Hypertension and nephrology

[Current diagnosis and treatment of membranous nephropathy]


DECEMBER 10, 2013

Hypertension and nephrology - 2013;17(05-06)

[Primary membranous nephropathy is a common glomerular disorder characterized by subepithelial immune deposits. The pathomechanism underlying these lesions has only recently been elucidated: M-type phospholipase A2receptor (PLA2R) protein emerged as being the leading autoantigen. Antibodies to PLA2R, typically of IgG4 subclass are expressed in 70-80% of patients with primary membranous nephropathy. The level of autoantibody to PLA2R was shown to correlate with disease severity and to change parallel with disease activity in response to therapy. While mild forms of the disease are prone to spontaneous remission and carry excellent prognosis, severe forms often progress into end-stage renal disease without treatment and necessitate immunosuppression. The latest guidelines recommend the application of corticosteroids with alkylating agents or calcineurin inhibitors as first-line therapy. Promising new therapies that are currently being explored for this disease include rituximab, mycophenolate mofetil, and adrenocorticotropic hormone.]



Further articles in this publication

Hypertension and nephrology

[Monitoring of effectiveness of ramipril-amlodipine fixed combination, a non-interventional trial (Ramona study). Subgroup analysis of patients with chronic kidney disease]


[Hypertension and chronic kidney disease are independent cardiovascular risk factors. The 5th Cardiovascular Consensus Conference has recommended chronic kidney disease in high-risk category. In chronic kidney disease hypertension is observed in most cases. In patients with chronic kidney disease blood pressure targets are as 140/90 mmHg blood pressure below must be achieved without overt proteinuria. In chronic kidney disease combined antihypertensive therapy treatment should be initiated according the Hungarian Society of Hypertension recommendations. Aims: Monitoring the effectiveness and safety of the fix combination of ramipril/amlodipine Egiramlon® therapy in chronic kidney disease suffering from mild or moderate hypertension despite antihypertensive treatment. Patients and methods: Open, prospective, phase IV clinical observational study, which involved known chronic kidney disease (age over 18 years) with mild or moderate hypertension. Ramipril/amlodipine fixed combination (5/5, 5/10, 10/5 or, 10/10 mg) were administered or titrated in three visits, during the 4 months of trial period. The doses of the fixed combination drugs were determined individually during the visits by the 923 physicians involved in the study. The target blood pressure value was <140/90 mmHg according the new guidelines of ESH/ESC. Results: 70.1% of total patient (9169) was fulfilled the protocol during the four month of trial (6423 patients). In this population 194 patients suffered from chronic kidney disease. The age of patients was 68.52±1.84 (mean±SD) years, 85 (43.8) women and 109 (56.2%) men. 74.74% of total patients with chronic kidney disease has reached target blood pressure at the end of 4th month (primary endpoint). The blood pressure has decreased significantly (all p<0.0001) from 158.04/90.46±9.97/8.30 mmHg (1. visit) to 138.77/82.12±10.68/7.21 mmHg 2. visit and to 130.40/78.59±7.56/5.75 at the and of trial (3. visit), it means -27.64/- 11.87 mmHg decrease from the beginning of the 4th Month (3. visit). eGFR level increased significantly from 46.3±16.49 ml/min/1,73m2 to 49.0±19.58 ml/min/1,73m2. Patients suffered from chronic kidney disease have tolerated well the various doses of fixed combination of ramipril/amlodipine, and adverse events have no occurred correlation of treatment.]

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Hypertension and nephrology

[Early histopathological changes in new onset diabetes mellitus after renal transplantation]

IBRAHIM Munir Yasmin, BORDA Bernadett, LENGYEL Csaba, VÁRKONYI Tamás, KEMÉNY Éva, SZABÓ Viktor, KUBIK András, LÁZÁR György

[Introduction: New-onset diabetes after transplantation (NODAT) is one of the most common complications following kidney transplantation. The diagnosis of NODAT is often late or missed, therefore it impairs the implanted renal allograft. Patients and methods: Patients were randomized to receive cyclosporine A- or tacrolimusbased immunosuppression. One year after the transplantation, fasting and oral glucose tolerance tests were performed, and the patients were assigned to one of the following three groups based on the results: normal, impaired fasting glucose/impaired glucose tolerance (IFG/IGT), NODAT. Age, laboratory results, renal function, morphological abnormalities, and changes in the Banff score were evaluated. Results: NODAT developed in 14% of patients receiving cyclosporine A-based immunosuppression and in 26% of patients taking tacrolimus (p=0.0002). Albumin levels were similar, but uric acid level (p=0.002) and the age of the recipient (p=0.003) were significantly different between the diabetic and the normal group. The evaluation of renal function showed no significant differences in case of serum creatinine level, eGFR, and urea level. Evaluation of tissue samples revealed that acute cellular rejection (ACR) and interstitial fibrosis/ tubular atrophy (IF/TA) were significantly different in the NODAT group. Changes in the Banff score provided significant difference regarding tubulitis (“t”) and interstitial inflammation (“i”) (p=0.05). Discussion: The pathological effect of new-onset diabetes after kidney transplantation can be detected in the morphology of the renal allograft earlier, before any signs of functional impairment.]

All articles in the issue

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Lege Artis Medicinae

[Substitution of drugs with narrow therapeutic window in transplant immunology]

LANGER Róbert, TÖRÖK Szilárd

[Because of the economic crisis affecting the health care system, the Hungarian government have envisaged a number of measures. In Hungary, the system of reference support or fixing is an excellent cost-saving tool in the financing of drugs that have a similar mechanism of effect or contain the same molecule. However, in case of certain patient groups and of “critical drugs”, it is to be feared that an inadequate agent might actually bring loss rather than benefit. In this paper, we would like to draw attention to the fact that switching the original microemulsion cyclosporin to generic, no-microemulsion preparations might pose a direct risk for the safety of the transplanted organ and the transplanted patient.]

Hungarian Immunology

[On the role of aging in etiology of autoimmunity]

SEMSEI Imre, ZEHER Margit, BAKÓ Gyula

[Several types of diseases, among others autoimmune illnesses, could be coupled with the general processes of aging. The two-edged sword of the immune defense is directed once against environmental attacks and on the other side against the self. However, one has to make a difference between normal (physiological) clearance and autoimmune diseases, although both sides of autoimmunity are influenced by the general processes of senescence. Aging of the thymus seems to be one of the key elements of the etiology of autoimmunity, although other cell types and their aging also play a substantial role in this process. The spontaneous genetic instability, the acquired genetic mutations due to aging and the age-related alterations of the information level of the body together may be important elements of the patomechanism of both the physiological autoimmunity and the autoimmune diseases. Nevertheless, physiological autoimmunity seems to be directed mostly by natural factors (such as aging and apoptosis) but primary autoimmune diseases may be caused by genetic instability that is enhanced by aging as well.]

Hypertension and nephrology

[Hungarian Vasculitis Registry – results of the first five years]

HARIS Ágnes, TISLÉR András, ONDRIK Zoltán, FILE Ibolya, MÁTYUS János, ZSARGÓ Eszter, DEÁK György, AMBRUS Csaba

[Launching the Hungarian Vasculitis Registry aimed to collect information about prevalence and outcome of our patients with ANCA-associated vasculitis, and treatment protocols of the disease. The on-line data collection has been developing dynamically since its initiation five years ago, presently 278 patients’ files are available. Patients’ mean age is 58.2±14.5 years, 62% are women; their disease is associated with c-ANCA positivity in 51% and p-ANCA in 49%. At diagnosis GFR was 24.6±21.6 ml/min/1,73 m2, that time 29%, during the total follow up 39% of the registered subjects needed dialysis. Renal replacement therapy could be discontinued in 23% of them. In cases with focal histological changes, also with upper respiratory tract and skin involvement dialysis was significantly less frequently necessary, which underlines the importance of early diagnosis. In induction therapy steroid was administered for 94% of the patients, 85% of them got cyclophosphamide, 59% was treated by plasmapheresis, 11% got rituximab. Maintenance treat ment contained steroid in 80%, per os cyclophosphamide in 23%, parenteral cyclophosphamide in 22%, furthermore 40% of the patients got azathioprin, 8 subjects got mycophenolate and 6 got methotrexate. Median follow up was 30 months (IQR 6-78), during which period 20% of the patients died, 5% got kidney transplantation, and 5% were lost to follow up. Median survival was 14.8 years, five years survival was 85%, and ten years survival was 70%. Long term survival in patients with c-ANCA vasculitis seemed better comparing to p-ANCA vasculitis, but when correcting by age this difference disappeared. Predictors of death were age and dialysis dependent renal failure. Relapses developed in 27% of patients, 28% of them presented in the first year, 21% suffered it after five years of care. Collected data by the Hungarian Vasculitis Registry shows our society’s successful professional activity. Our results are comparable to the published data in the literature, yet there are several areas in our care where further improvements are warranted in order to increase our patient’s survival and quality of life.]

Lege Artis Medicinae


SZEKANECZ Éva, SZŰCS Gabriella, KISS Emese, SZABÓ Zoltán, SZÁNTÓ Sándor, TARR Tünde, SZÁNTÓ János, SZEKANECZ Zoltán

[INTRODUCTION - Survival data for rheumatoid arthritis (RA) have improved during the past years. Due to longer life expectancy, more attention has to be paid to prevention and treatment of long-term sequelae, including secondary malignancies. Incidence of malignant lymphoproliferative diseases and bronchial cancer is higher in a number of rheumatic diseases including RA. Some drugs nowadays very rarely used in RA - primarily cyclophosphamide and azathioprine - may further increase cancer risk. According to several large meta-analyses, biological therapy may also increase the risk of lymphomas, however, as these agents are used for the treatment of active, refractory arthritis, benefit may override such risks. PATIENTS AND METHODS - Altogether 516 RA patients managed at our department were assessed for the incidence and type of secondary malignancies. Although the absolute number of RA patients with a tumor was relatively small, we compared our cohort to the Health for All database and calculated standard incidence ratios (SIR). RESULTS - We identified 13 cases of malignancy (11 females and 2 males) in 516 RA patients (2.5%). In two patients, cancer developed before the onset of RA. RA patients with malignancy had an even higher female predominance (5.5 to 1) than usual. Mean age at onset of RA was 51.4 years, while age at the diagnosis of malignancy was 61.8 years. Mean duration of RA at the time of cancer diagnosis was 11.2 years. Five patients died, 4 due to the underlying malignancy. In the fifth patient, the tumor was considered cured but the patient died of amyloidosis. Among the 8 surviving patients, mean survival is 7.3 years until now, while overall survival of all 13 cancer patients is 4.7 years. Regarding types of malignancies, there were 6 cases of bronchial cancer, 2 cases of follicular thyroid cancer, and one cutaneous B cell lymphoma, one breast cancer, one gall bladder cancer, one colorectal cancer, and one pancreatic cancer. In comparison to the Health for All database, the overall SIR of all malignancies in RA was 1.12 (CI 0,91-1,33), varying between 2.2 and 70.7 among different tumor types. Only one cancer patient received cyclophosphamide therapy and some received methotrexate or anti-TNF agents. CONCLUSION - We identified 13 cases of malignancy among our RA patients. In RA, secondary tumors including bronchial cancer and lymphomas are more common than in the general population. Adequate treatment and monitoring of these patients may help us to lower the risk of malignancies secondary to RA]

Hungarian Immunology

[Mutations of La gene: the proper reaction of the immune system]


[Numerous hypotheses have emerged to solve the problem and the pathomechanism of autoimmunity so far. Different factors are suspected, from viruses to neuroendocrine elements, to be a pathogen in the etiology of autoimmune diseases. Most of the theories are based on the assumption that something happens to the immune system and it leads to an autoimmune reaction against the proper self. This paper indicates that, at least in certain cases, the immune system reacts properly against the altered cells; therefore the cause of the autoimmunity lies in the other improper functioning of the body. Experimental data show that La autoantigen plays a role not only as a diagnostic marker but it may participate in the pathomechanism of certain autoimmune diseases as well. Mutations in the exon 7 of La gene have such consequences that could lead to the formation of autoimmune reactions detected.]