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Progression chronischer Nierenerkrankungen

Genetische Aspekte

Progression of chronic kidney diseases

Genetic aspects

  • Leitthema
  • Published:
Der Nephrologe Aims and scope

Zusammenfassung

Eine progrediente Nierenfunktionsverschlechterung ist mit einem hohen Risiko für terminale Nierenerkrankung und Mortalität assoziiert. 38 % der interindividuellen Variabilität des jährlichen Nierenfunktionsverlusts in einer Population ist auf genetische Variabilität zurückzuführen und ist die Rationale für die systematische Suche nach zugrunde liegenden genetischen Varianten mittels genomweiter Assoziationsstudien (GWAS). Mit GWAS konnten in der Allgemeinbevölkerung drei Loci identifiziert werden, die mit Nierenfunktionsverlustphänotypen assoziiert sind: UMOD, CHD23 und GALNT11. Varianten im UMOD-Locus sind zudem assoziiert mit dem Risiko für eine neu auftretende chronische Nierenerkrankung (CKD) sowie eine terminale Nierenerkrankung, möglicherweise bedingt durch eine Beeinflussung resorptiver Vorgänge im Nierentubulus und eine veränderte Expression des Genprodukts, Uromodulin. In monogenetischen Nierenerkrankungen wie ADPKD (autosomal-dominate polyzystische Nierenerkrankung) und Alport-Syndrom ist die Art der Mutation entscheidend für den Verlauf der Erkrankung. Risiko-Scores, die genetische Informationen einkalkulieren, können in Zukunft bei ADPKD möglicherweise Hilfestellung beim Einsatz von Therapien wie Tolvaptan leisten. Geplante GWAS in Kohorten mit manifester oder hohem Risiko für CKD haben das Potenzial, neue Erkenntnisse zu Faktoren zu liefern, die die Progression einer CKD beeinflussen.

Abstract

A progressive decline in renal function is associated with a high risk of end-stage renal disease (ESRD) and mortality. The interindividual variability of the annual decline in kidney function in a population ascribable to genetic variability is estimated to be 38 % and is the rationale for the systematic search for underlying genetic variants using genome-wide association studies (GWAS). With GWAS three loci associated with a decline in kidney function could be identified in the general population: UMOD, CHD23 and GALNT11. Variants at the UMOD locus are further associated with a risk for newly occurring chronic kidney disease (CKD) and for ESRD, possibly due to influences on resorptive processes in the kidney tubules and an altered expression of the gene product, uromodulin. In monogenetic kidney diseases, such as autosomal dominant polycystic kidney disease (ADPKD) and Alport syndrome, the type of mutation is decisive for the course of the disease. Risk scores that include genetic information can in the future possibly provide assistance to clinicians prescribing tolvaptan for treatment of ADPKD. Planned GWAS in cohorts with manifest or a high risk for CKD have the potential for identifying further genetic factors affecting the progression of CKD.

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  1. Abteilung für Nephrologie, Universitätsklinikum Regensburg, 93042, Regensburg, Deutschland

    C. A. Böger

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Böger, C.A. Progression chronischer Nierenerkrankungen. Nephrologe 11, 252–259 (2016). https://doi.org/10.1007/s11560-016-0056-3

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  • DOI: https://doi.org/10.1007/s11560-016-0056-3

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