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Arapović, Adela [Author]

Izražaj receptora za D vitamin, 25-hidroksivitamin D 1α–hidroksilaze i vitamin D3 24-hidroksilaze u bubrezima pacijenata s IgA nefropatijom ; Expression of renal vitamin D receptors and metabolizing enzymes in IgA Nephropathy

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  • Media type: E-Book
  • Title: Izražaj receptora za D vitamin, 25-hidroksivitamin D 1α–hidroksilaze i vitamin D3 24-hidroksilaze u bubrezima pacijenata s IgA nefropatijom ; Expression of renal vitamin D receptors and metabolizing enzymes in IgA Nephropathy
  • Contributor: Arapović, Adela [VerfasserIn]
  • imprint: [Erscheinungsort nicht ermittelbar]: Sveučilište u Splitu. Medicinski fakultet.; University of Split. School of Medicine., 2022
  • Language: Croatian
  • Origination:
  • University thesis: Dissertation, Sveučilište u Splitu. Medicinski fakultet.; University of Split. School of Medicine., 2022
  • Footnote:
  • Description: Perkutana biopsija bubrega izvodi se u KBC-u Split kontinuirano od 1994. Stroge indikacije za invazivni zahvat obuhvaćaju poznate bubrežne sindrome. Bubrežno tkivo se nakon postavljanja dijagnoze može naknadno analizirati radi novih biljega, važnih u patogenezi bubrežnih bolesti. Bubreg je mjesto aktivacije vitamina D koji ima pleiotropni povoljni učinak na organizam. Zbog bubrežne bolesti kompleksni mehanizam regulacije vitamina D može biti poremećen. Istražili smo izražaj receptora za vitamin D (VDR) te enzima aktivacje (1α-OHaza) i razgradnje (CYP24A1) vitamina D u bioptatima bubrega bolesnika s IgA nefropatijom (IgAN) i usporedili s kontrolnim tkivima. Za epidemiološku analizu prikupljeni su klinički i patološki padaci o 54 bolesnika bioptirana na Klinici za dječje bolesti od 2008. do 2017. Za eksperimentalnu analizu prikupljeni su arhivirani parafinski blokovi bubrežnog tkiva 12 bolesnika s IgAN-om (šestero djece i šestero odraslih). Izrezani su preparati debljine 5 µm, standardno priređeni za indirektno imunohistokemijsko bojenje protutijelima na VDR, 1α-OHazu i CYP24A1, analizirani na imunofluoroscencijskom mikroskopu, fotografirani i kvantificirani uporabom ImageJ računalnog programa. U statističkoj analizi je značajnim smatran P < 0,05. U epidemiološkoj analizi, od 54 ispitanika, 29 je bilo muškog i 25 ženskog spola, srednja dob 9,84 ± 5,4 godine. Polovina indikacija za biopsiju otpada na nefrotski sindrom (NS; 25,93%) i ne-nefrotsku proteinuriju s hematurijom (22,22%). Najčešće je dijagnosticirana IgAN, a potom bolest minimalnih promjena (MCD), Henoch-Schönlein nefritis (HSPN), fokalna segmentalna glomeruloskleroza (FSGS) i Alportov sindrom (AS). Spektar dijagnoza se promijenio u odnosu na prethodno analizirano razdoblje 1995 – 2005. jer je mali postotak prethodno često dijagnosticiranog mezangioproliferativnog glomerulonefritisa (MesPGN). Na promjene u indikacijama i veći broj bioptiranih s IH-om i ne-nefrotskom proteinurijom s hematurijom utjecale su nove klasifikacije i mogućnost boljeg dijagnosticiranja hereditarnih bolesti glomerularne bazalne membrane (GBM). U eksperimentalnoj analizi, izražaj VDR-a u bubrežnom tkivu je značajno veći u bolesnika s IgAN-om nego u kontroli (P = 0,037), a izražaj 1α-OHaze značajno manji nego u kontroli (P < 0,001). Izražaj CYP24A1 i postotak jezgara imunoreaktivnih na CYP24A1 u glomerulima i epitelu distalnih kanalića je značajno veći u bolesnika s IgAN-om nego u kontrolnim tkivima 67 (P < 0,001). Postotak nuklearnog izražaja CYP24A1 u epitelu proksimalnih kanalića pokazuje negativnu korelaciju s eGFR (P = 0,034). Raspodjela indikacija i patoloških nalaza slična je podacima iz većine drugih studija. Razlika u izražaju VDR-a i enzima povezanih s aktivacijom i degradacijom vitamina D upućuje na smanjenu proizvodnju kalcitriola i povećanu razgradnju vitamina D u bubregu bolesnika s IgAN-om. ; Percutaneous kidney biopsy has been performed at University Hospital of Split continuously since 1994. Strict indications for invasive procedure include well- known renal syndromes. After diagnosis, renal tissue can be subsequently analyzed for new markers, important in the pathogenesis of renal disease. The kidney is the site of activation of vitamin D, which has a pleiotropic beneficial effect on the body. Due to kidney disease, the complex mechanism of vitamin D regulation can be disrupted. We investigated the expression of vitamin D receptor (VDR) and the enzymes of activation (1α-OHase) and degradation (CYP24A1) of vitamin D in kidney biopsies of patients with IgA nephropathy (IgAN) and compared it with control. For epidemiological analysis, clinical and pathological data were collected on 54 patients biopsied in the Clinic for Children´s Diseases from 2008 to 2017. For experimental analysis, archived paraffin blocks of renal tissue of 12 patients with IgAN (6 children and 6 adults) were collected. Five µm thick slides, standardly prepared for indirect immunohistochemical staining with antibodies to VDR, 1α-OHase and CYP24A1, were analyzed on an immunofluorescence microscope, photographed and quantified using an Image J computer program. In the statistical analysis, P < 0.05 was considered significant. In the epidemiological analysis, out of the 54 patients, 29 were male and 25 female; mean age 9.84 ± 5.4 years. Half of the biopsyindications are nephrotic syndrome (NS; 25.93%) and non-nephrotic proteinuria with hematuria, 22.22%. IgAN was most commonly diagnosed, followed by minimal change disease (MCD), Henoch-Schönlein purpura nephritis (HSPN), focal segmental glomerulosclerosis (FSGS), and Alport syndrome (AS). The spectrum of diagnoses changed compared to the previously analyzed period 1995 – 2005 because a small percentage of previously frequently diagnosed mesangioproliferative glomerulonephritis (MesPGN). Changes in indications were influenced by new classifications and the possibility of better diagnosis of hereditary disease of the glomerular basement membrane (GBM). In the experimental analysis, the expression of VDR in renal tissue was higher in patients with IgAN (P = 0.037), and the expression of 1α-OHase was significantly lower than in control (P <0.001). CYP24A1 expression in renal tissue, as well as the percentage of positive nuclei int he glomeruli and epithelium of distal tubules were higher in patients with IgAN than in control (P <0.001). The percentage of nuclear CYP24A1 69 expression in the epithelium of the proximal tubules shows a negative correlation with the estimated glomerular filtration (eGFR; P = 0.034). The distribution of indications and pathological findings is similar to that of most other studies. The difference in the expression of VDR and enzymes associated with vitamin D activation and degradation suggests decreased calcitriol production and increased renal degradation of vitamin D in patients with IgAN.
  • Access State: Open Access