Skip to main content
SpringerLink
Log in

Childhood Polycystic Kidney Disease

  • Reference work entry
  • First Online:
Pediatric Nephrology

Abstract

Cystic kidney diseases (CKDs) are a clinically and genetically heterogeneous group of disorders that have renal cysts or cystic dysplasia as a component of their phenotype [1]. Cystic kidneys are an important feature of numerous genetic syndromes, such as the mainly recessively inherited ciliopathies Bardet–Biedl, nephronophthisis, and Joubert, Meckel, and Jeune syndromes or the dominant disorders of tuberous sclerosis (TSC), von Hippel–Lindau (VHL) disease, and branchio-oto-renal syndrome. In addition glomerulocystic kidney disease (GCKD) can be a feature of several inherited, sporadic, and syndromal conditions as well as an expression of ADPKD.

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 949.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,299.99
Price excludes VAT (USA)
  • Durable hardcover 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

Similar content being viewed by others

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. Bissler JJ, Siroky BJ, Yin H. Glomerulocystic kidney disease. Pediatr Nephrol (Berl, Germany). 2010;25:2049.

    Article  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Valente EM, Dallapiccola B, Bertini E. Joubert syndrome and related disorders. Handb Clin Neurol. 2013;113:1879–88.

    Article  PubMed  Google Scholar 

  5. Barker AR, Thomas R, Dawe HR. Meckel-Gruber syndrome and the role of primary cilia in kidney, skeleton, and central nervous system development. Organogenesis. 2014;10(1):96–107.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Brancati F, Dallapiccola B, Valente EM. Joubert syndrome and related disorders. Orphanet J Rare Dis. 2010;5:20.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Rodriguez MM. Congenital anomalies of the kidney and the urinary tract (CAKUT). Fetal Pediatr Pathol. 2014;33(5–6):293–320.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Chung EM, Conran RM, Schroeder JW, Rohena-Quinquilla IR, Rooks VJ. From the radiologic pathology archives: pediatric polycystic kidney disease and other ciliopathies: radiologic-pathologic correlation. Radiographics. 2014;34(1):155–78.

    Article  PubMed  Google Scholar 

  9. 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 Central  PubMed  Google Scholar 

  10. Hartung EA, Guay-Woodford LM. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects. Pediatrics. 2014;134(3):e833–45.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Guay-Woodford LM, Galliani CA, Musulman-Mroczek E, Spear GS, Guillot AP, Bernstein J. Diffuse renal cystic disease in children: morphologic and genetic correlations. Pediatr Nephrol (Berl Germany). 1998;12(3):173–82.

    Article  CAS  Google Scholar 

  12. McDonald RA, Avner ED. Inherited polycystic kidney disease in children. Semin Nephrol. 1991;11:632–42.

    CAS  PubMed  Google Scholar 

  13. Sweeney Jr WE, Avner ED. Pathophysiology of childhood polycystic kidney diseases: new insights into disease-specific therapy. Pediatr Res. 2014;75(1–2):148–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  16. Sweeney W, Avner ED. Polycystic kidney disease, autosomal recessive. Seattle: University of Washington; 2001 [updated 6 Mar 2014]. http://www.ncbi.clm.nih.gov/books/NBK1326].

    Google Scholar 

  17. Dell KM. The spectrum of polycystic kidney disease in children. Adv Chronic Kidney Dis. 2011;18(5):339–47.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet. 1994;343(8901):824–7.

    Article  CAS  PubMed  Google Scholar 

  19. 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. 2009;20(1):205–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Rossetti S, Consugar MB, Chapman AB, Torres VE, Guay-Woodford LM, Grantham JJ, et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2007;18(7):2143–60.

    Article  CAS  PubMed  Google Scholar 

  21. Harris PC. Smith award: insights into the pathogenesis of polycystic kidney disease from gene discovery. J Am Soc Nephrol. 2009;20(6):1188–98.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  23. Harris PC, Torres VE. Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease. J Clin Invest. 2014;124(6):2315–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Harris PC. What is the role of somatic mutation in autosomal dominant polycystic kidney disease? J Am Soc Nephrol. 2010;21(7):1073–6.

    Article  PubMed  Google Scholar 

  25. Harris PC, Rossetti S. Molecular diagnostics for autosomal dominant polycystic kidney disease. Nat Rev. 2010;6(4):197–206.

    CAS  Google Scholar 

  26. Avner ED, Sweeney Jr WE. Renal cystic disease: new insights for the clinician. Pediatr Clin North Am. 2006;53(5):889–909. ix.

    Article  PubMed  Google Scholar 

  27. Grantham JJ. Rationale for early treatment of polycystic kidney disease. Pediatr Nephrol (Berl, Germany). 2014. doi:10.1007/s00467-014-2882-8

    Google Scholar 

  28. 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 Central  PubMed  Google Scholar 

  29. Gunay-Aygun M, Gahl WA, Heller T. Congenital hepatic fibrosis overview. Seattle: University of Washington; 2008 [updated 24 Apr 2014]. http://www.ncbi.nlm.gov/books/NBK2701].

    Google Scholar 

  30. 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;56:1101–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  31. 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  PubMed Central  CAS  PubMed  Google Scholar 

  32. 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 

  33. 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. 2006;85(1):1–21.

    Article  PubMed  Google Scholar 

  34. Zerres K, Rudnik-Schoneborn S, Steinkamm C, Becker J, Mucher G. Autosomal recessive polycystic kidney disease. J Mol Med. 1998;76(5):303–9.

    Article  CAS  PubMed  Google Scholar 

  35. Zerres K, Mucher G, Bachner L, Deschennes G, Eggermann T, Kaariainen 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 

  36. 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;99:160–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. 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 

  38. Kaariainen 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 Central  CAS  PubMed  Google Scholar 

  39. Bergmann C. Autosomal-recessive polycystic kidney disease gets more complex. Gastroenterology. 2013;144(5):1155–6.

    Article  PubMed  Google Scholar 

  40. Dell KM, Sweeney WE, Avner ED. Polycystic kidney disease. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, editors. Pediatric nephrology, vol. 1. 6th ed. Berlin: Springer; 2009. p. 849–87.

    Chapter  Google Scholar 

  41. Bergmann C, Senderek J, Windelen E, Kupper 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 

  42. Bergmann C, Zerres K. Polycystic kidney disease: ADPKD and ARPKD. In: Geary DF, Schaefer F, editors. Comprehensive pediatric nephrology. Philadelphia: Mosby (Elsevier); 2008. p. 155–78.

    Chapter  Google Scholar 

  43. 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  PubMed Central  CAS  PubMed  Google Scholar 

  44. O’Brien K, Font-Montgomery E, Lukose L, Bryant J, Piwnica-Worms K, Edwards H, et al. Congenital hepatic fibrosis and portal hypertension in autosomal dominant polycystic kidney disease. J Pediatr Gastroenterol Nutr. 2012;54:83–9.

    Article  PubMed  CAS  Google Scholar 

  45. 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 

  46. 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. 2003;14(1):76–89.

    Article  CAS  PubMed  Google Scholar 

  47. Rossetti S, Torra R, Coto E, Consugar M, Kubly V, Malaga 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 

  48. Bergmann C, Senderek J, Kupper 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 

  49. Sharp AM, Messiaen LM, Page G, Antignac C, Gubler MC, Onuchic LF, et al. Comprehensive genomic analysis of PKHD1 mutations in ARPKD cohorts. J Med Genet. 2005;42(4):336–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  51. 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. 2003;14(8):2004–14.

    Article  CAS  PubMed  Google Scholar 

  52. 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  PubMed Central  CAS  PubMed  Google Scholar 

  53. 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. 2014;92(10):1045–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. 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 

  55. Zhang MZ, Mai W, Li C, Cho SY, 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  PubMed Central  CAS  PubMed  Google Scholar 

  56. Bergmann C. ARPKD and early manifestations of ADPKD: the original polycystic kidney disease and phenocopies. Pediatr Nephrol (Ber, Germany). 2015;30(1):15–30.

    Google Scholar 

  57. Osathanondh V, Potter EL. Pathogenesis of polycystic kidneys. Type 1 due to hyperplasia of interstitial portions of collecting tubules. Arch Pathol. 1964;77:466–73.

    CAS  PubMed  Google Scholar 

  58. Dalgaard OZ. Bilateral polycystic diseases of kidneys: a follow-up of two hundred and eighty-four patients and their families. Acta Med Scand. 1957;328(Suppl):1–255.

    CAS  Google Scholar 

  59. Faraggiana T, Bernstein J, Strauss L, Churg J. Use of lectins in the study of histogenesis of renal cysts. Lab Invest. 1985;53:575–9.

    CAS  PubMed  Google Scholar 

  60. Verani R, Walker P, Silva FG. Renal cystic disease of infancy: results of histochemical studies. A report of the Southwest Pediatric Nephrology Study Group. Pediatr Nephrol (Berl, Germany). 1989;3(1):37–42.

    Article  CAS  Google Scholar 

  61. 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. 2000;11(4):760–3.

    CAS  PubMed  Google Scholar 

  62. Kissane JM. Renal cysts in pediatric patients. A classification and overview. Pediatr Nephrol (Berl, Germany). 1990;4(1):69–77.

    Article  CAS  Google Scholar 

  63. Lieberman E, Salinas-Madrigal L, Gwinn JL, Brennan LP, Fine RN, Landing BH. Infantile polycystic disease of the kidneys and liver: clinical, pathological and radiological correlations and comparison with congenital hepatic fibrosis. Medicine. 1971;50:277–318.

    Article  CAS  PubMed  Google Scholar 

  64. 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 Central  PubMed  Google Scholar 

  65. Zerres K, Rudnik-Schoneborn 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 fur Padiatrische, Nephrologie. Acta Paediatr. 1996;85(4):437–45.

    Article  CAS  PubMed  Google Scholar 

  66. Kerr DN, Harrison CV, Sherlock S, Walker RM. Congenital hepatic fibrosis. Q J Med. 1961;30:91–117.

    CAS  PubMed  Google Scholar 

  67. 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 

  68. Gunay-Aygun M. Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Med Genet. 2009;151C(4):296–306.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  71. 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 

  72. 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 

  73. Zerres K, Hansmann M, Knopfle G, Stephan M. Prenatal diagnosis of genetically determined early manifestation of autosomal dominant polycystic kidney disease? Hum Genet. 1985;71(4):368–9.

    Article  CAS  PubMed  Google Scholar 

  74. Neumann HP, Zerres K, Fischer CL, Wolff G, Schaefer HE, Gal A, et al. Late manifestation of autosomal-recessive polycystic kidney disease in two sisters. Am J Nephrol. 1988;8(3):194–7.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  76. Kaplan BS, Kaplan P. Autosomal recessive polycystic kidney disease. In: Spitzer A, Avner ED, editors. Inheritance of kidney and urinary tract diseases. Dordrecht: Kluwer; 1990. p. 265–76.

    Chapter  Google Scholar 

  77. Traubici J, Daneman A. High-resolution renal sonography in children with autosomal recessive polycystic kidney disease. AJR Am J Roentgenol. 2005;184(5):1630–3.

    Article  PubMed  Google Scholar 

  78. 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 Central  PubMed  Google Scholar 

  79. Blickman JG, Bramson RT, Herrin JT. Autosomal recessive polycystic kidney disease: long-term sonographic findings in patients surviving the neonatal period. AJR Am J Roentgenol. 1995;164(5):1247–50.

    Article  CAS  PubMed  Google Scholar 

  80. Avni FE, Guissard G, Hall M, Janssen F, DeMaertelaer V, Rypens F. Hereditary polycystic kidney diseases in children: changing sonographic patterns through childhood. Pediatr Radiol. 2002;32(3):169–74.

    Article  PubMed  Google Scholar 

  81. Gunay-Aygun M, Turkbey BI, Bryant J, Daryanani KT, Gerstein MT, Piwnica-Worms K, et al. Hepatorenal findings in obligate heterozygotes for autosomal recessive polycystic kidney disease. Mol Genet Metab. 2011;104:677.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Akhan O, Karaosmanoglu AD, Ergen B. Imaging findings in congenital hepatic fibrosis. Eur J Radiol. 2007;61(1):18–24.

    Article  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  84. Romero R, Cullen M, Jeanty P, Grannum P, Reese EA, Venus I, et al. The diagnosis of congenital renal anomalies with ultrasound II. Infantile polycystic kidney disease. Am J Obstet Gynecol. 1984;150:259–62.

    Article  CAS  PubMed  Google Scholar 

  85. Zerres K, Hansmann M, Mallmann R, Gembruch U. Autosomal recessive polycystic kidney disease. Problems of prenatal diagnosis. Prenat Diagn. 1988;8(3):215–29.

    Article  CAS  PubMed  Google Scholar 

  86. Holthofer H, Kumpulainer T, Rapola J. Polycystic disease of the kidney: evaluation and classification based on nephron segment and cell-type specific markers. Lab Invest. 1990;62:363–9.

    CAS  PubMed  Google Scholar 

  87. Bergmann C, Senderek J, Schneider F, Dornia C, Kupper 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 

  88. Zerres K, Senderek J, Rudnik-Schoneborn 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 

  89. Bergmann C, Kupper 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 

  90. Losekoot M, Haarloo C, Ruivenkamp C, White SJ, Breuning MH, Peters DJ. 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 

  91. Zerres K, Mucher G, Becker J, Steinkamm C, Rudnik-Schoneborn S, Heikkila P, et al. Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): molecular genetics, clinical experience, and fetal morphology. Am J Med Genet. 1998;76(2):137–44.

    Article  CAS  PubMed  Google Scholar 

  92. Lau EC, Janson MM, Roesler MR, Avner ED, Strawn EY, Bick DP. Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification. J Assist Reprod Genet. 2010;27:397–407.

    Article  PubMed Central  PubMed  Google Scholar 

  93. 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 

  94. Munding M, Al-Uzri A, Gralnek D, Riden D. Prenatally diagnosed autosomal recessive polycystic kidney disease: initial postnatal management. Urology. 1999;54(6):1097.

    Article  CAS  PubMed  Google Scholar 

  95. Spechtenhauser B, Hochleitner BW, Ellemunter H, Simma B, Hormann C, Konigsrainer 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 

  96. 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 

  97. Ferguson MA, Flynn JT. Rational use of antihypertensive medications in children. Pediatr Nephrol (Berl, Germany). 2014;29(6):979–88.

    Article  Google Scholar 

  98. Gang DL, Herrin JT. Infantile polycystic disease of the liver and kidneys. Clin Nephrol. 1986;25:28–36.

    CAS  PubMed  Google Scholar 

  99. Lilova M, Kaplan BS, Meyers KE. Recombinant human growth hormone therapy in autosomal recessive polycystic kidney disease. Pediatr Nephrol (Berl, Germany). 2003;18(1):57–61.

    Article  Google Scholar 

  100. Fonck C, Chauveau D, Gagnadoux MF, Pirson Y, Grunfeld JP. Autosomal recessive polycystic kidney disease in adulthood. Nephrol Dial Transplant. 2001;16(8):1648–52.

    Article  CAS  PubMed  Google Scholar 

  101. Shneider BL, Magid MS. Liver disease in autosomal recessive polycystic kidney disease. Pediatr Transplant. 2005;9(5):634–9.

    Article  PubMed  Google Scholar 

  102. Megremis SD, Vlachonikolis IG, Tsilimigaki AM. Spleen length in childhood with US: normal values based on age, sex, and somatometric parameters. Radiology. 2004;231(1):129–34.

    Article  PubMed  Google Scholar 

  103. 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, Germany). 1999;13(8):678–82.

    Article  CAS  Google Scholar 

  104. Ninan VT, Nampoory MR, Johny KV, Gupta RK, Schmidt I, Nair PM, et al. Caroli’s disease of the liver in a renal transplant recipient. Nephrol Dial Transplant. 2002;17(6):1113–5.

    Article  PubMed  Google Scholar 

  105. Kamath BM, Piccoli DA. Heritable disorders of the bile ducts. Gastroenterol Clin North Am. 2003;32(3):857–75. vi.

    Article  PubMed  Google Scholar 

  106. Yonem O, Ozkayar N, Balkanci F, Harmanci O, Sokmensuer C, Ersoy O, et al. Is congenital hepatic fibrosis a pure liver disease? Am J Gastroenterol. 2006;101(6):1253–9.

    Article  PubMed  Google Scholar 

  107. Benador N, Grimm P, Lavine J, Rosenthal P, Reznik V, Lemire J. Transjugular intrahepatic portosystemic shunt prior to renal transplantation in a child with autosomal-recessive polycystic kidney disease and portal hypertension: a case report. Pediatr Transplant. 2001;5(3):210–4.

    Article  CAS  PubMed  Google Scholar 

  108. Tsimaratos M, Cloarec S, Roquelaure B, Retornaz K, Picon G, Chabrol B, et al. Chronic renal failure and portal hypertension–is portosystemic shunt indicated? Pediatr Nephrol. 2000;14(8–9):856–8.

    Article  CAS  PubMed  Google Scholar 

  109. De Kerckhove L, De Meyer M, Verbaandert C, Mourad M, Sokal E, Goffette P, et al. The place of liver transplantation in Caroli’s disease and syndrome. Transpl Int. 2006;19(5):381–8.

    Article  PubMed  Google Scholar 

  110. Adams HR, Szilagyi PG, Gebhardt L, Lande MB. Learning and attention problems among children with pediatric primary hypertension. Pediatrics. 2010;126(6):e1425–9.

    Article  PubMed  Google Scholar 

  111. Khan K, Schwarzenberg SJ, Sharp HL, Matas AJ, Chavers BM. Morbidity from congenital hepatic fibrosis after renal transplantation for autosomal recessive polycystic kidney disease. Am J Tranplant. 2002;2:360–5.

    Article  Google Scholar 

  112. Davis ID, Ho M, Hupertz V, Avner ED. Survival of childhood polycystic kidney disease following renal transplantation: the impact of advanced hepatobiliary disease. Pediatr Transplant. 2003;7(5):364–9.

    Article  PubMed  Google Scholar 

  113. Chapal M, Debout A, Dufay A, Salomon R, Roussey G, Burtey S, et al. Kidney and liver transplantation in patients with autosomal recessive polycystic kidney disease: a multicentric study. Nephrol Dial Transplant. 2012;27:2083–8.

    Article  PubMed  Google Scholar 

  114. Chapman AB. The fetal environment: a critical phase that determines future renal outcomes in autosomal dominant polycystic kidney disease. Kidney Int. 2012;81(9):814–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  115. Cadnapaphornchai MA. Hypertension in children with autosomal dominant polycystic kidney disease (ADPKD). Curr Hypertens Rev. 2013;9(1):21–6.

    Article  PubMed  Google Scholar 

  116. Chapman AB, Guay-Woodford LM. Renal volume in children with ADPKD: size matters. Clin J Am Soc Nephrol. 2009;4(4):698–9.

    Article  PubMed  Google Scholar 

  117. Fick-Brosnahan GM, Belz MM, McFann KK, Johnson AM, Schrier RW. Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: a longitudinal study. Am J Kidney Dis. 2002;39(6):1127–34.

    Article  PubMed  Google Scholar 

  118. Ariza M, Alvarez V, Marin R, Aguado S, Lopez-Larrea C, Alvarez J, et al. A family with a milder form of adult dominant polycystic kidney disease not linked to the PKD1 (16p) or PKD2 (4q) genes. J Med Genet. 1997;34(7):587–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. de Almeida S, de Almeida E, Peters D, Pinto JR, Tavora I, Lavinha J, et al. Autosomal dominant polycystic kidney disease: evidence for the existence of a third locus in a Portuguese family. Hum Genet. 1995;96(1):83–8.

    Article  PubMed  Google Scholar 

  120. Daoust MC, Reynolds DM, Bichet DG, Somlo S. Evidence for a third genetic locus for autosomal dominant polycystic kidney disease. Genomics. 1995;25(3):733–6.

    Article  CAS  PubMed  Google Scholar 

  121. Harris PC. Molecular basis of polycystic kidney disease: PKD1, PKD2 and PKHD1. Curr Opin Nephrol Hypertens. 2002;11(3):309–14.

    Article  PubMed  Google Scholar 

  122. Paul BM, Consugar MB, Ryan Lee M, Sundsbak JL, Heyer CM, Rossetti S, et al. Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families. Kidney Int. 2014;85(2):383–92.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  123. Schrier RW, Brosnahan G, Cadnapaphornchai MA, Chonchol M, Friend K, Gitomer B, et al. Predictors of autosomal dominant polycystic kidney disease progression. J Am Soc Nephrol. 2014;25(11):2399–418.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  124. Ravine D, Walker RG, Gibson RN, Forrest SM, Richards RI, Friend K, et al. Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease. Lancet. 1992;340(8831):1330–3.

    Article  CAS  PubMed  Google Scholar 

  125. Hateboer N, van Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet. 1999;353(9147):103–7.

    Article  CAS  PubMed  Google Scholar 

  126. Parfrey PS, Bear JC, Morgan J, Cramer BC, McManamon PJ, Gault MH, et al. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. N Engl J Med. 1990;323(16):1085–90.

    Article  CAS  PubMed  Google Scholar 

  127. 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 

  128. Harris PC, Torres VE. Polycystic kidney disease. Annu Rev Med. 2009;60:321–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  129. Selistre L, de Souza V, Ranchin B, Hadj-Aissa A, Cochat P, Dubourg L. Early renal abnormalities in children with postnatally diagnosed autosomal dominant polycystic kidney disease. Pediatr Nephrol. 2012;27(9):1589–93.

    Article  PubMed  Google Scholar 

  130. Reeders ST, Breuning MH, Davies KE, Nicholls RD, Jarman AP, Higgs DR, et al. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature. 1985;317:542–4.

    Article  CAS  PubMed  Google Scholar 

  131. TIPKD Consortium. Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. Cell. 1995;81(2):289–98.

    Article  Google Scholar 

  132. Rossetti S, Hopp K, Sikkink RA, Sundsbak JL, Lee YK, Kubly V, et al. Identification of gene mutations in autosomal dominant polycystic kidney disease through targeted resequencing. J Am Soc Nephrol. 2012;23(5):915–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  133. Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2002;13:2384–98.

    Article  CAS  PubMed  Google Scholar 

  134. Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hieseberger T, et al. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J Clin Invest. 2004;114(10):1433–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  135. Ward CJ, Turley H, Ong AC, Comley M, Biddolph S, Chetty R, et al. Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. Proc Natl Acad Sci U S A. 1996;93(4):1524–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  136. Geng L, Segal Y, Peissel B, Deng N, Pei Y, Carone F, et al. Identification and localization of polycystin, the PKD1 gene product. J Clin Invest. 1996;98(12):2674–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  137. Van Adelsberg JS, Frank D. The PKD1 gene produces a developmentally regulated protein in mesenchyme and vasculature. Nat Med. 1995;1(4):359–64.

    Article  PubMed  Google Scholar 

  138. Ibraghimov-Beskrovnaya O, Dackowski WR, Foggensteiner L, Coleman N, Thiru S, Petry LR, et al. Polycystin: in vitro synthesis, in vivo tissue expression, and subcellular localization identifies a large membrane-associated protein. Proc Natl Acad Sci U S A. 1997;94(12):6397–402.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  139. Geng L, Segal Y, Pavlova A, Barros EJ, Lohning C, Lu W, et al. Distribution and developmentally regulated expression of murine polycystin. Am J Physiol. 1997;272(4 Pt 2):F451–9.

    CAS  PubMed  Google Scholar 

  140. 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  PubMed Central  CAS  PubMed  Google Scholar 

  141. Peters DJ, Spruit L, Saris JJ, Ravine D, Sandkuijl LA, Fossdal R, et al. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nat Genet. 1993;5(4):359–62.

    Article  CAS  PubMed  Google Scholar 

  142. 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;272:1339–42.

    Article  CAS  PubMed  Google Scholar 

  143. Koulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, et al. Polycystin-2 is an intracellular calcium release channel. Nat Cell Biol. 2002;4(3):191–7.

    Article  CAS  PubMed  Google Scholar 

  144. Kottgen M. TRPP2 and autosomal dominant polycystic kidney disease. Biochim Biophys Acta. 2007;1772(8):836–50.

    Article  PubMed  CAS  Google Scholar 

  145. Gonzalez-Perret S, Kim K, Ibarra C, Damiano AE, Zotta E, Batelli M, et al. Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel. Proc Natl Acad Sci U S A. 2001;98(3):1182–7.

    Article  Google Scholar 

  146. 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 

  147. Tsoikas L, Kim E, Arnould T, Sukatme VP, Walz G. Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2. Proc Natl Acad Sci U S A. 1997;94:6965–70.

    Article  Google Scholar 

  148. Veldhuisen B, Saris JJ, de Haij S, Hayashi T, Reynolds DM, Mochizuki T, et al. A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2). Am J Hum Genet. 1997;61(3):547–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  149. 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. 2003;14(5):1164–74.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  152. Tee JB, Acott PD, McLellan DH, Crocker JF. Phenotypic heterogeneity in pediatric autosomal dominant polycystic kidney disease at first presentation: a single-center, 20-year review. Am J Kidney Dis. 2004;43(2):296–303.

    Article  PubMed  Google Scholar 

  153. Fick GM, Duley IT, Johnson AM, Strain JD, Manco-Johnson ML, Gabow PA. The spectrum of autosomal dominant polycystic kidney disease in children. J Am Soc Nephrol. 1994;4(9):1654–60.

    CAS  PubMed  Google Scholar 

  154. 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  PubMed Central  CAS  PubMed  Google Scholar 

  155. Kelleher CL, McFann KK, Johnson AM, Schrier RW. Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. Am J Hypertens. 2004;17(11 Pt 1):1029–34.

    Article  PubMed  Google Scholar 

  156. de Almeida EA, de Oliveira EI, Lopes JA, Almeida AG, Lopes MG, Prata MM. Ambulatory blood pressure measurement in young normotensive patients with autosomal dominant polycystic kidney disease. Rev Port Cardiol. 2007;26(3):235–43.

    PubMed  Google Scholar 

  157. Turgut F, Oflaz H, Namli S, Alisir S, Tufan F, Temiz S, et al. Ambulatory blood pressure and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease. Ren Fail. 2007;29(8):979–84.

    Article  CAS  PubMed  Google Scholar 

  158. Schrier RW, Johnson AM, McFann K, Chapman AB. The role of parental hypertension in the frequency and age of diagnosis of hypertension in offspring with autosomal-dominant polycystic kidney disease. Kidney Int. 2003;64(5):1792–9.

    Article  PubMed  Google Scholar 

  159. 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 

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

    CAS  PubMed  Google Scholar 

  161. Chapman AB, Stepniakowski K, Rahbari-Oskoui F. Hypertension in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):153–63.

    Article  PubMed Central  PubMed  Google Scholar 

  162. Doulton TW, Saggar-Malik AK, He FJ, Carney C, Markandu ND, Sagnella GA, et al. The effect of sodium and angiotensin-converting enzyme inhibition on the classic circulating renin-angiotensin system in autosomal-dominant polycystic kidney disease patients. J Hypertens. 2006;24(5):939–45.

    Article  CAS  PubMed  Google Scholar 

  163. Loghman-Adham M, Soto CE, Inagami T, Cassis L. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol. 2004;287(4):F775–88.

    CAS  Google Scholar 

  164. Lawson CR, Doulton TW, MacGregor GA. Autosomal dominant polycystic kidney disease: role of the renin-angiotensin system in raised blood pressure in progression of renal and cardiovascular disease. J Renin Angiotensin Aldosterone Syst. 2006;7(3):139–45.

    Article  CAS  PubMed  Google Scholar 

  165. McPherson EA, Luo Z, Brown RA, LeBard LS, Corless CC, Speth RC, et al. Chymase-like angiotensin II-generating activity in end-stage human autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2004;15(2):493–500.

    Article  CAS  PubMed  Google Scholar 

  166. Bardaji A, Martinez Vea A, Gutierrez C, Ridao C, Richart C, Oliver JA. Left ventricular mass and diastolic function in normotensive young adults with autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1998;32:970–5.

    Article  CAS  PubMed  Google Scholar 

  167. Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW. Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension. Kidney Int. 2008;74(9):1192–6.

    Article  PubMed Central  PubMed  Google Scholar 

  168. Martinez-Vea A, Bardaj A, Gutierrez C, Garca C, Peralta C, Marcas L, et al. Exercise blood pressure, cardiac structure, and diastolic function in young normotensive patients with polycystic kidney disease: a prehypertensive state. Am J Kidney Dis. 2004;44(2):216–23.

    Article  PubMed  Google Scholar 

  169. Almeida EA, Oliveira EI, Lopes JA, Almeida AG, Prata MM. Tissue Doppler imaging in the evaluation of left ventricular function in young adults with autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2006;47(4):587–92.

    Article  PubMed  Google Scholar 

  170. Oflaz H, Alisir S, Buyukaydin B, Kocaman O, Turgut F, Namli S, et al. Biventricular diastolic dysfunction in patients with autosomal-dominant polycystic kidney disease. Kidney Int. 2005;68(5):2244–9.

    Article  PubMed  Google Scholar 

  171. Gabow P. Autosomal dominant polycystic kidney disease. New Engl J Med. 1993;329:332–42.

    Article  CAS  PubMed  Google Scholar 

  172. Lumiaho A, Ikaheimo R, Miettinen R, Niemitukia L, Laitinen T, Rantala A, et al. Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1. Am J Kidney Dis. 2001;38(6):1208–16.

    Article  CAS  PubMed  Google Scholar 

  173. Ivy DD, Shaffer EM, Johnson AM, Kimberling WJ, Dobin A, Gabow PA. Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1995;5(12):2032–6.

    CAS  PubMed  Google Scholar 

  174. Fick GM, Johnson AM, Strain JD, Kimberling WJ, Kumar S, Manco-Johnson ML, et al. Characteristics of very early onset autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1993;3(12):1863–70.

    CAS  PubMed  Google Scholar 

  175. Seeman T, Dusek J, Vondrak K, Blahova K, Simkova E, Kreisinger J, et al. Renal concentrating capacity is linked to blood pressure in children with autosomal dominant polycystic kidney disease. Physiol Res. 2004;53(6):629–34.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  177. Chapman AB, Guay-Woodford LM, Grantham JJ, Torres VE, Bae KT, Baumgarten DA, et al. Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort. Kidney Int. 2003;64(3):1035–45.

    Article  PubMed  Google Scholar 

  178. Chapman AB, Bost JE, Torres VE, Guay-Woodford L, Bae KT, Landsittel D, et al. Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2012;7(3):479–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  179. Grantham JJ, Cook LT, Torres VE, Bost JE, Chapman AB, Harris PC, et al. Determinants of renal volume in autosomal-dominant polycystic kidney disease. Kidney Int. 2008;73(1):108–16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  180. 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. 2007;2(1):112–20.

    Article  PubMed  Google Scholar 

  181. 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 

  182. Kaehny WD, Everson GT. Extrarenal manifestations of autosomal dominant polycystic kidney disease. Semin Nephrol. 1991;11:661–70.

    CAS  PubMed  Google Scholar 

  183. 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. 2006;1(1):64–9.

    Article  PubMed  Google Scholar 

  184. Brun M, Maugey-Laulom B, Eurin D, Didier F, Avni EF. Prenatal sonographic patterns in autosomal dominant polycystic kidney disease: a multicenter study. Ultrasound Obstet Gynecol. 2004;24(1):55–61.

    Article  CAS  PubMed  Google Scholar 

  185. Pretorius DH, Lee ME, Manco-Johnson ML, Weingast GR, Sedman AB, Gabow PA. Diagnosis of autosomal dominant polycystic kidney disease in utero and in the young infant. J Ultrasound Med. 1987;6:249–55.

    CAS  PubMed  Google Scholar 

  186. Main D, Mennuti MT, Cornfeld D, Coleman B. Prenatal diagnosis of adult polycystic kidney disease. Lancet. 1983;2:337–8.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  188. 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. Am J Med Genet. 1984;18:45–53.

    Article  CAS  PubMed  Google Scholar 

  189. Pei Y, Hwang YH, Conklin J, Sundsbak JL, Heyer CM, Chan W, et al. Imaging-based diagnosis of autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2014;doi:10.1681/ASN.2014030297.

    Google Scholar 

  190. 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. 1997;8(1):105–10.

    CAS  PubMed  Google Scholar 

  191. Kielstein R, Sass H-M. Right not to know or duty to know? Prenatal screening for polycystic renal disease. J Med Philos. 1992;17:395–405.

    Article  CAS  PubMed  Google Scholar 

  192. Frost N. Ethical implications of screening asymptomatic individuals. FASEB J. 1992;6:2813–7.

    Google Scholar 

  193. Nelson RM, Botkjin JR, Kodish ED, Levetown M, Truman JT, Wilfond BS, et al. Ethical issues with genetic testing in pediatrics. Pediatrics. 2001;107(6):1451–5.

    Article  Google Scholar 

  194. Audrezet MP, Cornec-Le Gall E, Chen JM, Redon S, Quere I, Creff J, et al. Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Hum Mutat. 2012;33:1239.

    Article  CAS  PubMed  Google Scholar 

  195. Schrier R, McFann K, Johnson A, Chapman A, Edelstein C, Brosnahan G, et al. Cardiac and renal effects of standard versus rigorous blood pressure control in autosomal-dominant polycystic kidney disease: results of a seven-year prospective randomized study. J Am Soc Nephrol. 2002;13(7):1733–9.

    Article  PubMed  Google Scholar 

  196. Ecder T, Edelstein CL, Fick-Brosnahan GM, Johnson AM, Chapman AB, Gabow PA, et al. Diuretics versus angiotensin-converting enzyme inhibitors in autosomal dominant polycystic kidney disease. Am J Nephrol. 2001;21(2):98–103.

    Article  CAS  PubMed  Google Scholar 

  197. Watson ML, Macnicol AM, Allan PL, Wright AF. Effects of angiotensin converting enzyme inhibition in adult polycystic kidney disease. Kidney Int. 1992;41(1):206–10.

    Article  CAS  PubMed  Google Scholar 

  198. Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999;12:205S–13.

    Article  CAS  PubMed  Google Scholar 

  199. Schrier RW, Abebe KZ, Perrone RD, Torres VE, Braun WE, Steinman TI, et al. Blood pressure in early autosomal dominant polycystic kidney disease. New Engl J Med. 2014;371(24):2255–66.

    Google Scholar 

  200. 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.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  201. 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  PubMed Central  CAS  PubMed  Google Scholar 

  202. Gabow P. Autosomal dominant polycystic kidney disease. In: Gardner KD, editor. The cystic kidney. Dordrecht: Kluwer; 1990. p. 295–326.

    Chapter  Google Scholar 

  203. Sallee M, Rafat C, Zahar JR, Paulmier B, Grunfeld JP, Knebelmann B, et al. Cyst infections in patients with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2009;4(7):1183–9.

    Article  PubMed Central  PubMed  Google Scholar 

  204. Hogan MC, Norby SM. Evaluation and management of pain in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(3):e1–16.

    Article  PubMed Central  PubMed  Google Scholar 

  205. 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. 2001;38(4):770–6.

    Article  CAS  PubMed  Google Scholar 

  206. 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 

  207. Ring T, Spiegelhalter D. Risk of intracranial aneurysm bleeding in autosomal-dominant polycystic kidney disease. Kidney Int. 2007;72(11):1400–2.

    Article  CAS  PubMed  Google Scholar 

  208. 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 

  209. Abdollah Shamshirsaz A, Reza Bekheirnia M, Kamgar M, Johnson AM, McFann K, Cadnapaphornchai M, 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 

  210. Boyer O, Gagnadoux MF, 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, Germany). 2007;22(3):380–8.

    Article  Google Scholar 

  211. 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 

  212. Grantham JJ, Chapman AB, Torres VE. Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol. 2006;1(1):148–57.

    Article  PubMed  Google Scholar 

  213. Torra R, Badenas C, Darnell A, Nicolau C, Volpini V, Revert L, et al. Linkage, clinical features, and prognosis of autosomal dominant polycystic kidney disease types 1 and 2. J Am Soc Nephrol. 1996;7(10):2142–51.

    CAS  PubMed  Google Scholar 

  214. 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 

  215. 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  PubMed Central  CAS  PubMed  Google Scholar 

  216. Pei Y. A “two-hit” model of cystogenesis in autosomal dominant polycystic kidney disease? Trends Mol Med. 2001;7(4):151–6.

    Article  CAS  PubMed  Google Scholar 

  217. 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 

  218. Hopp K, Ward CJ, Hommerding CJ, Nasr SH, Tuan HF, Gainullin VG, et al. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Invest. 2012;122(11):4257–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  219. Pei Y, Lan Z, Wang K, Garcia-Gonzalez M, He N, Dicks E, et al. A missense mutation in PKD1 attenuates the severity of renal disease. Kidney Int. 2012;81(4):412–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  220. Tan AY, Blumenfeld J, Michaeel A, Donahue S, Bobb W, Parker T, et al. Autosomal dominant polycystic kidney disease caused by somatic and germline mosaicism. Clin Genet. 2014. doi:10.1111/cge.12383.

    Google Scholar 

  221. Menezes LF, Zhou F, Patterson AD, Piontek KB, Krausz KW, Gonzalez FJ, et al. Network analysis of a Pkd1-mouse model of autosomal dominant polycystic kidney disease identifies HNF4alpha as a disease modifier. PLoS Genet. 2012;8(11):e1003053.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  222. Bergmann C, von Bothmer J, Ortiz Bruchle 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. 2011;22(11):2047–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  223. Brook-Carter PT, Peral B, Ward CJ, Thompson P, Hughes J, Maheshwar MM, et al. Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease – a contiguous gene syndrome. Nat Genet. 1994;8(4):328–32.

    Article  CAS  PubMed  Google Scholar 

  224. Williams SS, Cobo-Stark P, Hajarnis S, Aboudehen K, Shao X, Richardson JA, et al. Tissue-specific regulation of the mouse Pkhd1 (ARPKD) gene promoter. Am J Physiol. 2014;307(3):F356–68.

    CAS  Google Scholar 

  225. Shibazaki S, Yu Z, Nishio S, Tian X, Thomson RB, Mitobe M, et al. Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkd1. Hum Mol Genet. 2008;17:1505.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  226. 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 Central  PubMed  Google Scholar 

  227. Fedeles SV, Tian X, Gallagher AR, 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  PubMed Central  CAS  PubMed  Google Scholar 

  228. Fedeles SV, Gallagher AR, Somlo S. Polycystin-1: a master regulator of intersecting cystic pathways. Trends Mol Med. 2014;20:251–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  229. Leonhard WN, Zandbergen M, Veraar K, van den Berg S, van der Weerd L, Breuning M, et al. Scattered deletion of PKD1 in kidneys causes a cystic snowball effect and recapitulates polycystic kidney disease. J Am Soc Nephrol. 2014. doi:10.1681/ASN.2013080864.

    Google Scholar 

  230. Roitbak T, Ward CJ, Harris PC, Bacallao R, Ness SA, Wandinger-Ness A. A polycystin-1 multiprotein complex is disrupted in polycystic kidney disease cells. Mol Biol Cell. 2004;15(3):1334–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  232. Li X, Luo Y, Starremans PG, McNamara CA, Pei Y, Zhou J. Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat Cell Biol. 2005;7(12):1202–12.

    Article  PubMed  CAS  Google Scholar 

  233. Wu G, Markowitz GS, Li L, D’Agati VD, Factor SM, Geng L, et al. Cardiac defects and renal failure in mice with targeted mutations in Pkd2. Nat Genet. 2000;24(1):75–8.

    Article  CAS  PubMed  Google Scholar 

  234. Chang MY, Parker E, Ibrahim S, Shortland JR, Nahas ME, Haylor JL, et al. Haploinsufficiency of Pkd2 is associated with increased tubular cell proliferation and interstitial fibrosis in two murine Pkd2 models. Nephrol Dial Transplant. 2006;21(8):2078–84.

    Article  CAS  PubMed  Google Scholar 

  235. Grimm DH, Karihaloo A, Cai Y, Somlo S, Cantley LG, Caplan MJ. Polycystin-2 regulates proliferation and branching morphogenesis in kidney epithelial cells. J Biol Chem. 2006;281(1):137–44.

    Article  CAS  PubMed  Google Scholar 

  236. Grimm DH, Cai Y, Chauvet V, Rajendran V, Zeltner R, Geng L, et al. Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells. J Biol Chem. 2003;278(38):36786–93.

    Article  CAS  PubMed  Google Scholar 

  237. Wu Y, Dai XQ, Li Q, Chen CX, Mai W, Hussain Z, et al. Kinesin-2 mediates physical and functional interactions between polycystin-2 and fibrocystin. Hum Mol Genet. 2006;15(22):3280–92.

    Article  CAS  PubMed  Google Scholar 

  238. Kim I, Fu Y, Hui K, Moeckel G, Mai W, Li C, et al. Fibrocystin/polyductin modulates renal tubular formation by regulating polycystin-2 expression and function. J Am Soc Nephrol. 2008;19(3):455–68.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  240. 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 

  241. 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  PubMed Central  CAS  PubMed  Google Scholar 

  242. 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  PubMed Central  CAS  PubMed  Google Scholar 

  243. Jiang ST, Chiou YY, Wang E, Lin HK, Lin YT, Chi YC, et al. Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1. Am J Pathol. 2006;168(1):205–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  244. Lantinga-van Leeuwen IS, Leonhard WN, van der Wal A, Breuning MH, de Heer E, Peters DJ. Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet. 2007;16(24):3188–96.

    Article  CAS  PubMed  Google Scholar 

  245. Welling LW, Grantham JJ. Cystic and development diseases of the kidney. In: Brenner BM, Rector FC, editors. The kidney. 4th ed. Philadelphia: WB Saunders; 1991. p. 1657–94.

    Google Scholar 

  246. Wilson PD. Polycystic kidney disease: new understanding in the pathogenesis. Int J Biochem Cell Biol. 2004;36(10):1868–73.

    Article  CAS  PubMed  Google Scholar 

  247. 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 

  248. Sweeney Jr WE, von Vigier RO, Frost P, Avner ED. Src inhibition ameliorates polycystic kidney disease. J Am Soc Nephrol. 2008;19(7):1331–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  249. Weimbs T, Olsan EE, Talbot JJ. Regulation of STATs by polycystin-1 and their role in polycystic kidney disease. Jak-Stat. 2013;2(2):e23650.

    Article  PubMed Central  PubMed  Google Scholar 

  250. Calvet JP. Polycystic kidney disease: primary extracellular matrix abnormality or defective cellular differentiation? Kidney Int. 1993;43(1):101–8.

    Article  CAS  PubMed  Google Scholar 

  251. Orellana SA, Avner ED. Cystic maldevelopment in the kidney. Semin Nephrol. 1995;15:341–52.

    CAS  PubMed  Google Scholar 

  252. Murcia NS, Sweeney Jr WE, Avner ED. New insights into the molecular pathophysiology of polycystic kidney disease. Kidney Int. 1999;55(4):1187–97.

    Article  CAS  PubMed  Google Scholar 

  253. Qian Q, Hunter LW, Li M, Marin-Padilla M, Prakash YS, Somlo S, et al. Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells. Hum Mol Genet. 2003;12(15):1875–80.

    Article  CAS  PubMed  Google Scholar 

  254. Starremans PG, Li X, Finnerty PE, Guo L, Takakura A, Neilson EG, et al. A mouse model for polycystic kidney disease through a somatic in-frame deletion in the 5′ end of Pkd1. Kidney Int. 2008;73:1394.

    Article  CAS  PubMed  Google Scholar 

  255. Menezes LF, Germino GG. Murine models of polycystic kidney disease. Drug Disc Today Dis Mech. 2013;10(3–4):e153–8.

    Article  Google Scholar 

  256. Avner ED, McAteer KA, Evan AP. Models of cysts and cystic kidneys. In: Gardner KD, editor. The cystic kidney. Dordrecht: Kluwer; 1990. p. 55–98.

    Chapter  Google Scholar 

  257. Avner ED, Sweeney WE. Apical epidermal growth factor receptor expression defines a distinct cystic tubular epithelial phenotype in autosomal recessive polycystic kidney disease. Pediatr Res. 1995;37:359A.

    Google Scholar 

  258. Sweeney WE, Avner ED. Functional activity of epidermal growth factor receptors in autosomal recessive polycystic kidney disease. Am J Physiol. 1998;275:F387–94.

    CAS  PubMed  Google Scholar 

  259. Grantham JJ. The etiology, pathogenesis, and treatment of autosomal dominant polycystic kidney disease: recent advances. Am J Kidney Dis. 1996;28:788–803.

    Article  CAS  PubMed  Google Scholar 

  260. Aguiari G, Bizzarri F, Bonon A, Mangolini A, Magri E, Pedriali M, et al. Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation. J Mol Med (Berl, Germany). 2012;90:1267.

    Article  CAS  Google Scholar 

  261. Welling LW. Pathogenesis of cysts and cystic kidneys. In: Gardner KD, editor. The cystic kidney. Dordrecht: Kluwer; 1990. p. 99–116.

    Chapter  Google Scholar 

  262. Nadasdy T, Laszik Z, Lajoie G, Blick KE, Wheeler DE, Silva FG. Proliferative activity of cyst epithelium in human renal cystic diseases. J Am Soc Nephrol. 1995;5(7):1462–8.

    CAS  PubMed  Google Scholar 

  263. Wilson PD, Sherwood AC. Tubulocystic epithelium. Kidney Int. 1991;39:450–63.

    Article  CAS  PubMed  Google Scholar 

  264. Hjelle JT, Waters DC, Golinska BT, Steidley KR, Burmeister V, Caughey R, et al. Autosomal recessive polycystic kidney disease: characterization of human peritoneal and cystic kidney cells in vitro. Am J Kidney Dis. 1990;15(2):123–36.

    Article  CAS  PubMed  Google Scholar 

  265. Klingel R, Dippold W, Storkel S, Meyer zum Buschenfelde KH, Kohler H. Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma. Am J Kidney Dis. 1992;19(1):22–30.

    Article  CAS  PubMed  Google Scholar 

  266. Du J, Wilson PD. Abnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD. Am J Physiol. 1995;269(2 Pt 1):C487–95.

    CAS  PubMed  Google Scholar 

  267. Orellana SA, Sweeney WE, Neff CD, Avner ED. Epidermal growth factor receptor expression is abnormal in murine polycystic kidney. Kidney Int. 1995;47(2):490–9.

    Article  CAS  PubMed  Google Scholar 

  268. Pugh JL, Sweeney Jr WE, Avner ED. Tyrosine kinase activity of the EGF receptor in murine metanephric organ culture. Kidney Int. 1995;47:774–81.

    Article  CAS  PubMed  Google Scholar 

  269. Sweeney WE, Futey L, Frost P, Avner ED. In vitro modulation of cyst formation by a novel tyrosine kinase inhibitor. Kidney Int. 1999;56:406–13.

    Article  CAS  PubMed  Google Scholar 

  270. Sweeney WE, Chen Y, Nakanishi K, Frost P, Avner ED. Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor. Kidney Int. 2000;57(1):33–40.

    Article  CAS  PubMed  Google Scholar 

  271. Richards WG, Sweeney WE, Yoder BK, Wilkinson JE, Woychik RP, Avner ED. Epidermal growth factor receptor activity mediates renal cyst formation in polycystic kidney disease. J Clin Invest. 1998;101(5):935–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  272. Torres VE, Sweeney Jr WE, Wang X, Qian Q, Harris PC, Frost P, et al. Epidermal growth factor receptor tyrosine kinase inhibition is not protective in PCK rats. Kidney Int. 2004;66(5):1766–73.

    Article  CAS  PubMed  Google Scholar 

  273. Sweeney Jr WE, Donohoe DL, Gibbons J, Avner ED. Pan-ErbB2 receptor inhibition decreases hepatic and renal fibrosis in an orthologous model of ARPKD. Pediatr Res. 2006;59:149.

    Google Scholar 

  274. Nakanishi K, Sweeney Jr W, Avner ED. Segment-specific c-ErbB2 expression in human autosomal recessive polycystic kidney disease. J Am Soc Nephrol. 2001;12(2):379–84.

    CAS  PubMed  Google Scholar 

  275. Hoxha N, Goto M, Dell KM. ErbB4 and HB-EGF Overexpression and Mislocalization in cystic kidneys of PCK rats suggest a common ARPKD pathogenic pathway. J Am Soc Nephrol 2006. 2006:ASN 2006 abstract edition, p. 492

    Google Scholar 

  276. Wilson PD, Du J, Norman JT. Autocrine, endocrine and paracrine regulation of growth abnormalities in autosomal dominant polycystic kidney disease. Eur J Cell Biol. 1993;61(1):131–8.

    CAS  PubMed  Google Scholar 

  277. Horikoshi S, Kubota S, Martin GR, Yamada Y, Klotman PE. Epidermal growth factor (EGF) expression in the congenital polycystic mouse kidney. Kidney Int. 1991;39(1):57–62.

    Article  CAS  PubMed  Google Scholar 

  278. Gattone 2nd VH, Calvet JP. Murine infantile polycystic kidney disease: a role for reduced renal epidermal growth factor. Am J Kidney Dis. 1991;17(6):606–7.

    Article  PubMed  Google Scholar 

  279. Dell KM, Nemo R, Sweeney Jr WE, Avner ED. EGF-related growth factors in the pathogenesis of murine ARPKD. Kidney Int. 2004;65(6):2018–29.

    Article  CAS  Google Scholar 

  280. Dell KM, Nemo R, Sweeney Jr WE, Levin JI, Frost P, Avner ED. A novel inhibitor of tumor necrosis factor-alpha converting enzyme ameliorates polycystic kidney disease. Kidney Int. 2001;60(4):1240–8.

    Article  CAS  PubMed  Google Scholar 

  281. Sweeney Jr WE, Hamahira K, Sweeney J, Garcia-Gatrell M, Frost P, Avner ED. Combination treatment of PKD utilizing dual inhibition of EGF-receptor activity and ligand bioavailability. Kidney Int. 2003;64(4):1310–9.

    Article  CAS  PubMed  Google Scholar 

  282. Hanaoka K, Guggino WB. cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells. J Am Soc Nephrol. 2000;11(7):1179–87.

    CAS  PubMed  Google Scholar 

  283. Yamaguchi T, Pelling JC, Ramaswamy NT, Eppler JW, Wallace DP, Nagao S, et al. cAMP stimulates the in vitro proliferation of renal cyst epithelial cells by activating the extracellular signal-regulated kinase pathway. Kidney Int. 2000;57(4):1460–71.

    Article  CAS  PubMed  Google Scholar 

  284. Belibi FA, Reif G, Wallace DP, Yamaguchi T, Olsen L, Li H, et al. Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells. Kidney Int. 2004;66(3):964–73.

    Article  CAS  PubMed  Google Scholar 

  285. Yamaguchi T, Wallace DP, Magenheimer BS, Hempson SJ, Grantham JJ, Calvet JP. Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype. J Biol Chem. 2004;279(39):40419–30.

    Article  CAS  PubMed  Google Scholar 

  286. Yamaguchi T, Hempson SJ, Reif GA, Hedge AM, Wallace DP. Calcium restores a normal proliferation phenotype in human polycystic kidney disease epithelial cells. J Am Soc Nephrol. 2006;17(1):178–87.

    Article  CAS  PubMed  Google Scholar 

  287. Yang J, Zhang S, Zhou Q, Guo H, Zhang K, Zheng R, et al. PKHD1 gene silencing may cause cell abnormal proliferation through modulation of intracellular calcium in autosomal recessive polycystic kidney disease. J Biochem Mol Biol. 2007;40(4):467–74.

    Article  CAS  PubMed  Google Scholar 

  288. Dumaz N, Marais R. Integrating signals between cAMP and the RAS/RAF/MEK/ERK signalling pathways. Based on the anniversary prize of the Gesellschaft fur Biochemie und Molekularbiologie Lecture delivered on 5 July 2003 at the Special FEBS Meeting in Brussels. Febs J. 2005;272(14):3491–504.

    Article  CAS  PubMed  Google Scholar 

  289. Nagao S, Yamaguchi T, Kusaka M, Maser RL, Takahashi H, Cowley BD, et al. Renal activation of extracellular signal-regulated kinase in rats with autosomal-dominant polycystic kidney disease. Kidney Int. 2003;63(2):427–37.

    Article  CAS  PubMed  Google Scholar 

  290. Yamaguchi T, Nagao S, Wallace DP, Belibi FA, Cowley BD, Pelling JC, et al. Cyclic AMP activates B-Raf and ERK in cyst epithelial cells from autosomal-dominant polycystic kidneys. Kidney Int. 2003;63(6):1983–94.

    Article  CAS  PubMed  Google Scholar 

  291. Silva CM. Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis. Oncogene. 2004;23(48):8017–23.

    Article  CAS  PubMed  Google Scholar 

  292. Talbot JJ, Song X, Wang X, Rinschen MM, Doerr N, Lariviere WB, et al. The cleaved cytoplasmic tail of polycystin-1 regulates Src-dependent STAT3 activation. J Am Soc Nephrol. 2014;25:1737–48.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  293. Talbot JJ, Shillingford JM, Vasanth S, Doerr N, Mukherjee S, Kinter MT, et al. Polycystin-1 regulates STAT activity by a dual mechanism. Proc Natl Acad Sci U S A. 2011;108(19):7985–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  294. 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  PubMed Central  CAS  PubMed  Google Scholar 

  295. 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. 2009;20(11):2389–402.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  296. Takikita-Suzuki M, Haneda M, Sasahara M, Owada MK, Nakagawa T, Isono M, et al. Activation of Src kinase in platelet-derived growth factor-B-dependent tubular regeneration after acute ischemic renal injury. Am J Pathol. 2003;163(1):277–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  297. Prasad S, McDaid JP, Tam FW, Haylor JL, Ong AC. Pkd2 dosage influences cellular repair responses following ischemia-reperfusion injury. Am J Pathol. 2009;175(4):1493–503.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  298. Woo D. Apoptosis and loss of renal tissue in polycystic kidney diseases. N Engl J Med. 1995;333(1):18–25.

    Article  CAS  PubMed  Google Scholar 

  299. Lanoix J, D’Agati V, Szabolcs M, Trudel M. Dysregulation of cellular proliferation and apoptosis mediates human autosomal dominant polycystic kidney disease (ADPKD). Oncogene. 1996;13(6):1153–60.

    CAS  PubMed  Google Scholar 

  300. Winyard PJ, Nauta J, Lirenman DS, Hardman P, Sams VR, Risdon RA, et al. Deregulation of cell survival in cystic and dysplastic renal development. Kidney Int. 1996;49(1):135–46.

    Article  CAS  PubMed  Google Scholar 

  301. Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys and hypopigmented hair. Cell. 1993;75:229–40.

    Article  CAS  PubMed  Google Scholar 

  302. Ali SM, Wong VY, Kikly K, Fredrickson TA, Keller PM, DeWolf Jr WE, et al. Apoptosis in polycystic kidney disease: involvement of caspases. Am J Physiol Regul Integr Comp Physiol. 2000;278(3):R763–9.

    CAS  PubMed  Google Scholar 

  303. Ecder T, Melnikov VY, Stanley M, Korular D, Lucia MS, Schrier RW, et al. Caspases, Bcl-2 proteins and apoptosis in autosomal-dominant polycystic kidney disease. Kidney Int. 2002;61(4):1220–30.

    Article  CAS  PubMed  Google Scholar 

  304. Goilav B. Apoptosis in polycystic kidney disease. Biochim Biophys Acta. 2011;1812(10):1272–80.

    Article  CAS  PubMed  Google Scholar 

  305. Cowley Jr BD, Smardo Jr FL, Grantham JJ, Calvet JP. Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease. Proc Natl Acad Sci U S A. 1987;84(23):8394–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  306. Cowley Jr BD, Chadwick LJ, Grantham JJ, Calvet JP. Elevated proto-oncogene expression in polycystic kidneys of the C57BL/6J (cpk) mouse. J Am Soc Nephrol. 1991;1(8):1048–53.

    PubMed  Google Scholar 

  307. Trudel M, Barisoni L, Lanoix J, D’Agati V. Polycystic kidney disease in SBM transgenic mice: role of c-myc in disease induction and progression. Am J Pathol. 1998;152(1):219–29.

    PubMed Central  CAS  PubMed  Google Scholar 

  308. Trudel M, D’Agati V, Costantini F. C-myc as an inducer of polycystic kidney disease in transgenic mice. Kidney Int. 1991;39(4):665–71.

    Article  CAS  PubMed  Google Scholar 

  309. Ricker JL, Mata JE, Iversen PL, Gattone VH. c-myc antisense oligonucleotide treatment ameliorates murine ARPKD. Kidney Int. 2002;61 Suppl 1:125–31.

    Article  Google Scholar 

  310. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell. 2006;124(3):471–84.

    Article  CAS  PubMed  Google Scholar 

  311. Edelstein CL. Mammalian target of rapamycin and caspase inhibitors in polycystic kidney disease. Clin J Am Soc Nephrol. 2008;3(4):1219–26.

    Article  CAS  PubMed  Google Scholar 

  312. 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 USA. 2006;103(14):5466–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  313. 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. 2009;24(8):2349–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  315. Shillingford JM, Leamon CP, Vlahov IR, Weimbs T. Folate-conjugated rapamycin slows progression of polycystic kidney disease. J Am Soc Nephrol. 2012;23(10):1674–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  316. Roman RJ. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev. 2002;82(1):131–85.

    Article  CAS  PubMed  Google Scholar 

  317. Lin F, Rios A, Falck JR, Belosludtsev Y, Schwartzman ML. 20-Hydroxyeicosatetraenoic acid is formed in response to EGF and is a mitogen in rat proximal tubule. Am J Physiol. 1995;269(6 Pt 2):F806–16.

    CAS  PubMed  Google Scholar 

  318. Muthalif MM, Benter IF, Uddin MR, Malik KU. Calcium/calmodulin-dependent protein kinase IIalpha mediates activation of mitogen-activated protein kinase and cytosolic phospholipase A2 in norepinephrine-induced arachidonic acid release in rabbit aortic smooth muscle cells. J Biol Chem. 1996;271(47):30149–57.

    Article  CAS  PubMed  Google Scholar 

  319. Muthalif MM, Karzoun NA, Gaber L, Khandekar Z, Benter IF, Saeed AE, et al. Angiotensin II-induced hypertension: contribution of Ras GTPase/Mitogen-activated protein kinase and cytochrome P450 metabolites. Hypertension. 2000;36(4):604–9.

    Article  CAS  PubMed  Google Scholar 

  320. Guo M, Roman RJ, Fenstermacher JD, Brown SL, Falck JR, Arbab AS, et al. 9L gliosarcoma cell proliferation and tumor growth in rats are suppressed by N-hydroxy-N′-(4-butyl-2-methylphenol) formamidine (HET0016), a selective inhibitor of CYP4A. J Pharmacol Exp Ther. 2006;317(1):97–108.

    Article  CAS  PubMed  Google Scholar 

  321. Guo M, Roman RJ, Falck JR, Edwards PA, Scicli AG. Human U251 glioma cell proliferation is suppressed by HET0016 [N-hydroxy-N′-(4-butyl-2-methylphenyl)formamidine], a selective inhibitor of CYP4A. J Pharmacol Exp Ther. 2005;315(2):526–33.

    Article  CAS  PubMed  Google Scholar 

  322. Muthalif MM, Benter IF, Karzoun N, Fatima S, Harper J, Uddin MR, et al. 20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin-dependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. Proc Natl Acad Sci U S A. 1998;95(21):12701–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  323. Park F, Sweeney WE, Jia G, Roman RJ, Avner ED. 20-HETE mediates proliferation of renal epithelial cells in polycystic kidney disease. J Am Soc Nephrol. 2008;19(10):1929–39.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  324. Park F, Sweeney Jr WE, Jia G, Akbulut T, Mueller B, Falck JR, et al. Chronic blockade of 20-HETE synthesis reduces polycystic kidney disease in an orthologous rat model of ARPKD. Am J Physiol. 2009;296(3):F575–82.

    CAS  Google Scholar 

  325. Akbulut T, Regner KR, Roman RJ, Avner ED, Falck JR, Park F. 20-HETE activates the Raf/MEK/ERK pathway in renal epithelial cells through an EGFR- and c-Src-dependent mechanism. Am J Physiol. 2009;297(3):F662–70.

    CAS  Google Scholar 

  326. Klawitter J, Klawitter J, McFann K, Pennington AT, Abebe KZ, Brosnahan G, et al. Bioactive lipid mediators in polycystic kidney disease. J Lipid Res. 2014;55:1139–49.

    Article  PubMed Central  CAS  Google Scholar 

  327. Grantham JJ, Geiser JL, Evan AP. Cyst formation and growth in autosomal dominant polycystic kidney disease. Kidney Int. 1987;31:1145–52.

    Article  CAS  PubMed  Google Scholar 

  328. Ye M, Grantham JJ. The secretion of fluid by renal cysts from patients with autosomal dominant polycystic kidney disease. N Engl J Med. 1993;329(5):310–3.

    Article  CAS  PubMed  Google Scholar 

  329. Potter EL. Pathogenesis of cystic kidneys. Birth Defects Orig Artic Ser. 1974;10(4):12–5.

    CAS  PubMed  Google Scholar 

  330. Mangoo-Karim R, Uchic M, Lechene C. Renal epithelial cyst formation and enlargement in vitro: dependence on cAMP. Proc Natl Acad Sci U S A. 1989;86:6007–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  331. Macias WL, McAteer JA, Tanner GA, Fritz AL, Armstrong WM. NaCl transport by Madin Darby canine kidney cyst epithelial cells. Kidney Int. 1992;42(2):308–19.

    Article  CAS  PubMed  Google Scholar 

  332. Grantham JJ, Ye M, Gattone 2nd VH, Sullivan LP. In vitro fluid secretion by epithelium from polycystic kidneys. J Clin Invest. 1995;95(1):195–202.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  333. Hanaoka K, Devuyst O, Schwiebert EM, Wilson PD, Guggino WB. A role for CFTR in human autosomal dominant polycystic kidney disease. Am J Physiol. 1996;270(1 Pt 1):C389–99.

    CAS  PubMed  Google Scholar 

  334. Wallace DP, Grantham JJ, Sullivan LP. Chloride and fluid secretion by cultured human polycystic kidney cells. Kidney Int. 1996;50(4):1327–36.

    Article  CAS  PubMed  Google Scholar 

  335. Wallace DP. Cyclic AMP-mediated cyst expansion. Biochim Biophys Acta. 2011;1812(10):1291–300.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  336. Mangoo-Karim R, Ye M, Wallace DP, Grantham JJ, Sullivan LP. Anion secretion drives fluid secretion by monolayers of cultured human polycystic cells. Am J Physiol. 1995;269(3 Pt 2):F381–8.

    CAS  PubMed  Google Scholar 

  337. Sullivan LP, Wallace DP, Grantham JJ. Chloride and fluid secretion in polycystic kidney disease. J Am Soc Nephrol. 1998;9:903–16.

    CAS  PubMed  Google Scholar 

  338. Sullivan LP, Wallace DP, Gover T, Welling PA, Yamaguchi T, Maser R, et al. Sulfonylurea-sensitive K(+) transport is involved in Cl(−) secretion and cyst growth by cultured ADPKD cells. J Am Soc Nephrol. 2002;13(11):2619–27.

    Article  CAS  PubMed  Google Scholar 

  339. 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 

  340. 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 

  341. 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. 2005;16(4):846–51.

    Article  CAS  PubMed  Google Scholar 

  342. Nagao S, Nishii K, Katsuyama M, Kurahashi H, Marunouchi T, Takahashi H, et al. Increased water intake decreases progression of polycystic kidney disease in the PCK rat. J Am Soc Nephrol. 2006;17:2220–7.

    Article  CAS  PubMed  Google Scholar 

  343. Wang X, Wu Y, Ward CJ, Harris PC, Torres VE. Vasopressin directly regulates cyst growth in polycystic kidney disease. J Am Soc Nephrol. 2008;19(1):102–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  344. Masyuk TV, Masyuk AI, Torres VE, Harris PC, Larusso NF. Octreotide inhibits hepatic cystogenesis in a rodent model of polycystic liver disease by reducing cholangiocyte adenosine 3′,5′-cyclic monophosphate. Gastroenterology. 2007;132(3):1104–16.

    Article  CAS  PubMed  Google Scholar 

  345. 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 

  346. Grantham JJ. Does extended-release somatostatin slow the growth of renal cysts in autosomal-dominant polycystic kidney disease? Nat Clin Pract Nephrol. 2006;2(2):66–7.

    Article  PubMed  Google Scholar 

  347. Davidow CJ, Maser RL, Rome LA, Calvet JP, Grantham JJ. The cystic fibrosis transmembrane conductance regulator mediates transepithelial fluid secretion by human autosomal dominant polycystic kidney disease epithelium in vitro. Kidney Int. 1996;50(1):208–18.

    Article  CAS  PubMed  Google Scholar 

  348. Sweeney WE, Avner ED, Elmer HL, Cotton CU. CFTR is required for cAMP-dependent in vitro renal cyst formation. J Am Soc Nephrol. 1998;9:38A.

    Google Scholar 

  349. O’Sullivan DA, Torres VE, Gabow PA, Thibodeau SN, King BF, Bergstralh EJ. Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease [see comments]. Am J Kidney Dis. 1998;32(6):976–83.

    Article  PubMed  Google Scholar 

  350. Persu A, Devuyst O, Lannoy N, Materne R, Brosnahan G, Gabow PA, et al. CF gene and cystic fibrosis transmembrane conductance regulator expression in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2000;11(12):2285–96.

    CAS  PubMed  Google Scholar 

  351. Li H, Findlay IA, Sheppard DN. The relationship between cell proliferation, Cl− secretion, and renal cyst growth: a study using CFTR inhibitors. Kidney Int. 2004;66(5):1926–38.

    Article  CAS  PubMed  Google Scholar 

  352. Nakanishi K, Sweeney Jr WE, Macrae Dell K, Cotton CU, Avner ED. Role of CFTR in autosomal recessive polycystic kidney disease. J Am Soc Nephrol. 2001;12(4):719–25.

    CAS  PubMed  Google Scholar 

  353. Schwiebert EM, Wallace DP, Braunstein GM, King SR, Peti-Peterdi J, Hanaoka K, et al. Autocrine extracellular purinergic signaling in epithelial cells derived from polycystic kidneys. Am J Physiol. 2002;282(4):F763–75.

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  355. Veizis IE, Cotton CU. Abnormal EGF-dependent regulation of sodium absorption in ARPKD collecting duct cells. Am J Physiol. 2005;288(3):F474–82.

    CAS  Google Scholar 

  356. Avner ED, Sweeney Jr WE, Finegold DN, Piesco NP, Ellis D. Sodium-potassium ATPase activity mediates cyst formation in metanephric organ culture. Kidney Int. 1985;28(3):447–55.

    Article  CAS  PubMed  Google Scholar 

  357. Avner ED, Sweeney Jr WE, Young MC, Ellis D. Congenital murine polycystic kidney disease. II. Pathogenesis of tubular cyst formation. Pediatr Nephrol. 1988;2(2):210–8.

    Article  CAS  PubMed  Google Scholar 

  358. Avner ED, Sweeney Jr WE, Ellis D. In vitro modulation of tubular cyst regression in murine polycystic kidney disease. Kidney Int. 1989;36:960–8.

    Article  CAS  PubMed  Google Scholar 

  359. Wilson PD, Burrow CR. Autosomal dominant polycystic kidney disease: cellular and molecular mechanisms of cyst formation. Adv Nephrol. 1992;21:125–42.

    CAS  Google Scholar 

  360. Wilson PD, Sherwood AC, Palla K, Du J, Watson R, Norman JT. Reversed polarity of Na(+) -K(+) -ATPase: mislocation to apical plasma membranes in polycystic kidney disease epithelia. Am J Physiol. 1991;260(3 Pt 2):F420–30.

    CAS  PubMed  Google Scholar 

  361. Avner ED, Sweeney Jr WE, Nelson WJ. Abnormal sodium pump distribution during renal tubulogenesis in congenital murine polycystic kidney disease. Proc Natl Acad Sci U S A. 1992;89(16):7447–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  362. Kawa G, Nagao S, Yamamoto A, Omori K, Komatz Y, Takahashi H, et al. Sodium pump distribution is not reversed in the DBA/2FG-pcy, polycystic kidney disease model mouse. J Am Soc Nephrol. 1994;4(12):2040–9.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  364. 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 

  365. Weimbs T. Polycystic kidney disease and renal injury repair: common pathways, fluid flow, and the function of polycystin-1. Am J Physiol. 2007;293(5):F1423–32.

    CAS  Google Scholar 

  366. Nauli SM, Rossetti S, Kolb RJ, Alenghat FJ, Consugar MB, Harris PC, et al. Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. J Am Soc Nephrol. 2006;17(4):1015–25.

    Article  CAS  PubMed  Google Scholar 

  367. Xu C, Rossetti S, Jiang L, Harris PC, Brown-Glaberman U, Wandinger-Ness A, et al. Human ADPKD primary cyst epithelial cells with a novel, single codon deletion in the PKD1 gene exhibit defective ciliary polycystin localization and loss of flow-induced Ca2+ signaling. Am J Physiol. 2007;292(3):F930–45.

    CAS  Google Scholar 

  368. Yoder BK, Tousson A, Millican L, Wu JH, Bugg Jr CE, Schafer JA, et al. Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium. Am J Physiol. 2002;282(3):F541–52.

    CAS  Google Scholar 

  369. Brown NE, Murcia NS. Delayed cystogenesis and increased ciliogenesis associated with the re-expression of polaris in Tg737 mutant mice. Kidney Int. 2003;63(4):1220–9.

    Article  PubMed  Google Scholar 

  370. Hou X, Mrug M, Yoder BK, Lefkowitz EJ, Kremmidiotis G, D’Eustachio P, et al. Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease. J Clin Invest. 2002;109(4):533–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  371. Praetorius HA, Spring KR. A Physiological view of the primary cilium. Annu Rev Physiol. 2005;67:515–29.

    Google Scholar 

  372. Huan Y, van Adelsberg J. Polycystin-1, the PKD1 gene product, is in a complex containing E-cadherin and the catenins. J Clin Invest. 1999;104(10):1459–68.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  373. Scheffers MS, Le H, van der Bent P, Leonhard W, Prins F, Spruit L, et al. Distinct subcellular expression of endogenous polycystin-2 in the plasma membrane and Golgi apparatus of MDCK cells. Hum Mol Genet. 2002;11(1):59–67.

    Article  CAS  PubMed  Google Scholar 

  374. Wilson PD, Geng L, Li X, Burrow CR. The PKD1 gene product, “polycystin-1,” is a tyrosine-phosphorylated protein that colocalizes with alpha2beta1-integrin in focal clusters in adherent renal epithelia. Lab Invest. 1999;79(10):1311–23.

    CAS  PubMed  Google Scholar 

  375. Silberberg M, Charron AJ, Bacallao R, Wandinger-Ness A. Mispolarization of desmosomal proteins and altered intercellular adhesion in autosomal dominant polycystic kidney disease. Am J Physiol. 2005;288(6):F1153–63.

    CAS  Google Scholar 

  376. Wilson PD, Hreniuk D, Gabow PA. Abnormal extracellular matrix and excessive growth of human adult polycystic kidney disease epithelia. J Cell Physiol. 1992;150(2):360–9.

    Article  CAS  PubMed  Google Scholar 

  377. Wilson PD, Norman JT, Kuo NT, Burrow CR. Abnormalities in extracellular matrix regulation in autosomal dominant polycystic kidney disease. Contrib Nephrol. 1996;118:126–34.

    Article  CAS  PubMed  Google Scholar 

  378. Grantham JJ, Donoso VS, Evan AP, Carone FA, Gardner KD. Viscoelastic properties of tubule basement membranes in experimental renal cystic disease. Kidney Int. 1987;32:187–97.

    Article  CAS  PubMed  Google Scholar 

  379. Joly D, Morel V, Hummel A, Ruello A, Nusbaum P, Patey N, et al. Beta4 integrin and laminin 5 are aberrantly expressed in polycystic kidney disease: role in increased cell adhesion and migration. Am J Pathol. 2003;163(5):1791–800.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  380. Shannon MB, Patton BL, Harvey SJ, Miner JH. A hypomorphic mutation in the mouse laminin alpha5 gene causes polycystic kidney disease. J Am Soc Nephrol. 2006;17(7):1913–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  381. Joly D, Berissi S, Bertrand A, Strehl L, Patey N, Knebelmann B. Laminin 5 regulates polycystic kidney cell proliferation and cyst formation. J Biol Chem. 2006;281(39):29181–9.

    Article  CAS  PubMed  Google Scholar 

  382. Rankin CA, Suzuki K, Itoh Y, Ziemer DM, Grantham JJ, Calvet JP, et al. Matrix metalloproteinases and TIMPS in cultured C57BL/6J-cpk kidney tubules. Kidney Int. 1996;50(3):835–44.

    Article  CAS  PubMed  Google Scholar 

  383. Rankin CA, Itoh Y, Tian C, Ziemer DM, Calvet JP. Gattone VHn. Matrix metalloproteinase-2 in a murine model of infantile-type polycystic kidney disease. J Am Soc Nephrol. 1999;10(2):210–7.

    CAS  PubMed  Google Scholar 

  384. Schaefer L, Han X, Gretz N, Hafner C, Meier K, Matzkies F, et al. Tubular gelatinase A (MMP-2) and its tissue inhibitors in polycystic kidney disease in the Han: SPRD rat. Kidney Int. 1996;49(1):75–81.

    Article  CAS  PubMed  Google Scholar 

  385. Nakamura T, Ushiyama C, Suzuki S, Ebihara I, Shimada N, Koide H. Elevation of serum levels of metalloproteinase-1, tissue inhibitor of metalloproteinase-1 and type IV collagen, and plasma levels of metalloproteinase-9 in polycystic kidney disease. Am J Nephrol. 2000;20(1):32–6.

    Article  CAS  PubMed  Google Scholar 

  386. Obermuller N, Morente N, Kranzlin B, Gretz N, Witzgall R. A possible role for metalloproteinases in renal cyst development. Am J Physiol. 2001;280(3):F540–50.

    CAS  Google Scholar 

  387. Cowley Jr BD, Ricardo SD, Nagao S, Diamond JR. Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats. Kidney Int. 2001;60(6):2087–96.

    Article  CAS  PubMed  Google Scholar 

  388. Maser RL, Vassmer D, Magenheimer BS, Calvet JP. Oxidant stress and reduced antioxidant enzyme protection in polycystic kidney disease. J Am Soc Nephrol. 2002;13:991–9.

    CAS  PubMed  Google Scholar 

  389. Ogborn MR, Crocker JF, McCarthy SC. RU38486 prolongs survival in murine congenital polycystic kidney disease. J Steroid Biochem. 1987;28(6):783–4.

    Article  CAS  PubMed  Google Scholar 

  390. Deshmukh GD, Radin NS, Gattone 2nd VH, Shayman JA. Abnormalities of glycosphingolipid, sulfatide, and ceramide in the polycystic (cpk/cpk) mouse. J Lipid Res. 1994;35(9):1611–8.

    CAS  PubMed  Google Scholar 

  391. Crocker JF, Blecher SR, Givner ML, McCarthy SC. Polycystic kidney and liver disease and corticosterone changes in the cpk mouse. Kidney Int. 1987;31(5):1088–91.

    Article  CAS  PubMed  Google Scholar 

  392. Bello-Reuss E, Holubec K, Rajaraman S. Angiogenesis in autosomal-dominant polycystic kidney disease. Kidney Int. 2001;60(1):37–45.

    Article  CAS  PubMed  Google Scholar 

  393. Hocher B, Zart R, Schwarz A, Vogt V, Braun C, Thone-Reineke C, et al. Renal endothelin system in polycystic kidney disease. J Am Soc Nephrol. 1998;9(7):1169–77.

    CAS  PubMed  Google Scholar 

  394. Preminger GM, Koch WE, Fried FA, McFarland E, Murphy ED, Mandell J. Murine congenital polycystic kidney disease: a model for studying development of cystic disease. J Urol. 1982;127:556–60.

    CAS  PubMed  Google Scholar 

  395. Gattone 2nd VH, MacNaughton KA, Kraybill AL. Murine autosomal recessive polycystic kidney disease with multiorgan involvement induced by the cpk gene. Anat Rec. 1996;245(3):488–99.

    Article  PubMed  Google Scholar 

  396. Gogusev J, Murakami I, Doussau M, Telvi L, Stojkoski A, Lesavre P, et al. Molecular cytogenetic aberrations in autosomal dominant polycystic kidney disease tissue. J Am Soc Nephrol. 2003;14(2):359–66.

    Article  CAS  PubMed  Google Scholar 

  397. 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 

  398. Mrug M, Li R, Cui X, Schoeb TR, Churchill GA, Guay-Woodford LM. Kinesin family member 12 is a candidate polycystic kidney disease modifier in the cpk mouse. J Am Soc Nephrol. 2005;16(4):905–16.

    Article  CAS  PubMed  Google Scholar 

  399. 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. 2000;11(7):1253–60.

    CAS  PubMed  Google Scholar 

  400. Cadnapaphornchai MA, George DM, McFann K, Wang W, Gitomer B, Strain JD, et al. Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2014;9(5):889–96.

    Article  PubMed Central  PubMed  Google Scholar 

  401. Leuenroth SJ, Bencivenga N, Igarashi P, Somlo S, Crews CM. Triptolide reduces cystogenesis in a model of ADPKD. J Am Soc Nephrol. 2008;19(9):1659–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  402. Huang JL, Woolf AS, Long DA. Angiogenesis and autosomal dominant polycystic kidney disease. Pediatr Nephrol (Berl, Germany). 2013;28(9):1749–55.

    Google Scholar 

  403. Fan LX, Zhou X, Sweeney Jr WE, Wallace DP, Avner ED, Grantham JJ, et al. Smac-mimetic-induced epithelial cell death reduces the growth of renal cysts. J Am Soc Nephrol. 2013;24:2010.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  404. Liu W, Fan LX, Zhou X, Sweeney Jr WE, Avner ED, Li X. HDAC6 regulates epidermal growth factor receptor (EGFR) endocytic trafficking and degradation in renal epithelial cells. PLoS One. 2012;7(11):e49418.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  405. Li X, Magenheimer BS, Xia S, Johnson T, Wallace DP, Calvet JP, et al. A tumor necrosis factor-alpha-mediated pathway promoting autosomal dominant polycystic kidney disease. Nat Med. 2008;14(8):863–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  406. Brookes 4ZL, Ruff LJ, Upadhyay VS, Huang L, Prasad S, Solanky T, et al. Pkd2 mesenteric vessels exhibit a primary defect in endothelial dependent vasodilatation restored by rosiglitazone. Am J Physiol Heart Circ Physiol. 2013;304(1):H33–41.

    Google Scholar 

  407. Bukanov NO, Smith LA, Klinger KW, Ledbetter SR, Ibraghimov-Beskrovnaya O. Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine. Nature. 2006;444(7121):949–52.

    Article  CAS  PubMed  Google Scholar 

  408. O’Meara CC, Hoffman M, Sweeney Jr WE, Tsaih SW, Xiao B, Jacob HJ, et al. Role of genetic modifiers in an orthologous rat model of ARPKD. Physiol Genomics. 2012;44(15):741–53.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  409. Dell KM, Sweeney WE, Avner ED. Polycystic kidney disease. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, editors. Pediatric nephrology. 6th ed. Berlin: Springer; 2009.

    Google Scholar 

Download references

Acknowledgments and Disclosures

Katherine MacRae Dell is acknowledged and thanked for her significant contributions to previous editions of this chapter.

W. E. Sweeney, Jr., and E. D. Avner are supported by the NIH-funded Children’s Research Center of Excellence in Pediatric Nephrology at the Children’s Research Institute and the Medical College of Wisconsin (NIH-P50DK076; P.I.- E.D.Avner), the Polycystic Kidney Research Foundation, the Advancing a Healthier Wisconsin Program of the Medical College of Wisconsin, and the Children’s Research Institute of the Children’s Hospital Health System of Wisconsin, the Ellsworth Family Trust, and the Lillian Goldman Charitable Trust.

The Avner–Sweeney laboratory at the Children’s Research Institute currently receives support administered entirely through the Medical College of Wisconsin from the following pharmaceutical companies: Taisho Pharmaceutical Co., Ltd. and Kadmon Corporation. E. D. Avner serves on the Medical Advisory Board of the ARPKD/CHF Alliance (without compensation).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Medical College of Wisconsin, Children’s Research Institute, Children’s Hospital Health System of Wisconsin, 8701 Watertown Plank Rd, TBRC-CRI Rm C-3570, Milwaukee, WI, 53226, USA

    William E. Sweeney Jr., Ameya Patil & Ellis D. Avner

  2. Medical Genetics Branch, The Intramural Program of the Office of Rare Diseases, National Human Genome Research Institute, Bethesda, MD, USA

    Meral Gunay-Aygun

  3. Department of Pediatrics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Meral Gunay-Aygun

Authors
  1. William E. Sweeney Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meral Gunay-Aygun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ameya Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ellis D. Avner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to William E. Sweeney Jr. or Ellis D. Avner .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Medical College of Wisconsin, Children’s Research Institute, Children’s Hospital, Health System of Wisconsin, Milwaukee, Wisconsin, USA

    Ellis D. Avner

  2. Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

    William E. Harmon

  3. Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, Université Paris-Descartes, Paris, France

    Patrick Niaudet

  4. Department of Pediatrics, Wakayama Medical University, Wakayama City, Japan

    Norishige Yoshikawa

  5. Division of Nephrology, Bambino Gesù Children’s Hospital – IRCCS, Rome, Italy

    Francesco Emma

  6. Division of Nephrology and Hypertension, The Heart Institute, Cincinnati Children’s Hospital Medical Center, College of Medicine, Cincinnati, Ohio, USA

    Stuart L. Goldstein

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer-Verlag Berlin Heidelberg (outside the USA)

About this entry

Cite this entry

Sweeney, W.E., Gunay-Aygun, M., Patil, A., Avner, E.D. (2016). Childhood Polycystic Kidney Disease. In: Avner, E., Harmon, W., Niaudet, P., Yoshikawa, N., Emma, F., Goldstein, S. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43596-0_32

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-43596-0_32

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-43595-3

  • Online ISBN: 978-3-662-43596-0

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation