Prediktori nepovoljnih kardiovaskularnih događaja u različitim stadijumima hronične bolesti bubrega
Predictors of Adverse Cardiovascular Events in Different Stages of Chronic Kidney Disease
Докторанд
Stopić, BojanМентор
Dimković, NadaЧланови комисије
Medić Brkić, BranislavaDekleva Manojlović, Milica
Savić-Vujović, Katarina
Ležaić, Višnja
Метаподаци
Приказ свих података о дисертацијиСажетак
Hronična bolest bubrega (HBB) je bitan faktor koji doprinosi povećanju sveukupnog
morbiditeta i mortaliteta u grupi nezaraznih bolesti, a ujedno je prepoznata kao snažan i nezavisan
faktor rizika koji doprinosi nastanku kardiovaskularnih bolesti (KVB). Teški kardiovaskularni (KV)
događaji predstavljaju oko 50% uzroka svih smrtnih ishoda u populaciji bubrežnih bolesnika. KV
bolesti istovremeno predstavljaju i grupu bolesti koje značajno utiču na povećanje troškova koji se
izdvajaju za prevenciju, lečenje i rehabilitaciju bubrežnih bolesnika. KVB su posledica delovanja
velikog broja faktora rizika poput tradicionalnih i netradicionalnih tj. uremija specifičnih faktora rizika
pri čemu su svi bili predmet velikog broja istraživanja čiji rezultati nisu mogli da objasne nepovoljan
KV ishod bubrežnih bolesnika. To je zahtevalo ispitivanje velikog broja kliničkih, radioloških i
biohumoralnih prediktora pogotovu u ranim fazama bubrežnih bolesti kada su preventivne mere
najdelotvornije, tj. u bo...lesnika sa klirensom kreatinina ispod 60 ml/min/1,73m2. Među ispitivanim
potencijalnim prediktorima ističu se biomarkeri inflamacije (Interleukin 18 - IL-18), oksidativnog
stresa (Ischemia modified albumin - IMA; superoksid dizmutaza - SOD), akutnog oštećenja bubrega (
Kidney injury molecule-1 – KIM-1; Neutrophil gelatinase-associated lipocalin - NGAL) i
mikroribonukleinske kiseline (specifična mikroRNK-133a). Našom studijom želeli smo da ispitamo
povezanost tradicionalnih i faktora rizika vezanih za HBB, primenjene terapije i novijih, ređe
ispitivanih biomarkera sa nastankom incidentnih KV događaja kod bubrežnih bolesnika, a ujedno i da
definišemo potencijalne prediktore KV obolevanja i ukupnog mortaliteta u HBB počevši od stadijuma
3a (jačina glomerulske filtracije – JGF manja od 60 ml/min/1,73m2).
Materijal i metode: Studija je dizajnirana kao longitudinalna studija praćenja u trajanju od 18 meseci
tokom koje je registrovan svaki novonastali KV događaj. U studiju su uključeni bolesnici koji se prate,
leče ili dijaliziraju na Kliničkom odeljenju za nefrologiju i metaboličke poremećaje sa dijalizom „ Prof.
dr Vasilije Jovanović, Kliničko bolničkog centra Zvezdara.“ Takođe, u studiju su kao kontrola
uključeni zdravi ispitanici, zdravstveni radnici zaposleni na pomenutom odeljenju. Ukupno je
uključeno 87 bolesnika i 8 zdravih kontrola. Navedeni ispitanici raspoređeni su u pet grupa: grupa
hemodijaliznih (HD) bolesnika (N=24); grupa bolesnika stadijuma 4 HBB (eJGF 29-15 ml/min)
(N=21); grupa bolesnika stadijuma 3b HBB (eJGF 44-30 ml/min) (N= 23); grupa bolesnika stadijuma
3a HBB (eJGF 59-45 ml/min) (N=19); kontrolna grupa zdravih osoba (N= 8). Na početku studije i
posle 12 meseci praćenja urađen je ehokardiosonografski pregled bolesnika. Na početku studije uzete
su standardne laboratorijske analize i biomarkeri inflamacije (IL-18), oksidativnog stresa (SOD, IMA),
akutnog oštećenja bubrega (KIM-1, NGAL) i mikroRNK-133a. Dobijeni rezultati su poređeni između
grupa bolesnika sa i bez KV događaja, sa i bez hipertrofije leve komore (HLK), sa i bez napredovanja
HBB i između preživelih i preminulih bolesnika. Takođe, ispitan je i uticaj najčešće primenjivane
terapije (ACE inhibitori, sartani, antiagregansi, kalcijumski antagonisti, agensi stimulacije eritropoeze)
na dobijene vrednosti biomarkera, kao i korelacija biomarkera sa standardnim laboratorijskim
analizama, ehokardiosonografskim parametrima i faktorima rizika.
Rezultati: U našoj ispitivanoj populaciji bolesnika najčešći uzroci nastanka HBB bili su hipertenzivna
nefroangioskleroza (50,6%) i dijabetesna nefropatija (34,5%). Tokom 18 meseci praćenja primećen je
najveći morbiditet kod bolesnika petog stadijuma HBB (45,9%) a potom i četvrtog (21,6%) i 3b
(24,3%) stadijuma što je u skladu sa ranijim KDIGO (The Kidney Disease: Improving Global
Outcomes) argumentom da incidenca KV bolesti raste sa padom JGF ispod 60 ml/min/1,73m2...
Chronic kidney disease (CKD) is an important factor that contributes to the increase of
overall morbidity and mortality in the group of non-communicable diseases, and it is also recognized as
a strong and independent risk factor that contributes to cardiovascular diseases (CVDs). Severe
cardiovascular (CV) events account for 50% of all deaths in the CKD population. At the same time, CV
diseases represent a group of diseases that significantly increase the costs allocated for the prevention,
treatment, and rehabilitation of kidney patients. CVDs are a consequence of the action of a large
number of risk factors among which are traditional and non-traditional, i.e. uremia specific. These risk
factors have been the subject of a large number of studies whose results could not explain the
unfavorable CV outcome of CKD patients. Therefore, valid studies about clinical, radiological, and
biohumoral predictors are of particular importance, especially in the early stages of renal disease i.e. in...
patients with creatinine clearance below 60 ml/min/1.73m2 when preventive measures are most
effective. Among potential predictors of adverse CV outcome are biomarkers of inflammation
(Interleukin 18 - IL-18), oxidative stress (Ischemia modified albumin-IMA; Superoxide dismutase-
SOD), acute kidney injury (Kidney injury molecule-1 - KIM-1; Neutrophil gelatinase-associated
lipocalin-NGAL), and microribonucleic acids (specific microRNA-133a). In our study, we aimed to
examine the relationship between traditional and CKD-related risk factors, applied therapy, and newer,
less frequently studied biomarkers with the occurrence of incidental CV events in renal patients. In
addition, we tried to define potential predictors of CV disease and total mortality in patients starting
from 3a stage of CKD ( glomerular filtration rate - GFR below 60 ml/min/1.73m2).
Material and methods: The study was designed as a longitudinal follow-up study lasting 18 months
during which each newly emerged CV event was registered. The study included 87 patients who were
monitored, treated or dialyzed at the Clinical Department of Nephrology and Metabolic Disorders with
dialysis "Prof. Dr. Vasilije Jovanović”, Clinical Hospital Center Zvezdara. Also, eight healthy
employees at the same department were included as a control group. All subjects were divided into five
groups: group of hemodialysis (HD) patients (N=24); groups of CKD patients stage 4 (eGFR 29-
15ml/min, N=21); group of CKD patients stage 3b (eGFR 44-30 ml/min, N=23); group of CKD
patients with stage 3a (eGFR 59-45 ml/min, N=19) and control group of healthy individuals (N=8). At
the beginning of the study and after 12 months of follow-up, an echocardiosonographic examination
was performed. Standard laboratory analyzes and biomarkers of inflammation (IL-18), oxidative stress
(SOD, IMA), acute kidney damage (KIM-1, NGAL) and microRNA-133a were taken at the beginning
of the study. The obtained results were analyzed depending on the CKD stage, newly diagnosed CV
events, presence of left ventricular hypertrophy (LVH), presence of CKD progression, and outcome
(survival). Also, the influence of the most frequently used therapy (ACE inhibitors, sartans, antiplatelet
agents, calcium antagonists, erythropoiesis stimulating agents) on the obtained values of biomarkers
was examined, as well as the correlation of biomarkers with standard laboratory analysis,
echocardiosonographic parameters and risk factors.
Results: In our study population, the most common causes of CKD were hypertensive
nephroangiosclerosis (50.6%) and diabetic nephropathy (34.5%). During 18 months of follow-up, the
highest morbidity was observed in patients with stage five CKD (45.9%) and then in patients with stage
four (21.6%) and 3b (24.3%), which is consistent with the previous KDIGO (The Kidney Disease:
Improving Global Outcomes) argument that the incidence of CV disease increases with a drop in GFR
below 60 ml/min/1.73 m2...