Promjena koncentracije čimbenika rasta fibroblasta 23 u odnosu na stadij akutnoga zatajenja bubrega [Fibroblast growth factor 23 concentration changes in relation to acute kidney failure stage]

Sakan, Sanja (2015) Promjena koncentracije čimbenika rasta fibroblasta 23 u odnosu na stadij akutnoga zatajenja bubrega [Fibroblast growth factor 23 concentration changes in relation to acute kidney failure stage]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Aim: Fibroblast growth factor 23 (FGF 23) is a novel potent phosphaturic hormon. The main reason for conducting this study was that present studies have shown the great significance of FGF 23 as a new, early biomarker in diagnosis and prognosis of acute renal insufficiency outcome, according to the new guideliness acute kidne injury (AKI). FGF 23 could be the early, novel renal biomarker that could help identify those subjects with early but still reversible AKI. Matherials and methods: We conducted a prospective cohort study at Department of surgery and Department of anesthesiology, reanimatology and intensive care Clinical Hospital Center Zagreb from February 2012 till January 2014. Our study enrolled two groups. The first group were adult subjects who developed postoperative AKI after scheduled and emergency large abdominal operations, or vascular operations on aorta and peripheral blood vessels, admitted to the surgical Intensive care unit afterwards. The second group was the control group which enrolled adult healthy subjects of both sex. Certainly, the subjects of both groups before comprising in the study had to content the inclusion and exclusion criteria. The subjects who contented the inclusion criteria for the study were monitored in the surgical intensive care unit for 24 hours postoperatively and diagnosed AKI according to RIFLE/AKIN criteria. Those who developed postoperative AKI serial mesurements of plasma FGF 23, serum and urine creatinine, calcium and phosphorus levels were done 24 hours after operation, on the third and fifth postoperative days. Control subjects who satisafied the inclusion criteria in the study according to history data were determined only one measurement of serum creatinine and plasma FGF 23. Plama FGF 23 samples were measured in the laboratory by imunoenzymatic method Enzyme-Linked Immunosorbent Assay-ELISA. Renal function outcome was assessed on the seventh and fourteenth postoperative day. There were two outcome posibilities: recovery of renal function or renal insufficiency. The subjects were followed until the release from the hospital. Results: Two-tailed p values <0,05 were considered significant. Data analysis was conducted by using SPSS 17.0 (SP22 Inc., Chicago, IL,USA). FGF 23 levels were significantly higher in subjects with AKI compared to subjects without AKI and heaalthy controls in all three mesurement points (p<0,001). Plasma FGF 23 levels significantly increased with the severity of AKI according to RIFLE/AKIN criteria in all measurement points except on the fifth postoperative day. Hypocalcemia and normophosphatemia were recorded during all three measurement points. Serum creatinine levels were incresed, while urinary calcium levels were decreased during all three measurement points. Urinary phosphorus levels were normal on the first postoperative day, but lower than normal values on the third and fifth postoperative days. Conclusion: Data on FGF 23 prognostic role in AKI, howevere, are insufficient. We compared prognostic role of FGF 23 with presently reliable and applicable diagnostic and prognostic scores, RIFLE and AKIN criteria according to AQDI consensus group. FGF 23 dynamics in our study have showen falling trend, and good correlation with RIFLE/AKIN criteria, currently clinically golden standards for renal function assessment. We have also demonstrated that FGF 23 could be not only novel, early renal biomarker of diagnosing AKI, but moreover a good prognostic renal biomarker in postoperative AKI. We have showed that FGF 23 has a good correlation with short-term prognostic role of RIFLE criteria. We conclude that FGF 23 is a novel, early, renal biomarker of AKI severity stratification and can also timely recognize subclinical AKI. Available data about mineral metabolism disturbances in AKI are insufficient or contradictory. During five postoperative days subjects with postoperative AKI had hypocalcemia and normophosphatemia. For the first time, we determined the plasma FGF 23 values in healthy subjects with the purpose of implementing FGF 23 measurements in everyday laboratory practice. The measured FGF 23 values matched normal FGF 23 values according to present available literature (median (IQR) 70 (62-95) RU/ml). Finally, we conclude that FGF 23 is a good, applicable, early, novel renal biomarker which could in time replace RIFLE criteria.

Abstract in Croatian

Cilj: FGF 23 je novi potentni fosfaturični hormon. Ono što je bio povod provođenju ovoga istraživanja je da su dosadašnja klinička mjerenja pokazala zasada veliku važnost određivanja FGF 23 kao novog, ranog biomarkera u dijagnostici i prognostici pogoršanja akutnog bubrežnog zatajenja, a prema novoj nomenklaturi akutne bubrežne ozljede (AOB). FGF 23 kao rani, novi biomarker bubrežne funkcije bi omogućio identificiranje onih osoba s no-vonastalom i još uvijek potencijalno reverzibilnom AOB. Materijali i metode: Proveli smo kohortno prospektivno istraživanje u Klinici za kirurgiji i Klinici za anesteziologiju, reanimatologiju i intenzivno liječenje Kliničkog bolničkog centra Zagreb u razdoblju od veljače 2012. do siječnja 2014. godine. Ispitanici su podijeljeni u dvije grupe. Grupu bolesnika sa AOB su činili odrasli ispitanici oba spola primljeni u jedinicu intenzivnog liječenja općih kirurških bolesnika u kojih se nakon elektivnih i hitnih velikih abdominalnih operativnih zahvata ili zahvata na aorti ili perifernim krvnim žilama razvila AOB. Druga grupa ispitanika je bila kontrolna grupa koju su činili zdravi odrasli ispitanici oba spola. Naravno, ispitanici obje grupe su prije uključenja u istraživanje morali zadovoljiti kriterije uključenja i isključenja. Ispitanicima koji su zadovoljili kriterije uključenja u studiju se u prva 24 h tijekom boravka u JIL-u općih kirurških bolesnika dijagnosticirala AOB na temelju RIFLE/AKIN kriterija. Oni ispitanici koji su razvili AOB odmah im se serijskim mjerenjima 24h nakon operacije, treći i peti dan nakon operacije odredila ulazna i kasnije izlazna vrijednost Simplified Acute Physiology Score (SAPS) II, uzela i nadopunila anamneza, te serumske i urinarne vrijednosti kreatinina, kalcija i fosfora. Kontrolnoj skupini ispitanika koja je zadovoljila anamnestičke kriterije uključenja u studiju se samo jednim mjerenjem odredila serumska vrijednost kreatinina i koncentracija FGF 23. Plazmatski uzorak FGF 23 se mjerio imunoenzimatskom metodom (engl. Enzyme-Linked Immunosorbent Assay, ELISA). Stanje bubrežne funkcije ispitanika se procjenjivalo sedmi i četrnaesti postoperativni dan sa mogućnošću 2 ishoda: ili oporavak bubrežne funkcije ili zatajenje bubrežne funkcije. Ispitanici su se pratili do otpusta iz bolnice. Rezultati: Razina statističke značajnosti je određena na p<0,05. Sve statističke obrade obavljene su u paketu SPSS 17.0 (SPSS Inc., Chicago, IL, USA). Utvrđene su statistički značajne razlike u razini FGF 23 između ispitanika bez AOB i ispitanika s AOB, te je FGF 23 bio veći kod ispitanika s AOB u sve tri točke mjerenja prema RIFLE i AKIN kriteriju (p<0,001). Utvrđene su statistički značajne razlike u razini FGF 23 s obzirom na težinu stadija AOB prema RIFLE i AKIN kriteriju u sve tri točke mjerenja. U sve tri točke FGF 23 raste s težinom AOB, osim peti dan nakon operacije. Hipokalcemija i normofosfatemija su bile prisutne tijekom pet dana od razvoja postoperativne AOB. Vrijednosti serumskog kreatinina su bile povišene u svim točkama mjerenja od nastanka postoperativne AOB u odnosu na normalnu vrijednost serumskog kreatinina dok su vrijednosti urinarnog kalcija tijekom pet dana od nastanka postoperativne AOB bile značajno snižene. Vrijednosti urinarnog fosfata su samo prvi dan nakon operacije bile u granicama normalnih vrijednosti, a u ostalim točkama mjerenja snižene. Zaključak: Podaci o prognostičkoj ulozi FGF 23 kod AOB su nedostatni. Prognostičku vrijednost FGF 23 uspoređivali smo sa trenutno pouzdanim i primjenjivim pokazateljima dijagnosticiranja i progresije AOB a to su RIFLE i AKIN kriteriji prema konsenzusu AQDI grupe. Dinamika kretanja FGF 23 u našem istraživanju dobro korelira sa dinamikom RIFLE i AKIN kriterija. Time smo pokazali da je FGF 23 u AOB ne samo novi rani biomarker dijagnosticiranja bubrežnog oštećenja nego je također pokazao i prognostičku ulogu u postoperativnoj AOB koja po značenju i vrijednosti dobro korelira sadašnjem zlatnom standardu, RIFLE kriterijima. Također FGF 23 se pokazao kao dobar biomarker stratifikacije težine AOB i prepoznavanja subkliničke postoperativne AOB. Podaci o poremećaju mineralnog metabolizma u AOB su naime, izuzetno nedostatni ili kontradiktorni. Tijekom sve tri vremenske točke mjerenja naši ispitanici su imali normofosfatemiju i hipokalcemiju. Po prvi puta smo odredili plazmatsku vrijednost FGF 23 u skupini zdravih ljudi u svrhu uvođenja metode mjerenja FGF 23 u laboratorij. Izmjerene vrijednosti FGF 23 su odgovarale normalnim vrijednostima navedenim u dosadašnjoj literaturi (medijan (IQR) 70 (62-95) RU/ml). Možemo zaključiti da je FGF 23 dobar, primjenjiv, rani, novi biomarker bubrežnog oštećenja koji bi s vremenom mogao zamijeniti RIFLE kriterije.

Item Type: Thesis (PhD)
Mentors:
Mentor
Bašić Jukić, Nikolina
Departments: Izvan medicinskog fakulteta
Depositing User: dr.med. Helena Markulin
University: Sveučilište u Zagrebu
Institution: Medicinski fakultet
Number of Pages: 92
Status: Unpublished
Creators:
CreatorsEmail
Sakan, SanjaUNSPECIFIED
Date: 15 December 2015
Date Deposited: 29 Apr 2016 10:08
Last Modified: 29 Apr 2016 10:08
Subjects: /
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/2594

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