Prediktori nepovoljnih kardiovaskularnih događaja u različitim stadijumima hronične bolesti bubrega

Abstract

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 bolesnika 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...