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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. Toxic shock syndrome is a potentially fatal toxin-mediated disease. The role of toxins in this clinical entity made us hypothesize that extracorporeal blood purification with CytoSorb® could play a beneficial role in the clinical management of toxic shock syndrome. This case report describes the successful treatment of toxic shock syndrome using a combination of renal replacement therapy and hemadsorption in a pediatric patient. Case Presentation. A 5-year-old girl with Down’s syndrome presented with an inflamed area surrounding an insect bite, signs of systemic inflammation, and multiple organ failure. As previous attempts of immune modulation therapy were unsuccessful, renal replacement therapy was supplemented by the cytokine absorber CytoSorb. Treatment using this combination was associated with a rapid and significant stabilization in the hemodynamic situation and a decrease in inflammatory mediators within hours after the initiation of therapy. The application of CytoSorb therapy was simple and safe. Conclusion. The use of extracorporeal blood purification with CytoSorb proved potentially beneficial by removing toxins and inflammatory mediators in this case and could therefore play a role in the clinical management of toxic shock syndrome. Whether CytoSorb has the potential to even positively influence mortality in patients with toxic shock syndrome still needs to be confirmed.

Magnesium participates in numerous enzymatic reactions in the human body and it has essential role in the maintenance of the antioxidant system. Since several magnesium compounds have been applied in the food and pharmaceutical industry, our purpose was to investigate the antioxidant/free radical scavenging activity of some magnesium compounds in vitro. The antioxidant/prooxidant effect of inorganic salts (e.g. MgCl2) and organic complexes (e.g. Mg-gluconate) was determined with chemiluminometric method (H2O2/•OH-microperoxidase-luminol) and heme mediated LDL oxidation (LDL-heme-H2O2 ) in vitro. It has been stated that the chemiluminescence method and LDL (low density lipoprotein) oxidation measurement is applicable in the presence of magnesium salts and complexes. Most of the compounds do not generate free radicals and the antioxidant/prooxidant effect depends on the quality of the ligand and the concentration. In the concentration range used, some representatives of the magnesium compounds (MgO, Mg-gluc...

Patients with renopulmonary syndrome who have both anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies have been described since 1989.The aim of the authors was to analyse the data of "double positive" patients diagnosed in their department, and compare these with previous studies.During the last 16 years, 87 anti-neutrophil cytoplasmic antibody positive and 11 anti-glomerular basement membrane antibody positive patients were diagnosed. Four patients with anti-glomerular basement membrane antibodies (36%) had detectable anti-neutrophil cytoplasmic antibodies, 2 patients were positive for anti-myeloperoxidase and 2 patients for anti-proteinase 3.In comparison with patients having anti-glomerular basement membrane antibodies, the double-positive patients were characterized by older age (median of 46 vs. 24 years), lack of male dominance (50% vs. 71%), more frequent presence of previous extrarenal symptoms (50% vs. 0%), and lower anti-glomerular basement membrane antibody levels (100EU/ml: 100% vs. 29%). The double-positive patients had more favourable 1-year survival (100% vs. 71%), despite their older age and similar treatment regimen (immunosuppression 100% in both groups, plasmapheresis in 75% vs. 86%), but 1-year renal survival was not different (25% vs. 14%).In agreement with literature data, about one third of patients with anti-glomerular basement membrane antibodies had detectable anti-neutrophil cytoplasmic antibodies, and the coexistence of the two antibodies may have clinical consequences.Bevezetés: A világirodalomban 1989 óta számolnak be olyan renopulmonalis szindrómás betegekről, akiknél mind az antiglomeruláris bazálmembrán, mind az antineutrofil citoplazmatikus antitest kimutatható. Célkitűzés: A szerzők célja az volt, hogy az intézetükben előfordult „kettős pozitív” eseteket felkutassák, adataikat feldolgozzák és összehasonlítsák az irodalomban leírtakkal. Módszer: Az elmúlt 16 évben 87 antineutrofil citoplazmatikus antitest pozitív vasculitises és 11 antiglomeruláris bazálmembrán antitest pozitív beteget kezeltek, közülük négy betegben (36%) volt az antineutrofil citoplazmatikus antitest is kimutatható (két antimieloperoxidáz-, két antiproteináz-3-pozitivitás). Eredmények: A csak antiglomeruláris bazálmembrán antitest pozitív betegekkel szemben a kettős pozitív betegekre magasabb átlagéletkor (46 vs. 24 év), a férfi dominancia hiánya (50% vs. 71%), megelőző extrarenalis tünetek gyakoribb jelenléte (50% vs. 0%), alacsonyabb antiglomeruláris bazálmembrán antitest szintek (100 EU/ml: 100% vs. 29%) voltak jellemzőek. A kettős pozitívak között jobb volt az egyéves betegtúlélés (100% vs. 71%) az idősebb kor és a hasonló kezelés ellenére (immunszuppresszió mindkét csoportban 100%, plazmaferézis 75%, illetve 86%), az egyéves vesetúlélés nem különbözött (25%, illetve 14%). Következtetések: A nemzetközi tapasztalatokhoz hasonlóan az antiglomeruláris bazálmembrán antitest pozitív hazai betegek harmadában antineutrofil citoplazmatikus antitest pozitivitás is észlelhető, ami eltérésekkel társul a renopulmonalis szindróma klinikai megjelenésében. Orv. Hetil., 2013, 154, 1696–1701.

Background: Recently several estimated GFR (eGFR) formulae have been developed and new creatinine methods were introduced to compensate for the effect of “pseudocreatinines”. These methods resulted in lower creatinine and higher eGFRs. Methods: Original 6-v MDRD (Modification of Diet in Renal Disease), 4-v MDRD, Cockcroft-Gault (C-G), Quadratic and the new MDRD-175 formulae were tested in 31 patients. The eGFR based on both Jaffe and compensated-Jaffe creatinine were compared to Tc-99m labeled diethylenetriamine pentaacetic acid clearance (DTPA-GFR). Results: All eGFRs correlated with DTPA-GFR (range 16–104 mL/min/1.73 m 2 ). Original MDRD and C-G showed high correlation coefficients (0.88 and 0.78), but original and 4-v MDRD tended to overestimate GFR below 60 ml/min/1.73 m 2 and underestimate it above 60 mL/min/1.73 m 2 . Using compensated-Jaffe creatinine reduced the underestimation of the original MDRD, but resulted in overestimation of the 4-v MDRD, C-G and quadratic GFR. With the exception of the or...

Az idült vesebetegség napjainkban népbetegséggé vált az atherogeneticus nephropathiák számának drámai megemelkedése miatt. A klasszikus vesetünetek hiánya miatt a betegséget legtöbbször csak az előrehaladott, súlyos vagy végstádiumú veseelégtelenség stádiumában ismerik fel, holott laboratóriumi vizsgálatokkal már jóval korábban diagnosztizálható lehetne. Ekkor már nem lehetséges a vesefunkció romlásának megállítása, a vesepótló kezelés elkerülése. Ugyanakkor az enyhe-mérsékelt súlyosságú idült vesebetegség is jelentősen fokozza, megsokszorozza az atherosclerosis kockázatát, így a betegek többsége cardiovascularis betegségekben meghal még a dialízis előtt. Ezek miatt a tünetmentes korai stádiumú vesebetegség szűrése alapvető fontosságú lenne. A glomerulus filtrációs ráta számítása segítheti leginkább a kórkép felismerését, a veseelégtelenség és cardiovascularis betegségek progressziójának csökkentését. A Magyar Nefrológiai Társaság és a Magyar Laboratóriumi és Diagnosztikai Társaság már 2005-ben javasolta a glomerulus filtrációs ráta laboratóriumokban történő kiszámítását és az eredmény automatikus közlését minden egyes szérumkreatinin vizsgálatakor. Ezt a gyakorlatot az országban már egyre több laboratórium alkalmazza. A jelen összefoglaló a számított glomerulus filtrációs ráta alkalmazásában, értékelésében kíván segítséget nyújtani.

Structural analogues (flavanone: 2-4 and flavone: 5 and 6, respectively) of silybin (1a) were synthesized and tested for inhibitory activity on O(2)(-) release and PKC translocation in PMA-stimulated neutrophils as well as xanthine oxidase activity in order to identify the molecular structures responsible for the antioxidant property of silybin. Concerning the prevention of hem-mediated oxidative modification of LDL by silybin, the hydroxyl radical scavenging activity of its structural analogues was also determined. We demonstrated that the basic skeleton of 1a (4) is responsible for its inhibitory activity on O(2)(-) release in PMA-stimulated neutrophils via inhibition of PKC translocation, since introduction of a double bound and hydroxyl groups at C-5 and C-7 position (5 and 6) did not result in further increase in inhibition of O(2)(-) release. It has been shown that the presence of the phenolic hydroxyl group at C-5 and C-7 of 1a is essential for the inhibition of xanthine oxidase activity. Moreover, introduction of a double bond into the C-ring of 2 and 3, resulting in flavone derivatives (5 and 6), markedly enhanced the antioxidant effect in all the tested systems. Finally, silybin (1a) and its flavon derivatives (5 and 6) directly scavenged hydroxyl radicals as well. On the basis of these results it might be concluded that different moiety of silybin is responsible for inhibition of overproduction of O(2)(-) in stimulated neutrophils, xanthine oxidase activity, and for prevention of hem-mediated oxidative modification of LDL.

The authors are presenting a rare paraneoplastic syndrome in Hodgkin's disease. Young female patient presented with symptoms of nephrotic syndrome. Renal biopsy showed mesangiocapillary glomerulonephritis. Remission was achieved with combined therapy. Four months later, when the nephrosis syndrome relapsed, Hodgkin's disease was diagnosed (nodular sclerosing subtype). Hodgkin's disease was staged as III/BS. Polychemotherapy resulted complete remission of both Hodgkin's disease and nephrotic syndrome. Causes of nephrotic syndrome in Hodgkin's disease can include renal vein thrombosis, amyloidosis or paraneoplastic syndrome. Nephrotic syndrome in Hodgkin's disease may relate to dysfunction of T-cells or altered cytokine balance, but the exact pathogenesis is not known. This case attracts attention that a rare cause of nephrotic syndrome can be Hodgkin's disease.

Mechanism of the action of silybin (1) and its derivatives (2-4), possessing different lipid solubility in PMA-stimulated neutrophils was evaluated. Silybin (1) inhibited the calcium, phosphatidylserine- and diacylglycerol-dependent protein kinase C translocation and the NADPH oxidase activity in PMA-stimulated neutrophils and resulted in decreased apoptosis. Furthermore, silybin (1) inhibited xanthine oxidase activity and hem-mediated oxidative degradation of low-density lipoprotein, as well. Its derivatives (2-4), possessing different lipid-solubility, affected all the studied parameters. The lipid solubility of silybin (1) was enhanced by methylation (5'7'4''trimethylsilybin: 2), whereas a decrease in lipid-solubility by acetylation of compound 2 (5',7,'4"-trimethylsilybin-acetate: 3) or all the hydroxyl groups of silybin (peracetyl-silybin: 4) attenuated the antioxidant capacity by decreasing the inhibition in PKC translocation and NADPH oxidase activation. All the derivatives of silybin (2-4) showed no inhibition in cell free systems; e.g. did not alter the xanthine oxidase activity and the hem-mediated oxidative degradation of LDL. In conclusion, the antioxidant activity of (1) might be due to its ability to inhibit PKC translocation and NADPH oxidase activation in PMA-stimulated neutrophils. The increase of lipid solubility of silybin (1) supports its penetration through cell membrane and enhances its inhibitory effects. This structural modification of (1) might have pharmacological consequences.

Deformability and lipid peroxidation (LP) have been compared in erythrocytes of 45 chronic hemodialysis patients and 30 healthy subjects. The relative cell transit time (RCTT), correlating negatively to deformability, was measured using a St. George filtrometer. Thiobarbituric acid reactive material was measured and expressed as nanomoles of malondialdehyde (MDA) per gram of hemoglobin as a marker of LP. RCTT and MDA were found to be significantly higher not only before but also after HD compared with controls. Weak negative correlations were found between RCTT and the dosage of EPO as well as between RCTT and the daily amount of urine. These observations indicate the importance of residual renal function and the beneficial effect of EPO on erythrocyte deformability. The mean values of results suggest that HD does not affect the erythrocyte injury. The individual modifications of RCTT and MDA are also discussed.

There's a fact, that Hungary has held the first places in suicidal statstics.The authors studied toxicological cases between 1989 and 1998 at the 1st Department of Medicine of the Medical and Health Science Centre, at the University of Debrecen, paying special attention to suicidal poisoning cases.2% of the patient turnover accounted for acute poisoning cases, the number of which increased during the 10 years in question. 70% of the cases were of suicidal intentions, 20% were unintentional, these poisonings were not committed on purpose, while the proportion of iatrogenic intoxication cases was 10%. Amongst the failed suicide cases there was a higher proportion of women, whereas a higher percentage of men accounted for "successful" suicide cases. When examining auto-intoxication cases it turned out that the medicine most frequently used was meprobamate, besides benzodiazepines. Mortality rate was highest in the glutethimide intoxication cases. Most poisonings with suicidal intentions took place in the 2nd quarter of the year. Most completed suicides were committed on Wednesdays and Thursdays. 81% of the iatrogenic intoxication cases happened to be with digitalis and coumarin overdose. Nearly 50% of the cases turned out to be combined intoxications. 40% of the men took alcoholic drinks during the auto-intoxications. In the case of 135 patients extracorporeal detoxification therapy was applied, which consisted mostly of hemoperfusion. Three quarters of the patients needed psychiatric care and every fourth patient was admitted to the Department of Psychiatry. 6.9% of the poisonings were fatal.The growing number of toxicological cases--amongst these suicidal poisonings--compels us to pay more attention to the setting up of interdisciplinary based prevention as well as running effective toxicological centres. All physicians have a responsibility to recommend psychiatric care for people suffering from mental problems or depression and for the unsuccessful or potential suicide seeking help for the first time. Family doctors in primary medical care and who meet patients first have an important role in this job.

Relapsing polychondritis (RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia, which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.

Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A1) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A1 levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A1 level decreases, we standardized the enzyme activity for HDL and Apo-A1 concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 ± 69.5) as compared with hyperlipidemic patients (137.64 ± 81.0) and controls (194.45 ± 94.45). The standardized values for Apo-A1 showed a similar tendency: paraoxonase/Apo-A1 ratio in uremic patients 89.64 ± 47.8, in hyperlipidemic patients 128.12 ± 69.83, and in controls 161.40 ± 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.

We are grateful to Meijers et al.1 for the comments on the dialytic removal of several protein-unbound metabolites that decrease the antioxidant capacity of plasma ultrafiltrate assessed by heme-mediated low-density lipoprotein (LDL) oxidation and subsequent endothelial cell reactions.2 The recent results on the limited removal of p-cresol and its conjugates by hemodialysis3, 4 have utmost importance in further development of detoxifying methods.