| Sažetak | Uvod: Upala i oksidativni stres smatraju se centralnim netradicionalnim čimbenicima visokog kardiovaskularnog rizika u bolesnika sa zatajenjem bubrega. Katestatin, autokrini inhibitor otpuštanja kateholamina i produkti uznapredovale glikacije, AGEs (engl. advanced glycosilation endproducts), biljezi metaboličkog i oksidativnog stresa, potencijalno su važni čimbenici KV rizika u bolesnika liječenih hemodijalizom. Ciljevi istraživanja: Glavni ciljevi su bili utvrditi moguću razliku u koncentraciji serumskog katestatina kao i kardiovaskularnom riziku mjerenom tkivnim razinama AGEs između bolesnika liječenih HD-om i kontrolne skupine ispitanika. Sporedni ciljevi istraživanja su bili procijeniti odnos katestatina i AGEs sa značajnim kliničkim, antropometrijskim i laboratorijskim parametrima kao i odnos oba biomarkera sa zbrojevima nutritivnog i upalnog statusa u bolesnika liječenih HD-om, MIS (engl. malnutrition inflammation score) i DMS (engl. dialysis malnutrition score). Ispitanici i metode: U istraživanje je prema prethodno definiranim kriterijima uključen 91 ispitanik liječen HD-om. Prosječna dob bolesnika liječenih HD-om je bila 68 godina (±12,6), a medijan liječenja dijalizom je bio 4 godine (2,0-8,0). U kontrolnu skupinu uključeno je 70 zdravih ispitanika koji su po antropometrijskim značajkama bili usklađeni s ispitivanom skupinom. Svim uključenim ispitanicima su nakon anamneze i kliničkog pregleda napravljena antropometrijska mjerenja, izmjerene tkivne razine AGEs i uzorkovana krv za laboratorijsko testiranje. Rezultati: Plazmatske koncentracije katestatina (32,85±20,18 ng/mL prema 5,39±1,24 ng/mL, P<0,001) i AGEs (4,74±1,50 prema 2,38±0,57 AU, P<0,001) su bile značajno više u bolesnika na HD-i u usporedbi s kontrolnom grupom. Pronađena je značajna pozitivna korelacija koncentracije plazmatskog katestatina i AGEs s oba nutritivna zbroja za bolesnike na dijalizi (MIS i DMS). Razine AGEs su se pokazale značajno negativno povezane s ukupnim proteinima i biomarkerima metaboličkog profila LDL-kolesterolom, trigliceridima i indeksom tjelesne mase. Pronađena je značajna pozitivna povezanost između katestatina i AGEs (r=0,492, P<0,001) u bolesnika na HD-i. Nadalje, nakon njihove podjele na tercile prema razinama AGEs i dalje je postojala značajna razlika u vrijednostima serumskog katestatina između svake tercile (prva tercila: 21,50±15,05 ng/mL, druga tercila: 33,04±18,64 ng/mL, treća tercila 44,79±20,08 ng/mL, F=12,54; P<0,001). Multipla linearna regresijska analiza je pokazala da je plazmatski katestatin povezan s razinama AGEs, dobi i opsegom struka nakon prilagodbe za zbunjujuće faktore. Zaključci: Ovim istraživanjem je utvrđeno da su serumske koncentracije katestatina i razine tkivnih AGEs značajno više u bolesnika liječenih HD-om u odnosu na kontrolnu skupinu ispitanika bez bubrežne bolesti. Utvrđena je i značajna pozitivna povezanost katestatina s razinama AGEs u hemodijaliziranih. Povišeni KV rizik mjeren tkivnim razinama AGEs podcrtava njihovu prethodno poznatu univerzalnu patogenetsku ulogu u stanjima kronične upale neovisno o glikemiji. Povišeni serumski katestatin može imati ulogu u negativnoj povratnoj sprezi u stanjima hiperaktivacije simpatičkog živčanog sustava poput kroničnog renokardijalnog sindroma i kao imunomodulatorni, antioksidativni i protuupalni peptid u kompleksnoj patofiziologiji zatajenja bubrega. Značajna pozitivna povezanost katestatina i AGEs sa zbrojevima pothranjenosti i upale na HD-i može značiti da su oba istraživana biomarkera povezana s ubrzanom aterosklerozom. Potrebna su longitudinalna multicentrična istraživanja koja će definirati njihovu međusobnu ulogu, uzročno-posljedične odnose i važnost u KV ishodima u bolesnika liječenih HD-om. |
| Sažetak (engleski) | Introduction: Inflammation and oxidative stress are considered central non-traditional factors of high cardiovascular risk in patients with renal failure. Catestatin, an autocrine inhibitor of catecholamine release, and advanced glycosylation endproducts (AGEs), markers of metabolic and oxidative stress, are potentially important CV risk factors in patients treated with hemodialysis. Objectives: The main objectives were to determine the possible difference in the concentration of serum catestatin as well as the cardiovascular risk measured by tissue levels of AGEs between patients treated with HD and the control group of subjects. The secondary objectives of the research were to evaluate the relationship between catestatin and AGEs with significant clinical, anthropometric and laboratory parameters, as well as the relationship of both biomarkers with sums of nutritional and inflammatory status in patients treated with HD, MIS and DMS. Materials and methods: According to previously defined criteria, 91 subjects treated with HD were included in the research. The average age of patients treated with HD was 68 years (±12.6), and the median of dialysis treatment was 4 years (2.0-8.0). The control group included 70 healthy subjects whose anthropometric characteristics matched the study group. After anamnesis and clinical examination, anthropometric measurements were taken, tissue levels of AGEs were measured, and blood was sampled for laboratory testing. Results: Plasma concentrations of catestatin (32.85±20.18 ng/mL vs. 5.39±1.24 ng/mL, P<0.001) and AGEs (4.74±1.50 vs. 2.38±0.57 AU, P<0.001) were significantly higher in HD patients compared to the control group. A significant positive correlation was found between the concentration of plasma catestatin and AGEs with both nutritional totals for dialysis patients (MIS and DMS). AGEs levels were shown to be significantly negatively associated with total proteins and metabolic profile biomarkers LDL-cholesterol, triglycerides and body mass index. A significant positive correlation was found between catestatin and AGEs (r=0.492, P<0.001) in HD patients. Furthermore, after dividing them into terciles according to the levels of AGEs, there was still a significant difference in serum catestatin values between each tertile (first tertile: 21.50±15.05 ng/mL, second tertile: 33.04±18.64 ng/mL mL, third tercile 44.79±20.08 ng/mL, F=12.54; P<0.001). Multiple linear regression analysis showed that plasma catestatin was associated with AGEs, age and waist circumference after adjustment for confounding factors. Conclusions: This study found that serum catestatin concentrations and tissue AGEs levels were significantly higher in patients treated with HD compared to the control group of subjects without kidney disease. A significant positive association of catestatin with AGEs levels in hemodialysis patients was also determined. The increased CV risk measured by tissue levels of AGEs underlines their previously known universal pathogenetic role in chronic inflammatory conditions independent of glycemia. Elevated serum catestatin may play a role in negative feedback in states of hyperactivation of the sympathetic nervous system such as chronic renocardial syndrome and as an immunomodulatory, antioxidant and anti-inflammatory peptide in the complex pathophysiology of kidney failure. The significant positive association of catestatin and AGEs with the sums of malnutrition and inflammation on HD may mean that both investigated biomarkers are associated with accelerated atherosclerosis. Longitudinal multicenter studies are needed to define their mutual role, cause-effect relationships and importance in CV outcomes in patients treated with HD. |
