Utjecaj pretvorbenog čimbenika rasta beta i endotelina-1 na tijek primarnog glomerulonefritisa [The influence of transforming growth factor beta and endothelin-1 in the course of primary glomerulonephritis]

Tišljar, Miroslav (2016) Utjecaj pretvorbenog čimbenika rasta beta i endotelina-1 na tijek primarnog glomerulonefritisa [The influence of transforming growth factor beta and endothelin-1 in the course of primary glomerulonephritis]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

OBJECTIVE: to investigate the level of immunoexpression and the tissue distribution of the TGF-β1 and the ET-1 in the kidney biopsy specimens of the patients with three the most common primary glomerulonephritides, and to examine the possible relationship between the immunoexpression of the cytokines and the course of glomerulonephritis. SUBJECTS AND METHODS: 91 patients who were diagnosed with the primary form of IgA nephropathy (IGAN), membranous nephropathy (MN) or focal segmental glomerulosclerosis (FSGS) were followed prospectively for one year. Initial clinical, laboratory and pathohistological parameters at the time of the renal biopsy as well as the laboratory parameters at the end of follow up period were compared with level of the TGF-β1 and the ET-1 immunoexpression in biopsy specimens. RESULTS: TGF-β1 renal immunoexpression was not significantly higher in comparation to control group. In IGAN patients, glomerular TGF-β1 expression was negatively correlated with the tubulointerstitial fibrosis and with serum creatinine level after one year, in MN group positively correlated with estimated glomerular filtration rate at the end of the study. Opposite results were found with ET-1 expression, where glomerular expression of ET-1 was significantly higher in all three patient subgroups compared to the control group. In IgAN group significant positive correlation is found between glomerular ET-1 expression level and the serume LDL concentration as well as with the endocapillary proliferation. In MN lower baseline serum albumine level and higher 24h proteinuria were corrleated with a higher glomerular ET-1 expression. In FSGS group glomerular ET-1 expression was in positive correlation with the grade of an arteriolar hyalinosis. In patients who achieved partial or complete remmison, glomerular ET-1 expression appeared significantly lower compared to those patients who experienced stationar course or disease progression. CONCLUSION: glomerular ET-1 immunoexpression was significantly higher among patients with glomerulonephritides compared to the control group and influenced on the course of glomerulonephritis. This should be further investigated in future long-term prospective studies with larger number of patients.

Abstract in Croatian

CILJ ISTRAŽIVANJA: ispitati intenzitet i tkivnu raspodjelu imunoekspresije pretvorbenog čimbenika rasta beta-1 (TGF-β1) i endotelina-1 (ET-1) u tri najčešća primarna glomerulonefritisa: IgA nefropatiji (IGAN), membranskom glomerulonefritisu (MN) i fokalnoj segmentalnoj glomerulosklerozi (FSGS), te njihovu povezanost s varijablama bubrežne funkcije odnosno tijekom bolesti. ISPITANICI I METODE: u 91 bolesnika dobi od 18 do 80 godina biopsijom bubrega uz druge laboratorijske pretrage definiran je jedan od gore navedenih primarnih glomerulonefritisa. Uz rutinski histološki pregled bioptata, na uzorcima bubrežnog parenhima provedeno je imunohistokemijsko ispitivanje ekspresije TGF-β1 i ET-1. Kao kontrolnu skupinu koristili smo bioptate 18 ispitanika s prolaznom blagom eritrociturijom ili proteinurijom, kojima u bubrežnom parenhimu nisu nađene patološke promjene. Bolesnicima su određeni klinički i laboratorijski parametri prilikom biopsije bubrega, te nakon godine dana praćenja. REZULTATI: ekspresija TGF-β1 nije se značajno razlikovala u odnosu na kontrolnu skupinu. U skupini bolesnika s IGAN, glomerularna ekspresija TGF-β1 povezana je s nižom koncentracijom serumskog kreatinina na kraju praćenja, te stupnjem intersticijske fibroze i tubularne atrofije, a u bolesnika s MN je pozitivno povezana s procijenjenom glomerularnom filtracijom na kraju praćenja. Nadalje, glomerularna ekspresija ET-1 statistički je značajno veća u svakoj od pojedinih skupina bolesnika s GN u odnosu prema kontrolnoj skupini. U bolesnika s MN glomerularna ekspresija ET-1 statistički je značajno povezana s 24h proteinurijom prilikom biopsije bubrega, a u bolesnika s FSGS sa stupnjem hijalinoze arteriola. Nađena je statistički značajno snižena glomerularna ekspresija ET-1 u bolesnika koji su postigli djelomičnu ili kompletnu remisiju. ZAKLJUČCI: glomerularna imunoekspresija ET-1 povezana je s tijekom bolesti, no za potvrdu toga potrebna su dugotrajna prospektivna istraživanja s većim brojem bolesnika.

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