dc.contributor.advisor | Gross, Oliver Prof. Dr. | de |
dc.contributor.author | Theisen, Stephanie | de |
dc.date.accessioned | 2013-01-14T15:19:10Z | de |
dc.date.available | 2013-01-30T23:51:06Z | de |
dc.date.issued | 2012-05-31 | de |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-000D-EFBF-4 | de |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-1536 | |
dc.description.abstract | In der vorliegenden Arbeit wurde der
Renininhibitor Aliskiren bei homozygoten Col4A3-Knockout-Mäusen auf
seine nephroprotektive Wirkung hin untersucht. | de |
dc.format.mimetype | application/pdf | de |
dc.language.iso | ger | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | de |
dc.title | Prävention des Nierenversagens und der Nierenfibrose bei hereditären Erkrankungen der glomerulären Basalmembran (Alport-Syndrom) bei COL4A3-Knockout-Mäusen mit dem Reninantagonisten Aliskiren | de |
dc.type | doctoralThesis | de |
dc.title.translated | Prevention of renal failure and renal fibrosis in hereditary diseases of glomerular basement membrane (Alport-Syndrome) in COL4A3 knockout mice with Aliskiren a direct renin inhibitor | de |
dc.contributor.referee | Gross, Oliver Prof. Dr. | de |
dc.date.examination | 2012-06-04 | de |
dc.subject.dnb | 610 Medizin, Gesundheit | de |
dc.subject.gok | MED 418 Nephrologie | de |
dc.description.abstracteng | The nephroprotectiv properties of the
direct renin inhibitor Aliskiren in homozygote COL4A3 knockout mice
were analysed in this paper. Consistent with the human disease
Alport Syndrome, the mouse model shows the same pathogenesis and
course of disease. Alport Syndrome is a progressive hereditary
glomerulonephritis with hematuria and proteinuria. Other extrarenal
symptoms are sensorineural deafness and ocular features. Finally
the glomerulonephritis leads to end-stage renal failure. The main
cause of the disease are mutations in the collagen type IV genes.
The aim of this study was to review whether Aliskiren has the
ability to prevent end-stage renal failure in Alport Syndrome in a
protective manner. A total of 39 mice were examined for survival,
histology and proteinuria. Untreated homozygote COL4A3 knockout
mice were used for control group. The survival was analysed in a
Kaplan-Meier curve and the histological specimens were evaluated by
a Score. For urine analysis protein samples were made and reviewed
with SDS-Page. Indeed a beneficial trend was observed by treatment
with Aliskiren. In particular the survival findings showed a
significant advantage of the direct renin inhibitor. Findings in
histology and proteinuria were less convincing because of a lacking
number of cases. Nevertheless even in histology nephrosclerosis was
less pronounced in the therapy group than in the control group. As
well the therapy group leads to a reduction of macroproteinuria. To
sum up, one could say that renin inhibition by Aliskiren, the
interference into the RAAS, leads to a prolongation of survival in
the investigated animal model. It seems that Aliskiren has the
opportunity to delay end-stage renal failure and displays a
potential therapy approach. At present Aliskiren is still not
accepted as first-line-therapy in chronic nephropathy or Alport
Syndrome. It has to be proved alongside medicaments like
ACE-Inhibitors or AT1-Antagonists in future studies. The pathogenic
development up to end-stage renal disease in Alport Syndrome
remains still unclear. To get a better understanding of the disease
it is important to have a better knowledge about the pathogenesis.
In fact this can lead to more efficient therapies or even stabilize
proven therapies. The significance of RAAS in the pathogenesis of
Alport Syndrome was presented in the present paper and as well in
papers with other RAAS Blocker in humans and animal models.
Currently transplantation is the only real curative option. It's a
wearing procedure and complications like graft loss are quite
possible. This shows the necessity to establish more sufficient
therapies with fewer adverse events. Blocking the RAAS could be a
good alternative to transplantation. Possible are monotherapies
with ACE-Inhibitors, AT1-Antagonists, Aldosteron-Antagonists and
the direct renin inhibitor Aliskiren as well as a combination of
the medicaments mentioned above in different variation. We expect
new findings from future studies like the Alport-Register, where
properties of ACE-Inhibitors are discovered in childhood. | de |
dc.contributor.coReferee | Krick, Wolfgang PD Dr. | de |
dc.contributor.thirdReferee | Virsik-Köpp, Patricia Prof. Dr. | de |
dc.subject.topic | Medicine | de |
dc.subject.ger | Renininhibitor Aliskiren | de |
dc.subject.ger | Col4A3-Knockout-Mäuse | de |
dc.subject.ger | Alport-Syndrom | de |
dc.subject.ger | Kollagen Typ IV | de |
dc.subject.ger | terminalen Nierenversagens | de |
dc.subject.ger | chronische Nierenerkrankungen | de |
dc.subject.ger | RAAS | de |
dc.subject.ger | RAAS-Blockade | de |
dc.subject.ger | ACE-Hemmer | de |
dc.subject.ger | AT1-Antagonisten | de |
dc.subject.eng | direct renin inhibitor Aliskiren | de |
dc.subject.eng | COL4A3 knockout mice | de |
dc.subject.eng | Alport Syndrome | de |
dc.subject.eng | collagen type IV | de |
dc.subject.eng | end-stage renal failure | de |
dc.subject.eng | chronic nephropathie | de |
dc.subject.eng | RAAS | de |
dc.subject.eng | RAAS-Blocker | de |
dc.subject.eng | ACE-Inhibitors | de |
dc.subject.eng | AT1-Antagonists | de |
dc.subject.bk | 44 Medizin | de |
dc.subject.bk | 44.88 Urologie | de |
dc.subject.bk | Nephrologie | de |
dc.identifier.urn | urn:nbn:de:gbv:7-webdoc-3534-5 | de |
dc.identifier.purl | webdoc-3534 | de |
dc.affiliation.institute | Medizinische Fakultät | de |
dc.identifier.ppn | 729080773 | de |