Skip to main content

Advertisement

SpringerLink
Log in

Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes

  • Nephrology – Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

ADPKD is one of the most common inherited disorders, with high risk for end-stage renal disease. Numerous patients, however, have no relatives in whom this disorder is known and are unsure whether they may transmit the disease to their offsprings. The aim of this study was to evaluate whether germline mutation analysis adds substantial information to clinical symptoms for diagnosis of ADPKD in these patients.

Methods

Clinical data included renal function and presence of liver or pancreas cysts, heart valve insufficiency, intracranial aneurysms, colonic diverticles, and abdominal hernias. Family history was evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes was performed for intragenic mutations and for large deletions.

Results

A total of 324 adult patients with ADPKD including 30 patients without a family history of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal involvement. Compared to the 294 patients with familial ADPKD, the clinical characteristics and the age at the start of dialysis were similar in those with sporadic ADPKD.

Conclusion

The clinical characteristics of patients with sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked because of the absence of a family history. Molecular genetic screening for germline mutations in both PKD1 and PKD2 genes is essential for the definitive diagnosis of ADPKD.

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

Similar content being viewed by others

References

  1. Gabow PA (1993) Autosomal dominant polycystic kidney disease. N Engl J Med 329(5):332–342. doi:10.1056/NEJM199307293290508

    Article  PubMed  CAS  Google Scholar 

  2. Torres VE, Harris PC, Pirson Y (2007) Autosomal dominant polycystic kidney disease. Lancet 369(9569):1287–1301. doi:10.1016/S0140-6736(07)60601-1

    Article  PubMed  Google Scholar 

  3. Wilson PD (2004) Polycystic kidney disease. N Engl J Med 350(2):151–164. doi:10.1056/NEJMra022161

    Article  PubMed  CAS  Google Scholar 

  4. Pirson Y (2010) Extrarenal manifestations of autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17(2):173–180. doi:10.1053/j.ackd.2010.01.003

    Article  PubMed  Google Scholar 

  5. Hateboer N, Lazarou LP, Williams AJ, Holmans P, Ravine D (1999) Familial phenotype differences in PKD11. Kidney Int 56(1):34–40. doi:10.1046/j.1523-1755.1999.00541.x

    Article  PubMed  CAS  Google Scholar 

  6. Chatha RK, Johnson AM, Rothberg PG, Townsend RR, Neumann HP, Gabow PA (2001) Von Hippel-Lindau disease masquerading as autosomal dominant polycystic kidney disease. Am J Kidney Dis 37(4):852–858

    Article  PubMed  CAS  Google Scholar 

  7. Neumann HP (1999) The spectrum of renal cysts in adulthood—discussion of eight cases. Nephrol Dial Transplant 14(9):2234–2244

    Article  PubMed  CAS  Google Scholar 

  8. Reeders ST, Breuning MH, Davies KE, Nicholls RD, Jarman AP, Higgs DR, Pearson PL, Weatherall DJ (1985) A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature 317(6037):542–544

    Article  PubMed  CAS  Google Scholar 

  9. Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Pierides A, Kimberling WJ, Breuning MH, Deltas CC, Peters DJ, Somlo S (1996) PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272(5266):1339–1342

    Article  PubMed  CAS  Google Scholar 

  10. The European Polycystic Kidney Disease Consortium (1994) The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. Cell 78(4):725

    Google Scholar 

  11. The European Polycystic Kidney Disease Consortium (1994) The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. Cell 77(6):881–894

    Article  Google Scholar 

  12. Rossetti S, Burton S, Strmecki L, Pond GR, San Millan JL, Zerres K, Barratt TM, Ozen S, Torres VE, Bergstralh EJ, Winearls CG, Harris PC (2002) The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease. J Am Soc Nephrol 13(5):1230–1237

    Article  PubMed  CAS  Google Scholar 

  13. Wu G, Hayashi T, Park JH, Dixit M, Reynolds DM, Li L, Maeda Y, Cai Y, Coca-Prados M, Somlo S (1998) Identification of PKD2L, a human PKD2-related gene: tissue-specific expression and mapping to chromosome 10q25. Genomics 54(3):564–568. doi:10.1006/geno.1998.5618

    Article  PubMed  CAS  Google Scholar 

  14. Rossetti S, Chauveau D, Kubly V, Slezak JM, Saggar-Malik AK, Pei Y, Ong AC, Stewart F, Watson ML, Bergstralh EJ, Winearls CG, Torres VE, Harris PC (2003) Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet 361(9376):2196–2201. doi:10.1016/S0140-6736(03)13773-7

    Article  PubMed  CAS  Google Scholar 

  15. Grantham R (1974) Amino acid difference formula to help explain protein evolution. Science 185(4154):862–864

    Article  PubMed  CAS  Google Scholar 

  16. Ng PC, Henikoff S (2006) Predicting the effects of amino acid substitutions on protein function. Annu Rev Genomics Hum Genet 7:61–80. doi:10.1146/annurev.genom.7.080505.115630

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study is supported by the Else-Kroener-Fresenius Foundation Grant 2009_A75. We acknowledge the support of this study by the following institutions and colleagues: Nephrology Center Lüdenscheid Dr Olaf Loke, Dr. Christoph Mohler. Nephrology Center Iserlohn Dr. Johannes Bunia. Nephrology Center Freiburg Wirthstrasse: PD Dr. Annette Krämer-Guth, Dr. Michaela Königer, Dr. Gunnar Schaeffer. Nephrology Center Freiburg Schreiberstrasse: Dr. Johannes Donauer, Dr.Thomas Watter, Dr. Eckhard Schwertfeger, Dr. Kristin Breitenfeldt. Nephrology Centers Müllheim-Bad Krozingen-Schopfheim: Dr. Markus Cybulla, Dr. Maria Macner, Dr. Christine Reichert-Jünger, Privatdozent Dr. Martin Johannes Bek. Nephrology Center Emmendingen: Dr. Ludwig Funk, Dr. Horst-Dieter Löffler, Dr. Beate Friedrich. Nephrology Center Lahr Schillerstrasse: Dr. Jörg Baumert, Dr. Klaus Sodemann. Nephrology Center Lahr Gutleutstrasse.: Dr. Iris Lubrich-Birkner, Dr. Walter. Nephrology Center Achern: Dr. Thomas Bott, Dr. Ursula Heim, Dr. Christian Just. Nephrology Center Offenburg: Dr. Johannes Duttlinger, Dr. Klaus-Peter Stoll, Dr. Martin Hornberger, Dr. Bernd Geiss-Zirn, Dr. Roland Weghaupt, Dr. Frank Hagenah, Dr. Elsbeth Schillinger-Pokorny. Nephrology Center Rastatt: Dr. Karlfried Bratzel, Dr. Anne Braun-Süß, Dr. Dietrich Paatz. Nephrology Center Singen: Dr. Jochen Wilpert. Nephrology Center Villingen-Schwenningen: Dr. Thomas Weinreich, Dr. Felix Banthin, Dr. Christian Friedrichsohn, Dr. Irene von Henning, Dr. Walter Luft, Prof. Dr. HelmutReichel, Prof. Dr. Georg Schultze, PD Dr. Thomas Quaschning. Nephrology Center Lörrach: Dr. Martin Herb, Dr. Holger Endress. Nephrology Center Waldshut: Dr. Jörg Schnierda, Dr. Carsten Kurth. Nephrology Center Bruchsal: Dr. Dieter Baumann, Dr. Ralf Dikow, Dr. Nicole Allendorf-Ostwald, Dr. Johannes Törnig. Nephrology Center Bretten, Dr. Gerald Hock, Dr. Susanne Schorn. Nephrology Center Karlsruhe Südend Strasse: Dr. Martin Andre, Dr. Wolfgang Fischinger, Dr. Hans Georg Röder. Nephrology Center Karlsruhe Zeppelinstrasse: Hans Martin Seuffert, Dr R. Voegtle, Dr. R. Reyher. Städtische Krankenanstalten Karlsruhe: Dr. Helmut Felten, Prof. Dr. Martin Hausberg. Nephrology Center Baden Baden: Dr. Markus Lahl, Dr. Kronauer, Dr. Just, Dr. Michael Schäfer. Nephrology Center Radolfzell: Dr. Karl Henke, Dr. Kurt Amann; Dr. Ulrich Hahn; Dr. Hermann Schulz.

Author information

Authors and Affiliations

  1. Department of Nephrology, Section of Preventive Medicine, Albert-Ludwigs-University, Freiburg, Germany

    Hartmut P. H. Neumann, Janina Bacher & Zinaida Nabulsi

  2. University of Aachen, Aachen, Germany

    Nadine Ortiz Brüchle & Klaus Zerres

  3. Department of Clinical Chemistry, Albert-Ludwigs-University, Freiburg, Germany

    Michael M. Hoffmann

  4. Department of Nephrology and Intensive Medicine, Charité, Berlin, Germany

    Elke Schaeffner

  5. Department of Nephrology, Schwerin, Germany

    Jens Nürnberger

  6. Institute of Dialysis, Müllheim, Germany

    Markus Cybulla

  7. Institute of Dialysis, Singen, Germany

    Jochen Wilpert

  8. Center for Nephrology and Dialysis, Merano, Italy

    Peter Riegler

  9. Department of Nephrology, General Hospital, Bolzano, Italy

    Robert Corradini

  10. Dialysis Training Center, Freiburg, Germany

    Annette Kraemer-Guth

  11. Instituto de Investigaciones Médicas A Lanari, Universidad de Buenos Aires, Buenos Aires, Argentina

    Pablo Azurmendi

  12. Department of Medicine, University of Salamanca, Salamanca, Spain

    Mercedes Nunez

  13. Department of Neurosurgery, Albert-Ludwigs-University, Freiburg, Germany

    Sven Gläsker

  14. Department of Urology, Albert-Ludwigs-University, Freiburg, Germany

    Cordula Jilg

Authors
  1. Hartmut P. H. Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janina Bacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zinaida Nabulsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nadine Ortiz Brüchle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael M. Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elke Schaeffner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jens Nürnberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Markus Cybulla
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jochen Wilpert
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Peter Riegler
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Robert Corradini
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Annette Kraemer-Guth
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Pablo Azurmendi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Mercedes Nunez
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sven Gläsker
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Klaus Zerres
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Cordula Jilg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hartmut P. H. Neumann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Neumann, H.P.H., Bacher, J., Nabulsi, Z. et al. Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes. Int Urol Nephrol 44, 1753–1762 (2012). https://doi.org/10.1007/s11255-012-0125-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-012-0125-0

Keywords

Search

Navigation