Biomedical subjects

R Rysavá

Publications and source records attributed to R Rysavá.

At least 19 recordsLinked to original sources

PubMed2006

Influence of endothelin-1 gene polymorphisms on the progression of autosomal dominant polycystic kidney disease.

BACKGROUND/AIM: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability cannot be fully explained by the genetic heterogeneity of the disease. Endothelin-1 (ET-1) has been suggested to be a major promoting factor in renal diseases. The role of the ET-1 gene locus (EDN1) in the renal function in the general nondiabetic population was evaluated. We examined the influence of three single-nucleotide polymorphisms of the ET-1 gene (EDN1)--K198N, 3A/4A, and T-1370G--on the progression of ADPKD towards end-stage renal disease (ESRD). METHODS: Two hundred and five ADPKD patients (113 males and 92 females) who had reached ESRD were analyzed. The patients were divided into three groups: (1) 48 patients (23 males and 25 females) with ESRD later than 63 years of age (slow progressors), (2) 74 patients (41 males and 33 females) with ESRD before 45 years of age (rapid progressors), and (3) 83 patients (49 males and 34 females) with ESRD between 45 and 63 years old. DNA samples from collected blood were genotyped for three single-nucleotide polymorphisms of EDN1: K198N, 3A/4A, and T-1370G. Haplotype analysis was also done in 200 healthy individuals. We compared the frequencies of the different genotypes between the groups of slow and rapid progressors and the ages at the time of ESRD regarding the EDN1 genotypes. RESULTS: The EDN1 genotype distribution showed no differences among the groups of slow progressors, rapid progressors, the ADPKD group with ESRD between 45 and 63 years old, and the control group. Comparing the ages of ESRD of all patients, we did not find significant differences with regard to the different genotypes. Furthermore, we compared the combinations of the different haplotypes and the ages at the time of ESRD. We found no differences in ages at the time of ESRD in patients with different haplotypes in the endothelin promoter (T-1370G) in combination with 3A/4A or K198N polymorphisms. Comparing the ages at the time of ESRD in patients with different 3A/4A and K198N haplotypes, we found a significantly lower age at the time of ESRD (47.1 +/- 8.7 years) in the carriers of the 4A allele in combination with the 198N allele (4A/4A, 3A/4A + 198KN,NN) than in the carriers of the 4A allele homozygous for the K198 allele (52.9 +/- 10.9 years; 4A/4A, 3A/4A + 198KK; t test: p < 0.01) and in the carriers of the 198N allele homozygous for the 3A allele (53 +/- 11.2 years; 3A/3A + 198KN,NN; t test: p < 0.05). CONCLUSIONS: We excluded an effect of K198N, 3A/4A, and T-1370G polymorphisms of EDN1 on the progression of ADPKD. However, a deleterious effect of the combination of 4A and 198N alleles of EDN1 was observed in APKDK individuals.

Aged↗

PubMed2006

The influence of the endothelin-converting enzyme-1 gene polymorphism on the progression of autosomal dominant polycystic kidney disease.

UNLABELLED: BACKGROUND; A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD), the most common renal hereditary disease. Endothelin-1 (ET-1) has been suggested to be an important disease-promoting factor of the kidney. Endothelin-converting enzyme-1 (ECE-1) is the main protease responsible for ET-1 generation by cleavage of its functionally inactive precursor. We examined the influence of the ECE-1b C-338A polymorphism on the progression of ADPKD toward end-stage renal disease (ESRD). The A allele was suggested to be associated with higher plasma level of ET-1. METHODS: 200 ADPKD patients (107 males, 93 females) who had reached ESRD were analyzed. Patients were divided into three groups: (1) 47 patients (23 males, 24 females) with ESRD later than in 63 yr (slow progressors); (2) 71 patients (38 males, 33 females) with ESRD before 45 yr (rapid progressors); and (3) 82 patients (46 males, 36 females) with ESRD between 45-63 yr. Moreover, we analyzed 160 genetically unrelated healthy Czech subjects as the control group (82 males, 78 females, mean age 51.4 +/- 8.2 yr). DNA samples from collected blood were genotyped for ECE-1b C-338A polymorphism using described polymerase chain reaction (PCR) followed by restriction enzyme digestion. We compared the frequencies of different genotypes between the groups of slow and rapid progressors and the ages of ESRD with regard to different genotypes. RESULTS: The ECE-1b C-338A genotype distribution showed no differences among the groups of slow progressors, rapid progressors, ADPKD group with ESRD between 45-63 yr and control group. Comparing the ages of ESRD of all patients, we did not find significant differences in the ages with regard to different genotypes: CC (51.5 +/- 10.1 yr), AC (51.6 +/- 11.4 yr), AA (48.2 +/- 5.9 yr). There was a tendency to lower age of ESRD in AA homozygotes in comparison with other genotypes (t-test, p = 0.12). We found no influence of gender. CONCLUSION: We excluded the effect of ECE-1b C-338A polymorphism on the progression of ADPKD. We could observe a mild tendency toward faster decline of renal function in AA homozygous individuals.

Aspartic Acid Endopeptidases↗

PubMed2006

Genetic basis of nephrotic syndrome--review.

Nephrotic syndrome (NS) is one of the most frequent syndromes characterized namely by heavy proteinuria. Majority of NS occurs as a sporadic form, the incidence of familial cases is from 3 to 5%. Seven genes have been recognized till present, which mutations are responsible for severe forms of NS: NPHS1, NPHS2, ACTN4, CD2AP and WT1, TRPC6, LAMB2. Proteins encoded by these genes (nephrin, podocin, alpha-actinin-4, an adapter protein anchoring CD2 and others) influence the function of the podocytes. In cases of mutation in NPHS1 gene, causing congenital nephrotic syndrome of the Finnish type (CNF), resistance to steroid therapy occurs regularly and recurrence of proteinuria after renal transplantation is about 20-25%. Mutations in NPHS2 gene lead to autosomal recessive steroid resistant nephrotic syndrome (histologically focal segmental glomerulosclerosis). It was concluded that patients with steroid resistant nephrotic syndrome (SRNS) with homozygous or compound heterozygous mutations in NPHS2 have reduced risk for recurrence of focal segmental glomerulosclerosis (FSGS) in renal transplant (only 8% in comparison with 35% in patients without mutation in NPHS2). A functional polymorphism of NPHS2 gene--R229Q was associated with a late-onset nephrotic syndrome and also with an increased risk of microalbuminuria in the general population. The R229Q variant encodes a protein with lower affinity for binding nephrin. This polymorphism appears to enhance susceptibility to FSGS in association with a second mutant NPHS2 allele. There are also 3 genetic loci connected with autosomal dominant forms of FSGS: ACTN4, TRPC6 and CD2AP (found only in the mice models). These forms of FSGS differ from the recessive form by later-onset and more slowly progressive course of the disease; these mutations seem to be responsible for only a fraction of the autosomal dominant pattern of FSGS.

Glomerulosclerosis, Focal Segmental↗

PubMed2006

[Urinary tract infection in patients with diabetes mellitus].

Urinary tract infection is an important infection in patients with diabetes mellitus. Asymptomatic and symptomatic infections of urinary tract, and also some rarer serious complications of urinary tract infections (papillary necrosis, renal and perirenal abscess, emphysematous and xantogranulomatous pyelonephritis and s.o.). Incidence, outcome and treatment in patients with diabetes, which deserve special clinical attention, are commonly viewed by prism of personal opinion, and should be based on clinical studies, focused on this topic.

Diabetes Complications↗

PubMed2006

The pathogenetic aspects and gene polymorphisms of IgA nephropathy.

Immunoglobulin A nephropathy is an immune-complex-mediated glomerulonephritis characterized by diffuse mesangial deposition of immunoglobulin A or IgA--containing immune complexes. Although its most common clinical presentation is macroscopic hematuria provoked by upper respiratory tract infection, this is neither universal nor necessary for the diagnosis. The patients with IgA nephropathy manifest with variable clinical symptoms (e.g., microhematuria with preserved renal function or progressive deterioration of renal functions resulting in end-stage renal disease). The pathogenetic mechanisms include the abnormality of O-glycosylation of the IgA1 molecule, genetic factors, environmental factors and various inflammatory mediators. The source of mesangial IgA deposits is total circulating serum IgA but the response of the mesangium and the mesangial cells to the deposited IgA is critical to the development of IgAN. Without a genetic predisposition to IgAN, IgA deposition can cause no risk for triggering glomerulonephritis. If generic progression risk factors of an unfavourable outcome coincide (e.g. hypertension, severe proteinuria, elevated serum creatinine level), this will increase the likelihood of progressive renal impairment. Further studies are needed to disclose the precise pathogenetic mechanisms involved in primary IgA nephropathy and to facilitate the development of newer therapeutic possibilities.

Glomerulonephritis, IGA↗

PubMed2006

Long-term outcome of patients with idiopathic membranous nephropathy.

Although idiopathic membranous nephropathy (iMN) is a common glomerular disease, its therapy still remains controversial. The aim of our study was to analyse the outcome of patients with iMN diagnosed and treated in our center. We retrospectively studied 82 patients with iMN that were diagnosed between January 1991 and June 2002. The group consisted of 57 males (69.5%) and 25 females (30.5%) with a mean age of 53 years. The mean follow-up was 56 +/- 38 months. Remission was achieved in 59.2% of patients treated with chlorambucil, 71.4% treated with cyclophosphamide, 85.7% treated with cyclosporine and in 71.4% of those who were left untreated intentionally. However, the proportion of patients in the different treatment subgroups differed significantly (60% vs. 8.5% vs. 8.5% vs. 23%, respectively). The relapse rate was 31.3%. The second-line treatment was effective in a majority of the patients. At the end of follow-up, almost 70% of the patients were in remission with the parameters of nephrotic syndrome significantly improved and renal function unchanged. The renal survival was 100%. Immunosuppressive therapy is effective in iMN, but spontaneous remissions occur as well. Although relapses are frequent, almost 70% of the patients were in remission at the end of follow-up. The renal survival in our group of iMN patients was very good, probably due to preserved renal function at diagnosis.

Adolescent↗

PubMed2006

Optimizing the therapeutic strategies in ANCA-associated vasculitis--single centre experience with international randomized trials.

ANCA-associated vasculitides, including Wegener's granulomatosis and microscopic polyangiitis, are systemic autoimmune diseases with poor prognosis in untreated patients, which can be dramatically improved by current therapeutic modalities. The aim of multi-centre randomized trials of the European Vasculitis Study Group is to optimise and standardise treatment of these diseases. From 1995-2001 our department contributed a total of 40 patients to the trials CYCAZAREM (cyclophosphamide versus azathioprine during remission for generalised vasculitis), MEPEX (plasma exchange versus methylprednisolone for severe renal vasculitis) and CYCLOPS (daily oral versus pulse cyclophosphamide during induction phase for generalised vasculitis). In this paper, we report on the preliminary results of long-term follow up of our patients included in international trials. The mean time of follow-up of the patients was 55.7 months with the patient survival rate of 72% and renal survival rate of 65%. Remission was achieved in 82% of patients, out of which 42% suffered a relapse. In generalised forms of vasculitides, treatment with cyclophosphamide is nowadays established as the standard therapy. The aim, however, is to further minimise its toxic effects by choosing the optimal therapeutic strategies. Complete results of all trials have not yet been published; nevertheless, the preliminary available data have already revealed new potential therapeutic approaches.

Adolescent↗

PubMed2005

[Reconstruction surgical procedures for iatrogenic injuries to the ureter. Examples of uncommon, however successful approaches to their management].

The authors present several less usual reconstructions of ureters after the primary iatrogenic lesions. The appropriate ureteric capacity to drain the urine after previous injury is quite demanding and hence before the definitive decision is made the wholesome health status of the patient is to be considered and all possible solutions should be weighted. The efficient primary urinary diversion above the lesion is unavoidable. The genuine reconstruction could be deferred by several weeks or months in the view that in some cases the least invasive (endourologic) methods can completely avoid the need of open surgery in difficult adhesions after previous major surgery.

Abdomen↗

PubMed2005

Does electron microscopy change the view of the diagnosis of IgA nephropathy?

Our study is aimed to reveal the frequency and clinical significance of the coincidence of two widely spread entities, e.g. minimal change disease (MCD) and IgA nephropathy (IgAN), claimed to be found in an overwhelming number in some Asian regions. We retrospectively analyzed clinical and histological data from 627 renal biopsies, performed in our department from January 2002 to January 2005 and completed electron microscopy in 112 specimens diagnosed as IgAN. The coincidence of IgAN and MCD was found in 8 patients (7.1%). The coincidence of IgAN and minimal change nephrotic syndrome (MCNS) clinically--especially presence of nephrotic syndrome and the response to drug therapy (with corticosteroids)--behaves as "pure" MCN. Our data from Czech Republic seem to suggest that the combination of IgAN with MCNS can be found relatively frequently not only in Asian patients (as stressed by some authors of Asian origin) but also in European inhabitants. The pathogenesis of the coincidence of IgAN and MCD needs to be elucidated by further studies.

Biopsy↗

PubMed2004

Daily oral versus pulse intravenous cyclophosphamide in the therapy of ANCA-associated vasculitis--preliminary single center experience.

The aim of the multicentric randomized trial CYCLOPS is to optimize the treatment of induction of remission in patients with generalized, but not immediately life-threatening ANCA (antineutrophil cytoplasmic antibodies) -associated vasculitis. This will be achieved by reducing the dose of cyclophosphamide by administering it as intermittent pulses. The lower cumulative dose will be very probably accompanied with lower toxicity, whereas the effectivity should be comparable. We have enrolled 28 patients to the study. At present, 18 of them are suitable for evaluation. Our preliminary results show that pulse intermittent administration of cyclophosphamide is safer from the point of morbidity and mortality due to infectious complications. In our hands, this treatment modality does not seem to be less effective than the conventional daily oral cyclophosphamide. However, unambiguous results and treatment recommendations will not be available until the final evaluation of all patients enrolled in the trial.

Administration, Oral↗

PubMed2004

Focal segmental glomerulosclerosis in solitary kidney in WAGR syndrome.

WAGR syndrome consists of Wilms' tumour, aniridia, genitourinary malformations and mental retardation, and is associated with chromosomal microdeletion of 11p13. We report a case of young male, exhibiting several typical features of WAGR syndrome (e.g. WT, aniridia and genitourinary abnormalities), but missing some other (mental retardation and chromosomal abnormality absent). Renal biopsy performed in our patient for unexplained proteinuria showed focal segmental glomerulosclerosis, presumably of secondary origin; the decrease of proteinuria was achieved by the firm control of BP in conjunction with the reduction of body weight.

Adult↗

PubMed2003

Current treatment strategies in ANCA-positive renal vasculitis-lessons from European randomized trials.

Antineutrophil cytoplasmic antibody (ANCA)-positive renal vasculitis is the most common cause of rapidly progressive (crescentic) glomerulonephritis. Its life-threatening natural course may be modified substantially by current treatment modalities. The European Vasculitis Study Group (EUVAS) developed a subclassification of ANCA-positive vasculitides based on the disease severity at presentation, and have organized (so far) two waves of clinical trials. The first wave of randomized clinical trials had the aim of optimizing the existing therapeutic regimens; the second wave concentrated on testing some newer therapeutic approaches. Here, the design and available results of the first wave and the design of some second wave trials are reviewed briefly. The potential of the new targeted approaches (e.g. anti-tumour necrosis factor therapy) is also briefly mentioned.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2003

Genetics of diabetic nephropathy.

Diabetic nephropathy (DN) develops in approximately 40% of type 1 diabetic patients and is a leading cause of end-stage renal failure. Its rate of progression varies greatly among individuals. Several factors, including genetic predisposition, metabolic and haemodynamic alterations and various growth factors, may contribute to the initiation and progression of DN. The genetic background of DN is believed to be polygenic. Polymorphisms of different genes, mainly from the renin-angiotensin system, have been studied extensively, and some of them have been suggested to contribute to the development of DN. A search for genes and combinations of genes which could influence the development and progression of DN is in progress.

Diabetes Mellitus, Type 1↗

PubMed2003

Current therapeutic possibilities in primary and secondary amyloidosis and our experience with 31 patients.

Primary (AL) and secondary (AA) amyloidosis are systemic diseases characterized by a process of amyloid deposition in many organs with unsatisfactory survival of patients. Apart from surgical intervention in those patients with bronchiectasias or osteomyelitis, the possibilities of influencing the development of AA amyloidosis are limited. The milestone therapy in patients with rheumatic diseases includes early treatment with DMARDs (disease-modifying antirheumatic drugs). A new promising therapeutic alternative is represented by anti-tumour necrosis factor-alpha (TNF-alpha) drugs such as infliximab and etanercept. The last class of agents used in the treatment of AA interferes with fibril formation: iododoxorubicin and low molecular weight sulfates (fibrilex). In the group of patients with AL, in addition to the standard combination of melphalan and prednisone, other therapeutic approaches such as ASCT (autologous stem cell transplantation) and new drugs with different mechanisms of action have been added recently. For the future, we can expect the development of immunotherapy (both active vaccination and passive immunization). In our department, we have treated 17 patients with AL and 14 patients with AA amyloidosis since 1995. We used various treatment regimens in both groups of patients. The treatment stabilized the disease or achieved partial remission in only 36% of patients with AA amyloidosis despite the use of intensive therapeutic modalities, while in the AL group a response was achieved in 82% of patients. ASCT improves patients survival in AL amyloidosis, but strict selection criteria are necessary (less than two affected organs and no signs of myocardial dysfunction).

Adult↗

PubMed2003

Role of endothelin and nitric oxide in the pathogenesis of arterial hypertension in autosomal dominant polycystic kidney disease.

The pathogenesis of arterial hypertension in autosomal dominant polycystic kidney disease (ADPKD) is complex and likely dependent on interaction of hemodynamic, endocrine and neurogenic factors. We decided to evaluate the role of endothelin (ET1) and nitric oxide (NO) in the regulation of arterial blood pressure (BP) and to determine plasma levels of ET1 and NO in the group of patients with ADPKD. The ADPKD group (18 patients, 6 men + 12 women, mean age 44.6+/-11.7 years, with creatinine clearancecorrig > 1.1 ml/s) was compared with a control group of 27 healthy volunteers of comparable age. Plasma levels of ET1 assessed by direct RIA determination in the group of ADPKD patients (11.03+/-1.8 fmol/ml) were significantly increased (p<0.001) in comparison with the control group (2.66+/-0.58 fmol/ml), while no significant differences were observed between normotensive and hypertensive patients in the ADPKD group. Serum levels of NO were evaluated according to the determination of serum levels of their metabolites - nitrites/nitrates. Serum levels of NO in the group of ADPKD patients (39.85+/-.38 micro mol/l) were significantly higher (p<0.05) in comparison with the control group (22.7+/-1.20 micro mol/l), whereas in the ADPKD group no significant differences were observed between normotensive and hypertensive patients. Thus, our study supports the concept of complex alteration of both vasoconstrictor and vasodilator systems in the pathogenesis of arterial hypertension in ADPKD.

Adult↗

PubMed2003

[Is the current treatment of primary and secondary amyloidosis effective?].

BACKGROUND: Retrospective study about results of treatment of patients (pts) with primary (AL) and secondary (AA) amyloidosis is given. 31 pts with systemic forms of amyloidosis have been treated and followed-up in our department since 1993. METHODS AND RESULTS: 6 men and 11 women were in the AL group with the mean age of 59 years. Multiple myeloma was diagnosed in 9 pts, monoclonal gammapathy of undetermined significance (MGUS) was found in 8 pts. The kidneys were affected in all pts, heart in 59% of pts, liver, joints and skin in 26% of pts and polyneuropathy was detected only in 1 pt. Progression of renal insufficiency with decrease of glomerular filtration rate (GFR) was detected in the AL group at the end of follow-up period compared with the initial level (p < 0.05) despite the intensive treatment. The difference did not reach statistical significance in other investigated parameters. Median of survival was 13 months from the assessment of diagnosis. Partial remission of amyloidosis was achieved in 9 pts, stable disease was in 5 pts and in 3 pts the disease progressed. 4 men and 10 women were in the AA group with mean age of 58 years. Underlying disease was rheumatoid arthritis in 7 pts, ankylosing spondylitis in 2 pts, juvenile chronic arthritis in 1 pt, Crohn's disease in 2 pts, eosinophilic fasciitis in 1 pt and chronic abscesses in NK cell deficiency in 1 pt. The kidneys were affected in all pts, bowels and heart in 36% of pts. GFR (p < 0.05) and plasma creatinine (p < 0.01) significantly decreased at the end of follow-up period compared with initial levels. Median of survival was 30 months. Partial remission was achieved in 2 pts, stable disease was in 3 pts and progression was detected in 9 pts despite the use of various treatment regimens. CONCLUSIONS: Both forms of systemic amyloidosis represent severe disease with limited response to treatment. The use of new drugs is promising and could lead to better response to treatment.

Adult↗

PubMed2003

[Fibrillary glomerulonephritis].

An overview of fibrillary glomerulonephritis (GN) is given as well as the description of clinical course in four patients diagnosed and treated in our department. Fibrillary GN and immunotactoid glomerulopathy are entities, characterized by fibrillar and microtubular deposits in mesangium and the glomerular capillary loops. Decisive for diagnosis of fibrillary GN (resp. immunotactoid GN) remains the electron microscopy (EM) of the renal biopsy (RB) specimen. At the nephrologic division of 1st Internal Department of 1st Medical School of Charles University four cases of patients with fibrillary GN were diagnosed from the mid seventies (when both entities were newly described) by the end of the year 2001. In all patients the diagnosis was proven by EM. RB was indicated mainly for proteinuria, hematuria and decrease of renal function. On conclusion: though fibrillary GN/immunotactoid GN are relatively rare disorders, they represent entities, which should not be omitted in the differential diagnosis of nephrotic syndrome/renal insufficiency and which deserve further study.

Aged↗

PubMed2003

[Leptin in patients wit nephrotic syndrome].

Nephrotic syndrome (NS) remains a serious clinical setting characterized by marked proteinuria, hypoproteinemia and hypercholesterolemia, usually accompanied by the presence of oedemas. It could be presumed, that the newly discovered hormone leptin plays an important role in the complex metabolic processes occurring in patients with NS, in which apart from the changes in the hydratation, and the protein and lipid spectre profile changes, the alteration of the metabolism of glycides elicited by the treatment with corticosteroids (CS) is often observed. The aim of the study was to investigate the plasma levels of leptin and its plasma soluble receptor (sLe-R) before and after the treatment with CS and to evaluate their relationship with albuminemia and/or proteinuria. The study group consisted of 15 men and 15 women (mean age 49 +/- 13.7 years) with newly diagnosed NS, verified by renal biopsy, in which subsequently CS treatment was started. Before the treatment (period 1) and further one month (period 2) and six months (period 3) after the start of the treatment the following parameters were measured: body mass index (BMI), serum levels of creatinine, albumin, cholesterol, triglyceride, cholinesterase, proteinuria/24 hour and plasma levels of leptin and sLe-R. In comparison to the relatively high values of BMI in the period 1 a decrease of BMI towards the physiologic range was observed during the treatment periods. Statistically significant changes were also observed in proteinuria (decrease) and in serum cholesterol and albumin levels of whereas in other biochemical parameters, including plasma leptin and sLe-R levels, statistically significant changes were not found. A trend to negative correlation with borderline statistical significance could be observed between leptin and sLe-R. The results of our relatively unique study on leptin--dealing with long-term follow-up of the patients with NS suggest that regardless prominent metabolic alterations present in NS the plasma levels of leptin and sLe-R remain relatively stable, and that of regulation of leptin in this setting is probably complex and multifactorial.

Adolescent↗