doktorska disertacija
Evgenija Homšak (Author), Robert Ekart (Mentor), Robert Ekart (Thesis defence commission member), Dušanka Mičetić-Turk (Thesis defence commission member), Pika Meško-Brguljan (Thesis defence commission member)

Abstract

Izhodišča: Bolniki s kronično ledvično boleznijo (KLB) in še posebej dializni bolniki (KLB 5D) so izpostavljeni visokemu tveganju za razvoj srčnega popuščanja in različnih življenjsko ogrožajočih dogodkov, vključno s srčno-žilnimi (SŽ) neželenimi dogodki in smrtjo. Zato je izrednega pomena tudi pravočasna napoved teh dogodkov oziroma opredelitev bolnikov, ki so izpostavljeni večjemu tveganju. Na osnovi dosedanjih kliničnih in biokemijskih parametrov pogosto pravočasna napoved neželenih dogodkov in smrti pri teh bolnikih, še posebej pri skupini dializnih bolnikov, ni mogoča. Zato so intenzivne raziskave usmerjene v iskanje novih potencialnih prognostičnih označevalcev. Namen: Namen naše raziskave je bil proučiti vlogo topnega receptorja ST2 (sST2) kot potencialnega prognostičnega označevalca hospitalizacij, SŽ in smrti iz vseh vzrokov pri bolnikih s KLB in posebej pri dializnih bolnikih (KLB 5D) ter njegov pomen primerjati z dosedanjimi biokemijskimi označevalci srčnega popuščanja in ledvićnih bolezni (NT-proBNP, TnI). Glede na specifično populacijo dializnih bolnikov je bilo smiselno proučiti tudi njegove značilnosti, zlasti vpliv hemodiafiltracijskega postopka (HDF) na njegovo serumsko koncentracijo pred in po opravljeni HDF. Zato smo v naši raziskavi poskušali potrditi dve hipotezi: (1) sST2 je biokemijski označevalec, katerega koncentracija v serumu je zaradi svoje molekularne strukture neodvisna od HDF in (2) sST2 kot novejši prognostični označevalec omogoča pri bolnikih z različno stopnjo KLB identificirati bolnike, ki imajo večje tveganje za razvoj SŽ dogodkov, hospitalizacijo in smrt. Metode: V raziskavo smo vključili 91 bolnikov (57 moških, 34 žensk) s KLB 1. do 5. stopnje in 123 bolnikov (75 moških, 48 žensk) s KLB 5D stopnje na nadomestnem zdravljenju s HDF. Vsem bolnikom smo ob vstopu v raziskavo odvzeli vzorce krvi za določitev hematoloških in koncentracije biokemijskih parametrov, vključno s sST2, NT-proBNP in TnI. Bolnike smo vključevali 12 mesecev, nato smo jih ob naročenih kontrolnih pregledih spremljali najmanj 18 mesecev. Beležili smo morebitne SŽ zaplete, hospitalizacije in smrt. Za ugotavljanje vpliva HDF na koncentracije biokemijskih označevalcev smo iz proučevane populacije izbrali 55 naključnih bolnikov s KLB 5D, ki smo jim izmerili serumske koncentracije pred in po HDF in statistično ovrednotili nastale spremembe. Statistično analizo pridobljenih podatkov smo izvedli z uporabo programske opreme Medcalc® (Ostend, Belgija). Razlike koncentracij pred/po HDF za oba parametra pri posameznih bolnikih smo testirali s parnim T-testom ter jih izrazili v odstotkih. Bolnike s KLB 1-5 in s KLB 5D smo na začetku raziskave razdelili, glede na začetno vrednost koncentracije sST2, v skupino z nizkim sST2 (sST2 <35 ng/ml) ali skupino z visokim sST2 (sST2 ≥35 ng/mL). Za oceno prognostične vrednosti serumskih označevalcev smo uporabili Kaplan-Meierjevo analizo preživetja in regresijsko Cox analizo. Z ROC (receiver operating characteristic) analizo smo določili in primerjali prognostično moč NT-proBNP, sST2 in njune kombinacije. Kot statistično značilna pomembna vrednost je bila P<0.05. Zaključki: V naši raziskavi smo uspeli potrditi obe zastavljeni hipotezi. Naši rezultati potrjujejo, da je sST2 neodvisen od ledvične funkcije in od postopka HDF, saj njegove serumske koncentracije niso statistično značilno različne glede na stopnjo KLB in se ne spremenijo po procesu HDF. Prav tako smo potrdili, da je sST2 kot označevalec fibroze in remodelacije sposoben opredeliti bolnike s KLB 1-5 in KLB 5D, glede na njihovo tveganje za razvoj življensko ogrožajočih dogodkov, hospitalizacije in smrti. Njegova dodana vrednost se kaže v primeru kombinirane rabe več označevalcev, kjer skupaj z NT-proBNP omogoča boljšo oceno tveganja kot kateri koli od posamičnih označevalcev. Ta ugotovitev potrjuje, da je sST2 neodvisen prognostičen označevalec, ki se odziva in nastaja preko drugih patofizioloških mehanizmov kot NT-proBNP.

Keywords

sST2;kronična ledvična bolezen;prognostični označevalec;hemodiafiltracija;disertacije;Bolezni izločal;Disertacije;Dializno zdravljenje;Zapleti;Napovedni dejavniki;Bolezni krvožilja;biokemijski vidik;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UM - University of Maribor
Publisher: E. Homšak]
UDC: 616.61-008.6-78:615.35:577.1(043.3)
COBISS: 512906808 Link will open in a new window
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Other data

Secondary language: English
Secondary title: Soluble receptor ST2 as prognostic marker in patients with Chronic kidney disease
Secondary abstract: Background: Patients with Chronic Kidney Disease (CKD) and especially the end-stage renal disease (ESRD) patients are prone to severe heart failure (HF) and to several life-threatening events. Therefore, the ability to assess disease prognosis and the risk of short-term events or death is of great importance. Unfortunately, we still don't have a good prognostic marker for the population of CKD and especially fort he ESRD patients, particularly to predict CV events or HF. The role of soluble ST2 (sST2) as a potential new prognostic marker in ESRD patients is not yet known. Aim: The first objective of this study was to evaluate the impact of hemodiafiltration (HDF) process on the concentration of the potential prognostic marker sST2 in a group of ESRD patients, that are prone to develop CV diseases and life-threatening events. The main important aim of our study was to assess the prognostic value of sST2 for prediction of hospitalization, CV and all-cause death in CKD 1-5 and ESRD patients on HDF and compare it with other established prognostic marker for HF and renal disease (NT-proBNP and TnI). According to these aims we established two hypothesizes to be evaluated: (1) sST2 serum concentration is according to its molecular characteristics not affected by HDF and (2) sST2 could be a potentially useful prognostic marker, capable of stratifying CKD 1-5 and ESRD patients at high risk for life-threatening events, hospitalization, and death. Methods: 91 patients with CKD 1-5 and 123 ESRD patients on HDF were prospectively followed up from the date of the retrieved samples for sST2/NTproBNP measurement until their death or at least 18 months. All patients were followed up to record episodes of hospitalization due to cerebrovascular, cardiovascular and other events. For the evaluation of the impact of HDF on the prognostic markers sST2, TnI and NT-proBNP were measured in the serum samples of 55 ESRD patients before and after HDF. Patients were divided into a low sST2 group (<35 ng/mL) or a high sST2 group (≥35 ng/mL) according to their measured sST2 concentration at the start of the study. Statistical analysis was performed using the Medcalc® software (Ostend, Belgium). For the evaluation of a difference between measured NT-proBNP and sST2 before and after HDF, we have used paired T-test. Kaplan-Meier survival curves, Cox regression model and ROC analyses were used in statistical analysis for evaluation of the prognostic value. P<0.05 was used as the level of significance. Conclusions: In our study, we were able to confirm both hypotheses. Our results confirm that sST2 is independent of the renal function and the HDF process since its serum concentrations are not statistically significantly different from the KLB stage and do not change after the HDF process. Namely, we found a statistically significant difference between measured values of NT-proBNP before/after HDF, whereby for sST2 this difference was not statistically significant. We also confirmed that sST2 as a marker of fibrosis and remodeling is capable of identifying patients with KLB 1-5 and KLB 5D, considering their risk of developing life-threatening events, hospitalization, and death. sST2 added value is reflected also in the case of the combined use of multiple markers, which, together with NT-proBNP, provide a better risk assessment than any of the individual markers. This finding confirms that sST2 is an independent prognostic marker that responds and is generated through other pathophysiological mechanisms than NT-proBNP. Therefore, in combination and with the use of multiple markers, sST2 adds value to a more complex and effective patient monitoring, thereby enabling a better assessment of the risk of death of patients with KLB and, in particular, patients on substitution treatment with HDF.
Secondary keywords: sST2;chronic kidney disease;prognostic marker;hemodiafiltration;
Type (COBISS): Dissertation
Thesis comment: Univ. v Mariboru, Medicinska fak.
Pages: 93 str.
ID: 11002514