Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Autosomal dominante polyzystische Nierenerkrankung

Die autosomal dominanten Zystennieren sind eine Erkrankung vornehmlich des Erwachsenenalters, die durch Mutationen im PKD1- oder PKD2-Gen hervorgerufen werden, und in der Hälfte der Fälle zur Dialysepflichtigkeit führt. Dabei tritt die Dialysepflichtigkeit bei PKD2-Mutationen deutlich später (80. Lebensjahr) auf als bei PKD1-Mutationen (60. Lebensjahr).

Epidemiologie

Die Schätzungen für die Prävalenz der Erkrankungen liegen zwischen 1:500 bis 1:2000.

Klinischer Befund

Die Klinik der autosomal dominanten polyzystischen Nierenerkrankung ADPKD ist durch multiple Zysten unterschiedlichster Größe in Leber und Nieren gekennzeichnet. Die klinischen Symptome werden im wesentlichen durch diese Zysten bestimmt. Bei wenigen Patienten werden zusätzlich intrancranielle Aneurysmen gefunden, die wenn sie rupturieren das Krankheitsbild und vor allem die Mortalität dominieren können.

Nierenzysten

Die Nierenzysten führen zu einer stetigen Abnahme der Nierenfunktion, so dass ab etwa der 4.Lebensdekade bis zu 50% der Anlageträger dialysepflichtig werden. Weit vor der Entwicklung der Niereninsuffizienz kann sich ein Hypertonus manifestieren, der dringend einer guten medikamentösen Einstellung bedarf, da sich bei hohen Blutdruckwerten die Nierenfunktion deutlich schneller verschlechtert. Der Ziielblutdruck für Zystennierenpatienten scheint bei 120/80 zu liegen. Vor der Niereninsuffizienz und manchmal auch deutlich vor dem sonographischen Nachweis von Nierenzysten kann eine Konzentrationsstörung nachgewiesen werden. Weitere Symptome der Nierenzysten sind Schmerzen durch Zysteninfektionen und Einblutungen, sowie Hämaturie durch Zystenruptur.

Nierenfunktionsverschlechterung

Die Nierenfunktionsverschlechterung hängt vor allem von der Nierengröße ab. Bei einem Nierenvolumen kleiner 750ml ist kaum mit einer Funktionsverschlechterung zu rechnen. Bei einem Nierenvolumen von größer 1500ml hingegen nimmt die Nierenfunktion rasch ab.

Leberzysten

Leberzysten werden bei sehr vielen Patienten mit ADPKD und mit zunehmendem Alter immer häufiger gefunden. Frauen sind häufiger betroffen. Leberzysten sind im Unterschied zu den Nierenzysten meist harmlos. Nur sehr selten kann es zu Kompression von Venen oder Gallenwegen mit entsprechender Symptomatik kommen. Sehr selten können auch Schmerzen durch die Raumforderung der Zysten oder durch Infektionen und Einblutungen entstehen.

Zerebrales Aneurysma

Bei etwa 6-10% der ADPKD Patienten werden zerebrale Aneurysmen beobachtet. Diese treten häufiger bei positiver Familienanamnese auf (20%) und führen häufiger zu intrazerebralen Blutungen als ähnliche Aneurysmen anderer Genese. Dabei konnte festgestellt werden, dass die Ruptur nicht von einem erhöhten Blutdruck oder einer eingeschränkten Nierenfunktion abhängt. Die Mortalität bei solchen Rupturen ist sehr hoch (30-60%). Damit mach die Aneurysmaruptur 4-7% der Sterbllichkeit von ADPKD-Patienten aus. Die PPatienten sollten über die Komplikation aufgeklärt werden. Bei der Diagnostik mittels MRT-Angio ist jedoch zu berüccksichtigen dass auch die Interventionen eine hohe Komplikationsrate besitzen.

Diagnosestellung

Bildgebende Verfahren

Das Ergebnis umfangreicher sonographischer und MRT-Untersuchung hat ergeben, dass Sichere Diagnose der Erkrankung mit bildgebenden Verfahren vor dem 40.Lebenjahr nicht möglich ist. Hier ist vor allem eine molekulargenetische Diagnostik zu erwägen.

Molekulargenetik

Die molekulargenetische Diagnostik ist vor allem indiziert bei Lebendnierenspende, in der Familienberatung und zur Diagnostik unklarer Fälle. Es muss jedoch festgestellt werden, dass in 10-20% der Fälle die zugrundeliegende Mutatiion nachzuweisen.

Symptome

Nierenzysten
Die bilateralen Nieren- und Leberzystenzysten sich das pathognomonische Zeichen der ADPKD. Leider erlauben diese erst eine sichere Diagnose nach dem 40. Lebensjahr.
Hepatische Fibrose
In seltenen Fällen entwickelt sich bei ADPKD auch eine CFH wie sie eher für die ARPKD typisch ist.

Gliederung

Zystische Nierenerkrankungen
Alagille-Syndrom 2
Autosomal dominante polyzystische Nierenerkrankung
GANAB
PKD1
PKD2
Autosomal rezessive polyzystische Nieren und Lebererkrankung
Branchio-Oto-Renale Dysplasie
Hajdu-Cheney-Syndrom
Komplex medullärer Zystennierenerkrankungen
Nierenzysten und Diabetes (RCAD)
Polyzystische Nierenerkrankung mit hyperinsulinämischer Hypoglycämie

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