Metabolické aspekty regionální citrátové antikoagulace během kontinuální náhrady funkce ledvin

• Název práce v češtině: Metabolické aspekty regionální citrátové antikoagulace během kontinuální náhrady funkce ledvin
• Název v anglickém jazyce: Metabolic aspects of regional citrate anticoagulation during continuous renal replacement therapy
• Klíčová slova: akutní poškození ledvin, kontinuální náhrada funkce ledvin, hemodiafiltrace, hemofiltrace, regionální citrátová antikoagulace, citrát, laktát, kalcium, magnezium, deficit magnezia, ionizované magnezium, laktátový pufr
• Klíčová slova anglicky: acute kidney injury, continuous renal replacement therapy, hemodiafiltration, hemofiltration, regional citrate anticoagulation, citrate, lactate, calcium, magnesium, magnesium deficiency, ionized magnesium, lactate buffer
• Akademický rok vypsání: 2015/2016
• Typ práce: disertační práce
• Jazyk práce: čeština
• Ústav: Klinika anesteziologie, resuscitace a intenzivní medicíny 1. LF UK a VFN (11-00700)
• Vedoucí / školitel: doc. MUDr. Martin Balík, Ph.D.
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 02.11.2015
• Datum zadání: 02.11.2015
• Datum potvrzení stud. oddělením: 02.11.2015
• Datum a čas obhajoby: 31.03.2025 12:00
• Místo konání obhajoby: Děkanát 1. LF UK, místnost č. 2.108
• Datum odevzdání elektronické podoby: 26.02.2025
• Datum proběhlé obhajoby: 31.03.2025
• Předmět: Obhajoba dizertační práce (B90002)
• Oponenti: doc. MUDr. Marek Nalos, Ph.D.

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Předběžná náplň práce

Regionální citrátová antikoagulace (RCA) během kontinuální náhrady funkce ledvin (CRRT) je u kriticky nemocných pacientů preferována pro nižší riziko krvácení a spolehlivou prevenci srážení krve v mimotělním okruhu. Přestože je tato metoda široce využívána, některé její metabolické aspekty zůstávaly dosud nedostatečně popsány, zejména systémový přísun bioenergetických substrátů obsažených v používaných roztocích a vliv citrátové chelatace na homeostázu magnezia.
Cílem disertační práce bylo podrobně zmapovat tyto metabolické důsledky RCA-CRRT, kvantifikovat bilanci substrátů (citrátu, laktátu, glukózy) a iontů (magnezia, kalcia) a ověřit možnosti optimalizace terapie úpravou složení náhradních roztoků. Metodologicky je práce založena na třech navazujících klinických studiích. V první studii byla detailně analyzována bilance bioenergetických substrátů při různých režimech a roztocích RCA-CRRT. Druhá studie sledovala dynamiku ionizovaného magnezia a kalcia, přičemž se zaměřila na kvantifikaci systémových ztrát potencovaných citrátem. Ve třetí studii byl testován nový laktátový bezkalciový náhradní roztok vyvinutý námi pro potřeby RCA-CRRT, jehož složení bylo optimalizováno s využitím zjištění prvních dvou studií.
Bylo prokázáno, že dávkování citrátu a použití roztoků s vyšším obsahem laktátu a glukózy může aditivním způsobem výrazně navyšovat energetickou zátěž pacienta a vyžadovat individualizovanou nutriční strategii během RCA-CRRT. Zároveň se ukázalo, že standardní koncentrace magnezia v běžně používaných náhradních roztocích nezabraňuje jeho výrazně negativní bilanci. Nově navržený náhradní roztok prokázal schopnost efektivně předcházet metabolickým a iontovým dysbalancím, čímž představuje bezpečnou a klinicky relevantní alternativu pro RCA-CRRT.
Zjištění práce významně rozšiřují poznání o metabolických dopadech RCA-CRRT a poskytují podklady pro optimalizaci a individualizaci péče o kriticky nemocné pacienty.

Předběžná náplň práce v anglickém jazyce

Regional citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT) is preferred for critically ill patients due to its lower risk of bleeding and reliable prevention of extracorporeal circuit clotting. Despite its widespread use, certain metabolic aspects of this therapy have remained insufficiently described, particularly the systemic supply of bioenergetic substrates present in replacement solutions and the impact of citrate chelation on magnesium homeostasis.
The aim of this dissertation was to comprehensively investigate these metabolic effects of RCA-CRRT, quantify the balance of substrates (citrate, lactate, glucose) and ions (magnesium, calcium), and evaluate the potential for therapy optimization through modifications to replacement solution composition. Three consecutive clinical studies formed the methodological basis. The first study provided a detailed analysis of the bioenergetic substrate balance under different RCA-CRRT regimens and solutions. The second study explored ionized magnesium and calcium dynamics, with an emphasis on systemic losses potentiated by citrate. The third study tested a novel lactate-buffered calcium-free replacement solution we developed specifically for RCA-CRRT, with its composition optimized based on findings from the first two studies.
It was demonstrated that citrate dosing and the use of solutions with elevated lactate and glucose content can cumulatively provide significant increase in patient’s energy load, necessitating an individualized nutritional strategy during RCA-CRRT. Additionally, it was shown that standard magnesium concentration in commonly used replacement solutions does not prevent markedly negative magnesium balance. The newly formulated replacement solution effectively prevented both metabolic and ionic disturbances, presenting a safe and clinically relevant alternative for RCA-CRRT.
These findings considerably expand current knowledge of RCA-CRRT's metabolic impact and provide a foundation for optimizing and individualizing care for critically ill patients.