doktorska disertacija
Petra Bratina (Author), Tanja Kersnik-Levart (Mentor), Darja Paro Panjan (Co-mentor)

Abstract

Izhodišče in namen: Prirojena dilatacija votlega sistema ledvic (angleško »urinary tract dilatation«, UTD) je ena najpogostejših napak, ugotovljenih z rutinsko ultrazvočno (UZ) preiskavo pri plodu. Včasih lahko UTD privede do ledvične okvare, ki je vodilni razlog za kronično ledvično bolezen pri otrocih, zato je potrebna zgodnja prepoznava in zdravljenje. Trenutno najbolj raziskan in obetaven biološki označevalec ledvične okvare je lipokalin, povezan z gelatinazo nevtrofilcev, določen v urinu (uNGAL), ki ima zaradi neinvazivnega odvzema vzorca urina še dodatno veliko prednost prav pri populaciji novorojenčkov. Želeli smo ovrednotiti njegovo vlogo pri novorojenčkih s prirojeno enostransko UTD. UZ-preiskava sečil ostaja prva in najvarnejša preiskava pri obravnavi ploda in novorojenčka s sumom na UTD. Ovrednotiti smo želeli UTD A (antenatalno) in P (postnatalno) klasifikacijski sistem, ki ga uporabljamo od leta 2014, glede porazdelitve specifičnih uropatij in določenih kliničnih izhodov. Preiskovanci in metode dela: V prospektivnem delu raziskave smo vključili 38 donošenih novorojenčkov s prirojeno enostransko UTD; 38 zdravih, donošenih novorojenčkov pa je predstavljalo kontrolno skupino. Pri vseh smo opravili UZ sečil, z razvrstitvijo bolnikov po klasifikaciji UTD P in izmerili uNGAL s kemiluminiscenčno metodo. Pri nekaterih preiskovancih smo za postavitev končne etiološke diagnoze opravili dodatne preiskave (cistogram, scintigrafija ledvic). Novorojenčke v skupini preiskovancev smo razdelili v dve podskupini glede na obstrukcijo sečil, naknadno pa smo jih razdelili v dve podskupini tudi glede na obliko zdravljenja, ki je bilo kirurško ali konzervativno. V retrospektivnem delu raziskave smo vključili 126 novorojenčkov z enostransko in 40 novorojenčkov z obojestransko UTD. Zbrali smo podatke o stopnji UTD A in UTD P ter klinične podatke o specifičnih uropatijah, okužbah sečil in antibiotični zaščiti, potrebi po kirurški intervenciji, spontani resoluciji in času, ki je bil za to potreben, ter končnem izhodu glede ledvične funkcije ob koncu sledenja. Rezultati: V prospektivnem delu raziskave smo ugotovili statistično značilno višje vrednosti uNGAL-a v podskupini novorojenčkov z obstrukcijo sečil v primerjavi s skupino zdravih novorojenčkov (mediana 15,9 (IQR 6,4–25,0) in mediana 5,7 (IQR 3,6–11,1), Kruskal-Wallisov test, p = 0,016). Z ROC (angl. receiver operating curve) analizo smo določili diagnostični profil uNGAL-a za odkrivanje obstrukcije sečil in ugotovili, da je pri mejni vrednosti uNGAL-a 5,5 µg/L senzitivnost 89 % in specifičnost 51 %. AUC (angl. area under the curve) je bila 0,72 (95 % CI 0,59–0,85). V retrospektivnem delu raziskave smo dokazali statistično značilno povezavo med UTD A 2–3 in UTD P 2 ali 3 s senzitivnostjo 88 % in specifičnostjo 32 % (p < 0,005). Dokazali smo tudi statistično značilno povezanost stopnje UTD P s specifičnimi uropatijami (refluksna, obstrukcijska, idiopatska) (?2-test, p < 0,001), pojavnostjo okužbe sečil (?2-test, p = 0,003), potrebo po antibiotični zaščiti (?2-test, p < 0,001), potrebo po kirurškem zdravljenju (?2-test, p < 0,001), stopnjo spontane resolucije (?2-test, p < 0,001) in časom do le-te (Log-rank test, p = 0,011), medtem ko nismo dokazali povezanosti stopnje UTD P z ledvično funkcijo ob koncu sledenja; vsi bolniki so imeli ob koncu sledenja (mediani čas spremljanja 24 mesecev (IQR – 12–48 mesecev)) normalno ledvično funkcijo. Sklepi: V prospektivnem delu raziskave smo dokazali možno uporabnost uNGAL-a iz enkratnega vzorca neinvazivno odvzetega urina v prvih dneh po rojstvu kot označevalca ledvične okvare pri novorojenčkih s prirojeno enostransko UTD. V drugem, retrospektivnem delu raziskave smo potrdili uporabnost in zanesljivost klasifikacijskega sistema UTD A/P pri napovedi različnih kliničnih izhodov pri novorojenčkih s prirojeno eno- ali obojestransko UTD.

Keywords

nefrologija;Bolezni izločal;Disertacije;Okvare ledvic;Pediatrija;Novorojenčki;Prirojene nepravilnosti;Diagnostika;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UL MF - Faculty of Medicine
Publisher: [P. Bratina]
UDC: 616.6-053.2(043.3)
COBISS: 57513731 Link will open in a new window
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Other data

Secondary language: English
Secondary title: ǂThe ǂrole of urinary neutrophil gelatinase - associated lipocalin as a biomarker of subclinical kidney injury in newborns with congenital unilateral urinary tract dilatation
Secondary abstract: Background and purpose of the study: Urinary tract dilatation (UTD) is the most common genitourinary abnormality detected in routine prenatal ultrasound (US) examinations. Some UTDs can lead to kidney damage, which is the primary cause of chronic renal disease in children, so a timely diagnosis and treatment are mandatory. The currently most investigated and promising biomarker is neutrophil gelatinase-associated lipocalin in urine (uNGAL), which is of special importance in the neonatal population due to its non-invasive urine collection. The aim of our study was to evaluate its role in newborns with congenital unilateral UTD. US of the urinary tract, though, remains the first and safest investigation needed for the evaluation of fetuses and newborns with suspected UTD. We evaluated the ultrasound UTD A (antenatal)/P (postnatal) classification system, which has been in use since 2014, and its association with specific uropathies and different clinical outcomes. Patients and methods: In the first, prospective part of the study, we enrolled 38 term newborns with congenital unilateral UTD, while 38 healthy term newborns represented the control group. US of the urinary tract was done according to the UTD P classification system, and the uNGAL concentration was measured by chemiluminescence analysis. Some of the newborns needed additional workup to define the etiology of the congenital kidney disease (cystograms, scintigraphies, urography). The newborns in the study group were further divided into 2 subgroups regarding the urinary tract obstruction, and subsequently according to the need for surgical or conservative treatment. In the retrospective part of our study, we enrolled 126 newborns with unilateral UTD and 40 newborns with bilateral UTD. Data was obtained on UTD A and UTD P grades, as well as clinical events such as specific uropathies, urinary tract infections, the need for prophylactic antibiotic therapy or surgical intervention, the rate and timing of spontaneous resolution, and renal function outcome at the end of follow-up. Results: Our prospective study showed significantly higher uNGAL values in the study subgroup with urinary tract obstruction compared to the control group (median 15.9 (IQR 6.4-25.0) vs median 5.7 (IQR 3.6-11.1), Kruskal-Wallis test, p = 0.016). A receiver operating curve (ROC) analysis was performed to determine the diagnostic profile of uNGAL to detect newborns with urinary tract obstruction. The analysis showed sensitivity to be 89 % and specificity 51 % at the cut-off point of uNGAL 5.5 μg/L. The area under the curve (AUC) was 0.72 (95 % CI 0.59⠒0.85). Our retrospective study showed a statistically significant association of UTD A 2-3 with UTD P 2 or 3 (sensitivity 88 %, specificity 32 %, p < 0.005). We have also proven a statistically significant association between different UTD P grades and specific clinical outcomes: specific uropathies (reflux, obstructive, idiopathic) (χ2 test, p < 0.001), urinary tract infections rate (χ2 test, p = 0.003), antibiotic prophylactic treatment (χ2 test, p < 0.001), the need for surgical procedure (χ2 test, p < 0.001), spontaneous resolution rate (χ2 test, p < 0.001), and time to spontaneous resolution (log-rank test, p = 0.011). We did not find any association with renal function at the end of follow-up, as all our patients had normal renal function at the end of follow-up (the median follow-up time was 24 months (IQR 12⠒48)). Conclusions: The prospective part of our study confirmed the potential usefulness of uNGAL from a single urine sample in the first few days of life as a non-invasive marker of kidney injury in newborns with congenital unilateral UTD. In the second, retrospective part of our study, we confirmed the validity and utility of the UTD A/P classification system in predicting different clinical outcomes in newborns with congenital unilateral or bilateral UTD.
Secondary keywords: Bolezni sečil;Ledvične bolezni;Novorojenčki;Kongenitalne anomalije;Urinary tract;Congenital abnormalities;Acute kidney injury;Etiology;Urine;Biomarkers;Lipocalins;Neutrophils;Infant, newborn;Neonatology;Data analysis;Statistics and numerical data;Retrospective studies;Prospective studies;Sečila;Akutna ledvična okvara;Etiologija;Urin;Biomarkerji;Lipokalini;Nevtrofilci;Novorojenček;Neonatologija;Analiza podatkov;Statistika;Retrospektivne študije;Prospektivne študije;Univerzitetna in visokošolska dela;
Type (COBISS): Dissertation
Study programme: 0
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. v Ljubljani, Medicinska fak.
Pages: XXVII, 81, [6] str.
ID: 12615425