Proteomska analiza potencijalnih biljega akutne ozljede bubrega u urinu pacijenata na terapiji vankomicinom

Cilj: Vankomicin je antibiotik koji se koristi za liječenje infekcija uzrokovanih Gram- -pozitivnim bakterijama, no kod nekih pacijenata uzrokuje ozljedu bubrega. Budući da standardni biomarkeri ozljede bubrega ne pokazuju dovoljnu osjetljivost i specifičnost, potrebno je pronaći nove biomarkere kako bismo mogli ranije detektirati poremećaje bubrežne funkcije te pravovremenim prekidom ili promjenom terapije spriječiti daljnje ozljede bubrega. Cilj je rada bio usporediti proteomske profile urina dviju pacijentica oboljelih od upale pluća koje su primale terapiju vankomicinom sa i bez kliničkih znakova ozljede bubrega uzrokovanih navedenim antibiotikom, kako bismo identificirali nove potencijalne proteinske biomarkere akutne ozljede bubrega uzrokovanog vankomicinom. Prikaz slučaja: Uzorci urina prikupljeni su treći i sedmi dan terapije vankomicinom od pacijentice sa i pacijentice bez kliničkih znakova bubrežne disfunkcije te su analizirani dvodimenzionalnom gel elektroforezom kombiniranom s MALDI-TOF/TOF masenom spektrometrijom. Vidljive razlike u proteomskim profilima urina između dviju pacijentica javljaju se treći, a naročito su izražene sedmi dan terapije. Dvodimenzionalna gel elektroforeza kombinirana s masenom spektrometrijom potvrdila je već ranije dokazanu ulogu proteina neutrofilnog lipokalina povezanog s gelatinazom (NGAL, engl. neutrophil gelatinase-associated lipocalin) kao biomarkera akutne ozljede bubrega, te otkrila ekspresiju citoskeletnog keratina 1 tipa II i retinol-vezujućeg proteina 4 (RBP4, engl. retinol-binding protein 4) samo u urinu pacijentice kod koje je terapija vankomicinom uzrokovala poremećaj bubrežne funkcije. Zaključci: Citoskeletni keratin 1 tipa II i retinol-vezujući protein 4 mogli bi predstavljati nove potencijalne biomarkere ozljede bubrega uzrokovane vankomicinom. Potrebne su daljnje studije na većem broju pacijenata kako bi se validirali dobiveni rezultati i utvrdio njihov potencijalni dijagnostički i klinički značaj.
Aim: Vancomycin is an antibiotic used to treat infections caused by Gram-positive bacteria which can induce renal injury in some patients. Since standard biomarkers of kidney injury lack sufficient sensitivity and specificity, there is an unmet need for novel biomarkers that would enable early detection of renal injury and timely cessation or modification of treatment to prevent more severe kidney injury. The goal of this paper was to compare proteomics profiles of urine samples collected from two vancomycin-treated patients suffering from pneumonia with and without clinical symptoms of drug-induced renal dysfunction as to identify novel potential protein biomarkers of vancomycin-induced kidney injury. Case report: Urine samples were collected on the third and seventh day of vancomycin therapy from patients with and without clinical signs of acute kidney injury. Samples were analysed by two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry. Differences in urinary proteomes between these two patients could be observed on the third and especially on the seventh day of therapy. Two-dimensional gel electrophoresis combined with mass spectrometry confirmed previously established role of neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of renal injury, and revealed the expression of keratin 1 type II cytoskeletal and retinol-binding protein 4 (RBP4) only in urine from the patient with vancomycin- induced renal dysfunction. Conclusions: Keratin 1 type II cytoskeletal and retinol-binding protein 4 could be considered novel potential biomarkers of vancomycin-induced kidney injury. Additional studies with larger patient cohorts are needed to validate these findings and investigate their potential diagnostic and clinical significance.