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Seltene nephrotische Syndrome

Relevanz für zukünftige Behandlungsstrategien
  • S. LovricEmail author
Leitthema
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Zusammenfassung

Das nephrotische Syndrom (NS) ist eine Entität an Erkrankungen mit den klinischen Merkmalen Proteinurie (>3,5 g/Tag), Ödeme, Hypoalbuminämie und Hypercholesterinämie. Histologisch findet sich nicht selten eine fokal-segmentale Glomerulosklerose (FSGS) als Ausdruck der Podozytenschädigung. Eine Vielzahl der NS v. a. bei der FSGS beruht auf einer genetischen Mutation. Mittlerweile konnten mehr als 60 Gene identifiziert werden, die, wenn eine Mutation vorliegt, ein NS auslösen können. Durch den zunehmenden Einsatz von Whole-exome-Sequenzierung (WES) werden neue Gene entdeckt, die wichtige Signalwege im Podozyten darstellen und so einen Einblick in behandelbare Formen des NS geben. Die Behandlungsstrategie beim NS wird im Augenblick noch auf dem Boden der vorliegenden histologischen Läsion und danach, ob es zu einem Ansprechen der Erkrankung auf Glukokortikoide kommt, gestellt, nicht auf dem Boden einer genetischen Testung. Eine genetische Testung wird zunehmend auch beim erwachsenen Patienten eingesetzt, hat sich aber im Augenblick noch nicht als Teil der Standardtherapie durchgesetzt. Die genetische Testung sollte frühzeitig erfolgen mit dem Ziel, in Zukunft die Therapie für jeden einzelnen Patienten angepasst durchzuführen, auch um unnötige Exposition gegenüber Immunsuppressiva zu minimieren. Langfristig ist davon auszugehen, dass es zu einer individualisierten Therapie bei Patienten mit NS kommen wird, sobald die Erkenntnisse über Genmutation weiter voranschreiten und neue Behandlungsstrategien maßgeschneidert angewendet werden können. Hierzu müssen allerdings noch weitere neue therapeutische Angriffsziele identifiziert werden.

Schlüsselwörter

Fokal-segmentale Glumerulosklerose Genetische Testung Proteinurie Seltene Erkrankungen Individualisierte Therapie 

Rare nephrotic syndromes

Relevance for future treatment strategies

Abstract

Nephrotic syndrome (NS) is an entity of diseases with the clinical features of proteinuria (>3.5 g/day), edema, hypoalbuminemia and hypercholesterolemia. Histologically, a focal segmental glomerulosclerosis (FSGS) is found as an expression of podocyte damage. Many nephrotic syndromes, particularly in FSGS are based on a genetic mutation. More than 60 genes have now been identified that can cause nephrotic syndrome when a mutation is present. Increasing use of whole-exome sequencing (WES) has led to the discovery of new genes that cluster around specific signalling pathways in podocyte structures, providing insights into treatable forms of nephrotic syndrome. The treatment strategy for nephrotic syndrome is currently still based on the histological lesions present and afterwards on the response of the disease to glucocorticoids and not based on genetic testing. Genetic testing is also increasingly being used in adult patients but has not yet become established as part of standard care. Genetic testing should be carried out at an early stage, with the goal of adjusting the treatment in individual patients and also to minimize unnecessary exposure to immunosuppressant drugs in the future. In the long run individualized treatment in patients with nephrotic syndrome is expected to occur as long as knowledge on gene mutation continues to progress and new treatment strategies can be used in a tailored manner; however, for this further new therapeutic targets must be identified.

Keywords

Focal segmental glomerulosclerosis  Genetic testing Proteinuria Rare diseases Precision medicine 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

S. Lovric gibt an, dass kein Interessenkonflikt besteht.

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

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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Klinik für Nieren- und HochdruckkrankheitenMedizinische Hochschule HannoverHannoverDeutschland

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