title: Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.
abstract: Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of chronic kidney disease in children. The care of ARPKD patients has traditionally been the realm of pediatric nephrologists; however, the disease has multisystem effects, and a comprehensive care strategy often requires a multidisciplinary team. Most notably, ARPKD patients have congenital hepatic fibrosis, which can lead to portal hypertension, requiring close follow-up by pediatric gastroenterologists. In severely affected infants, the diagnosis is often first suspected by obstetricians detecting enlarged, echogenic kidneys and oligohydramnios on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Surgical considerations can include the possibility of nephrectomy to relieve mass effect, placement of dialysis access, and kidney and/or liver transplantation. Families of patients with ARPKD also face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. They may therefore interface with genetic counselors, geneticists, and reproductive endocrinologists. Children with ARPKD may also be at risk for neurocognitive dysfunction and may require neuropsychological referral. The care of patients and families affected by ARPKD is therefore a multidisciplinary effort, and the general pediatrician can play a central role in this complex web of care. In this review, we outline the spectrum of clinical manifestations of ARPKD and review genetics of the disease, clinical and genetic diagnosis, perinatal management, management of organ-specific complications, and future directions for disease monitoring and potential therapies.
authors.affiliation: Division of Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and hartunge@email.chop.edu.
authors.forename: Erum A
authors.initials: EA
authors.lastname: Hartung
authors.affiliation: Center for Translational Science, Children's National Health System, Washington, District of Columbia.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Guay-Woodford
mesh_terms: D000818:Animals; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D058685:Genetic Pleiotropy / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D017044:Polycystic Kidney, Autosomal Recessive / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*
keywords: congenital hepatic fibrosis; dialysis; genetic testing; kidney transplantation; liver transplantation; polycystic kidney disease; preimplantation genetic diagnosis
references.citation: J Am Soc Nephrol. 2008 Jan;19(1):102-8
references.pmid: 18032793
references.citation: N Engl J Med. 2006 May 18;354(20):2122-30
references.pmid: 16707749
references.citation: Acta Paediatr. 1996 Apr;85(4):437-45
references.pmid: 8740301
references.citation: Adv Nephrol Necker Hosp. 1989;18:33-57
references.pmid: 2493722
references.citation: Kidney Int. 2004 Oct;66(4):1345-55
references.pmid: 15458427
references.citation: Prenat Diagn. 2006 Apr;26(4):392-3
references.pmid: 16566041
references.citation: Nat Genet. 1997 Jun;16(2):179-83
references.pmid: 9171830
references.citation: Nat Genet. 2002 Mar;30(3):259-69
references.pmid: 11919560
references.citation: Am J Transplant. 2008 Nov;8(11):2243-51
references.pmid: 18808402
references.citation: Nat Genet. 2003 Aug;34(4):355-6
references.pmid: 12923538
references.citation: Kidney Blood Press Res. 2010;33(2):129-38
references.pmid: 20460933
references.citation: Gastroenterology. 2013 Jan;144(1):112-121.e2
references.pmid: 23041322
references.citation: J Clin Hypertens (Greenwich). 2012 Jun;14(6):353-9
references.pmid: 22672088
references.citation: Hum Mutat. 2004 May;23(5):487-95
references.pmid: 15108281
references.citation: Pediatr Nephrol. 2011 May;26(5):725-31
references.pmid: 21279811
references.citation: Pediatr Nephrol. 2003 Jan;18(1):57-61
references.pmid: 12488992
references.citation: J Am Soc Nephrol. 2007 Mar;18(3):923-33
references.pmid: 17267738
references.citation: Cell Tissue Res. 2006 Dec;326(3):671-85
references.pmid: 16767405
references.citation: N Engl J Med. 2008 Jul 17;359(3):318-9
references.pmid: 18635443
references.citation: J Assist Reprod Genet. 2010 Jul;27(7):397-407
references.pmid: 20490649
references.citation: Clin J Am Soc Nephrol. 2011 Aug;6(8):1824-30
references.pmid: 21737850
references.citation: Reprod Biomed Online. 2008 Jan;16(1):152-8
references.pmid: 18252063
references.citation: Pediatr Nephrol. 2013 Mar;28(3):401-8
references.pmid: 22692504
references.citation: Nephrol Dial Transplant. 2011 Jan;26(1):92-100
references.pmid: 20615907
references.citation: Clin J Am Soc Nephrol. 2011 Aug;6(8):1831-7
references.pmid: 21700829
references.citation: Pediatr Transplant. 2003 Oct;7(5):364-9
references.pmid: 14738296
references.citation: AJR Am J Roentgenol. 2004 Mar;182(3):689-95
references.pmid: 14975971
references.citation: Pediatr Transplant. 2010 Sep 1;14(6):E75-8
references.pmid: 19413724
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6965-70
references.pmid: 9192675
references.citation: AJR Am J Roentgenol. 1995 May;164(5):1247-50
references.pmid: 7717240
references.citation: Kidney Blood Press Res. 2007;30(3):129-44
references.pmid: 17446713
references.citation: Pediatrics. 2010 Feb;125(2):e349-57
references.pmid: 20083528
references.citation: Liver Transpl. 2009 Nov;15(11):S1-34
references.pmid: 19877213
references.citation: Kidney Int. 2001 Oct;60(4):1240-8
references.pmid: 11576338
references.citation: Hum Mutat. 2005 Mar;25(3):225-31
references.pmid: 15706593
references.citation: J Biol Chem. 2004 Sep 24;279(39):40419-30
references.pmid: 15263001
references.citation: Ultrasound Obstet Gynecol. 2004 Jul;24(1):55-61
references.pmid: 15229917
references.citation: Nephrol Dial Transplant. 2012 May;27(5):2083-8
references.pmid: 22076432
references.citation: Clin Investig. 1992 Sep;70(9):794-801
references.pmid: 1450634
references.citation: Acta Paediatr. 1995 Nov;84(11):1227-32
references.pmid: 8580616
references.citation: Am J Hum Genet. 1995 May;56(5):1101-7
references.pmid: 7726165
references.citation: Nephrol Dial Transplant. 2013 Mar;28(3):518-26
references.pmid: 23314319
references.citation: Pediatr Radiol. 2000 Mar;30(3):156-60
references.pmid: 10755752
references.citation: Nat Genet. 1994 Jul;7(3):429-32
references.pmid: 7920664
references.citation: J Biol Chem. 2008 Nov 14;283(46):31559-66
references.pmid: 18782757
references.citation: J Hum Genet. 2006;51(9):788-793
references.pmid: 16897190
references.citation: Pediatr Transplant. 2013 Jun;17(4):328-35
references.pmid: 23593929
references.citation: Kidney Int. 2004 Sep;66(3):964-73
references.pmid: 15327388
references.citation: J Am Soc Nephrol. 2004 Oct;15(10):2528-36
references.pmid: 15466257
references.citation: Clin Genet. 2004 Jul;66(1):53-7
references.pmid: 15200508
references.citation: J Child Neurol. 2015 Apr;30(5):543-6
references.pmid: 23877480
references.citation: Medicine (Baltimore). 2006 Jan;85(1):1-21
references.pmid: 16523049
references.citation: Hum Reprod. 2005 Jan;20(1):35-48
references.pmid: 15539444
references.citation: J Am Soc Nephrol. 2006 Jan;17(1):178-87
references.pmid: 16319189
references.citation: J Am Soc Nephrol. 2002 Sep;13(9):2246-58
references.pmid: 12191969
references.citation: Pediatr Nephrol. 1999 Oct;13(8):678-82
references.pmid: 10502126
references.citation: J Am Soc Nephrol. 2010 Mar;21(3):489-97
references.pmid: 20075061
references.citation: Nat Med. 2003 Oct;9(10):1323-6
references.pmid: 14502283
references.citation: J Am Soc Nephrol. 2008 Mar;19(3):455-68
references.pmid: 18235088
references.citation: Pediatr Nephrol. 1989 Jan;3(1):43-9
references.pmid: 2702087
references.citation: Pediatrics. 2010 Dec;126(6):e1425-9
references.pmid: 21059718
references.citation: Hum Genet. 2005 Nov;118(2):185-206
references.pmid: 16133180
references.citation: Kidney Int. 2000 Apr;57(4):1460-71
references.pmid: 10760082
references.citation: Am J Med Genet. 1998 Mar 5;76(2):137-44
references.pmid: 9511976
references.citation: Am J Kidney Dis. 2005 Jan;45(1):77-87
references.pmid: 15696446
references.citation: Clin Exp Nephrol. 2014 Feb;18(1):157-65
references.pmid: 23864346
references.citation: Urology. 1993 Sep;42(3):309-12
references.pmid: 8379031
references.citation: J Am Soc Nephrol. 2007 May;18(5):1381-8
references.pmid: 17429051
references.citation: N Engl J Med. 2011 Apr 21;364(16):1533-43
references.pmid: 21506742
references.citation: Pediatr Nephrol. 2014 Oct;29(10):1957-65
references.pmid: 24828609
references.citation: Pediatr Nephrol. 1997 Jun;11(3):302-6
references.pmid: 9203177
references.citation: J Am Soc Nephrol. 2005 Jan;16(1):46-51
references.pmid: 15563559
references.citation: Clin J Am Soc Nephrol. 2010 Jun;5(6):972-84
references.pmid: 20413436
references.citation: Am J Hum Genet. 2002 May;70(5):1305-17
references.pmid: 11898128
references.citation: Pediatr Nephrol. 2003 Feb;18(2):119-26
references.pmid: 12579400
references.citation: Kidney Int. 2005 Mar;67(3):829-48
references.pmid: 15698423
references.citation: Nephrol Dial Transplant. 2011 Nov;26(11):3514-22
references.pmid: 21389070
references.citation: Hepatology. 2013 Jul;58(1):409-21
references.pmid: 23172758
references.citation: Ultrasound Obstet Gynecol. 2006 Dec;28(7):911-7
references.pmid: 17094077
references.citation: Pediatr Nephrol. 1988 Jul;2(3):296-302
references.pmid: 3153029
references.citation: Kidney Int. 1998 Jul;54(1):80-6
references.pmid: 9648066
references.citation: Clin Transl Sci. 2011 Dec;4(6):460-5
references.pmid: 22212229
references.citation: Genet Test Mol Biomarkers. 2010 Aug;14(4):505-10
references.pmid: 20575693
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2311-6
references.pmid: 14983006
references.citation: Hum Mol Genet. 2003 Oct 15;12(20):2703-10
references.pmid: 12925574
references.citation: Hum Mol Genet. 2010 Sep 1;19(17):3306-19
references.pmid: 20554582
references.citation: J Am Soc Nephrol. 2011 Dec;22(12):2266-77
references.pmid: 22021705
references.citation: Pediatr Transplant. 2007 May;11(3):267-71
references.pmid: 17430481
references.citation: J Med Genet. 2005 Apr;42(4):336-49
references.pmid: 15805161
references.citation: Methods Cell Biol. 2009;94:273-97
references.pmid: 20362096
references.citation: J Am Soc Nephrol. 2008 Jul;19(7):1331-41
references.pmid: 18385429
references.citation: Nephrol Dial Transplant. 2006 Mar;21(3):598-604
references.pmid: 16221708
references.citation: N Engl J Med. 2009 Oct 22;361(17):1639-50
references.pmid: 19846849
references.citation: Hum Mutat. 2004 May;23(5):453-63
references.pmid: 15108277
references.citation: Kidney Int. 2000 Jan;57(1):33-40
references.pmid: 10620185
references.citation: J Pediatr. 1995 Aug;127(2):311-3
references.pmid: 7636663
references.citation: Mol Cell Biol. 2007 Apr;27(8):3241-52
references.pmid: 17283055
references.citation: Pediatr Radiol. 1988;18(1):45-50
references.pmid: 3277138
references.citation: Medicine (Baltimore). 1971 Jul;50(4):277-318
references.pmid: 5143572
references.citation: Nephrol Dial Transplant. 2009 Jun;24(6):1819-27
references.pmid: 19176689
references.citation: Lancet. 2013 Nov 2;382(9903):1485-95
references.pmid: 23972263
references.citation: J Bras Nefrol. 2010 Jul-Sep;32(3):263-7
references.pmid: 21103689
references.citation: Transpl Int. 2013 Jun;26(6):640-50
references.pmid: 23582048
references.citation: Kidney Int. 2003 Jun;63(6):1983-94
references.pmid: 12753285
references.citation: J Am Soc Nephrol. 2004 Mar;15(3):592-602
references.pmid: 14978161
references.citation: J Am Soc Nephrol. 2000 Jul;11(7):1179-1187
references.pmid: 10864573
references.citation: N Engl J Med. 2010 Aug 26;363(9):820-9
references.pmid: 20581391
references.citation: Nephrol Dial Transplant. 2001 Aug;16(8):1648-52
references.pmid: 11477168
references.citation: Kidney Int. 2003 Aug;64(2):391-403
references.pmid: 12846734
references.citation: J Am Soc Nephrol. 2003 Aug;14(8):2004-14
references.pmid: 12874454
references.citation: Nephrol Dial Transplant. 2007 Feb;22(2):432-9
references.pmid: 17065192
references.citation: Am J Pathol. 2008 Feb;172(2):417-29
references.pmid: 18202188
references.citation: Pediatr Nephrol. 2013 Feb;28(2):285-93
references.pmid: 23052652
references.citation: N Engl J Med. 2010 Aug 26;363(9):830-40
references.pmid: 20581392
references.citation: J Am Soc Nephrol. 2003 Jan;14(1):76-89
references.pmid: 12506140
references.citation: J Am Soc Nephrol. 2007 May;18(5):1374-80
references.pmid: 17429049
references.citation: Pediatrics. 2003 May;111(5 Pt 1):1072-80
references.pmid: 12728091
references.citation: AJR Am J Roentgenol. 1993 Feb;160(2):359-62
references.pmid: 8424350
references.citation: Nephrol Dial Transplant. 2008 Sep;23(9):3026-9
references.pmid: 18503009
references.citation: J Am Soc Nephrol. 2011 Nov;22(11):2047-56
references.pmid: 22034641
references.citation: J Urol. 2004 Nov;172(5 Pt 1):2000-1
references.pmid: 15540776
references.citation: J Pediatr Gastroenterol Nutr. 2012 May;54(5):580-7
references.pmid: 22197937
references.citation: Pediatr Radiol. 2002 Mar;32(3):169-74
references.pmid: 12164348
references.citation: Pediatr Transplant. 1999 Aug;3(3):246-8
references.pmid: 10487288
references.citation: Gastroenterology. 2013 May;144(5):1155-6
references.pmid: 23523842
references.citation: Mol Genet Metab. 2010 Feb;99(2):160-73
references.pmid: 19914852
references.citation: J Am Soc Nephrol. 2010 Jul;21(7):1097-102
references.pmid: 20558538
references.citation: Kidney Int. 2010 Feb;77(4):350-8
references.pmid: 19940839
references.citation: Am J Pathol. 2005 Jan;166(1):49-60
references.pmid: 15631999
references.citation: Eur J Radiol. 2014 Mar;83(3):450-5
references.pmid: 23891139
references.citation: Kidney Int. 2003 Oct;64(4):1310-9
references.pmid: 12969149
references.citation: Medicina (B Aires). 2013;73(2):155-62
references.pmid: 23570767
references.citation: Ultrasound Med Biol. 1991;17(7):687-94
references.pmid: 1781072
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5466-71
references.pmid: 16567633
references.citation: N Engl J Med. 2012 Dec 20;367(25):2407-18
references.pmid: 23121377
references.citation: J Pediatr. 1987 Nov;111(5):693-9
references.pmid: 3668738
references.citation: Am J Transplant. 2002 Apr;2(4):360-5
references.pmid: 12118859
references.citation: Nephrol Dial Transplant. 2008 Mar;23(3):880-9
references.pmid: 18042615
references.citation: Pediatr Nephrol. 2010 Dec;25(12):2449-57
references.pmid: 20798958
references.citation: Am J Hum Genet. 1994 Dec;55(6):1281-4
references.pmid: 7977390
references.citation: Am J Med Genet. 1985 Mar;20(3):505-17
references.pmid: 3887913