Title Biljezi oštećenja proksimalnoga tubula u endemskoj nefropatiji Title (english) Biomarkers of proximal tubule injury in endemic nephropathy Author Jelena Kos305683907 Mentor Bojan Jelaković (mentor)Committee member Krešimir Galešić (predsjednik povjerenstva)Committee member Duško Kuzmanić (član povjerenstva)Committee member Živka Dika (član povjerenstva)Granter University of Zagreb Defense date and country 2020-02-24, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract Endemska nefropatija kronična je tubulointersticijska bolest bubrega koja se u hrvatskom endemskom žarištu proteže na 14 sela uz rijeku Savu zapadno od Slavonskoga Broda. Kako je glavno mjesto djelovanja okolišnog uzročnika u endemskoj nefropatiji proksimalni tubul, željeli smo utvrditi ulogu novih biljega bubrežnoga tubularnog oštećenja KIM-1, HGF i IP-10 u endemskoj nefropatiji. Također, cilj nam je bio utvrditi prediktivnu vrijednost navedenih biljega na nastanak kronične bubrežne bolesti odnosno pogoršanje bubrežne funkcije u sedmogodišnjem periodu.
U prvi dio presječnog istraživanja uključeno je 978 ispitanika iz 3 endemska i 2 kontrolna sela. Ispitanici iz endemskih sela klasificirani su u podskupine „Bolesni i sumnjivi“, „Rizični“ i „Ostali“. Svi ispitanici ispunili su detaljan upitnik, učinjen je fizikalni pregled, uzeti su im uzorci krvi te prvoga i drugoga jutarnjeg urina za analizu. U drugi longitudinalni dio istraživanja uključeno je 418 ispitanika koji su dali svoj pristanak za kontrolni pregled nakon 7 godina.
Prema našim rezultatima nema razlike u novim biljezima bubrežnoga oštećenje KIM-1, HGF između endemskih i kontrolnih bolesnika, dok je IP-10 bio nešto viši u endemskih u odnosu na kontrolne ispitanike što nema kliničko značenje jer nije bilo razlike kad se analiziraju međusobno endemske podskupine i kontrolni ispitanici. Međutim, „Bolesni i sumnjivi“ ispitanici imali su značajno više vrijednosti KIM-1 i HGF u odnosu na sve ostale ispitanike što ukazuje na još prisutan određeni stupanj aktivnoga tubularnog oštećenja odnosno reparatornih procesa u ovih ispitanika. Prema ROC analizi KIM-1 i HGF nemaju ulogu u dijagnostičkom algoritmu za endemsku nefropatiju s obzirom na nisku osjetljivost i specifičnost. Uspoređujući vrijednosti novih biljega između ispitanika koji u endemskom kraju borave dulje odnosno kraće od 20 godina nismo dobili značajnu razliku što je još jedan od dokaza smanjene izloženosti uzročnom agensu. U ovom istraživanju KIM-1 i IP-10 nisu pokazali prediktivnu vrijednost za razvoj novonastale kronične bubrežne bolesti, niti za pogoršanje bubrežne funkcije u sedmogodišnjem periodu praćenja. HGF je pokazao prediktivnu vrijednost za razvoj novonastale kronične bubrežne bolesti, no ne doprinosi značajno tradicionalnim prognostičkim biljezima poput procijenjene glomerularne filtracije. S druge strane HGF nema prediktivnu vrijednost za pogoršanje bubrežne funkcije u sedmogodišnjem periodu.
Abstract (english) Endemic nephropathy is a chronic tubulointerstitial kidney disease that in Croatia affects rural population west of Slavonski Brod along the Sava river. As proximal tubule injury is a hallmark of initial kidney damage in EN, our aim was to determine the role of the novel markers of tubular injury KIM-1, HGF and IP-10 in EN and to determine prognostic value of these biomarkers in chronic kidney disease.
In the first part of the study (cross-sectional) 978 participants from 3 endemic villages and 2 non-endemic control villages were enrolled. Participants from endemic villages were classified in 3 subgroups: “EN diseased and suspects”, “EN at risk”, “EN others“. All participants fulfilled extensive questionnaire, underwent physical examination, their blood was drawn and urine sample collected. In the second, longitudinal part of the study 418 participants were included in the follow up visit after 7 years.
We failed to find any differences in KIM-1 and HGF values between endemic and control participants while IP-10 showed a slightly higher levels in endemic participants. However, when we analized IP-10 values among the EN subgroups and control participants there were no significant differences. But significantly higher levels of KIM-1 and HGF were found in the urine of „EN diseased and suspects“ in comparison to all other groups, which could be attributed to the persistance of ongoing active tubular damage and reparatory processes in these patients. KIM-1 and HGF were not found to have specificity and sensitivity high enough to be incorporable into the diagnostic algorithm for EN. We found no differences in KIM-1, HGF and IP-10 values between endemic residents who live in these villages for more than 20 years in comparison to the residents who live less than 20 years confirming that exposure to the environmental agent is obviously diminished. In this study KIM-1 and IP-10 had no predictive value for the development of chronic kidney disease, or for the decline in renal function in 7-year follow-up. HGF showed predictive value for the development of chronic kidney disease, but when analyzed in model together with ACR and eGFR, HGF had no added value. On the other side, there was no predictive value of HGF for the decline in renal function in 7-year follow up.
Keywords
endemska nefropatija
nefropatija aristolohične kiseline
biljezi bubrežnog tubularnog oštećenja
KIM-1
HGF
IP-10
Keywords (english)
endemic nephropathy
aristolochic acid nephropathy
markers of tubular kidney injury
KIM-1
HGF
IP-10
Language croatian URN:NBN urn:nbn:hr:105:362748 Project Number: 108-0000000-0329 Study programme Title: Biomedicine and Health Sciences Catalog URL https://katalog.nsk.hr/F/19IT7Y755V1NXQJPHCLYSQGPF6BLAPPF179HQ7FAXXMYBYGMV5-28036?func=find-e&request=Biljezi+o%C5%A1te%C4%87enja+proksimalnoga+tubula+u+endemskoj+nefropatiji&find_scan_code=FIND_NAS&adjacent=N&local_base=MF_WEB&x=54&y=5&filter_code_1=WLN&filter_request_1=&filter_code_2=WYR&filter_request_2=&filter_code_3=WYR&filter_request_3=&filter_code_4=WFM&filter_request_4= Type of resource Text Extent 118 str. File origin Born digital Access conditions Open access Terms of use Created on 2021-04-12 08:26:25
