Réka P. Szabó

Oxidation of hemoglobin by lipid hydroperoxide associated with low-density lipoprotein (LDL) and increased cytotoxic effect by LDL oxidation in heme oxygenase-1 (HO-1) deficiency

Heme-catalyzed oxidation of low-density lipoprotein (LDL) is one of the relevant mechanisms involved in LDL modification. We previously revealed a substantial oxidation of plasma hemoglobin to methemoglobin and a subsequent heme-catalyzed LDL oxidation generating moieties toxic to endothelium in heme oxygenase-1 (HO-1)-deficiency in human. Drawing upon our previous observation we posited a pathway for oxidation of plasma hemoglobin in the HO-1-deficient child involving LDL-associated lipid hydroperoxide. In support, LDL-associated lipid hydroperoxide oxidized ferrohemoglobin to methemoglobin--known to readily release its heme moieties--in a dose-dependent manner. Repeated heme exposure of the child s LDL further increased its lipid hydroperoxide content within min leading to additional cytotoxic effect on endothelium. Both cytotoxicity and HO-1 inducing ability of the oxidized LDL were strongly dependent on its lipid hydroperoxide content. We wondered if cells of the HO-1-deficient patient were prone to oxidative damage arising from heme-mediated oxidation of LDL. Indeed, we found elevated cytotoxicity induced by heme-catalyzed oxidation of LDL in lymphoblastoid cells derived from the HO-1-deficient patient. We conclude that oxidation of hemoglobin to methemoglobin by LDL-associated lipid hydroperoxide and increased sensitivity of cells of the HO-1-deficient child to stress of oxidized LDL might contribute to the vascular disorders reported earlier.

Eredményeink a teljes jogú Eurotransplant-tagság óta. A Debreceni Vesetranszplantációs Központ tapasztalatai

Absztrakt Bevezetes: A Debreceni Egyetemen 1991-ben vegeztek el az első veseatultetest. Hazank 2013-ban csatlakozott az Eurotransplanthoz. Celkitűzes: A szerzők elemeztek a tapasztalatokat. Modszer: 2008. januar 1. es 2013. augusztus 31. kozott (A csoport = 163) es 2013. szeptember 1. es 2015. oktober 22. kozott vegzett cadavervese-atultetesek (B csoport = 90) adatait elemeztek. Eredmenyek: Az elődonorok aranya 3,5%-rol 9,1%-ra nőtt. 2013 ota a recipiensek 25%-a 60 evesnel idősebb, a >30 kg/m2 testtomegindex aranya 31%-ra, a diabetesesek aranya ketszeresere emelkedett. Az ureteroneocystostomia mellett bevezetesre kerult a veg az oldalhoz ureteroureteralis anastomosis. Indukcios kezeles mellett az akut rejectios epizod jelentősen csokkent (34%-rol 8%-ra). A technikai szovődmenyek aranya nem valtozott. A bakterialis fertőzesek aranya csokkent (41%-rol 33%-ra). Az 1, 3 es 5 eves veseallograft-tulelesek 86,6%, 85% es 82,7%, valamint 88%, 84% es 84% voltak a ket csoportban. Kovetkeztetesek: Az extended criteri...

Prognosis of dialysed patients after kidney transplant failure

Background/Aims: Patients with a failed kidney transplant represent a unique, high-risk chronic kidney disease population that is increasing in number, and may be sub-optimally managed. Our aim was to compare the survival of patients with failed allografts to patients with native kidney failure and to assess whether their survival is affected by the graft resection. Methods: Kaplan-Meier and Cox-regression survival analyses were performed on the data of 57 patients with graft failure and of 123 transplant-naive haemodialysed patients. Results: After adjustment for age and gender, there was no statistically significant difference in the mortality of patients in the two groups. The 43 patients, who had a transplanted kidney nephrectomy had a statistically not significant survival benefit over non-nephrectomised patients (age and gender adjusted hazard ratio: 0.56 95 % confidence interval: 0.24-1.58, p-value: 0.18). Conclusion: Elective graft resection is a safe, effective alternative for both the treatment and the prevention of the chronic inflammatory state associated with a failed kidney transplant.

Cardiovascular Screening and Management Among Kidney Transplant Candidates in Hungary.

INTRODUCTION Cardiovascular disease is a major cause of morbidity and mortality in end-stage renal disease patients on dialysis and the most common cause of death in the immediate post-transplantation period. The aim of our study was to describe a novel approach of cardiovascular screening and management of dialysis patients evaluated for the transplant waiting list. METHODS Twenty-eight patients with end-stage renal disease put on the waiting list between July 2013 and July 2014 were subjected to a prespecified cardiovascular screening protocol utilizing noninvasive and/or invasive tests. Patients were subsequently divided into 3 strata in terms of their estimated cardiovascular risk. Each of these groups were then prescribed interventions aiming to improve their cardiovascular condition. RESULTS According to our prespecified protocol of cardiovascular screening studies, 15 (54%) patients were identified as low, 5 (18%) as intermediate, and 8 (28%) as high risk. Four (14%) patients were current smokers. In the low-risk group, we initiated a patient education program involving counseling on regular exercise such as swimming or cycling to improve their functional capacity. In the high-risk group revascularization was done in 5 cases (63%), including 3 percutaneous transluminal coronary angioplasties (PTCA) with stents for single-vessel disease, and coronary artery bypass graft surgeries (CABG) for triple-vessel disease in 2 cases. In the medium-risk group medical management was opted for, including introduction of beta-blockers, inhibitors, statins, and ezetimibe, as well as efforts to optimize anemia management, indices of bone-mineral disease, and fluid status. CONCLUSION In our regional transplant program, we introduced a comprehensive multidisciplinary approach to treat potential transplant candidates according to cardiovascular risk stratification based on a prespecified screening protocol. Further studies are needed to correlate this novel strategy with post-transplantation outcomes.

Validation of a prognostic function for renal transplant recipients in Hungary

BACKGROUND Renal transplantation (RTx) is the treatment of choice for end-stage renal failure, but these patients are increasingly older and have additional conditions leading to high mortality after RTx. The aim of our study was to validate a Spanish prognostic function that estimates survival in Hungarian renal transplant recipients. METHODS We estimated the 5-year survival of 339 patients who received a cadaver kidney between 1 January 1991 and 15 September 2004 at the Center of Transplantation, Medical and Health Science Centre, University of Debrecen, and who were followed up until death or 15 September 2009. To assess the calibration, we used the Hosmer-Lemeshow test to compare the observed and expected numbers of deaths in the deciles of the predicted 5-year risk of death. Additionally, we applied a smoother to obtain a nonparametric estimate of the 5-year cumulative incidence of death by robust locally weighted regression. To describe the discriminative power of the function, we calculated the area under the receiver operating characteristic (ROC) curve. RESULTS The range of the estimated 5-year risk of death was 7%-100%. In the high-risk groups, the function severely overestimated the risk of death. The area under the ROC curve was 0.65 (95% confidence interval, 0.60-0.70). CONCLUSIONS The poor performance of the prognostic function studied limits its clinical applicability.

Donorszelekciós kritériumok vizsgálata a debreceni veseátültetési programban

Absztrakt Bevezetes: A donorszervhiany, a donorok eletkoranak novekedese es a tarsbetegsegek gyakoribba valasa arra osztonzi a transzplantalokozpontokat, hogy olyan donorvesek elfogadasat is merlegeljek, amelyeket korabban elutasitottak volna. A donorszelekcios kriteriumok segithetnek ennek eldonteseben. Celkitűzes: A kulonboző kriteriumok hasznossagat illetően nincs egyseges allaspont, ezert a szerzők megvizsgaltak az expanded criteria donor, a deceased donor score es a kidney donor risk index donorszelekcios kriteriumok hatasat a posztoperativ vesefunkciora es grafttulelesre. Modszer: Oteves intervallumban 205 donor parametereinek es 138 veseatultetes kimenetelenek retrospektiv elemzeset vegeztek el. Eredmenyek: Az expanded criteria donor rendszer szerint optimalisnak velemenyezett donorok negyede a magas kockazatu csoportba kerult a deceased donor score alapjan. A magas kockazatu csoportokban rosszabb volt a műtet utani graftfunkcio. A deceased donor score segitsegevel tovabb lehetett bontani a magas k...

Chlamydia pneumoniae okozta infektív endocarditis májtranszplantációt követően

Absztrakt Az infektiv endocarditis a szervtranszplantalt betegek koreben aluldiagnosztizalt korkep. A korokozok spektruma kulonbozik az atlagpopulaciot erintőtől. A szerzők az 58 eves nőbetegben atipusos korokozo altal okozott, atipusos megjelenesű infektiv endocarditis eredmenyes kezeleseről szamolnak be. A betegnel alkoholos majcirrhosis talajan kialakult majelegtelenseg miatt 2000. februarban majatultetest vegeztek. Egy evvel a majatultetest kovetően kronikus hepatitis B-virus-fertőzest allapitottak meg, es a beteg antiviralis kezelesben reszesult. Kalcineurintoxicitas miatt veseelegtelenseg alakult ki, ezt kovetően a beteg 2007 juliusaban vesepotlo kezelesre szorult. 2013 novembereben rovid ideig tarto afazia jelentkezett. A transoesophagealis echokardiografia az aortabillentyűn vegetaciot talalt, a magneses rezonancias vizsgalat agyi embolisatiot mutatott ki. A laboratoriumi vizsgalatok enyhen emelkedett C-reaktiv protein- es normalis prokalcitoninszinteket igazoltak, verkepeben leukopenia volt latha...The incidence of infective endocarditis is underestimated in solid organ transplant recipients. The spectrum of pathogens is different from the general population. The authors report the successful treatment of a 58-year-old woman with infective endocarditis caused by atypical microorganism and presented with atypical manifestations. Past history of the patient included alcoholic liver cirrhosis and cadaver liver transplantation in February 2000. One year after liver transplantation hepatitis B virus infection was diagnosed and treated with antiviral agents. In July 2007 hemodialysis was started due to progressive chronic kidney disease caused by calcineurin toxicity. In November 2013 the patient presented with transient aphasia. Transesophageal echocardiography revealed vegetation in the aortic valve and brain embolization was identified on magnetic resonance images. Initial treatment consisted of a 4-week regimen with ceftriaxone (2 g daily) and gentamycin (60 mg after hemodialysis). Blood cultures were all negative while serology revealed high titre of antibodies against Chlamydia pneumoniae. Moxifloxacin was added as an anti-chlamydial agent, but neurologic symptoms returned. After coronarography, valvular surgery and coronary artery bypass surgery were performed which resulted in full clinical recovery of the patient.