Changes in serum pigment epithelium-derived factor levels after kidney transplantation in patients with end-stage renal disease.

BACKGROUND: Pigment epithelium-derived factor (PEDF) is a serin protease inhibitor and a potent inhibitor of angiogenesis. Its serum level has significant associations with metabolic parameters. However, little is known about the association between PEDF levels and lipid parameters in renal transplanted (TX) patients. Therefore, our aim was to investigate the relationship between PEDF level and lipid parameters in TX patients. METHODS: Seventy TX patients (47 males, 23 females, mean age 51.7 ± 12.4 years) and 34 healthy controls were enrolled. We examined the serum creatinine, C-reactive protein, fasting glucose and lipid parameters right before, then 1 and 6 months after TX. High-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) activities were measured spectrophotometrically. Lipoprotein subfractions were determined by Lipoprint. PEDF and oxidized low-density liporotein (oxLDL) levels were measured by ELISA. RESULTS: Before transplantation, patients had had a significantly higher PEDF level compared to control subjects (p < 0.001). One month after transplantation, their PEDF level decreased significantly reaching the healthy controls' level, and this lower level was maintained during the 6 months follow-up period as well. The initial oxLDL level was significantly higher, while PON1 activities were significantly lower in the patient group compared to the control group. We found a significant positive correlation between PEDF and total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, oxLDL and small HDL subfraction; while negative correlations were found between PEDF and mean LDL size and large HDL subfraction during the entire follow-up period. CONCLUSION: PEDF may play an important role in the increased oxidative stress and enhanced atherogenesis in renal transplant patients.

[Diabetology and solid organ transplantation]. / Diabetológia és szervátültetés.

Diabetes increases the risk of different kidney diseases. The most important is diabetic nephropathy, however, ischemic kidney disease, chronic pyleonephritis and papilla necrosis may also develop. The prognosis of diabetic nephropathy has improved recently, however, it is still the primary cause of dialysis and transplantation. Cardiovascular diseases predict mostly mortality in diabetic patients, however, cerebrovascular insults and peripheral obstructive arterial diseases necessitating lower limb amputations are also important. Diabetic retinopathy is almost always present with diabetic nephropathy. Diabetic neuropathy may also develop, furthermore vascular complications often combine. All these urge complex workup, follow-up and early treatment. If transplantation is indicated, preemptive operation should be preferred, and living donation shows the best outcomes. Different forms of carbohydrate disorder may occur after transplantation: new-onset diabetes or diabetes known before transplantation may progress. Renal transplantation with pancreas transplantation may be indicated in type 1 diabetes with end-stage diabetic nephropathy, most often simultaneously. This may result in normoglycemia and insulin-independence and the progression of other complications may also halt. Transplant associated hyperglycemia occurs in most of the patients early, however, it is often transitory. Despite stabilization of the patient and of the immunosuppressive therapy, about one third of the patients may develop posttransplant diabetes. Insulin secretion disorder is the primary cause, but insulin resistance is also needed. Insulin administration may help, however, other antidiabetics can also be useful. Carbohydrate metabolism should be checked in both cadaveric and living donors. The authors make an attempt to summarize the above conditions with Hungarian relevance as well. Orv Hetil. 2018; 159(46): 1930-1939.

[Antibody-mediated rejection: challenge of the treatment in kidney transplantated patients]. / Antitestmediált rejekció: kihívás a veseátültetett betegek kezelésében.

Antibody-mediated rejection (ABMR) is one of the factors affecting the long-term graft survival after kidney transplantation (KT). Two kidney transplant centres (University of Debrecen and University of Pécs) followed up their data of cadaveric KTs that had been performed between 2013 and 2017, and reviewed the literature. There were 454 KTs in the mentioned period, 18 cases (4%) were recognised as ABMRs. Biopsy has been performed in all cases. 22% were primary, and 78% retransplanted patients. The average age was 51.2 ± 6 years. ABMR occurred 15.4 ± 22.1 months after KT. Histology showed C4d positivity in 39% of the cases. The treatment was steroid bolus + intravenous immunoglobulin (IVIG) + plasma exchange (PE) in 16 cases, rituximab was additionally given in 5 cases. 47.4% of the patients are alive with a functioning graft, four (21%) died, and 31% of the patients had a graft loss due to ABMR. ABMR is a dangerous complication after KT. Diagnostic criteria has been unclear for years. Gold standard is the histology, however, accelerated ABMR may occur even in C4d negative cases. The exposed group includes young, retransplanted patients, having a preformed donor-specific antibody (DSA), and receiving a graft from an EC donor. The occurrence of de novo DSA and the kinetics of mean fluorescence intensity (MFI) of existing ones can be a signal for the risk of an ABMR. The effectiveness of rituximab is not proven, there is a lack of long-term controlled trials for new drugs. Our results of over 40% recovery is an extensively good result. Orv Hetil. 2018; 159(46): 1913-1929.

[Analysis of donor scoring systems in a single Hungarian transplant centre]. / Donorszelekciós kritériumok vizsgálata a debreceni veseátültetési programban.

INTRODUCTION: To ease organ shortage many transplant centres developed different donor scoring systems, however, a general consensus among clinicians on the use of these systems does not still exist. AIM: The aim of the authors was to analyse the effect of expanded criteria donor, deceased donor score and kidney donor risk index on postoperative kidney function and graft survival. METHOD: Analysis of the characteristics of 138 kidney transplantations and 205 donors in a retrospective study of a five-year period. RESULTS: There was a trend towards rejecting donors in higher risk groups; 22.7% of standard criteria donors belonged to the high risk group of deceased donor score. Graft function was worse in high risk patients. High risk donors can be divided due to the use of deceased donor score. Patients with the highest risk had worse graft function and survival. CONCLUSIONS: With the use of these scoring systems grafts with favourable outcome can be selected more precisely.

[First outcomes, since being full member of Eurotransplant. A single center experience of cadaveric kidney transplantation]. / Eredményeink a teljes jogú Eurotransplant-tagság óta. A Debreceni Vesetranszplantációs Központ tapasztalatai.

INTRODUCTION: The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant. AIM: The authors retrospectively compared the trends. METHOD: Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015). RESULTS: The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age. Recipients with body mass index above 30 kg/m(2) increased from 12% to 31%. Prevalence of diabetes among recipients rose twofold. Uretero-neocystostomy was used during period A (99%) while in period B end to side uretero-ureteral anastomosis has also gained popularity (68%). In 2013 the authors introduced routine use of induction treatment. Acute rejection rate decreased from 34% to 8%. The rate of surgical complications did not change. Acute bacterial infections decreased from 41% to 33%. Cumulative renal allograft 1, 3 and 5 year survival rates were 86.6%, 85% and 82.7% in group A vs. projected rates 88%, 84% and 84% in group B, respectively. CONCLUSIONS: Despite the growing proportion of expanded criteria donors, the authors were able to maintain a low incidence of delayed graft function and a favorable graft survival. Since 2013 the authors introduced treatments for acute humoral rejection according to international standards.

[Infective endocarditis caused by Chlamydia pneumoniae after liver transplantation. Case report]. / Chlamydia pneumoniae okozta infektív endocarditis májtranszplantációt követoen.

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.

Management of antibody-mediated rejection after kidney transplantation in our clinical practice / Az antitestmediált rejekció diagnosztikája és kezelése gyakorlatunkban.

Összefoglaló. Bevezetés: Az antitest közvetítette kilökodés a graftvesztés gyakori oka a vesetranszplantáltak körében. Célkituzés: Célul tuztük ki, hogy ismertetjük a centrumunkban biopsziával igazolt humorális kilökodéssel rendelkezo betegeknek a kezelésre (standard kezelés: plazmaferézis, immunglobulin, rituximab) adott válaszát, valamint hogy vizsgáljuk a proteinuria grafttúlélésre kifejtett hatását és azt, hogy ezt a DSA-tól függetlenül teszi-e. Vizsgáltuk az eGFR-, a DSA-MFI-értéknek az antirejekciós terápia hatására bekövetkezo változásait is. Módszer: 85 beteg retrospektív analízisét végeztük el. A szövettani elemzésben a Banff-klasszifikációt vettük alapul. A csoportok összehasonlításához kategorikus változók esetén a Fisher-féle egzakt próbát, folyamatos változók esetén a Kruskal-Wallis-próbát használtuk. Eredmények: A biopsziával igazolt humorális rejekciós csoportba (ABMR-csoport) 19, a DSA-pozitív csoportba 14, a DSA-negatív csoportba 52 beteget választottunk be. A DSA-érték az ABMR-csoportban 61,16%-kal csökkent, a DSA-pozitív csoportban 42,86%-kal redukálódott (Fisher-féle egzakt: p = 0,1). Az ABMR-csoportban 9 betegnek a jelentos, 4-nek a nephroticus mértéku proteinuriája csökkentheto volt (az ABMR-csoport 68%-a). A legjobb grafttúlélés a legalacsonyabb fehérjeürítésnél adódott. Az antirejekciós terápiát követoen készült biopsziákban: a glomerulitis, az interstitialis gyulladás, az arteritis mértéke csökkent az antihumorális kezelés hatására, azonban krónikus elváltozások jelentek meg. Következtetés: Az ABMR-csoportban az antirejekciós terápiát követoen a fehérjeürítés monitorizálása javasolt, hiszen becsülheto vele a grafttúlélés. Orv Hetil. 2021; 162(26): 1029-1037. INTRODUCTION: Antibody-mediated rejection is a common cause of graft loss among kidney transplant recipients. OBJECTIVE: We aimed to describe the response of patients with biopsy-proven humoral rejection to treatment (standard treatment: plasmapheresis, immunoglobulin, rituximab) in our center. We also analyzed the effect of proteinuria on graft survival and whether this effect is independent of donor-specific antibodies (DSAs). Changes of eGFR and level of DSA following rejection treatment were examined. METHOD: In this study, laboratory data of 85 patients were analysed. Histological analysis was based on the Banff classification. Fisher's exact test was used for statistical analysis, and Kruskal-Wallis test was used to compare patient groups per variable. RESULTS: Data from 85 patients were processed retrospectively. 19 patients were selected for the biopsy-confirmed humoral rejection group (ABMR group), 14 for the DSA-positive group, and 52 for the DSA-negative group. DSA titer decreased by 61.16% in the ABMR group after treatment and by 42.86% in the DSA-positive group (Fisher's exact test: p = 0.1). In the ABMR group, significant nephrotic proteinuria in 4 patients and severe proteinuria in 9 patients were reduced (68% of ABMR group). The patients with the lowest protein excretion had the best graft survival. In biopsies performed after antirejection therapy, the extent of glomerulitis, interstitial inflammation, arteritis decreased with antihumoral treatment, but chronic lesions appeared. CONCLUSION: Following treatment of biopsy-proven ABMR, reduction of proteinuria predicts graft survival and should be monitored as an important factor-predicting prognosis. Orv Hetil. 2021; 162(26): 1029-1037.

Early postoperative effects of kidney transplantation on the cardiovascular system in our clinical practice / A vesetranszplantáció korai posztoperatív hatásai a szív- és érrendszeri betegségekre klinikai gyakorlatunkban.

Összefoglaló. Bevezetés: Mind a dializált, mind a veseátültetett betegek körében vezeto haláloknak számít a cardiovascularis megbetegedés. E mögött foképp bal kamrai hypertrophia, volumenterheltség, következményes szívritmuszavar, szívbillentyu-elégtelenség, fokozott atherosclerosis állhat. Célkituzés: Célunk a vesetranszplantáció hatásának vizsgálata a bal kamra pumpafunkciójára, a szívritmuszavarokat kiváltó és meghatározó tényezokre és a vitiumokra nézve. Módszerek: A 2014. december 20. és 2018. június 21. közti idointervallumban, a Debreceni Egyetem Szervtranszplantációs Tanszékén felnott betegeken végzett veseátültetéseket vizsgáltuk retrospektív analízissel (n = 184). Vesetranszplantációt megelozoen, illetve azt követoen 6 és 12 hónappal az echokardiográfiás, a laboratóriumi és a gyógyszeres terápiás értékeket tanulmányoztuk. A statisztikai elemzéseket khi-négyzet-próbával, Fisher-féle egzakt teszttel és Kruskal-Wallis-féle varianciaanalízissel (ANOVA) végeztük (szignifikancia: p<0,05). Eredmények: A bal kamra végsystolés tágassága az átültetés elott 34,67 mm volt, míg a 6 hónapos eredmény 31,82 mm, a 12 hónapos 32,68 mm volt (p = 0,01). Átültetés elott a stroke prevalenciája 7,87% volt, míg a beavatkozás után nem fordult elo szélütés (p<0,001). Transzplantáció hatására a bal pitvari átméro (43,68 mm; 41,59 mm; 41,00 mm; p = 0,0417) és a káliumszint (4,98 mmol/l; 4,49 mmol/l; 4,49 mmol/l; p = 0,01) szignifikáns változást igazolt. Mutét elott II. fokú mitralis regurgitatiót észleltünk 10,7%-nál, mely 4,3%-ra, majd 2,1%-ra csökkent (p = 0,03). Transzplantációt megelozoen a billentyumeszesedés elofordulása diabetesesek között 45% (p = 0,20), 6 hónap múlva 46,7% (p = 0,018), 12 hónap múlva 60,0% (p = 0,024) volt. Következtetés: Transzplantáció után a bal pitvari átméro, a végsystolés bal kamrai átméro regrediál, csökken a pitvari ritmuszavarok kialakulásának gyakorisága. A mitralis regurgitatio közepesen súlyos fokainál szignifikáns javulást, a diabeteses populáción belül szignifikáns emelkedést tapasztaltunk a meszes billentyuk számát tekintve. Orv Hetil. 2021; 162(26): 1052-1062. INTRODUCTION: Among the population suffering from end-stage renal failure and the population after kidney transplantation, the leading reason of death is cardiovascular triggered by left ventricular hypertrophy, volume overload, consecutive arrhythmias, valvular insufficiency and increased artherosclerosis. OBJECTIVE: This study was aimed at examining the effect of kidney transplantation on pump function of the left ventricle, arrhythmic substrates and valvular heart diseases. METHODS: At the Division of Organ Transplantation, University of Debrecen, we carried out a retrospective data analysis of adult patients (n = 184) who had kidney transplantation in the period between December 2014 and June 2018. Preoperatively and, then, postoperatively (at 6 and 12 months) we studied the echocardiographic parameters, the laboratory results. Statistical analyses were performed using the chi-square/Fisher's exact test and Kruskal-Wallis analysis of variance (ANOVA) test. The results were regarded significant if p<0.05 was found. RESULTS: Preoperatively the end-systolic diameter of the left ventricle was 34.67 mm, whereas 6 and 12 months later these values were 31.82 mm and 32.68 mm (p = 0.01). The prevalence of stroke was 7.87% preoperatively; there was no stroke detected postoperatively (p<0.001). The impact of transplantation on the left atrial diameter (43.68 mm; 41.59 mm; 41.00 mm; p = 0.04) and seral potassium level (4.98 mmol/l; 4.49 mmol/l; 4.49 mmol/l; p<0.01) showed significant improvement. Before transplantation, grade 2 mitral regurgitation was observed in 10.7% of the patients, whereas it reduced to 4.3%, then to 2.1% 6 and 12 months postoperatively (p = 0.03). Preoperative valvular calcification was detected in 45% of the diabetic study population (p = 0.20), 6 and 12 months later, in 46.7% (p = 0.018) and 60.0% (p = 0.024). CONCLUSION: After transplantation, the left atrial and the end-systolic diameter of the left ventricle regrediated, decreasing the frequency of arrhythmic episodes. The number of the middle grade mitral valve regurgitation decreased and the calcification among diabetic population increased significantly. Orv Hetil. 2021; 162(26): 1052-1062.