No public access
master's thesis
Analysis of potential protein biomarkers of nephrotoxicity in urine from patients receiving antibiotics

Ivona Štanfel (2016)
Sveučilište u Rijeci
Odjel za biotehnologiju
Metadata
TitleANALIZA POTENCIJALNIH PROTEINSKIH BILJEGA NEFROTOKSIČNOSTI U URINU PACIJENATA NA TERAPIJI ANTIBIOTICIMA
AuthorIvona Štanfel
Mentor(s)Mirela Sedić (thesis advisor)
Abstract
Vankomicin je antibiotik koji se koristi za liječenje infekcija uzrokovanih bakterijama koje su otporne na druge antibiotike, no kod nekih pacijenata liječenih tim lijekom dolazi do oštećenja bubrega. Budući da dosadašnji biomarkeri nefrotoksičnosti ne pokazuju dovoljnu osjetljivost i specifičnost, potrebno je pronaći nove biomarkere koji bi omogućili ranu detekciju poremećaja bubrežne funkcije kako bi bilo moguće pravovremenim prekidom terapije spriječiti daljnje oštećenje bubrega. Cilj ovoga rada je bio usporediti proteomske profile urina pacijentica na terapiji vankomicinom sa i bez kliničkih znakova oštećenja bubrega uslijed terapije navedenim antibiotikom s ciljem detekcije potencijalnih proteinskih biomarkera toksičnog učinka vankomicina na bubrege. Analiza jednodimenzionalnom gel elektroforezom je pokazala da se količina, ali i sastav proteina urina mijenjaju ovisno o danu uzimanja terapije. Nadalje, značajne razlike u proteinskim profilima urina pacijentica sa i bez oštećenja bubrega kao posljedica terapije vankomicinom se javljaju tek nakon trećeg, a naročito su izražene nakon sedmog dana terapije, pri čemu su najveće razlike uočene u rasponu molekulskih masa od približno 25-75 kDa. Dvodimenzionalna gel elektroforeza u kombinaciji sa MALDI-TOF/TOF masenom spektrometrijom je otkrila ekspresiju proteina keratina 1 tipa II, NGAL i retinol-vezujućeg proteina 4 u urinu pacijentice kod koje je terapija vankomicinom uzrokovala poremećaj u radu bubrega, što sugerira da bi ova tri proteina mogla predstavljati potencijalne biomarkere nefrotoksičnosti vankomicina. Daljnje studije su potrebne na većem broju pacijenata kako bi se validirali dobiveni rezultati i ispitao njihov potencijalni dijagnostički i klinički značaj.
Keywordsvancomycin nephrotoxicity kidney damage biomarker urine proteomics two-dimensional gel electrophoresis MALDI TOF/TOF
Parallel title (English)Analysis of potential protein biomarkers of nephrotoxicity in urine from patients receiving antibiotics
Committee MembersMirela Sedić (committee chairperson)
Sandra Kraljević Pavelić (committee member)
Miranda Mladinić Pejatović (committee member)
GranterSveučilište u Rijeci
Lower level organizational unitsOdjel za biotehnologiju
PlaceRijeka
StateCroatia
Scientific field, discipline, subdisciplineBIOTECHNICAL SCIENCES
Biotechnology
Study programme typeuniversity
Study levelgraduate
Study programmeBiotechnology in medicine
Academic title abbreviationmag. biotech. in med.
Genremaster's thesis
Language Croatian
Defense date2016-10-25
Parallel abstract (English)
Vancomycin is an antibiotic used for treating infections caused by bacteria which are resistant to other antibiotics, but in some of the treated patients it causes kidney damage. Since the currently known biomarkers of nephrotoxicity do not show sufficient sensitivity and specificity, it is necessary to find new biomarkers which would enable to discover disorders in kidney function in early stages and stop the therapy at the right time with the aim to prevent further development of kidney damage. The main goal of this study was to compare proteomic profiles of urine samples collected from patients on vancomycin therapy with and without clinical signs of kidney damage detected during the therapy in order to find potential protein biomarkers of vancomycin nephrotoxicity. Analysis of samples by one-dimensional gel electrophoresis showed that both quantity and composition of urinary proteins change depending on the day of therapy. Furthermore, significant differences in proteomic profiles of urine samples collected from patients with and without kidney damage caused by vancomycin therapy occur only after third, and are especially evident after seventh day of therapy, with the biggest differences observed within a range of molecular weights of about 25-75 kDa. Two-dimensional gel electrophoresis combined with MALDI-TOF/TOF revealed expression of keratin 1 type II, NGAL and retinol-binding protein 4 in urine of patient with kidney damage caused by vancomycin therapy, which suggests that those three proteins could present potential biomarkers of vancomycin nephrotoxicity. It is necessary to conduct further studies including larger number of patients in order to validate these results and to investigate their potential diagnostic and clinical significance.
Parallel keywords (Croatian)vankomicin nefrotoksičnost oštećenje bubrega biomarker urin proteomika dvodimenzionalna gel elektroforeza MALDI-TOF/TOF.
Resource typetext
Access conditionNo public access
Terms of usehttp://rightsstatements.org/vocab/InC/1.0/
URN:NBNhttps://urn.nsk.hr/urn:nbn:hr:193:295747
CommitterLea Lazzarich