Advertisement

Der Nephrologe

, Volume 12, Issue 4, pp 297–308 | Cite as

Autosomal-dominante polyzystische Nierenerkrankung

Neue Konzepte zur Betreuung und Behandlung von Patienten mit Zystennieren
  • Johan LorenzenEmail author
  • Rudolf P. Wüthrich
CME
  • 435 Downloads

Zusammenfassung

Die autosomal-dominante polyzystische Nierenerkrankung (ADPKD) ist eine progrediente Nierenfunktionsstörung, welche mit einem über das Leben fortschreitenden Zystenwachstum der Nieren einhergeht. Bei etwa zwei Dritteln der Patienten liegt eine positive Familienanamnese vor, beim Rest der Patienten könnte es sich um eine Spontanmutation handeln. Zwei Genmutation sind als ursächlich identifiziert worden: Mutationen im PKD1-Gen machen 85 % der Fälle aus, während 15 % der Fälle auf eine Mutation im PKD2-Gen zurückgehen. Ultimativ resultiert die Erkrankung, v. a. bei PKD1-Mutation, in einer terminalen Niereninsuffizienz. Therapeutisch kann die Progression günstig beeinflusst werden durch Einstellung der Patienten auf Hemmer des Renin-Angiotensin-Aldosteron-Systems. Seit Kurzem ist mit der Einführung des selektiven Antagonisten des V2-Vasopressin-Rezeptors Tolvaptan eine weitere Therapie verfügbar. Im folgenden Artikel möchten wir die Grundlagen und therapeutischen Möglichkeiten dieser Erkrankung darlegen.

Schlüsselwörter

Nierenerkrankungen Terminale Niereninsuffizienz Genmutation Nierenvolumen Tolvaptan 

Autosomal dominant polycystic kidney disease

Novel management and treatment concepts

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a chronic renal impairment that is associated with a progressive growth of kidney cysts. In approximately two-thirds of the patients, a positive family history is present; in the remaining patients it could be due to a spontaneous mutation. Two gene mutations have been identified as causative: Mutations in the PKD1 gene account for 85% of the cases, while 15% of the cases are due to a mutation in the PKD2 gene. Ultimately, the disease results in end-stage kidney disease (ESRD). Further progression of the disease can be therapeutically influenced by treating patients with inhibitors of the renin–angiotensin–aldosterone system. Recently, tolvaptan, a selective antagonist of the V2-vasopressin receptor, has been introduced. In the following article, we present the pathophysiological background as well as therapeutic possibilities of this disease.

Keywords

Kidney diseases Chronic renal failure Mutation Kidney volume Tolvaptan 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

J. Lorenzen geben an, dass kein Interessenkonflikt besteht. R.P. Wüthrich war in den letzten 4 Jahren beratend für die Firmen Novartis und Otsuka tätig.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Torres VE, Harris PC, Pirson Y (2007) Autosomal dominant polycystic kidney disease. Lancet 369:1287–1301CrossRefPubMedGoogle Scholar
  2. 2.
    Hateboer N, v Dijk MA, Bogdanova N et al (1999) Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet 353:103–107CrossRefPubMedGoogle Scholar
  3. 3.
    Ong AC, Devuyst O, Knebelmann B et al (2015) Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet 385:1993–2002CrossRefPubMedGoogle Scholar
  4. 4.
    Grantham JJ, Torres VE, Chapman AB et al (2006) Volume progression in polycystic kidney disease. N Engl J Med 354:2122–2130CrossRefPubMedGoogle Scholar
  5. 5.
    Grantham JJ (2008) Autosomal dominant polycystic kidney disease. N Engl J Med 359:1477–1485CrossRefPubMedGoogle Scholar
  6. 6.
    Pirson Y (2010) Extrarenal manifestations of autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17:173–180CrossRefPubMedGoogle Scholar
  7. 7.
    Pirson Y, Chauveau D, Torres V (2002) Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 13:269–276PubMedGoogle Scholar
  8. 8.
    Schrier RW (2006) Optimal care of autosomal dominant polycystic kidney disease patients. Nephrology (Carlton) 11:124–130CrossRefGoogle Scholar
  9. 9.
    Pei Y, Obaji J, Dupuis A et al (2009) Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol 20:205–212CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bhutani H, Smith V, Rahbari-Oskoui F et al (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 88:146–151CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Rahbari-Oskoui F, Mittal A, Mittal P et al (2014) Renal relevant radiology: radiologic imaging in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 9:406–415CrossRefPubMedGoogle Scholar
  12. 12.
    Irazabal MV, Rangel LJ, Bergstralh EJ et al (2015) Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol 26:160–172CrossRefPubMedGoogle Scholar
  13. 13.
    Chapman AB, Bost JE, Torres VE et al (2012) Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 7:479–486CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Cornec-Le Gall E, Audrezet MP, Chen JM et al (2013) Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol 24:1006–1013CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Chapman AB, Devuyst O, Eckardt KU et al (2015) Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 88:17–27CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Spithoven EM, Kramer A, Meijer E et al (2014) Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe: prevalence and survival – an analysis of data from the ERA-EDTA registry. Nephrol Dial Transplant 29(Suppl 4):iv15–iv25CrossRefPubMedGoogle Scholar
  17. 17.
    Rahbari-Oskoui F, Williams O, Chapman A (2014) Mechanisms and management of hypertension in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 29:2194–2201CrossRefPubMedGoogle Scholar
  18. 18.
    Schrier RW, Abebe KZ, Perrone RD et al (2014) Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 371:2255–2266CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Torres VE, Abebe KZ, Chapman AB et al (2014) Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med 371:2267–2276CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Serra AL, Poster D, Kistler AD et al (2010) Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med 363:820–829CrossRefPubMedGoogle Scholar
  21. 21.
    Walz G, Budde K, Mannaa M et al (2010) Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med 363:830–840CrossRefPubMedGoogle Scholar
  22. 22.
    Wüthrich RP, Mei C (2014) Pharmacological management of polycystic kidney disease. Expert Opin Pharmacother 15:1085–1095CrossRefPubMedGoogle Scholar
  23. 23.
    Caroli A, Perico N, Perna A et al (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 382:1485–1495CrossRefPubMedGoogle Scholar
  24. 24.
    Torres VE (2008) Vasopressin antagonists in polycystic kidney disease. Semin Nephrol 28:306–317CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Blair HA, Keating GM (2015) Tolvaptan: a review in autosomal dominant polycystic kidney disease. Drugs 75:1797–1806CrossRefPubMedGoogle Scholar
  26. 26.
    Torres VE, Harris PC (2014) Strategies targeting cAMP signaling in the treatment of polycystic kidney disease. J Am Soc Nephrol 25:18–32CrossRefPubMedGoogle Scholar
  27. 27.
    Torres VE, Chapman AB, Devuyst O et al (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367:2407–2418CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Higashihara E, Torres VE, Chapman AB et al (2011) Tolvaptan in autosomal dominant polycystic kidney disease: three years’ experience. Clin J Am Soc Nephrol 6:2499–2507CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Watkins PB, Lewis JH, Kaplowitz N et al (2015) Clinical pattern of Tolvaptan-associated liver injury in subjects with autosomal dominant polycystic kidney disease: analysis of clinical trials database. Drug Saf 38:1103–1113CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Gansevoort RT, Arici M, Benzing T et al (2016) Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. Nephrol Dial Transplant 31:337–348CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Torres VE, Chapman AB, Devuyst O et al (2017) Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 trial. Nephrol Dial Transplant. doi: 10.1093/ndt/gfx043 Google Scholar

Copyright information

© Springer Medizin Verlag GmbH 2017

Authors and Affiliations

  1. 1.Klinik für NephrologieUniversitätsspitalZürichSchweiz

Personalised recommendations