Einfluss von salzreicher Ernährung auf die hyperperfundierte Niere nach Uninephrektomie bei hereditären Nierenerkrankungen wie dem Alport-Syndrom im Mausmodell
Influence of a high-salt diet on the hyperperfused kidney after uninephrectomy in hereditary kidney diseases such as the Alport syndrome in the mouse model
by Stefan Benda
Date of Examination:2021-08-24
Date of issue:2021-08-12
Advisor:Prof. Dr. Oliver Gross
Referee:Prof. Dr. Oliver Gross
Referee:Prof. Dr. Chris Mühlhausen
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Abstract
English
The filtration function of the kidney in the glomerulum consists of the endothelial cell, basement membrane (GBM) and podocyte. Collagen IV is, among other things, a major component of GBM. Homozygous mutations in type IV collagen (COL4A3, COL4A4 and COL4A5) lead to Alport's syndrome. Heterozygous mutations lead to heterozygous Alport syndrome (formerly: thin basement membrane nephropathy or benign familial hematuria). Patients with Alport syndrome develop end-stage renal disease early in life. The current therapy of choice are ACE inhibitors. Kidney donation is another pillar of therapy. Possible donors often have a heterozygous mutation. In this work, the donation of a kidney was simulated in a mouse model (SvJ-129 mouse). The thesis was intended to answer the question of what influence do modifier genes (here NPHS2), increased salt intake and hyperfiltration have on a previously damaged basement membrane of the kidney. The results show that there are no general differences between the treatment groups with regard to the individual genotypes. Compared to the homozygous Alport control group (COL4A3 knockout), however, the different genotypes often show significantly better results or results similar to those of healthy kidneys. Based on these results, the scope for possible kidney donors can be expanded. Donors with one of the mutations examined here should not generally be excluded from donating. There is no influence of NPHS2 as a modifier gene on the previously damaged basement membrane. Furthermore, the influences investigated here (0.9% NaCl drinking water and hyperperfusion after uninephrectomy) did not have a significantly negative effect on kidney performance. In addition, proteinuria did not generally increase after uninephrectomy. There was also no further increase in proteinuria through the administration of salt. However, subsequent moderate kidney damage cannot be ruled out with certainty, even if there was no evidence of this on the basis of the parameters weight, histology and serum levels of cholesterol and urea-N.
Keywords: Alport-Syndrome; Alport-Syndrome