.

    CAS  PubMed  Google Scholar 

  230. Pazour GJ, Dickert BL, Vucica Y, Seeley ES, Rosenbaum JL, Witman GB, et al. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J Cell Biol. 2000;151(3):709–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Ma M, Tian X, Igarashi P, Pazour GJ, Somlo S. Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease. Nat Genet. 2013;45(9):1004–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Patel V, Chowdhury R, Igarashi P. Advances in the pathogenesis and treatment of polycystic kidney disease. Curr Opin Nephrol Hypertens. 2009;18(2):99–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Watnick T, Germino GG. mTOR inhibitors in polycystic kidney disease. N Engl J Med. 2010;363(9):879–81.

    Article  CAS  PubMed  Google Scholar 

  234. Seeger-Nukpezah T, Proia DA, Egleston BL, Nikonova AS, Kent T, Cai KQ, et al. Inhibiting the HSP90 chaperone slows cyst growth in a mouse model of autosomal dominant polycystic kidney disease. Proc Natl Acad Sci U S A. 2013;110(31):12786–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Grantham JJ, Mulamalla S, Swenson-Fields KI. Why kidneys fail in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2011;7(10):556–66.

    Article  CAS  PubMed  Google Scholar 

  236. Gattone 2nd VH, Wang X, Harris PC, Torres VE. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med. 2003;9(10):1323–6.

    Article  CAS  PubMed  Google Scholar 

  237. Torres VE, Wang X, Qian Q, Somlo S, Harris PC, Gattone 2nd VH. Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med. 2004;10(4):363–4.

    Article  CAS  PubMed  Google Scholar 

  238. Wang X, Gattone 2nd V, Harris PC, Torres VE. Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat. J Am Soc Nephrol JASN. 2005;16(4):846–51.

    Article  CAS  PubMed  Google Scholar 

  239. Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367(25):2407–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Ruggenenti P, Remuzzi A, Ondei P, Fasolini G, Antiga L, Ene-Iordache B, et al. Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int. 2005;68(1):206–16.

    Article  CAS  PubMed  Google Scholar 

  241. Caroli A, Perico N, Perna A, Antiga L, Brambilla P, Pisani A, et al. Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial. Lancet. 2013;382(9903):1485–95.

    Article  CAS  PubMed  Google Scholar 

  242. Schrier RW, Abebe KZ, Perrone RD, Torres VE, Braun WE, Steinman TI, et al. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med. 2015;372(10):976–7.

    CAS  PubMed  Google Scholar 

  243. Torres VE, Abebe KZ, Chapman AB, Schrier RW, Braun WE, Steinman TI, et al. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med. 2014;371:2267–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  244. Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, et al. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci U S A. 2006;103(14):5466–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Novalic Z, van der Wal AM, Leonhard WN, Koehl G, Breuning MH, Geissler EK, et al. Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease. J Am Soc Nephrol JASN. 2012;23(5):842–53.

    Article  CAS  PubMed  Google Scholar 

  246. Shillingford JM, Piontek KB, Germino GG, Weimbs T. Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J Am Soc Nephrol JASN. 2010;21(3):489–97.

    Article  CAS  PubMed  Google Scholar 

  247. Torres VE, Boletta A, Chapman A, Gattone V, Pei Y, Qian Q, et al. Prospects for mTOR inhibitor use in patients with polycystic kidney disease and hamartomatous diseases. Clin J Am Soc Nephrol CJASN. 2010;5(7):1312–29.

    Article  CAS  PubMed  Google Scholar 

  248. Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wüthrich RP. Inhibition of mTOR with sirolimus slows disease progression in Han: SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2006;21(3):598–604.

    CAS  Google Scholar 

  249. Wu M, Wahl PR, Le Hir M, Wackerle-Men Y, Wuthrich RP, Serra AL. Everolimus retards cyst growth and preserves kidney function in a rodent model for polycystic kidney disease. Kidney Blood Press Res. 2007;30(4):253–9.

    Article  PubMed  Google Scholar 

  250. Wu M, Arcaro A, Varga Z, Vogetseder A, Le Hir M, Wüthrich RP, et al. Pulse mTOR inhibitor treatment effectively controls cyst growth but leads to severe parenchymal and glomerular hypertrophy in rat polycystic kidney disease. Am J Physiol Renal Physiol. 2009;297(6):F1597–605.

    Article  CAS  PubMed  Google Scholar 

  251. Zafar I, Belibi FA, He Z, Edelstein CL. Long-term rapamycin therapy in the Han: SPRD rat model of polycystic kidney disease (PKD). Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2009;24(8):2349–53.

    CAS  Google Scholar 

  252. Serra AL, Poster D, Kistler AD, Krauer F, Raina S, Young J, et al. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010;363(9):820–9.

    Article  CAS  PubMed  Google Scholar 

  253. Cinà DP, Onay T, Paltoo A, Li C, Maezawa Y, De Arteaga J, et al. Inhibition of MTOR disrupts autophagic flux in podocytes. J Am Soc Nephrol JASN. 2012;23(3):412–20.

    Article  PubMed  CAS  Google Scholar 

  254. Gödel M, Hartleben B, Herbach N, Liu S, Zschiedrich S, Lu S, et al. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J Clin Invest. 2011;121(6):2197–209.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  255. Hartleben B, Gödel M, Meyer-Schwesinger C, Liu S, Ulrich T, Köbler S, et al. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest. 2010;120(4):1084–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Inoki K, Mori H, Wang J, Suzuki T, Hong S, Yoshida S, et al. mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice. J Clin Invest. 2011;121(6):2181–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  257. Liebau MC, Braun F, Höpker K, Weitbrecht C, Bartels V, Müller R-U, et al. Dysregulated autophagy contributes to podocyte damage in Fabry’s disease. PLoS ONE. 2013;8(5):e63506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  258. Walz G, Budde K, Mannaa M, Nürnberger J, Wanner C, Sommerer C, et al. Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2010;363(9):830–40.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

CB is an employee of Bioscientia/Sonic Healthcare and holds a part-time faculty appointment at the University of Freiburg. His research lab received support from the Deutsche Forschungsge-meinschaft (DFG), Deutsche Nierenstiftung, and PKD Foundation. MCL was supported by the Köln Fortune and the GEROK program of the medical faculty of the University of Cologne, the Marga and Walter Boll-Stiftung and the PKD Familiäre Zystennieren e.V. (PKD Foundation) CB and MCL are supported by a grant from the German Ministry of Education and Research (Grant No. 01GM1515). We thank Klaus Zerres (Aachen, Germany) for his valuable contributions to the chapter originally published in the first edition of the book.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Nephrology and Center for Molecular Medicine, University Hospital of Cologne, Kerpener Strasse 62, 50937, Cologne, Germany

    Max Christoph Liebau

  2. Renal Division, Department of Medicine, University of Freiburg Medical Center, Hugstetter Straße 55, 79106, Freiburg, Germany

    Carsten Bergmann

Authors
  1. Max Christoph Liebau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carsten Bergmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Max Christoph Liebau or Carsten Bergmann .

Editor information

Editors and Affiliations

  1. Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada

    Denis F. Geary

  2. Division of Pediatric Nephrology, University of Heidelberg, Heidelberg, Germany

    Franz Schaefer

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Liebau, M.C., Bergmann, C. (2016). Polycystic Kidney Disease: ADPKD and ARPKD. In: Geary, D., Schaefer, F. (eds) Pediatric Kidney Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-52972-0_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-52972-0_12

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-52970-6

  • Online ISBN: 978-3-662-52972-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation