Case report: Targeted treatment strategies for Erdheim-Chester disease.

Introduction: Erdheim-Chester disease (ECD) is a rare disease that belongs to the group of Dendritic and histiocytic neoplasms. Only 2000 cases have been reported worldwide. It can present with a wide range of symptoms, making a differential diagnosis especially difficult. The primary and most important diagnostic tool is a biopsy of the affected organ/tissue. Nowadays the analysis of different mutations affecting the BRAF and MAPK pathways makes it possible to use targeted treatments, such as vemurafenib, dabrafenib, or cobimetinib. Objective: Our aim is to present the results of three male patients treated in our hematology department. Results: Our BRAF mutation-positive patient presented with retroperitoneal tissue proliferation and diabetes insipidus. The initial therapy of choice was dabrafenib. After 3 months of treatment, 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) scans showed regression, and after 2 years of treatment, no disease activity was detected. In our second patient, a recurrent febrile state (not explained by other reasons) and diabetes insipidus suggested the diagnosis. A femoral bone biopsy confirmed BRAF-negative ECD. The first-line therapy was interferon-alpha. After 3 months of treatment, no response was observed on 18FDG-PET/CT, and treatment with cobimetinib was started. The control 18FDG-PET/CT imaging was negative. Our third patient was evaluated for dyspnea, and a CT scan showed fibrosis with hilar lymphadenomegaly. A lung biopsy confirmed BRAF-negative ECD. We started treatment with interferon-alpha, but unfortunately, no improvement was observed. Second-line treatment with cobimetinib resulted in a partial metabolic response (PMR) according to control 18FDG-PET/CT. Conclusions: Our results demonstrate that an appropriately chosen treatment can lead to a good therapeutic response, but dose reduction may be necessary due to side effects. With advanced targeted therapeutic treatment options, survival and quality of life are significantly improved.

Tubular basement membrane amyloid deposition: is it an indicator of renal progression in light chain amyloidosis?

In light chain amyloidosis (LA), the massive glomerular and vascular amyloid deposition leading to interstitial fibrosis/tubular atrophy (IFTA) is thought to be responsible for renal failure. The amyloid deposition in the interstitium and the tubular basement membrane (TBM) has received less attention in the study of LA. We, therefore, collected clinical and laboratory data on patients diagnosed with LA in our Nephrology Department and studied amyloid deposition in the TBM. Twelve LA patients were diagnosed by renal biopsy during a seven-year period. In 4 of the 12, amyloid deposition could also be detected in the TBM. In our first case of a patient with diabetes mellitus, non-amyloid fibrils resembling 'diabetic fibrillosis' were also seen by electron microscopy. Despite the double damage, IFTA was negligible, blood vessels were unaffected, and the glomerular deposition was segmental. In the other three cases, significant (>50%) IFTA and a severely reduced estimated glomerular filtration rate were already detected at the time of diagnosis and amyloid deposition was also observed in the blood vessels. These findings indicate the importance of TBM amyloid deposition in the progression of renal disease. This may represent a late-stage presentation of the disease with a heavy LC burden.

Occurrence and prevention of iodinated contrast agent-induced kidney injury in light of the newest literature data: Time to change our clinical practice! / Radiojód kontrasztanyagok által okozott vesekárosodás és megelozése az újabb irodalmi adatok tükrében: Változtassunk a gyakorlaton!

Összefoglaló. A jelenlegi hazai gyakorlatban sokszor indokolatlanul korlátozzák a vesebetegek kontrasztanyagos vizsgálatát, és halasztódik a metformint szedok vizsgálata is, kontrasztanyag által okozott akut vesekárosodástól (contrast-induced acute kidney injury, CI-AKI) tartva. Összefoglalónk célja az ezzel kapcsolatos újabb ismeretek áttekintése és egy szakmai javaslat ismertetése annak érdekében, hogy a betegellátás szempontjából fontos vizsgálatok ne maradjanak el, ugyanakkor azok a maximális betegbiztonság jegyében készüljenek. Az elmúlt évek tanulmányai alapján a CI-AKI elofordulása a korábbinál kevésbé gyakori, és jelentosen különbözo a kontrasztanyag intravénás vagy intraarteriális alkalmazásától függoen. Legfontosabb rizikótényezoje a csökkent glomerulusfiltrációs ráta (GFR), mely stabil állapotú vesebetegnél, intravénás kontrasztanyag adásakor 30 ml/min/1,73 m2 alatt, intraarteriális alkalmazásakor 45 ml/min/1,73 m2 alatt képez magas rizikót. Proteinuria esetén a CI-AKI és a kontrasztanyaggal társult akut vesekárosodás (contrast-associated kidney injury, CA-AKI) kockázata is nagyobb, ezért a számított GFR mellett indokolt a vizelet albumin/kreatinin vagy fehérje/kreatinin hányados meghatározása is a vizsgálat elott. Az instabil állapot, az akut veseelégtelenség mindenkor magas kockázatot jelent, ilyenkor a számított GFR pontatlan, nem használható. Csökkent vesefunkció mellett figyelni kell a beadott kontrasztanyag mennyiségére, a vizsgálat 48-72 órán belüli ismétlésének kerülésére, a nemszteroid gyulladásgátlók vagy más nephrotoxicus szerek lehetoség szerinti szüneteltetésére. Prevenciós intézkedés a magas rizikóval bíró betegek esetében javasolt intravénás hidrálás formájában, fiziológiás koncentrációjú nátrium-klorid vagy nátrium-bikarbonát infúziójával. Az egyéb eljárások hatástalanok, és nem indokolt a beavatkozás utáni dialízis végzése sem végstádiumú veseelégtelen betegekben. A metformint 60 ml/min/1,73 m2 feletti eGFR-rel rendelkezo beteg vizsgálata kapcsán szükségtelen elhagyni, ettol rosszabb vesemuködés esetén kell szüneteltetni. Amennyiben a vizsgálat indikációja sürgosségi, az a metformin egyideju elhagyásával elvégezheto, de a gyógyszer csak 48 óra múlva, az akut vesekárosodás kizárását követoen adható vissza. Orv Hetil. 2022; 163(3): 83-91. Summary. In the current clinical practice, studies with iodinated contrast agents are often limited in patients with kidney disease and delayed in those on metformin therapy due to fear of contrast-induced acute kidney injury (CI-AKI). We aim to review the most recent information about CI-AKI and provide recommendations in order to avoid cancellation of important contrast-enhanced tests, but maximize safety considerations. According to the most recent findings, CI-AKI occurs less frequently nowadays than previously, and depends significantly on the route of contrast administration (intraarterial or intravenous). The most important risk factor is the decreased GFR, which, in stable patients with intravenous contrast administration provides high risk if the eGFR is less than 30 ml/min/1.73 m2, and with intraarterial contrast is less than 45 ml/min/1.73 m2. In patients with proteinuria, the risk of both CI-AKI and CA-AKI (contrast-associated kidney injury) is increased, therefore urinary albumin/creatinine or protein/creatinine ratios are recommended to measure before the contrast material administration, beside the eGFR determination. Unstable condition, acute renal failure always mean high risk; in these cases, eGFR calculation is imprecise and useless. If renal function is decreased, the amount of contrast material needs consideration, repeated contrast-enhanced studies should be avoided in 48-72 hours, the non-steroidal anti-inflammatory agents and other nephrotoxic drugs have to be discontinued. For high risk patients, preventive intravenous hydration should be given, either by physiologic saline or sodium bicarbonate infusion. Other drugs aiming prevention have proved to be useless; dialysis treatment immediately after contrast administration in end-stage renal disease patients is unnecessary. There is no indication to discontinue metformin if eGFR is higher than 60 ml/min/1.73 m2, but if the patient has less than that value, the metformin needs to be stopped. In urgent studies with contrast agent, metformin administration has to be discontinued simultaneously with the intervention, and this drug can only be readministered after ruling out acute kidney injury in 48 hours following contrast exposure. Orv Hetil. 2022; 163(3): 83-91.

Ibrutinib-induced acute kidney injury via interstitial nephritis.

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.

Alport Patients without Classic Ocular Symptoms Have Smaller Lens Diameter.

BACKGROUND The aim of this study was to present ophthalmological findings regarding Alport syndrome and report refractometry data and to present possible early signs of the syndrome. MATERIAL AND METHODS Seven patients suffering from Alport syndrome were referred to the Department of Ophthalmology at the University of Debrecen between January 1st, 2014, and December 31st, 2015. All patients underwent slit lamp evaluation and dilated fundus biomicroscopy, with special attention paid to lenticonus and retinal changes. IOL Master, Pentacam HR, and ultrasound biomicroscopy were performed to assess keratometry, corneal thickness, anterior chamber depth, lens size, and axial length data. RESULTS One patient out of seven had ocular symptoms. Posterior polymorphous corneal dystrophy (PPMD) and dot-and-fleck retinopathy were seen. Meanwhile, although keratoconus was not proven, remarkable astigmatism with high myopia was detected. The other six patients were found to have a significantly smaller lens diameter (an average of 7.82±0.66 mm, p=0.035) compared to normal controls (an average of 8.65±0.46 mm). Lenses also tended to be thicker in Alport patients (3.48±0.19 mm) compared to controls (3.4±0.2 mm), although the difference was not significant (p=0.394). The power of the lens also showed a significant difference (p=0.026), with Alport patients having lower lens power. CONCLUSIONS Alport syndrome patients without classical ophthalmological findings have smaller crystalline lens diameter and lower lens power. These signs may support the diagnosis of Alport syndrome. Ophthalmologists should not only seek for the known classic signs, but also the parameters of the crystalline lens, especially if genetic testing is not available.

Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

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.

[Clinical consequence and significance of anti-neutrophil cytoplasmic antibody positivity in anti-glomerular basement membrane disease]. / Antiglomeruláris bazálmembrán betegségben észlelt antineutrofil citoplazmatikus antitest pozitivitás klinikuma, jelentosége.

INTRODUCTION: Patients with renopulmonary syndrome who have both anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies have been described since 1989. AIM: The aim of the authors was to analyse the data of "double positive" patients diagnosed in their department, and compare these with previous studies. METHOD: 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. RESULTS: 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%). CONCLUSIONS: 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.

WT1 microdeletion and slowly progressing focal glomerulosclerosis in a patient with male pseudohermaphroditism, childhood leukemia, Wilms tumor and cerebellar angioblastoma.

The Wilms tumor 1 (WT1) gene is currently in focus by pediatric nephrologists as its mutations are associated with nephrotic syndrome, especially as part of complex clinical entities like Denys-Drash or Frasier syndrome. Renal failure may also develop in young WAGR patients, whose condition is attributed to a deletion at chromosomal region 11p13. However, only limited data exist on WT1 microdeletions. A 30-year-old male patient, with a history of genital malformations, a Wilms tumor manifested during the treatment of acute lymphoid leukemia (ALL) at the age of 4, and a cerebellar angioblastoma, was referred with proteinuria and a reduced glomerular filtration rate (GFR). Kidney biopsy revealed FSGS. Although all WT1 exons were amplified with polymerase chain reaction (PCR) and sequenced, none of them showed a mutation. However, an formalin-fixed, paraffin- embedded (FFPE) tissue sample of the patient's childhood Wilms tumor showed WT1- positivity restricted to the renal tumor cells, so the WT1 gene was investigated further. Using quantitative reverse transcription PCR (qRT-PCR), the gene was found to be present in only one copy in the patient's genomic DNA sample, while both copies were detected in both parents. In the patient's sister, the proximal region of WT1 was shown to have an extra copy. Evidence suggests that a heterozygous microdeletion of the gene WT1 is responsible for the patient's disease. It seems reasonable to assume a possible abnormality affecting meiotic crossing over at the WT1 locus in one of the parents.

[Proposal for the modification of metformin use in patients with chronic kidney disease]. / Javaslat a metformin idült vesebetegségben történo alkalmazásának módosítására.

Metformin is the first-line, widely used oral antidiabetic agent for the management of type 2 diabetes. There is increasing evidence that metformin use results in a reduction in cardiovascular morbidity and mortality, and might have anticancer activity. An extremely rare, but potentially life-threatening adverse effect of metformin is lactic acidosis, therefore, its use is traditionally contraindicated if the glomerular filtrate rate is below 60 mL/min. However, lactic acidosis is always associated with acute events, such as hypovolemia, acute cardiorespiratory illness, severe sepsis and acute renal or hepatic failure. Furthermore, administration of insulins and conventional antihyperglycemic agents increases the risk of severe hypoglycemic events when renal function is reduced. Therefore, the magnitude of the benefit of metformin use would outweigh potential risk of lactic acidosis in moderate chronic renal disease. After reviewing the literature, the authors give a proposal for the administration of metformin, according to the calculated glomerular filtrate rate.

Association of ANCA-associated vasculitis-rheumatoid arthritis overlap syndrome in four patients: rituximab may be the right choice?

OBJECTIVES: There have been few reports on the association of rheumatoid arthritis (RA) with anti-neutrophil cytoplasmic antigen (ANCA)-associated systemic vasculitides. METHODS: Here we present four cases of RA overlapping with Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS). All these cases had both the diagnosis of RA and that of ANCA-associated vasculitis. RESULTS: After we tried corticosteroids, multiple immunosuppressive drugs, sometimes plasmapheresis, rituximab was introduced to 3 out of 4 cases. Rituximab therapy was found to be effective in these three overlap cases. In the fourth case, rituximab was and will be considered; however, the patient has not given consent. CONCLUSION: To our knowledge, this is the first report on RA+CSS association. Common pathogenic background, such as genetic predisposition and ANCA may account for the development of RA+vasculitis overlaps. In DMARD-refractory cases, such as the ones presented here, biologics, especially rituximab may be highly effective.

[Advances in the prevention, diagnosis and therapy of vascular diseases]. / Újabb ismeretek a különbözo vascularis kórképek megelozésében, diagnosztikájában és terápiájában.

Atherosclerosis is a systemic disease affecting the coronary, carotid, intracerebral, renal and peripherial arteries. The early morphological and functional impairments could be detected in the second or third decades of life and their progression depend on the number and severity of risk factors and individual susceptility. Although the vascular risk factors (smoking, overweight, age, unhealthy diet, lack of physical exercise, hypertension, diabetes mellitus, chronic kidney disease and dyslipidemia) are the same and common in the different vascular diseases, the present clinical routine artificially classifies the diagnosis and therapy of different vascular diseases into different subfields of medicine with the negative impact of possible polypragmasia. Recently, worldwide health surveys (e.g. REACH registry) have proven the usefulness of a holistic approach in the diagnosis and therapy of multiorgan-affected vascular patients. This review summarizes the multidisciplinary advances and future perspective of vascular diseases.

[New trends in the laboratory diagnostics of proteinuria and albuminuria]. / Uj irányzatok a proteinuria és albuminuria laboratóriumi diagnosztikájában.

According to current clinical trials, albumin excretion is an early indicator of cardiovascular damage. While proteinuria is considered as a marker of kidney function, albuminuria indicates cardiovascular risk first of all. Sensitivity of the previous laboratory tests does not meet the clinical requirements, and the error of urine collection makes the results misleading. For that reason recent guidelines suggest to calculate albumin/creatinine (ACR) and protein/creatinine (PCR) measured from the first morning urine. For the clinical diagnosis of albuminuria the sensitive immunoturbidimetric assays are suggested. Albumin dipsticks are not recommended for the measurement of albuminuria. Wide-range urinary protein reagents are also available with high sensitivity, while serum reagents are not applicable (Biuret). The traceability of calibrator to a reference material is a critical requirement. Proteinuria and albuminuria of a patient should be monitored in the same laboratory, using a fixed method and cut-off value. Albumin/creatinine value should be reported together with gender-dependent reference range.

Relationship between serum nickel and homocysteine concentration in hemodialysis patients.

Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis (HD) patients, one of the main causes of death is cardiovascular disease. In animals, trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B(12) deficiency-induced HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B(12), trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP), and interleukin-6 concentrations were determined in 122 hemodialysis patients. When patients were divided into groups according to their tHcy, we found no significant differences in concentrations of cobalt, copper, and total protein, while nickel was higher, and folate, vitamin B(12), and iron were lower in patients with lower than higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations of folate (r = -0.302, p < 0.006), vitamin B(12) (r = -0.347, p < 0.0001), nickel (r = -0.289, p < 0.006), and CRP (r = -0.230, p < 0.02) and positively with serum albumin (r = 0.316, p < 0.0004) and hemoglobin (r = 0.329, p < 0.0001) values. No relationship between tHcy and serum concentrations of cobalt, copper, iron, or other laboratory parameters was found in HD patients. The effect of cobalt and nickel on homocysteine production was assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs. These results suggest that nickel might also be involved in the regulation of the methionine-folate cycle in humans, as was demonstrated in animal experiments.

[The epidemic of chronic kidney disease requires the estimation of glomerular filtration rate]. / Az idült vesebetegség epidémiája szükségessé teszi a glomerulus filtrációs ráta számítását.

Nowadays chronic kidney disease has become a major public health problem due to the great increase in atherogenic nephropathies. In the absence of classic renal symptoms, chronic kidney disease is mostly diagnosed when renal failure is already advanced, although it can be revealed by laboratory tests in the earlier stages. When diagnosis is late, the progression to end-stage renal failure is unavoidable and renal replacement therapy is needed. Even early-moderate renal failure significantly increases the risks for atherosclerosis, thereby leading to the deaths of patients from cardiovascular disease before initiation of dialysis. Therefore screening for asymptomatic chronic kidney disease is urgently needed. Estimated glomerular filtration rate has the greatest importance in the screening and in the timely intervention to slow down the progression of renal failure and cardiovascular disease. In 2005, the Hungarian Society of Nephrologists and the Hungarian Society of Laboratory Medicine suggested the automatic estimation and reporting of glomerular filtration rate, each time serum creatinine measurements were made. This practice is used more frequently by laboratories in Hungary. This article aims to help facilitate the utilization and evaluation of estimated glomerular filtration rate.

Identification of sulfhemoglobinemia after surgical polypectomy.

Sulfhemoglobinemia (SHb) is an uncommon cause of cyanosis that is predominantly drug-induced in adults. We report an unusual case of sodium sulfate-induced sulfhemoglobinemia in a 61-year-old woman after surgical polypectomy. Fractional hemoglobin derivates were assayed by spectrophotometry and high-performance liquid chromatography. The SHb ratio was 8.6% in the first sample and 3.77% a month later measured by spectrophotometry. In the blood hemolysate, a new peak was identified as SHb with high-performance liquid chromatography (HPLC). HPLC showed the presence of 9.37% SHb in the first sample and 4.88% a month later. After removing the suspected toxic agent the cyanosis decreased significantly. The findings underline the importance of routine SHb detection in cyanosis of unknown origin especially in emergency cases.

[Treatment of hepatitis C in patients on renal replacement therapy]. / A hepatitis C-vírusfertozés terápiája vesepótló kezelésben részesülô betegekben.

The prevalence of hepatitis C virus infection among patients on hemodialysis is about ten times higher than in the normal population. The infection can induce chronic glomerulonephritis, as an extrahepatic manifestation, which can lead to end stage renal disease. However, in the majority of the patients hepatitis C virus is acquired as a nosocomial infection during the hemodialysis. In most of the infected patients the liver enzymes are usually normal and need regular screening of the hepatitis C antibody to detect the infection. Despite of the normal liver enzymes, the liver disease may progress to cirrhosis. A part of the patients wait for renal transplantation. The immunosuppressive treatment after the renal transplantation results in a significantly increased viral replication which might induce further progression of the liver disease. Interferon treatment given after the transplantation can induce rejection and graft failure. Therefore the antiviral treatment should be administered during the hemodialysis or earlier. Only limited data are available with the treatment of patients with impaired renal function. Mostly alfa-interferon was used in these patients. Due to the impaired renal clearance and higher serum concentration interferon seems to be more effective, but less tolerable in patients with end stage renal disease than in normal patients. Ribavirin is also excreted exclusively by the kidney and the anemia is even more pronounced in these patients, therefore it is contraindicated in patients on hemodialysis. The pharmacokinetics of the pegylated interferon alfa-2a is very advantageous for the patients with end stage renal disease. The safety and efficacy of peginterferon alfa-2a is now being confirmed in many publications.

Hyperleptinemia is not responsible for decreased paraoxonase activity in hemodialysis patients.

BACKGROUND: Exogenous leptin markedly decreased plasma paraoxonase (PON1) activity in rats. Hyperleptinemia and decreased PON1 activity have previously been demonstrated in uremia. Therefore, we investigated the relationship between leptin level and PON1 activity in hemodialysis (HD) patients. METHODS: Leptin and PON1 were determined in 40 HD patients and 40 age-matched controls with similar body mass index (BMI). RESULTS: Leptin was higher (p < 0.001) and PON1 activity was lower (p < 0.001) in HD patients than in controls. PON1 and PON1/HDL ratio was higher in HD patients with BMI >25 kg/m2 than in HD patients with BMI <25 kg/m2. It was not due to a difference in frequency of high activity phenotype of PON1 among subgroups of HD patients. There was no similar difference in controls. Spearman analysis showed a significant correlation between leptin and PON1 activity (p < 0.02), BMI (p < 0.001), triglyceride (TG) (p < 0.03), and Kt/V (-0.323, p < 0.03), but multiparametric regression analysis did not reveal it. PON1 activity depended on BMI in both models. In controls, leptin correlated with BMI (p < 0.001) and TG (p < 0.002) but not PON1 activity. A slight decrease in leptin concentration and PON1 activity during HD was observed. CONCLUSION: Our results suggest the role of other pathophysiological conditions besides hyperleptinemia resulting in decreased PON1 activity in HD patients.

Dent Disease with mutations in OCRL1.

Dent disease is an X-linked renal proximal tubulopathy associated with mutations in the chloride channel gene CLCN5. Lowe syndrome, a multisystem disease characterized by renal tubulopathy, congenital cataracts, and mental retardation, is associated with mutations in the gene OCRL1, which encodes a phosphatidylinositol 4,5-bisphosphate (PIP(2)) 5-phosphatase. Genetic heterogeneity has been suspected in Dent disease, but no other gene for Dent disease has been reported. We studied male probands in 13 families, all of whom met strict criteria for Dent disease but lacked mutations in CLCN5. Linkage analysis in the one large family localized the gene to a candidate region at Xq25-Xq27.1. Sequencing of candidate genes revealed a mutation in the OCRL1 gene. Of the 13 families studied, OCRL1 mutations were found in 5. PIP(2) 5-phosphatase activity was markedly reduced in skin fibroblasts cultured from the probands of these five families, and protein expression, measured by western blotting, was reduced or absent. Slit-lamp examinations performed in childhood or adulthood for all five probands showed normal results. Unlike patients with typical Lowe syndrome, none of these patients had metabolic acidosis. Three of the five probands had mild mental retardation, whereas two had no developmental delay or behavioral disturbance. These findings demonstrate that mutations in OCRL1 can occur with the isolated renal phenotype of Dent disease in patients lacking the cataracts, renal tubular acidosis, and neurological abnormalities that are characteristic of Lowe syndrome. This observation confirms genetic heterogeneity in Dent disease and demonstrates more-extensive phenotypic heterogeneity in Lowe syndrome than was previously appreciated. It establishes that the diagnostic criteria for disorders resulting from mutations in the Lowe syndrome gene OCRL1 need to be revised.

Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.

[Successful combined kidney-liver transplantation in Hungary]. / Sikeres kombinált máj- és vesetranszplantáció Magyarországon.

The authors report a case of 47 years patient, who underwent successful combined liver-kidney transplantation. The primary cause of cirrhosis was HCV infection combined with membranoproliferative glomerulonephritis, witch resulted end stage kidney and liver disease. One and half year after operation the patient has full rehabilitation. By the case report the authors overview the indications and techniques of combined kidney-liver transplantation.