Skip to main content

Advertisement

SpringerLink
Log in

The spectrum of autosomal dominant polycystic kidney disease in children and adolescents

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. It is characterized by the development of renal cysts and kidney enlargement and ultimately leads to renal failure typically in the sixth decade of life. Although most patients are asymptomatic until well into adulthood, renal cysts develop much earlier, often in utero. Significant renal anatomic and cystic expansion typically occurs before clinical manifestations in children and young adults with AKPKD. The cyst burden detected by imaging represents the minority of cyst burden, and renal and cardiovascular abnormalities are the most common manifestations in children with ADPKD. Here we review the molecular pathogenesis of ADPKD, discuss the screening, diagnosis and clinical manifestations of this renal disorder in childhood and adolescents and review treatment options and potential therapies currently being tested.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

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

    CAS  PubMed  Google Scholar 

  2. Pretorius DH, Lee ME, Manco-Johnson ML, Weingast GR, Sedman AB, Gabow PA (1987) Diagnosis of autosomal dominant polycystic kidney disease in utero and in the young infant. J Ultrasound Med 6(5):249–255

    CAS  PubMed  Google Scholar 

  3. MacDermot KD, Saggar-Malik AK, Economides DL, Jeffery S (1998) Prenatal diagnosis of autosomal dominant polycystic kidney disease (PKD1) presenting in utero and prognosis for very early onset disease. J Med Genet 35(1):13–16, Review

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hateboer N, van Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, Torra R, Breuning M, Ravine D (1999) Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet 353:103–107

  5. Cornec-Le Gall E, Audrézet MP, Chen JM, Hourmant M, Morin MP, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo MP, Grall-Jezequel A, Saliou P, Férec C, Le Meur Y (2013) Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol 24(6):1006–1013

    Article  PubMed  PubMed Central  Google Scholar 

  6. Harris PC, Bae KT, Rossetti S, Torres VE, Grantham JJ, Chapman AB, Guay-Woodford LM, King BF, Wetzel LH, Baumgarten DA, Kenney PJ, Consugar M, Klahr S, Bennett WM, Meyers CM, Zhang QJ, Thompson PA, Zhu F, Miller JP (2006) Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 17(11):3013–3019

    Article  CAS  PubMed  Google Scholar 

  7. Fencl F, Janda J, Bláhová K, Hríbal Z, Stekrová J, Puchmajerová A, Seeman T (2009) Genotype-phenotype correlation in children with autosomal dominant polycystic kidney disease. Pediatr Nephrol 24(5):983–989

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Tsiokas L, Kim S, Ong EC (2007) Cell biology of polycystin-2. Cell Signal 19(3):444–453

    Article  CAS  PubMed  Google Scholar 

  10. Torres VE, Harris PC (2006) Mechanisms of disease: autosomal dominant and recessive polycystic kidney diseases. Nat Clin Pract Nephrol 2(1):40–55, quiz 55

    Article  CAS  PubMed  Google Scholar 

  11. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33(2):129–137

    Article  CAS  PubMed  Google Scholar 

  12. Yamaguchi T, Nagao S, Kasahara M, Takahashi H, Grantham J (1997) Renal accumulation and excretion of cyclic adenosine monophosphate in a murine model of slowly progressive polycystic kidney disease. Am J Kidney Dis 30:703–709

    Article  CAS  PubMed  Google Scholar 

  13. Gattone VH 2nd, Wang X, Harris PC, Torres VE (2003) Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med 9(10):1323–1326

    Article  CAS  PubMed  Google Scholar 

  14. Zittema D, Boertien WE, van Beek AP, Dullaart RP, Franssen CF, de Jong PE, Meijer E, Gansevoort RT (2012) Vasopressin, copeptin, and renal concentrating capacity in patients with autosomal dominant polycystic kidney disease without renal impairment. Clin J Am Soc Nephrol 7(6):906–913

    Article  CAS  PubMed  Google Scholar 

  15. Yamaguchi T, Wallace DP, Magenheimer BS, Hempson SJ, Grantham JJ, Calvet JP (2004) Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype. J Biol Chem 279(39):40419–40430

    Article  CAS  PubMed  Google Scholar 

  16. Yamaguchi T, Nagao S, Wallace DP, Belibi FA, Cowley BD, Pelling JC, Grantham JJ (2003) Cyclic AMP activates B-Raf and ERK in cyst epithelial cells from autosomal-dominant polycystic kidneys. Kidney Int 63(6):1983–1994

    Article  CAS  PubMed  Google Scholar 

  17. Nagao S, Yamaguchi T, Kusaka M, Maser RL, Takahashi H, Cowley BD, Grantham JJ (2003) Renal activation of extracellular signal-regulated kinase in rats with autosomal-dominant polycystic kidney disease. Kidney Int 63(2):427–437

    Article  CAS  PubMed  Google Scholar 

  18. Davidow CJ, Maser RL, Rome LA, Calvet JP, Grantham JJ (1996) The cystic fibrosis transmembrane conductance regulator mediates transepithelial fluid secretion by human autosomal dominant polycystic kidney disease epithelium in vitro. Kidney Int 50(1):208–218

    Article  CAS  PubMed  Google Scholar 

  19. Du J, Wilson PD (1995) Abnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD. Am J Physiol 269(2 Pt 1):C487–C495

    CAS  PubMed  Google Scholar 

  20. Wilson SJ, Amsler K, Hyink DP, Li X, Lu W, Zhou J, Burrow CR, Wilson PD (2006) Inhibition of HER-2(neu/ErbB2) restores normal function and structure to polycystic kidney disease (PKD) epithelia. Biochim Biophys Acta 1762(7):647–655

    Article  CAS  PubMed  Google Scholar 

  21. Distefano G, Boca M, Rowe I, Wodarczyk C, Ma L, Piontek KB, Germino GG, Pandolfi PP, Boletta A (2009) Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1. Mol Cell Biol 29:2359–2371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bhunia AK, Piontek K, Boletta A, Liu L, Qian F, Xu PN, Germino FJ, Germino GG (2002) PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell 109(2):157–168

    Article  CAS  PubMed  Google Scholar 

  23. Li X, Luo Y, Starremans PG, McNamara CA, Pei Y, Zhou J (2005) Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat Cell Biol 7(12):1202–1212

    Article  PubMed  Google Scholar 

  24. Nicolau C, Torra R, Badenas C, Vilana R, Bianchi L, Gilabert R, Darnell A, Brú C (1999) Autosomal dominant polycystic kidney disease types 1 and 2: assessment of US sensitivity for diagnosis. Radiology 213(1):273–276

    Article  CAS  PubMed  Google Scholar 

  25. Gabow PA, Kimberling WJ, Strain JD, Manco-Johnson ML, Johnson AM (1997) Utility of ultrasonography in the diagnosis of autosomal dominant polycystic kidney disease in children. J Am Soc Nephrol 8(1):105–110

    CAS  PubMed  Google Scholar 

  26. Vester U, Kranz B, Hoyer PF (2010) The diagnostic value of ultrasound in cystic kidney diseases. Pediatr Nephrol 25(2):231–240

    Article  PubMed  Google Scholar 

  27. Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM (1994) Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet 343(8901):824–827

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  29. Rahbari-Oskoui F, Mittal A, Mittal P, Chapman A (2014) Renal relevant radiology: radiologic imaging in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 9(2):406–415

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  31. Reed B, Nobakht E, Dadgar S, Bekheirnia MR, Masoumi A, Belibi F, Yan XD, Cadnapaphornchai M, Schrier RW (2010) Renal ultrasonographic evaluation in children at risk of autosomal dominant polycystic kidney disease. Am J Kidney Dis 56(1):50–56

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, Kasiske BL, Odland D, PeiY, Perrone RD, Pirson Y, Schrier RW, Torra R, Torres VE, Watnick T, Wheeler DC; for Conference Participants (2015) Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 88(1):17–27

  34. Gabow PA, Kaehny WD, Johnson AM, Duley IT, Manco-Johnson M, Lezotte DC, Schrier RW (1989) The clinical utility of renal concentrating capacity in polycystic kidney disease. Kidney Int 35(2):675–680

    Article  CAS  PubMed  Google Scholar 

  35. Seeman T, Dusek J, Vondrák K, Bláhová K, Simková E, Kreisinger J, Dvorák P, Kyncl M, Hríbal Z, Janda J (2004) Renal concentrating capacity is linked to blood pressure in children with autosomal dominant polycystic kidney disease. Physiol Res 53(6):629–634

    CAS  PubMed  Google Scholar 

  36. Helal I, Reed B, McFann K, Yan XD, Fick-Brosnahan GM, Cadnapaphornchai M, Schrier RW (2011) Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 6(10):2439–2443

    Article  PubMed  PubMed Central  Google Scholar 

  37. Meijer E, Rook M, Tent H, Navis G, van der Jagt EJ, de Jong PE, Gansevoort RT (2010) Early renal abnormalities in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 5(6):1091–1098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Torres VE, King BF, Chapman AB, Brummer ME, Bae KT, Glockner JF, Arya K, Risk D, Felmlee JP, Grantham JJ, Guay-Woodford LM, Bennett WM, Klahr S, Meyers CM, Zhang X, Thompson PA, Miller JP, Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) (2007) Magnetic resonance measurements of renal blood flow and disease progression in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 2(1):112–120

    Article  PubMed  Google Scholar 

  39. Gabow PA, Duley I, Johnson AM (1992) Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease. Am J Kidney Dis 20(2):140–143

    Article  CAS  PubMed  Google Scholar 

  40. Chapman AB, Johnson AM, Gabow PA, Schrier RW (1994) Overt proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 5(6):1349–1354

    CAS  PubMed  Google Scholar 

  41. Sharp C, Johnson A, Gabow P (1998) Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 9(10):1908–1914

    CAS  PubMed  Google Scholar 

  42. Torres VE, Wilson DM, Hattery RR, Segura JW (1993) Renal stone disease in autosomal dominant polycystic kidney disease. Am J Kidney Dis 22(4):513–519

    Article  CAS  PubMed  Google Scholar 

  43. Martinez-Vea A, Gutierrez C, Bardaji A, Pastor R, Garcia C, Peralta C, Richart C, Oliver JA (1998) Microalbuminuria in normotensive patients with autosomal-dominant polycystic kidney disease. Scand J Urol Nephrol 32:356–359

    Article  CAS  PubMed  Google Scholar 

  44. Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM, Baumgarten DA, King BF Jr, Wetzel LH, Kenney PJ, Brummer ME, Bennett WM, Klahr S, Meyers CM, Zhang X, Thompson PA, Miller JP, Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) (2006) 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 1(1):64–69

    Article  PubMed  Google Scholar 

  45. Chapman AB, Rubinstein D, Hughes R, Stears JC, Earnest MP, Johnson AM, Gabow PA, Kaehny WD (1992) Intracranial aneurysms in autosomal dominant polycystic kidney disease. N Engl J Med 327(13):916–920

    Article  CAS  PubMed  Google Scholar 

  46. Huston J 3rd, Torres VE, Sulivan PP, Offord KP, Wiebers DO (1993) Value of magnetic resonance angiography for the detection of intracranial aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 3(12):1871–1877

    PubMed  Google Scholar 

  47. Ivy DD, Shaffer EM, Johnson AM, Kimberling WJ, Dobin A, Gabow PA (1995) Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 5(12):2032–2026

    CAS  PubMed  Google Scholar 

  48. Fick-Brosnahan GM, Tran ZV, Johnson AM, Strain JD, Gabow PA (2001) Progression of autosomal-dominant polycystic kidney disease in children. Kidney Int 59(5):1654–1662

    Article  CAS  PubMed  Google Scholar 

  49. Seeman T, Dusek J, Vondrichová H, Kyncl M, John U, Misselwitz J, Janda J (2003) Ambulatory blood pressure correlates with renal volume and number of renal cysts in children with autosomal dominant polycystic kidney disease. Blood Press Monit 8(3):107–110

    Article  PubMed  Google Scholar 

  50. Grantham JJ, Mulamalla S, Grantham CJ, Wallace DP, Cook LT, Wetzel LH, Fields TA, Bae KT (2012) Detected renal cysts are tips of the iceberg in adults with ADPKD. Clin J Am Soc Nephrol 7(7):1087–1093

    Article  PubMed  PubMed Central  Google Scholar 

  51. Grantham JJ, Cook LT, Torres VE, Bost JE, Chapman AB, Harris PC, Guay-Woodford LM, Bae KT (2008) Determinants of renal volume in autosomal-dominant polycystic kidney disease. Kidney Int 73(1):108–116

    Article  CAS  PubMed  Google Scholar 

  52. Cadnapaphornchai MA, Masoumi A, Strain JD, McFann K, Schrier RW (2011) Magnetic resonance imaging of kidney and cyst volume in children with ADPKD. Clin J Am Soc Nephrol 6(2):369–376

    Article  PubMed  PubMed Central  Google Scholar 

  53. Shamshirsaz AA, Reza Bekheirnia M, Kamgar M, Johnson AM, McFann K, Cadnapaphornchai M, Nobakhthaghighi N, Schrier RW (2005) Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome. Kidney Int 68(5):2218–2224

    Article  PubMed  Google Scholar 

  54. Chapman AB, Guay-Woodford LM, Grantham JJ, Torres VE, Bae KT, Baumgarten DA, Kenney PJ, King BF Jr, Glockner JF, Wetzel LH, Brummer ME, O’Neill WC, Robbin ML, Bennett WM, Klahr S, Hirschman GH, Kimmel PL, Thompson PA, Miller JP, Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort (2003) Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort. Kidney Int 64(3):1035–1045

    Article  PubMed  Google Scholar 

  55. O’Neill WC, Robbin ML, Bae KT, Grantham JJ, Chapman AB, Guay-Woodford LM, Torres VE, King BF, Wetzel LH, Thompson PA, Miller JP (2005) Sonographic assessment of the severity and progression of autosomal dominant polycystic kidney disease: the Consortium of Renal Imaging Studies in Polycystic Kidney Disease (CRISP). Am J Kidney Dis 46(6):1058–1064

    Article  PubMed  Google Scholar 

  56. Bhutani H, Smith V, Rahbari-Oskoui F, Mittal A, Grantham JJ, Torres VE, Mrug M, Bae KT, Wu Z, Ge Y, Landslittel D, Gibbs P, O’Neill WC, Chapman AB, Investigators CRISP (2015) A comparison of ultrasound and magnetic resonance imaging shows that kidney length predicts chronic kidney disease in autosomal dominant polycystic kidney disease. Kidney Int 88(1):146–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chapman AB, Johnson A, Gabow PA, Schrier RW (1990) The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. N Engl J Med 323:1091–1096

    Article  CAS  PubMed  Google Scholar 

  58. Doulton TW, Saggar-Malik AK, He FJ, Carney C, Markandu ND, Sagnella GA, MacGregor GA (2006) 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 24(5):939–945

    Article  CAS  PubMed  Google Scholar 

  59. Torres VE, Donovan KA, Sicli G, Holley KE, Thibodeau ST, Carretero OA, Inagami T, McAteer JA, Johnson CM (1992) Synthesis of renin by tubulocystic epithelium in autosomal dominant polycystic kidney disease. Kidney Int 42:364–373

    Article  CAS  PubMed  Google Scholar 

  60. Loghman-Adham M, Soto CE, Inagami T, Cassis L (2004) The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Ren Physiol 287(4):F775–F788

    Article  CAS  Google Scholar 

  61. Kelleher CL, McFann KK, Johnson AM, Schrier RW (2004) Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. Am J Hypertens 17(11 Pt 1):1029–1034

    Article  PubMed  Google Scholar 

  62. Selistre L, de Souza V, Ranchin B, Hadj-Aissa A, Cochat P, Dubourg L (2012) Early renal abnormalities in children with postnatally diagnosed autosomal dominant polycystic kidney disease. Pediatr Nephrol 27:1589–1593

    Article  PubMed  Google Scholar 

  63. Zeier M, Geberth S, Schmidt KG, Mandelbaum A, Ritz E (1993) Elevated blood pressure profile and left ventricular mass in children and young adults with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 3(8):1451–1457

    CAS  PubMed  Google Scholar 

  64. de Almeida EA, de Oliveira EI, Lopes JA, Almeida AG, Lopes MG, Prata MM (2007) Ambulatory blood pressure measurement in young normotensive patients with autosomal dominant polycystic kidney disease. Rev Port Cardiol 26(3):235–243

    PubMed  Google Scholar 

  65. Martinez-Vea A, Bardaj A, Gutierrez C, Garca C, Peralta C, Marcas L, Oliver JA (2004) Exercise blood pressure, cardiac structure, and diastolic function in young normotensive patients with polycystic kidney disease: a prehypertensive state. Am J Kidney Dis 44(2):216–223

    Article  PubMed  Google Scholar 

  66. Handa SP (2006) Cardiovascular manifestations of autosomal dominant polycystic kidney disease in young adults. Clin Invest Med 29(6):339–346

    PubMed  Google Scholar 

  67. McGrath J, Somlo S, Makova S, Tian X, Brueckner M (2003) Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114(1):61–73

    Article  CAS  PubMed  Google Scholar 

  68. Pennekamp P, Karcher C, Fischer A, Schweickert A, Skryabin B, Horst J, Blum M, Dworniczak B (2002) The ion channel polycystin-2 is required for left-right axis determination in mice. Curr Biol 12(11):938–943

    Article  CAS  PubMed  Google Scholar 

  69. AbouAlaiwi WA, Takahashi M, Mell BR, Jones TJ, Ratnam S, Kolb RJ, Nauli SM (2009) Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circ Res 104(7):860–869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Klawitter J, Reed-Gitomer BY, McFann K, Pennington A, Klawitter J, Abebe KZ, Klepacki J, Cadnapaphornchai MA, Brosnahan G, Chonchol M, Christians U, Schrier RW (2014) Endothelial dysfunction and oxidative stress in polycystic kidney disease. Am J Physiol Ren Physiol 307(11):F1198–F1206

    Article  CAS  Google Scholar 

  71. Chapman AB, Johnson AM, Rainguet S, Hossack K, Gabow P, Schrier RW (1997) Left ventricular hypertrophy in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 8(8):1292–1297

    CAS  PubMed  Google Scholar 

  72. Bardají A, Vea AM, Gutierrez C, Ridao C, Richart C, Oliver JA (1998) Left ventricular mass and diastolic function in normotensive young adults with autosomal dominant polycystic kidney disease. Am J Kidney Dis 32(6):970–975

    Article  PubMed  Google Scholar 

  73. Gabow PA, Johnson AM, Kaehny WD, Manco-Johnson ML, Duley IT, Everson GT (1990) Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease. Hepatology 11(6):1033–1037

    Article  CAS  PubMed  Google Scholar 

  74. Hogan MC, Abebe K, Torres VE, Chapman AB, Bae KT, Tao C, Sun H, Perrone RD, Steinman TI, Braun W, Winklhofer FT, Miskulin DC, Rahbari-Oskoui F, Brosnahan G, Masoumi A, Karpov IO, Spillane S, Flessner M, Moore CG, Schrier RW (2014) Liver involvement in early autosomal-dominant polycystic kidney disease. Clin Gastroenterol Hepatol 13:155–164

    Article  PubMed  PubMed Central  Google Scholar 

  75. Sherstha R, McKinley C, Russ P, Scherzinger A, Bronner T, Showalter R, Everson GT (1997) Postmenopausal estrogen therapy selectively stimulates hepatic enlargement in women with autosomal dominant polycystic kidney disease. Hepatology 26(5):1282–1286

    CAS  PubMed  Google Scholar 

  76. Graf S, Schischma A, Eberhardt KE, Istel R, Stiasny B, Schulze BD (2002) Intracranial aneurysms and dolichoectasia in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 17(5):819–823

    Article  PubMed  Google Scholar 

  77. Kubo S, Nakajima M, Fukuda K, Nobayashi M, Sakaki T, Aoki K, Hirao Y, Yoshioka A (2004) A 4-year-old girl with autosomal dominant polycystic kidney disease complicated by a ruptured intracranial aneurysm. Eur J Pediatr 163(11):675–677

    PubMed  Google Scholar 

  78. Thong KM, Ong AC (2014) Sudden death due to subarachnoid haemorrhage in an infant with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 29[Suppl 4]:iv121–iv123

    Article  CAS  PubMed  Google Scholar 

  79. Irazabal MV, Huston J 3rd, Kubly V, Rossetti S, Sundsbak JL, Hogan MC, Harris PC, Brown RD Jr, Torres VE (2011) Extended follow-up of unruptured intracranial aneurysms detected by presymptomatic screening in patients with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 6(6):1274–1285

    Article  PubMed  PubMed Central  Google Scholar 

  80. Schrier RW, Belz MM, Johnson AM, Kaehny WD, Hughes RL, Rubinstein D, Gabow PA (2004) Repeat imaging for intracranial aneurysms in patients with autosomal dominant polycystic kidney disease with initially negative studies: a prospective ten-year follow-up. J Am Soc Nephrol 15(4):1023–1028

    Article  PubMed  Google Scholar 

  81. Jafar TH, Stark PC, Schmid CH, Strandgaard S, Kamper AL, Maschio G, Becker G, Perrone RD, Levey AS (2005) The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease. ACE Inhibition in Progressive Renal Disease (AIPRD) Study Group. Kidney Int 67(1):265–271

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  83. Nutahara K, Higashihara E, Horie S, Kamura K, Tsuchiya K, Mochizuki T, Hosoya T, Nakayama T, Yamamoto N, Higaki Y, Shimizu T (2005) Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease. Nephron Clin Pract 99(1):c18–c23

    Article  CAS  PubMed  Google Scholar 

  84. van Dijk MA, Breuning MH, Duiser R, van Es LA, Westendorp RG (2003) No effect of enalapril on progression in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 18(11):2314–2320

    Article  PubMed  Google Scholar 

  85. Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW (2009) Prospective change in renal volume and function in children with ADPKD. Clin J Am Soc Nephrol 4(4):820–829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Schrier RW, Abebe KZ, Perrone RD, Torres VE, Braun WE, Steinman TI, Winklhofer FT, Brosnahan G, Czarnecki PG, Hogan MC, Miskulin DC, Rahbari-Oskoui FF, Grantham JJ, Harris PC, Flessner MF, Bae KT, Moore CG, Chapman AB, Trial Investigators HALT-PKD (2014) Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 371(24):2255–2266

    Article  PubMed  PubMed Central  Google Scholar 

  87. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114[2 Suppl 4th Report]:555–576

    Article  Google Scholar 

  88. Gile RD, Cowley BD Jr, Gattone VH 2nd, O’Donnell MP, Swan SK, Grantham JJ (1995) Effect of lovastatin on the development of polycystic kidney disease in the Han:SPRD rat. Am J Kidney Dis 26(3):501–507

    Article  CAS  PubMed  Google Scholar 

  89. Zafar I, Tao Y, Falk S, McFann K, Schrier RW, Edelstein CL (2007) Effect of statin and angiotensin-converting enzyme inhibition on structural and hemodynamic alterations in autosomal dominant polycystic kidney disease model. Am J Physiol Ren Physiol 293(3):F854–F859

    Article  CAS  Google Scholar 

  90. van Dijk MA, Kamper AM, van Veen S, Souverijn JH, Blauw GJ (2001) Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 16(11):2152–2157

    Article  PubMed  Google Scholar 

  91. Cadnapaphornchai MA, George DM, McFann K, Wang W, Gitomer B, Strain JD, Schrier RW (2014) 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 9(5):889–896

    Article  PubMed  PubMed Central  Google Scholar 

  92. Torres VE, Grantham JJ, Chapman AB, Mrug M, Bae KT, King BF Jr, Wetzel LH, Martin D, Lockhart ME, Bennett WM, Moxey-Mims M, Abebe KZ, Lin Y, Bost JE, Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) (2011) Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 6(3):640–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Torres VE, Chapman AB, Perrone RD, Bae KT, Abebe KZ, Bost JE, Miskulin DC, Steinman TI, Braun WE, Winklhofer FT, Hogan MC, Oskoui FR, Kelleher C, Masoumi A, Glockner J, Halin NJ, Martin DR, Remer E, Patel N, Pedrosa I, Wetzel LH, Thompson PA, Miller JP, Meyers CM, Schrier RW, HALT PKD Study Group (2012) Analysis of baseline parameters in the HALT polycystic kidney disease trials. Kidney Int 81(6):577–885

    Article  CAS  PubMed  Google Scholar 

  94. Wang CJ, Grantham JJ, Wetmore JB (2013) The medicinal use of water in renal disease. Kidney Int 84(1):45–53

    Article  PubMed  Google Scholar 

  95. Torres VE, Bankir L, Grantham JJ (2009) A case for water in the treatment of polycystic kidney disease. Clin J Am Soc Nephrol 4(6):1140–1150

    Article  CAS  PubMed  Google Scholar 

  96. Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS, TEMPO 3:4 Trial Investigators (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367(25):2407–2418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Serra AL, Poster D, Kistler AD, Krauer F, Raina S, Young J, Rentsch KM, Spanaus KS, Senn O, Kristanto P, Scheffel H, Weishaupt D, Wüthrich RP (2010) Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med 363(9):820–829

    Article  CAS  PubMed  Google Scholar 

  98. Walz G, Budde K, Mannaa M, Nürnberger J, Wanner C, Sommerer C, Kunzendorf U, Banas B, Hörl WH, Obermüller N, Arns W, Pavenstädt H, Gaedeke J, Büchert M, May C, Gschaidmeier H, Kramer S, Eckardt KU (2010) Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med 363(9):830–840

    Article  CAS  PubMed  Google Scholar 

  99. van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MG, Hoffmann AL, Dekker HM, de Man RA, Drenth JP (2009) Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 137(5):1661–1668. e1-2

    Article  PubMed  Google Scholar 

  100. Hogan MC, Masyuk TV, Page L, Holmes DR 3rd, Li X, Bergstralh EJ, Irazabal MV, Kim B, King BF, Glockner JF, Larusso NF, Torres VE (2012) Somatostatin analog therapy for severe polycystic liver disease: results after 2 years. Nephrol Dial Transplant 27(9):3532–3539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Caroli A, Perico N, Perna A, Antiga L, Brambilla P, Pisani A, Visciano B, Imbriaco M, Messa P, Cerutti R, Dugo M, Cancian L, Buongiorno E, De Pascalis A, Gaspari F, Carrara F, Rubis N, Prandini S, Remuzzi A, Remuzzi G, Ruggenenti P, ALADIN study group (2013) Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial. Lancet 382(9903):1485–1495

    Article  CAS  PubMed  Google Scholar 

  102. Riella C, Czarnecki PG, Steinman TI (2014) Therapeutic advances in the treatment of polycystic kidney disease. Nephron Clin Pract 28(3–4):297–302

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Chicago, 5841, S. Maryland Avenue Suite S-511, MC 5100, Chicago, IL, 60637, USA

    Bharathi V. Reddy & Arlene B. Chapman

Authors
  1. Bharathi V. Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arlene B. Chapman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bharathi V. Reddy.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reddy, B.V., Chapman, A.B. The spectrum of autosomal dominant polycystic kidney disease in children and adolescents. Pediatr Nephrol 32, 31–42 (2017). https://doi.org/10.1007/s00467-016-3364-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-016-3364-y

Keywords

Search

Navigation