Genetik in der Nephrologie – was ist neu?

Was ist neu?

Hohe Prävalenz genetischer Nierenerkrankungen In Kohorten von Nieren-Transplantationsempfängern findet sich bei bis zu 30% eine monogene Ursache. Die Aufdeckung der genetischen Ursache von Nierenerkrankungen ist durch den technologischen Fortschritt in der DNA-Sequenzierung deutlich einfacher geworden.

CKD unklarer Ätiologie Weiterhin können nicht alle Fälle aufgeklärt werden. Wichtig ist in jedem Fall, bei Patienten mit unklarer Ätiologie die Frage zu stellen, ob der diagnostische Algorithmus komplett durchlaufen wurde. Die klare Benennung einer CKDu (Chronic Kidney Disease of unknown aetiology) ist bedeutend besser als das Heranziehen schlecht definierter und damit oft fehlleitender Diagnosen.

Genetische Diagnostik – Diagnostische Lücken Die Aussagekraft der genetischen Diagnostik hängt wesentlich von einer guten klinischen Phänotypisierung des Patienten ab. Eine umfassende Abstimmung mit den Kollegen der Humangenetik – unter Berücksichtigung der klinischen Präsentation und der vermuteten genetischen Nierenerkrankung – ist sinnvoll, um die geeignete Diagnostik auszuwählen.

Gezielte Therapien für genetische Nierenerkrankungen Das zunehmende Wissen über die Pathophysiologie genetischer Nierenerkrankungen führt zu einer wachsenden Zahl zielgerichteter Therapien. Kürzlich sind spannende, neue Ansätze hinzugekommen, wie z.B. die ersten siRNA-Therapien in der Nephrologie für die primäre Hyperoxalurie Typ 1, die gezielte Behandlung der Hyperphagie bei Bardet-Biedl-Syndrom, die Therapie der APOL1-assoziierten Nierenerkrankung oder die Verwendung des HIF-2-Antagonisten Belzutifan für das Nierenzell-Karzinom bei Von-Hippel-Lindau-Syndrom.

Zentren für seltene Erkrankungen In der Verbesserung der Versorgung spielt die flächendeckende Einrichtung von inzwischen 36 Zentren für Seltene Erkrankungen eine wichtige Rolle.

Abstract

While genetic kidney diseases were long regarded as a rare cause of kidney failure, it has been shown in recent years that they account for a relevant proportion of cases. In cohorts of kidney transplant recipients, a monogenic cause is found in up to 30% of cases. Identifying the genetic cause of kidney disease has become much easier thanks to technological advances in DNA sequencing. The focus has now shifted to understanding the significance of the findings and identifying diagnostic gaps. It is still not possible to clarify all CKD cases of unclear aetiology. Besides very effective generic treatments for monogenic kidney disease (e.g., ACE-inhibitor use in Alport Syndrome), increasing knowledge of the pathophysiology of genetic kidney diseases has led to a growing number of targeted therapies. These include the treatment of ADPKD with Tolvaptan, which has now been in use for 10 years. Recently, exciting, and completely new approaches have been added, such as the first siRNA therapies in nephrology for primary hyperoxaluria type 1, the targeted treatment of hyperphagia in Bardet-Biedl syndrome, the therapy of APOL1-associated kidney disease or the use of the HIF-2 antagonist Belzutifan for renal cell carcinoma associated with Von-Hippel-Lindau syndrome. The new possibilities in the treatment of patients with genetic kidney diseases have also clearly revealed deficits in current patient care. Centers of excellence with extensive experience in this area therefore play an important role in improving care. This also applies to the further training of colleagues in the field. In Germany, the National Action Alliance for People with Rare Diseases (NAMSE) and the nationwide establishment of – to date – 36 centers for rare diseases play an important role in this regard.

Schlüsselwörter

Genetik - genetische Nierenerkrankung - seltene Erkrankung - CKDu

Keywords

genetics - genetic kidney disease - rare disease - CKDu

Publication History

Article published online:
22 October 2024

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