Influence of deceased donor corticosteroid treatment on kidney transplant outcome

Uvod: Nedovoljan broj raspoloživih organa za transplantaciju je posledica nedovoljne identifikacije potencijalnih moždano mrtvih davaoca u jedinicama intenzivnog lečenja i nedovoljne konverzije potencijalnih u aktuelne davaoce iz medicinskih i organizacionih razloga. Moždana smrt ima brojne posledice kao što su hemodinamski poremećaji, hormonski disbalans i inflamacija, što sveukupno utiče na kvalitet organa i ishod transplantacije. Hipoperfuzija organa donora ima za posledicu ishemijsko oštećenje i oksidativni stres, što povećava učestalost odložene funkcije alografta (OFA). Zbog povećane ekspresije citokina, adhezivnih molekula i antigena tkivne histokompatibilnosti, nastale inflamatorne promene organa donora utiču na povećanje učestalosti akutnih odbacivanja (AO) posle transplantacije. Zbog prevazilaženja ovih poremećaja, primenjuju se različite terapijske opcije kod donora, koje su važan deo strategije za popravljanje kvaliteta organa i ishoda transplantacije. Ciljevi istraživanja: Sa ciljem održavanja aktivnosti programa kadaverične transplantacije bubrega u Kliničkom centru Srbije ispitivali smo uticaj primene indikatora efikasnosti programa kadaverične transplantacije bubrega u periodu 2010- 2012. Pored toga, ispitivali smo efikasnost primene metil-prednizolona (MP) na hemodinamiku i bubrežnu funkciju davaoca, kao i učestalost OFA, AO i funkciju presađenog bubrega do kraja prve godine od transplantacije. Uzimajući u obzir povezanost moždane smrti, oksidativnog stresa i inflamacije, određivali smo serumsku koncentraciju 8-hidroksi 2-deoksi guanozina (8-OH-dG), trombospondina-1 (TSP-1) i nuklearnog faktora kapa B (NF-κB) kod donora organa posle dijagnoze moždane smrti i njihove kasnije implikacije kod primaoca. Metode: Studija je prospektivna interventna i opservaciona sprovedena je u Centralnoj aseptičnoj jedinici intenzivne nege Urgentnog Centra Kliničkog centra Srbije i Centru za transplantaciju bubrega Kliničkog Centra Srbije u periodu 2010-2013. godine. U periodu istraživanja smo analizirali tri grupe indikatora efikasnosti programa kadaverične transplantacije koji se odnose na potencijal za donaciju organa, organizacione nedostatke i ukupnu efikasnost programa...Introduction: Shortage of organs available from brain dead donors is attributed to the insufficient reporting of potential donors as well as to low conversion rates of potential donors into actual donors due to medical and organisational issues. Brain death has numerous consequences, including hemodynamic disorders, hormonal imbalance and inflammation, which together influence organ quality and consequently transplantation outcome. Hypoperfusion of donor organs leads to ischemic lesions and also increases oxidative stress, which raises the frequency of delayed graft function (DGF). Due to enhanced expression of cytokines, adhesion molecules and tissue histocompatibility antigens, subsequent inflammatory changes in donor organs increase the rate of acute rejection (AR) after transplantation. With the aim of overcoming these disorders donors are subject to various therapy options that are an important part of the strategy for improvement of organ quality and transplantation outcome. Objective: With aim to maintain deceased donor kidney transplant program, we assessed the impact of indicators of program effectiveness application in Clinical center of Serbia, between 2010–2012. In adition, we examined the efficiency of methylprednisolone (MP) applied to potential donors on donor hemodinamics and kidney function, as well as frequency of DGF, AR and kidney allograft function during the first posttransplant year. Considering the link between brain death, oxidative stress and inflammation, we measured the serum concentration of 8-hydroxy 2-deoxy guanosine (8-OH-dG), thrombospondin-1 (TSP-1) and nuclear factor kappa B (NF-κB) in organ donors after diagnosed brain death, as well as their further implications in recipients. Method: Prospective interventional and observational study was conducted in Central aseptic intensive care unit, Emergency center, Clinical center of Serbia and Kidney transplant center, Clinical center of Serbia. Deceased donor kidney transplant program involved 172 potential kidney donors that were identified between 2010-2012. Brain death was confirmed in 163 patients. We conducted an analysis of an effectiveness indicators of deceased donor kidney transplant program. Three groups of indexes presenting potential for donation, areas of improvement and global effectiveness indicators were used..