Title Primjena takrolimusa u osoba s transplantacijom bubrega Title (english) Use of tacrolimus in patients with kidney transplantation Author Branimir Krtalić Mentor Nikolina Bašić Jukić (mentor)Committee member Željko Kaštelan (predsjednik povjerenstva)Committee member Jasenka Markeljević (član povjerenstva)Committee member Nikolina Bašić Jukić (član povjerenstva)Granter University of Zagreb Defense date and country 2018-07-13, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Takrolimus je kalcineurinski inhibitor koji je važan dio imunosupresivnog protokola nakon transplantacije bubrega. Prvi put je odobren 1997. godine za prevenciju akutnog odbacivanja bubrežnog presatka, a u posljednjem desetljeću postao je kalcineurinski inhibitor izbora. Kliničke studije su pokazale da je takrolimus bolji od ciklosporina u pogledu prevencije akutnog odbacivanja i preživljenja presatka. Iako je prelazak s ciklosporina na takrolimus poboljšao ishode bubrežne transplantacije i
uklonio nuspojave ciklosporina, takrolimus ima i mnoge svoje neželjene učinke poput nefrotoksičnosti, neurotoksičnosti, povećanog rizika od posttransplantacijske šećerne bolesti i poremećaja elektrolita. Još jedna nuspojava je BK poliomavirus nefropatija koja se češće javlja u pacijenata koji su na terapiji takrolimusom, nego kod onih koji su na terapiji ciklosporinom. Kako bi se ublažile ove nuspojave, prihvaćene su različite strategije koje nastoje smanjiti izloženost takrolimusu bez gubitka pozitivnih učinaka na akutno odbacivanje. Jedna od njih je kombinacija takrolimusa s drugim imunosupresivima poput mikofenolat mofetila, azatioprina i kortikosteroida. Nesuradljivost u uzimanju terapije je čest i važan uzrok propadanja bubrežnog
presatka. Osmišljene su nove formulacije kako bi se poboljšala suradljivost pacijenta. Formulacija s produljenim otpuštanjem koja se uzima jednom dnevno (Advagraf) može poboljšati suradljivost i dugoročne ishode u usporedbi s formulacijom koja se brzo otpušta i uzima dva puta dnevno. Razvijena je nova formulacija s produljenim otpuštanjem (Envarsus) i dokazana je jednaka učinkovitost u sprječavanju akutnog odbacivanja, ali otvoreno ostaje pitanje ima li manje nuspojava od Advagrafa.
Također ostaje pitanje hoće li doći do razvoja novog lijeka koji će zamijeniti takrolimus ili će se eventualna nova kombinacija postojećih lijekova pokazati kao bolje rješenje.
Abstract (english) Tacrolimus is a calcineurin inhibitor used as an integral part of an immunosuppressive regimen after kidney transplantation. It was first approved in 1997 for prevention of acute rejection in kidney transplantation, and in the last decade it has become the calcineurin inhibitor of choice. Clinical trials have shown tacrolimus to be superior to cyclosporine, another calcineurin inhibitor, in terms of acute rejection prevention and allograft survival. Although switching from cyclosporine to tacrolimus has improved outcomes of kidney transplantation and eliminated cyclosporine's adverse effects, tacrolimus itself has many undesirable effects such as nephrotoxicity, neurotoxicity, post-transplant diabetes mellitus, and electrolyte disorders. Another concerning adverse effect of tacrolimus is BK polyomavirus associated nephropathy which occurs more frequently in those patients who use tacrolimus than those who use cyclosporine. To alleviate these concerning adverse effects, several strategies have been adopted that aim at minimizing exposure to tacrolimus, while keeping its positive effect on acute rejection. One of these strategies includes combining tacrolimus with other immunosuppressive agents, such as mycophenolate mofetil, azathioprine, or corticosteroids. Nonadherence is a common and major cause of kidney transplantation failure. To improve adherence to therapy, new formulations of the drug have been developed. Once-daily prolonged release formulations (Advagraf) of tacrolimus may improve adherence and long-term outcomes compared to twice-daily immediate release formulations. A new extended-release formulation (Envarsus) has been developed and it has been shown to be equally effective in acute rejection prevention, but it remains to be seen if it has fewer adverse effects than Advagraf. It also remains to be seen if a new and better drug will be developed that will replace tacrolimus’ role, or if maybe a new combination of some familiar drugs will be shown as a better solution.
Keywords
transplantacija
kalcineurinski inhibitori
takrolimus
Keywords (english)
chronic kidney disease
calcineurin inhibitors
tacrolimus
Language croatian URN:NBN urn:nbn:hr:105:028415 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2019-03-14 10:20:58
