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Pediatric Nephrology

, Volume 28, Issue 11, pp 2143–2147 | Cite as

High frequency of kidney and urinary tract anomalies in asymptomatic first-degree relatives of patients with CAKUT

  • Burcu Bulum
  • Z. Birsin Özçakar
  • Evren Üstüner
  • Ebru Düşünceli
  • Aslı Kavaz
  • Duygu Duman
  • Katherina Walz
  • Suat Fitoz
  • Mustafa Tekin
  • Fatoş YalçınkayaEmail author
Original Article

Abstract

Background

Congenital anomalies of the kidney and urinary tract (CAKUT) commonly cause chronic kidney disease in children. While most CAKUT cases are sporadic, observed familial clustering suggests that the pathogenesis is influenced by genetic factors.

Methods

The purpose of the present study is to determine the frequency of the kidney and urinary tract anomalies in asymptomatic first-degree relatives of patients with CAKUT. A total of 218 index patients and their families followed at an academic hospital in Ankara, Turkey, were enrolled in the study.

Results

Family histories revealed at least one other member with a known kidney or urinary tract disease in 50 % and CAKUT in 22.9 % of the families. All asymptomatic first-degree relatives of 180 index patients were screened for kidney and urinary tract anomalies using ultrasound. New anomalies were diagnosed in 116 asymptomatic first-degree relatives (23 %) in 87 families (48.3 %). When family histories and ultrasound findings of 180 index patients were evaluated together, 129 first-degree relatives in 92 families (51.1 %) had CAKUT.

Conclusions

This study suggests that genetic mechanisms might be very important in the pathogenesis of apparently sporadic CAKUT. Identification of the underlying gene mutations will provide further insights into the knowledge of the kidney and urinary tract development and pathogenesis of CAKUT.

Keywords

CAKUT Familial clustering First-degree relatives Kidney and urinary tract anomalies Renal ultrasound 

References

  1. 1.
    Queisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger J (2002) Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990–1998). Arch Gynecol Obstet 266:163–167PubMedCrossRefGoogle Scholar
  2. 2.
    Wiesel A, Queisser-Luft A, Clementi M, Bianca S, Stoll C, EUROSCAN Study Group (2005) Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709,030 births in 12 European countries. Eur J Med Genet 48:131–144PubMedCrossRefGoogle Scholar
  3. 3.
    Pohl M, Bhatnagar V, Mendoza SA, Nigam SK (2002) Toward an etiological classification of developmental disorders of the kidney and upper urinary tract. Kidney Int 61:10–19PubMedCrossRefGoogle Scholar
  4. 4.
    Bek K, Akman S, Bilge I, Topaloğlu R, Calişkan S, Peru H, Cengiz N, Söylemezoğlu O (2009) Chronic kidney disease in children in Turkey. Pediatr Nephrol 24:797–806PubMedCrossRefGoogle Scholar
  5. 5.
    Ardissino G, Daccò V, Testa S, Bonaudo R, Claris-Appiani A, Taioli E, Marra G, Edefonti A, Sereni F, ItalKid Project (2003) Epidemiology of chronic renal failure in children: data from the ItalKid Project. Pediatrics 111:e382–e387PubMedCrossRefGoogle Scholar
  6. 6.
    Mong Hiep TT, Ismaili K, Collart F, Van Damme-Lombaerts R, Godefroid N, Ghuysen MS, Van Hoeck K, Raes A, Janssen F, Robert A (2010) Clinical characteristics and outcomes of children with stage 3–5 chronic kidney disease. Pediatr Nephrol 25:935–940PubMedCrossRefGoogle Scholar
  7. 7.
    McTaggart S, McDonald S, Henning P, Dent H (2009) Paediatric Report. ANZDATA Registry Report 2009, Australia and New Zealand Dialysis and Transplant Registry. Adelaide, South AustraliaGoogle Scholar
  8. 8.
    ESPN/ERA-EDTA Registry (2010) ESPN/ERA-EDTA registry annual report 2008. http://www.espn-reg.org/
  9. 9.
    Lewis MA, Shaw J, Sinha MD, Adalat S, Hussain F, Castledine C, van Schalkwyk D, Inward C (2010) UK Renal Registry 12th Annual Report (December 2009): chapter 14: demography of the UK paediatric renal replacement therapy population in 2008. Nephron Clin Pract 115:c279–c288PubMedCrossRefGoogle Scholar
  10. 10.
    Renkema KY, Winyard PJ, Skovorodkin IN, Levtchenko E, Hindryckx A, Jeanpierre C, Weber S, Salomon R, Antignac C, Vainio S, Schedl A, Schaefer F, Knoers NV, Bongers EM, EUCAKUT consortium (2011) Novel perspectives for investigating congenital anomalies of the kidney and urinary tract (CAKUT). Nephrol Dial Transplant 26:3843–3851PubMedCrossRefGoogle Scholar
  11. 11.
    Shnorhavorian M, Bittner R, Wright JL, Schwartz SM (2011) Maternal risk factors for congenital urinary anomalies: results of a population-based case–control study. Urology 78:1156–1161PubMedCrossRefGoogle Scholar
  12. 12.
    McPherson E (2007) Renal anomalies in families of individuals with congenital solitary kidney. Genet Med 9:298–302PubMedCrossRefGoogle Scholar
  13. 13.
    Weber S, Moriniere V, Knüppel T, Charbit M, Dusek J, Ghiggeri GM, Jankauskiené A, Mir S, Montini G, Peco-Antic A, Wühl E, Zurowska AM, Mehls O, Antignac C, Schaefer F, Salomon R (2006) Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J Am Soc Nephrol 17:2864–2870PubMedCrossRefGoogle Scholar
  14. 14.
    Weber S, Taylor JC, Winyard P, Baker KF, Sullivan-Brown J, Schild R, Knüppel T, Zurowska AM, Caldas-Alfonso A, Litwin M, Emre S, Ghiggeri GM, Bakkaloglu A, Mehls O, Antignac C, Network E, Schaefer F, Burdine RD (2008) SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol 19:891–903PubMedCrossRefGoogle Scholar
  15. 15.
    Saisawat P, Tasic V, Vega-Warner V, Kehinde EO, Günther B, Airik R, Innis JW, Hoskins BE, Hoefele J, Otto EA, Hildebrandt F (2012) Identification of two novel CAKUT-causing genes by massively parallel exon resequencing of candidate genes in patients with unilateral renal agenesis. Kidney Int 81:196–200PubMedCrossRefGoogle Scholar
  16. 16.
    Song R, Yosypiv IV (2011) Genetics of congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 26:353–364PubMedCrossRefGoogle Scholar
  17. 17.
    Woolf AS (2000) A molecular and genetic view of human renal and urinary tract malformations. Kidney Int 58:500–512PubMedCrossRefGoogle Scholar
  18. 18.
    Miyazaki Y, Ichikawa I (2003) Ontogeny of congenital anomalies of the kidney and urinary tract, CAKUT. Pediatr Int 45:598–604PubMedCrossRefGoogle Scholar
  19. 19.
    Squiers EC, Morden RS, Bernstein J (1987) Renal multicystic dysplasia: an occasional manifestation of the hereditary renal adysplasia syndrome. Am J Med Genet Suppl 3:279–284PubMedCrossRefGoogle Scholar
  20. 20.
    Roodhooft AM, Birnholz JC, Holmes LB (1984) Familial nature of congenital absence and severe dysgenesis of both kidneys. N Engl J Med 310:1341–1345PubMedCrossRefGoogle Scholar
  21. 21.
    Belk RA, Thomas DF, Mueller RF, Godbole P, Markham AF, Weston MJ (2002) A family study and the natural history of prenatally detected unilateral multicystic dysplastic kidney. J Urol 167:666–669PubMedCrossRefGoogle Scholar
  22. 22.
    Schwaderer AL, Bates CM, McHugh KM, McBride KL (2007) Renal anomalies in family members of infants with bilateral renal agenesis/adysplasia. Pediatr Nephrol 22:52–56PubMedCrossRefGoogle Scholar
  23. 23.
    Decter RM (1997) Renal duplication and fusion anomalies. Pediatr Clin North Am 44:1323–1341PubMedCrossRefGoogle Scholar
  24. 24.
    Williams H (2007) Renal revision: from lobulation to duplication-what is normal? Arch Dis Child Educ Pract Ed 92:152–158Google Scholar
  25. 25.
    Whitaker J, Danks DM (1966) A study of the inheritance of duplication of the kidneys and ureters. J Urol 95:176–178PubMedGoogle Scholar
  26. 26.
    Yosypiv IV (2012) Congenital anomalies of the kidney and urinary tract: a genetic disorder? Int J Nephrol. doi: 10.1155/2012/909083 Google Scholar
  27. 27.
    Schuchardt A, D’Agati V, Larsson-Blomberg L, Costantini F, Pachnis V (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367:380–383PubMedCrossRefGoogle Scholar
  28. 28.
    Jain S, Knoten A, Hoshi M, Wang H, Vohra B, Heuckeroth RO, Milbrandt J (2010) Organotypic specificity of key RET adaptor-docking sites in the pathogenesis of neurocristopathies and renal malformations in mice. J Clin Invest 120:778–790PubMedCrossRefGoogle Scholar
  29. 29.
    Skinner MA, Safford SD, Reeves JG, Jackson ME, Freemerman AJ (2008) Renal aplasia in humans is associated with RET mutations. Am J Hum Genet 82:344–351PubMedCrossRefGoogle Scholar
  30. 30.
    Chatterjee R, Ramos E, Hoffman M, VanWinkle J, Martin DR, Davis TK, Hoshi M, Hmiel SP, Beck A, Hruska K, Coplen D, Liapis H, Mitra R, Druley T, Austin P, Jain S (2012) Traditional and targeted exome sequencing reveals common, rare and novel functional deleterious variants in RET-signaling complex in a cohort of living US patients with urinary tract malformations. Hum Genet 131:1725–1738PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2013

Authors and Affiliations

  • Burcu Bulum
    • 1
  • Z. Birsin Özçakar
    • 1
  • Evren Üstüner
    • 2
  • Ebru Düşünceli
    • 2
  • Aslı Kavaz
    • 1
  • Duygu Duman
    • 3
  • Katherina Walz
    • 4
  • Suat Fitoz
    • 2
  • Mustafa Tekin
    • 3
    • 4
  • Fatoş Yalçınkaya
    • 1
    Email author
  1. 1.Division of Pediatric NephrologyAnkara University School of MedicineAnkaraTurkey
  2. 2.Division of RadiologyAnkara University School of MedicineAnkaraTurkey
  3. 3.Division of Pediatric GeneticsAnkara University School of MedicineAnkaraTurkey
  4. 4.John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human GeneticsUniversity of Miami Miller School of MedicineMiamiUSA

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