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One of the most important possible complications determining long-term graft survival after kidney transplant is antibody-mediated rejection (ABMR). The criterion standard approach to recognize ABMR is currently the kidney biopsy with histopathologic analysis. However, this test has limitations because of difficulties in timing of sampling, the evaluability of histology because of the questionable representativeness of specimens, and the limited number of this intervention. Hence, new reliable, noninvasive biomarkers are required to detect the development of ABMR in time.In this study, we analyzed the clinical data of 45 kidney transplant patients (mean age of 44.51 years, 20 male and 25 female subjects). These participants were recruited into 5 subcohorts based on their clinical status, histologic findings, and level of donor-specific anti-HLA antibodies. Circulating microRNAs (miR-21, miR-181b, miR-146a, miR-223, miR-155, miR-150) in plasma samples were quantified by quantitative polymerase chain reaction and their levels were correlated with the clinical characteristics in different subgroups.The relative expression of plasma miR-155 (P = .0003), miR-223 (P = .0316), and miR-21 (P = .0147) were significantly higher in patients who had subsequent histology-approved ABMR with donor-specific anti-HLA antibody positivity (n = 10) than in the "triple negative" group (n = 21), and miR-155 showed the highest sensitivity (90%) and specificity (81%) to indicate ABMR development based on receiver operating characteristic analysis.According to our preliminary data, plasma miR-155, miR-21, and miR-223 can indicate the development of ABMR after kidney transplant in correlation with classic clinical parameters. However, future studies with larger number of participants are necessary to further evaluate the diagnostic properties of blood miRNAs in prediction of this life-threatening condition.

Összefoglaló. Bevezetés: A kis méretű vesedaganatok között lényegesen gyakoribbak a benignus elváltozások, és a kis malignus tumorok biológiai tulajdonságai is kedvezőbbek, mint a nagyobb daganatokéi. Célkitűzés: Szerzők a kis méretű vesetumorok tulajdonságait vizsgáltuk különböző alcsoportokban. Módszer: 2000. január 1. és 2015. január 1. között 1272 beteg esetén végeztünk műtétet vesedaganat miatt. Közülük 496 betegnek volt kis méretű vesetumora. A betegek átlagéletkora 59 ± 12 év volt. A betegeket a tumorméret alapján három csoportba osztottuk. Az 1. csoportban a daganat mérete ≤4 cm, a 2. csoportban ≤3 cm és a 3. csoportban ≤2 cm volt. Eredmények: Az eltávolított daganat nagysága átlagosan 29 ± 8 mm volt. A szövettan 418 esetben (84%) malignus, míg 78 alkalommal (16%) benignus elváltozást mutatott. A 2 cm-nél kisebb daganatoknál malignitás csak az esetek 73,2%-ában fordult elő. A malignus és a benignus tumorok méretében szignifikáns eltérés volt (p = 0,008). Rosszul differenciált daganat – grade 3. és 4. – az esetek 10,8%-ában, 14,4%-ában, illetve 20,7%-ában volt jelen, amikor a tumorméret kisebb mint 2 cm, 2,1–3 cm, illetve 3,1–4,0 cm volt. A vesecarcinomáknál az átlagosan 10 éves utánkövetési idő alatt progresszió az esetek 5,5%-ában fordult elő. Következtetés: A kis méretű vesetumor az összes vesedaganat 39%-át tette ki. Ezek nagy része malignus volt, és benignus elváltozás az esetek 16%-ában fordult elő. A malignitás előfordulása a 2 cm-nél kisebb tumoroknál volt a legalacsonyabb. A tumorméret szoros összefüggést mutatott a malignitás gyakoriságával és a daganat differenciáltságával. A kedvező patológiai és biológiai eredmények alapján a 2 cm alatti daganatoknál felmerül annak lehetősége, hogy esetükben az aktív követés vagy minimálisan invazív kezelés alkalmazása kerüljön előtérbe. Orv Hetil. 2021; 162(42): 1693–1697. Summary. Introduction: The incidence of benign lesions is more common in small renal masses (SRMs) and biological behavior of small malignancies is better compared to larger ones. Objective: The authors measured the characteristics of SRMs in different subgroups. Method: From January 1, 2000 to January 1, 2015, 1272 patients underwent surgery for renal tumors. In 496 of the 1272 cases, the patients had SRMs. The mean age of the patients was 59 ± 12 years. Based on the sizes, the SRMs were divided into three groups. The sizes of the renal tumors were ≤4 cm in Group 1, ≤3 cm in Group 2 and ≤2 cm in Group 3. Results: The mean diameter of the removed SRMs was 29 ± 8 mm. Histology confirmed renal cell carcinoma in 418 cases (84%), while benign tumor was present in 78 patients (16%). However, with the tumor size ≤2 cm, malignancy was detected in 73.2% of the cases. There was a significant difference in the sizes of the malignant and the benign masses (p = 0.008). Grade 3 or 4 tumors were present in 10.8%, 14.4% and 20.7% when the tumor size was ≤2 cm, 2.1 to 3 cm, and 3.1 to 4 cm in diameter, respectively. During the mean 10-year follow-up period, tumor progression was detected only in 5.5% of malignancies. Conclusion: In 39% of all cases, the patients had SRMs. The majority of SRMs were malignant, and benign lesion occurred only in 16% of the cases. The incidence of malignant tumors was the lowest when the size of SRMs was ≤2 cm. The size of the tumor was highly associated with probability of malignancy and tumor grading. Based on the favorable pathological and biological results in tumors below 2 cm, active surveillance or minimally invasive treatment could be the preferred management. Orv Hetil. 2021; 162(42): 1693–1697.

Duchenne muscular dystrophy (DMD) is the most common inherited muscle dystrophy. Patients are characterized by muscle weakness, gross motor delay, and elevated serum creatinine kinase (CK) levels. The disease is caused by mutations in the DMD gene located on the X chromosome. Due to the X-linked recessive inheritance pattern, DMD most commonly affects males, who are generally diagnosed between the age of 3–5 years. Here we present an ultra-rare manifestation of DMD in a female patient. Cytogenetic examination showed that she has a t(X;10)(p21.1;p12.1) translocation, which turned out to affect the DMD gene with one of the breakpoints located in exon 54 (detected by genome sequencing). The X-inactivation test revealed skewed X-inactivation (ratio 99:1). Muscle histology and dystrophin immunohistochemistry showed severe dystrophic changes and highly reduced dystrophin expression, respectively. These results, in accordance with the clinical picture and a highly elevated serum CK, led to the diagnosis of DMD. In conclusion, although in very rare cases, DMD can manifest in female patients as well. In this case, a balanced X-autosome reciprocal translocation disrupts the DMD gene and skewed X-inactivation leads to the manifestation of the DMD phenotype.

Összefoglaló. Bevezetés: Az antitest közvetítette kilökődés a graftvesztés gyakori oka a vesetranszplantáltak körében. Célkitűzés: Célul tűztük ki, hogy ismertetjük a centrumunkban biopsziával igazolt humorális kilökődéssel rendelkező 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 bekövetkező 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 jelentős, 4-nek a nephroticus mértékű proteinuriája csökkenthető volt (az ABMR-csoport 68%-a). A legjobb grafttúlélés a legalacsonyabb fehérjeürítésnél adódott. Az antirejekciós terápiát követően 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 követően a fehérjeürítés monitorizálása javasolt, hiszen becsülhető vele a grafttúlélés. Orv Hetil. 2021; 162(26): 1029–1037. Summary. 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.

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 μmol/L to 125 μmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.

BACKGROUND: The optimal timing of remote ischemic preconditioning (RIPC) in renal ischemia-reperfusion (I/R) injury is still unclear. We aimed to compare early- and delayed-effect RIPC with hematological, microcirculatory and histomorphological parameters. METHODS: In anesthetized male CrI:WI Control rats (n = 7) laparotomy and femoral artery cannulation were performed. In I/R group (n = 7) additionally a 45-minute unilateral renal ischemia with 120-minute reperfusion was induced. The right hind-limb was strangulated for 3×10 minutes (10-minute intermittent reperfusion) 1 hour (RIPC-1 group, n = 7) or 24 hour (RIPC-24 group, n = 6) prior to the I/R. Hemodynamic, hematological parameters and organs’ surface microcirculation were measured. RESULTS: Control and I/R group had the highest heart rate (p

Abstract: 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.

Összefoglaló. Bevezetés: Az antitest közvetítette kilökődés a graftvesztés gyakori oka a vesetranszplantáltak körében. Célkitűzés: Célul tűztük ki, hogy ismertetjük a centrumunkban biopsziával igazolt humorális kilökődéssel rendelkező 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 bekövetkező 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 jelentős, 4-nek a nephroticus mértékű proteinuriája csökkenthető volt (az ABMR-csoport 68%-a). A legjobb grafttúlélés a legalacsonyabb fehérjeürítésnél adódott. Az antirejekciós terápiát követően 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 követően a fehérjeürítés monitorizálása javasolt, hiszen becsülhető vele a grafttúlélés. Orv Hetil. 2021; 162(26): 1029-1037.Antibody-mediated rejection is a common cause of graft loss among kidney transplant recipients.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.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.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.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.

Összefoglaló. Bevezetés: A kis méretű vesedaganatok között lényegesen gyakoribbak a benignus elváltozások, és a kis malignus tumorok biológiai tulajdonságai is kedvezőbbek, mint a nagyobb daganatokéi. Célkitűzés: Szerzők a kis méretű vesetumorok tulajdonságait vizsgáltuk különböző alcsoportokban. Módszer: 2000. január 1. és 2015. január 1. között 1272 beteg esetén végeztünk műtétet vesedaganat miatt. Közülük 496 betegnek volt kis méretű vesetumora. A betegek átlagéletkora 59 ± 12 év volt. A betegeket a tumorméret alapján három csoportba osztottuk. Az 1. csoportban a daganat mérete ≤4 cm, a 2. csoportban ≤3 cm és a 3. csoportban ≤2 cm volt. Eredmények: Az eltávolított daganat nagysága átlagosan 29 ± 8 mm volt. A szövettan 418 esetben (84%) malignus, míg 78 alkalommal (16%) benignus elváltozást mutatott. A 2 cm-nél kisebb daganatoknál malignitás csak az esetek 73,2%-ában fordult elő. A malignus és a benignus tumorok méretében szignifikáns eltérés volt (p = 0,008). Rosszul differenciált daganat - grade 3. és 4. - az esetek 10,8%-ában, 14,4%-ában, illetve 20,7%-ában volt jelen, amikor a tumorméret kisebb mint 2 cm, 2,1-3 cm, illetve 3,1-4,0 cm volt. A vesecarcinomáknál az átlagosan 10 éves utánkövetési idő alatt progresszió az esetek 5,5%-ában fordult elő. Következtetés: A kis méretű vesetumor az összes vesedaganat 39%-át tette ki. Ezek nagy része malignus volt, és benignus elváltozás az esetek 16%-ában fordult elő. A malignitás előfordulása a 2 cm-nél kisebb tumoroknál volt a legalacsonyabb. A tumorméret szoros összefüggést mutatott a malignitás gyakoriságával és a daganat differenciáltságával. A kedvező patológiai és biológiai eredmények alapján a 2 cm alatti daganatoknál felmerül annak lehetősége, hogy esetükben az aktív követés vagy minimálisan invazív kezelés alkalmazása kerüljön előtérbe. Orv Hetil. 2021; 162(42): 1693-1697.The incidence of benign lesions is more common in small renal masses (SRMs) and biological behavior of small malignancies is better compared to larger ones.The authors measured the characteristics of SRMs in different subgroups.From January 1, 2000 to January 1, 2015, 1272 patients underwent surgery for renal tumors. In 496 of the 1272 cases, the patients had SRMs. The mean age of the patients was 59 ± 12 years. Based on the sizes, the SRMs were divided into three groups. The sizes of the renal tumors were ≤4 cm in Group 1, ≤3 cm in Group 2 and ≤2 cm in Group 3.The mean diameter of the removed SRMs was 29 ± 8 mm. Histology confirmed renal cell carcinoma in 418 cases (84%), while benign tumor was present in 78 patients (16%). However, with the tumor size ≤2 cm, malignancy was detected in 73.2% of the cases. There was a significant difference in the sizes of the malignant and the benign masses (p = 0.008). Grade 3 or 4 tumors were present in 10.8%, 14.4% and 20.7% when the tumor size was ≤2 cm, 2.1 to 3 cm, and 3.1 to 4 cm in diameter, respectively. During the mean 10-year follow-up period, tumor progression was detected only in 5.5% of malignancies.In 39% of all cases, the patients had SRMs. The majority of SRMs were malignant, and benign lesion occurred only in 16% of the cases. The incidence of malignant tumors was the lowest when the size of SRMs was ≤2 cm. The size of the tumor was highly associated with probability of malignancy and tumor grading. Based on the favorable pathological and biological results in tumors below 2 cm, active surveillance or minimally invasive treatment could be the preferred management. Orv Hetil. 2021; 162(42): 1693-1697.

Background and Aims Kidney diseases with heavy chain deposition are rare, including AHL amyloidosis also. The mutation/deletion of the constant domain (CH1/CH2) of the heavy chain causing high tissue affinity seems most likely in its pathogenesis. The very low serum level is responsible for the difficult diagnosis, which is often based on kidney biopsy or laser microdissection / mass spectrometry. Method Case study of a 76-year-old male patient, examined in January, 2019. Results Besides treatment for Ménière syndrome and benign prostatic hyperplasia there was no other important event in patient’s history. Significant proteinuria and microscopic haematuria were observed from May 2016, but eGFR was 70 ml/min/1,73 m2 at that time. By April, 2018 nephrotic range proteinuria (10 g/day) with full nephrotic syndrome developed. Screening tests for cancer were negative. Despite symptomatic treatment, half year later eGFR decreased to 27 ml/min/1,73 m2, therefore he was referred to nephrology. Serum protein electrophoresis verified IgG lambda (8,1 g/l) and free lambda (0,5 g/l) monoclonal light chains, and in addition the possibility of IgG heavy chain accumulation. Urine electrophoresis showed also IgG lambda (1720,1 mg/l), and free lambda light chain (552,1 mg/l) monoclonality. Serum free lambda and kappa light chain ratio was 0,06, complement serology was normal. Kidney biopsy was done, which showed IgG heavy and light chain restriction, Congo red stain positivity and apple green birefringence under the polarized microscope in the expanded mesangium, in the interstitium and along the tubular basement membrane and the blood vessels. The electron microscope detected fibrillary deposits (10 nm) in the same structures, therefore diagnosis of AHL amyloidosis was established. He had no extrarenal symptoms. Bone marrow aspiration flow cytometry verified 1,11% plasma cell accumulation, 93% of them had pathological immunphenotype. Bone marrow morphology assay showed 30-40% plasma cell infiltration, and chromosome assay detected monoallelic deletion of IgH and MAF and gains of 1q region, suggesting myeloma multiplex in the background of AHL amyloidosis. VCD (bortezomib-cyclophosphamide-dexamethason) treatment was started, so far he has received 8 cycles. He is asymptomatic, proteinuria decreased, kidney function stabilized, eGFR 23 ml/min/1,73 m2. Conclusion only about 20 cases of AHL amyloidosis have been reported in the literature so far. In the context of longstanding kidney failure with nephrotic syndrome, we should consider renal disease associated with plasma cell dyscrasia also. If case of an AHL amyloidosis caused by myeloma multiplex, effective anti-plasma cell therapy can improve the hematological and the renal outcome.

Background and Aims There are numerous studies on AAV, however, data describing the use of immunosuppressive treatment in AAV patients (pts) on chronic dialysis are limited. Most studies found that the incidence of infection is much higher than that of relapses (0.05-0.1 pt per year), suggesting that immunosuppression should be stopped after 3 months in pts with end-stage renal failure. Material, Method Retrospective analysis of immunosuppressive treatment in pts on chronic dialysis due to AAV. From 1995 to 2019 139 pts were diagnosed with AAV. Among them 38 patients (26 female, 12 male, mean age 58 years) needed chronic dialysis (>90 days) due to severe renal AAV (29), relapsing renal disease (6) or progressive CKD without active vasculitis (3). Results Microscopic polyangiitis was diagnosed in 20, granulomatosis with polyangiitis in 14, eosinophilic granulomatosis with polyangiitis in 4 cases. MPO-ANCA was more frequent than PR3-ANCA (23 vs 12), in one case both ANCAs were positive, and in two cases both were negative. The mean dialysis duration was 55 months (4–180 months). 18 pts (47%) had at least one relapse during the observation period. The mean age, the clinical diagnosis, the type of ANCA did not cause any difference, the dialysis time was longer in the relapsed pts group (72+/-38 vs. 40+/-29 months) compared to pts without relapse. High relapse rate was seen in 6 cases. Three patient had continuously high level of PR3-ANCA without relapse or any sign of disease. Relapses were treated mostly with combined therapy of corticosteroids and oral/intravenous cyclophosphamide followed by azathioprin maintenance therapy. Cortocosteroid alone was used in 7 pts, rituximab in five pts as maintenance therapy. Serious infection (needing hospital care) rate during any immunosuppressive treatment was 0.12 per patient-years. There were 12 deaths on dialysis, the median time to death was 61 months (range 3–132). The deaths rate was higher (9/18 vs. 4/20) in relapsed pts, 4 occurring during immunosuppressive treatment. Causes of deaths were cardiovascular (8), sepsis (3), malignancy (2 pts). Seven pts received kidney grafts, 15 pts remained on dialysis, but in three case dialysis could be discontinued after 16, 35 and 36 months. Conclusion Our study points to higher relapse rate and lower serious infection rate in AAV pts on chronic dialysis compared to previous studies. It seems reasonable to continue immunosuppression above 3 months in pts remaining on chronic dialysis. This approach may decrease the relapse rate preventing damage of other organs, allowing transplantation and in some pts recovery of renal function could be achieved.

Background Micro-rheological relations of renal ischemia-reperfusion (I/R) have not been completely elucidated yet. Concerning anti-inflammatory agents, it is supposed that sigma-1 receptor agonist N,N-dimethyl-tryptamin (DMT) can be useful to reduce I/R injury. Objective To investigate the micro-rheological and metabolic parameters, and the effects of DMT in renal I/R in rats. Methods In anesthetized rats from median laparotomy both kidneys were exposed. In Control group (n = 6) no other intervention happened. In I/R group (n = 10) the right renal vessels were ligated and after 60 minutes the organ was removed. The left renal vessels were clamped for 60 minutes followed by 120-minute reperfusion. In I/R+DMT group (n = 10) DMT was administered 15 minutes before the ischemia. Blood samples were taken before/after ischemia and during the reperfusion for testing hematological, metabolic parameters, erythrocyte deformability and aggregation. Results Lactate concentration significantly increased and accompanied with decreased blood pH. Enhanced erythrocyte aggregation and impaired deformability were observed from the 30th minute of reperfusion. In I/R+DMT group we found diminished changes compared to the I/R group (lactate, pH, electrolytes, red blood cell deformability and aggregation). Conclusions Metabolic and micro-rheological parameters impair during renal I/R. DMT could reduce but not completely prevent the changes in this rat model.

Background Chronic kidney disease (CKD) models are known to study pathophysiology and various treatment methods. Renal dysfunction could influence erythrocytes through several pathways. However, hemorheological and microcirculatory relation of CKD models are not completely studied yet. Objective To evaluate erythrocyte micro-rheology, microcirculatory and structural compensatory mechanisms in a rat model of CKD. Methods Female Sprague-Dawley rats were subjected to nephrectomy group (NG, n = 6) or sham-operated group (SG, n = 6). NG rats were subjected to 5/6 nephrectomy in two stages. In SG no intervention was made on kidneys. Hemorheological and hematological measurements were carried out after each stage, and 5 weeks after the last operation. Histological and microcirculatory studies were done on the remaining kidney and compared with sham rats. Results Serum creatinine increased in NG (p = 0.008), accompanied with decrease of red blood cell count (p = 0.028) and hemoglobin (p = 0.015). Erythrocyte aggregation parameters slightly increased in NG, while the elongation index didn't show significant changes. Microcirculation was intact in the remnant kidney of NG. However, in comparison with SG, the diameter of glomeruli increased significantly (p Conclusions Erythrocyte mass was influenced more than micro-rheological properties in this model. The main compensation mechanism was rather structural than at microcirculatory level.

Background Intestinal ischemia-reperfusion (I/R) is a potentially life-threatening situation and its pathomechanism is not fully understood yet. Objective To investigate the early micro-rheological, microcirculatory and morphological consequences of intestinal I/R in a rat model. Methods CD rats were anesthetized and subjected to Control (n = 7) or I/R (n = 7) groups. Left femoral artery cannulation and median laparotomy were performed. In the I/R group the superior mesenteric artery was clamped for 30 minutes. Blood samples were taken before (Base) and after the ischemia, at the 30th, 60th and 120th minutes of the reperfusion (R-30, R-60, R-120). Hematological parameters, erythrocyte deformability and aggregation were determined. On the jejunum, the liver and the right kidney laser Doppler flowmetry tests were completed. At the end of experiment histological samples were taken. Results Hematocrit, leukocyte and platelet counts increased during the reperfusion. Erythrocyte deformability worsened versus Control. All erythrocyte aggregation index values of I/R group increased gradually. Intestinal microcirculatory blood flux units (BFU) did not recover completely after ischemia, at R-30 liver BFU values were lower, and kidney values decreased by R-120. Histology showed signs of I/R injury. Conclusions Micro-rheological parameters may show early and significant deterioration during the reperfusion that might contribute further to microcirculatory alterations.

Background Ischemia reperfusion (I/R) injury remains one of the most challenging fields of organ transplantation. It is highly associated with the use of expanded criteria donors that might conclude to delayed graft function or early or late graft failure. Objective To investigate the metabolic, microcirculatory parameters, and histologic changes under the effect of N,N-dimethyltryptamine (DMT) in a renal I/R model in rats. Method In 26 anesthetized rats both kidneys were exposed. In the control group (n = 6) no other intervention happened. In 20 other animals, the right renal vessels were ligated, and after 60 minutes the right kidney was removed. The left renal vessels were clamped for 60 minutes then released, followed by 120 minutes of reperfusion. In the I/R group (n = 10), there was no additive treatment, while in I/R + DMT group (n = 10) DMT was administered 15 minutes before ischemia. Blood samples were taken, laser Doppler measurement was performed, and both kidneys were evaluated histologically. Results Microcirculation (blood flux units [BFU]) diminished in all groups, but remarkably so in the I/R + DMT group. This group compensated better after the 30th minute of reperfusion. The control and I/R + DMT groups had similar BFUs after 120 minutes of reperfusion, but in the I/R group BFU was higher. Tubular necrosis developed in the I/R and I/R + DMT groups too; it was moderated under DMT effect, and severe without. Histologic injuries were less in I/R + DMT Group compared to non-treated animals. Conclusion Histologic changes characteristic to I/R injuries were reversible and microcirculation recovered at the end of 120 minutes reperfusion under the administration of DMT. DMT can be used for renoprotection in kidney transplantation.

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.Absztrakt: A veseátültetés utáni hosszú távú túlélést befolyásoló tényezők egyike az antitestmediált rejekció (ABMR). A szerzők áttekintést nyújtanak az ABMR jelenleg ismert diagnosztikai és kezelési hátteréről. A Debreceni és a Pécsi Egyetem transzplantációs központjainak együttműködése alapján áttekintik a 2013 és 2017 közötti időszakban végzett veseátültetések után kialakult korai ABMR-eseteket és a releváns közleményeket. A két központban összesen 454 veseátültetés történt. ABMR-diagnózist összesen 18 esetben állítottunk fel (4%). Minden esetben perkután biopszia történt. A betegek közül 22% volt primer, 78% retranszplantált eset. Az átlagéletkor 51,2 ± 6 év volt. A veseátültetés után az ABMR diagnózisáig eltelt idő 15,4 ± 22,1 hónap volt. A C4d-pozitivitást 7 esetben sikerült igazolni, ami az összes ABMR-eset 39%-a. Összesen 16 betegnél történt szteroidbolus + intravénás immunglobulin (IVIG) + plazmaferézis (PF) kezelés, a 6 debreceni beteg közül 5 kapott ezenfelül rituximabot és 1 alemtuzumabot. 9 (47,4%) beteg él működő beültetett vesével, 4 beteg meghalt (21%), és 5 került vissza művesekezelésre graftvesztés miatt (31%). Az ABMR veszélyes szövődmény a veseátültetés után. A diagnosztikus kritériumok sokáig változtak. A gold standard a szövettan. A C4d-esetekben is lehet akcelerált ABMR. A retranszplantáción átesett fiatalabb, preformált donorspecifikus antitesttel (DSA) jelentkező betegek és azok, akik EC-donorból kapnak vesét, kockázati csoportot jelentenek. A de novo DSA megjelenése, az átlagos fluoreszcenciaintenzitás (MFI) kinetikája lehet az a pont, amely felhívja a figyelmet az akut ABMR veszélyére. A rituximab hatékonyságát megkérdőjelezik, az új gyógyszerekkel (belatacept, bortezomib vagy ekulizumab) még nincs elég tapasztalat, vagy rendkívül drágák. Saját anyagunkban a 40% feletti gyógyulási arány kiemelkedően jó eredmény. Orv Hetil. 2018; 159(46): 1913–1929.

The ultrastructural quantitative aspects of peritubular capillary basement membrane multilayering (PTCBML) were examined in 57 kidney transplant biopsies with transplant glomerulopathy (TG). The measurements included three cutoffs [permissive: 1 PTC with 5 basement membrane (BM) layers, intermediate: 3 PTCs with 5 layers or 1 PTC with 7 layers, strict: 1 PTC with 7 layers and 2 PTCs with 5 layers] and the mean number of BM layers (PTCcirc). Two groups were assigned, namely patients with mild TG (Banff cg1a and cg1b) and those with moderate-to-severe TG (cg2 and cg3). Their respective clinical, serological, and morphological characteristics were then compared. The clinical data revealed that mild TG corresponded to early chronic antibody-mediated rejection (cABMR), while moderate-to-severe TG corresponded to the advanced stage of the disease. The permissive threshold displayed the lowest specificity (73 %) and the highest sensitivity (83 %) for moderate-to-severe TG, and its corresponding PTCcirc value was 3 layers. In contrast, the strict threshold-adopted by the Banff 2013 classification-displayed a specificity and sensitivity of 93 and 52 %, respectively, and the corresponding PTCcirc was 4 layers. In mild TG, 26 % of the cases met the permissive cutoff and 6 % the strict cutoff. Mild TG was associated with a lower PTCcirc (2.6 layers vs 4.5 layers in moderate-to-severe TG; p

Antiphospholipid syndrome is characterized by multiple arterial and/or venous thrombotic events, recurrent fetal losses in the presence of antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome is a life-threatening, rare subset of antiphospholipid syndrome when the thrombotic events affect at least three organs, and clinical manifestations develop simultaneously or within a week. Diagnostically, small vessel occlusions can be detected by histopathology in the presence of aPL. Our case report describes an 18-year-old man who has been treated for antiphospholipid syndrome associated with systemic lupus erythematosus (SLE) since 2011. The clinical findings were dominated by recurrent deep vein thrombosis, and severe proteinuria caused by lupus nephritis, accompanied by mild serological and laboratory findings. The patient was hospitalized in March 2014 because of severe thrombocytopenia and infective diarrhoea. At this time the renal functions deteriorated rapidly. Simultaneously, left upper extremity paresis was observed; computed tomography showed ischaemic lesions in the territory of the middle cerebral artery. Abdominal discomfort and pain occurred. On computed tomography scan ischaemic lesions were seen in the spleen, the right kidney and the coeliac trunk. Laboratory and serological findings verified the presence of aPL and anti-DNA antibodies, anaemia and thrombocytopenia. Based on the above-mentioned clinical and laboratory findings, the diagnosis of catastrophic antiphospholipid syndrome was established. Anticoagulation, corticosteroids and plasma exchange treatment, as well as haemodiafiltration were initiated. Although the thrombotic cascade decelerated following these interventions, we could not see an improvement in the renal function. Rituximab treatment was started, leading to a significant improvement in renal function. After 5 weeks of treatment the patient was discharged from hospital.

Background: Arteriovenous fistulae impair the distal circulation, but their effects at the microcirculatory level are not well understood. This study presents the carotid-jugular fistula (CJF) as a model to evaluate fistula-related microcirculatory and systemic changes. Materials and Methods: Female Wistar rats were anesthetized and divided into a fistula group (FG, n = 10) and a sham group (SG, n = 6). End-to-end anastomosis was performed between the right carotid artery and the jugular vein in the FG. The hemodynamic status was followed for 6 weeks. On the sixth postoperative week, liver and kidney microcirculation was measured using laser Doppler; then microcirculatory changes were assessed after occlusion of the carotid artery. At the end of the experiment, histological samples were taken and the weights of the organs were measured. Results: The heart rate and systolic blood pressure decreased significantly due to the CJF. Laser Doppler showed a reduction in liver blood flow units (BFU) in the FG in comparison with the SG (p = 0.01), and they increased (p < 0.01) after occlusion of the fistula. Kidney BFU showed slight changes only. The comparative morphological study revealed significant increases in heart weight (p < 0.001) and left ventricular hypertrophy (p = 0.008) in the FG. Conclusion: Beside hemodynamic and morphologic changes, a CJF causes a deterioration in the microcirculation of the liver rather than of the kidney, but occlusion of the CJF immediately reverses these changes.

Background Remote ischemic preconditioning (RIPC) can be protective against the damage. However, there is no consensus on the optimal amount of tissue, the number and duration of the ischemic cycles, and the timing of the preconditioning. The hemorheological background of the process is also unknown. Objective To investigate the effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in rats. Methods In anesthetized rats 60-minute partial liver ischemia was induced with 120-minute reperfusion (Control, n = 7). In the preconditioned groups a tourniquet was applied on the left thigh for 3×10 minutes 1 hour (RIPC-1, n = 7) or 24 hours (RIPC-24, n = 7) prior to the liver ischemia. Blood samples were taken before the operation and during the reperfusion. Acid-base, hematological parameters, erythrocyte aggregation and deformability were tested. Results Lactate concentration significantly increased by the end of the reperfusion. Erythrocyte deformability was improved in the RIPC-1 group, erythrocyte aggregation increased during the reperfusion, particularly in the RIPC-24 group. Conclusions RIPC alleviated several hemorheological changes caused by the liver I/R. However, the optimal timing of the RIPC cannot be defined based on these results.

Background/Aims: The pathogenesis of the human polyomavirus (PyV) KI, WU, MW, and STL has not been elucidated yet. Respiratory transmission is suggested, but the site of the replication, tissue, and cell tropism is not clarified. KIPyV and WUPyV DNA and/or antigen were detected in normal lung tissues previously by others. In fact, a KIPyV DNA sequence was found in lung cancer samples. Up to date, there is no publication about the DNA prevalence of MWPyV and STLPyV neither in normal nor in cancerous lung tissues. The aim of the present study was to examine the DNA prevalence of these polyomaviruses in cancerous and non-cancerous lung tissue samples, in order to study the possible site for viral replication and/or persistence, and the potential association of these viruses with lung carcinogenesis as well. Methods: 100 cancerous and 47 non-cancerous, formalin-fixed paraffin-embedded lung tissue samples were studied for KIPyV, WUPyV, MWPyV, and STLPyV by real-time PCR. Results and Conclusion: Neither of the viruses was found in samples from small-cell, non-small-cell (adenocarcinoma, squamous-cell carcinoma and large-cell neuroendocrine lung cancer), mixed-type and non-differentiated lung carcinoma, and non-cancerous lung tissues (from patients with pneumonia, emphysema and fibrosis).

Background/Aims: The oncogenic potential of human polyomaviruses (HPyVs) has been proposed, but so far only Merkel cell carcinoma polyomavirus seems to be associated with a human tumour. The role of BK polyomavirus (BKPyV) in human tumourigenesis remains controversial. BKPyV establishes persistent infection in the urinary tract, and renal and bladder neoplasms have been studied extensively, but conflicting prevalence data are reported. KI, WU and HPyV9 were detected in urine samples suggesting that these viruses may also infect the urinary tract, but their presence in urinary tract tumours has not been studied. The aim of this work was to examine the prevalence of KIPyV, WUPyV, HPyV9 and BKPyV by PCR in renal and bladder neoplasms. Methods: A total of 190 formalin-fixed paraffin-embedded renal neoplasms, bladder cancer and kidney biopsy samples were analysed for the presence of BKPyV, KIPyV, WUPyV and HPyV9 DNA by real-time and nested PCR. Results: Amplifiable DNA was extracted from all the samples, but none of the studied viruses were detected in benign renal neoplasia (0/23), malignant renal tumours (0/89) or bladder cancer (0/76). Conclusion: Our study did not find any evidence that BKPyV, KIPyV, WUPyV or HPyV9 are associated with bladder and renal tumours.

The most serious complication of novel influenza virus (H1N1) infections is the progressive respiratory insufficiency caused by diffuse alveolar damage (DAD) which can be overinfected by opportunistic pathogens. Clinically manifest acute respiratory distress syndrome leads to death in the most severe forms of the disease. However, despite the H1N1 positivity determined by RT-PCR, signs of virus pneumonia could not be demonstrated in several cases belonging to the high-risk patient group, therefore, the role of the virus infection in the course of the disease remained unclear. In this paper, a case with a complicated, partially organized hemorrhagic pneumonia and DAD is presented in a patient with H1N1 virus positivity, which can be referred as a classical pulmonary change. In order to obtain correct statistical data on virus related mortality, only unambiguous cases with clear virus associated morphological changes should be considered.

Primary angiosarcoma of the pancreas is an extremely rare neoplasm that often mimicks severe acute pancreatitis. A 58-year-old man was admitted with clinical and laboratory signs of severe acute pancreatitis. Contrast enhanced CT scan demonstrated haemorrhagic necrotizing inflammation of the pancreas involving the pancreatic tail, splenic hilum and small bowels with multiple peripancreatic and free abdominal fluid collection. Percutaneous drainage was performed. After 13 days, laparotomy was indicated because of persistent intra-abdominal bleeding, fever and a palpable, rapidly growing mass in the left upper quadrant of the abdomen. During the operation a necrotic, haemorrhagic mass was found in the pancreatic tail; a frozen section showed malignancy, although the tumour was unresectable. Despite all conservative and surgical therapeutic attempts, the patient died within four weeks after diagnosis. Final histology justified primary angiosarcoma of the pancreas. If a patient with signs of severe acute pancreatitis has fever without elevated PCT, the presence of a malignant tumour of the pancreas should be considered.

Herpes simplex virus encephalitis (HSVE) is a rare and life-threatening infection. The clinical signs are diverse and often misleading regarding the aetiology. However, focal seizure with fever and typical CT/MRI finding should always raise the possibility of HSVE as early diagnosis and antiviral therapy is crucial. Before the advent of molecular techniques and high-tech imaging histological examination from multiple brain biopsies were often necessary. Although nowadays PCR and other molecular methods may provide an aetiological diagnosis some cases need neuropathological verification. Due to the high IgG seropositivity rate in the population the plasma IgG titer is not diagnostic and elevation of its plasma level requires several weeks. We report the case of a 25-years old male patient who initially presented with epileptic seizures. There was no final diagnosis and no causal treatment in the district general hospital. The patient was admitted to our institution in comatose state on day 9; the initiated diagnostic tests and therapy could not save the patient who died next day. The autopsy and subsequent neuropathological examination revealed HSVE. We present a flowchart on diagnostic work-up and special techniques to aid diagnosis in suspected viral encephalitis.