Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations.

• Klíčová slova
• Focal segmental glomerulosclerosis, Infections, Long-term remission, Minimal change disease, Nephrotic syndrome, Rituximab,
• MeSH
• dospělí MeSH
• fokálně segmentální glomeruloskleróza * farmakoterapie   MeSH
• imunologické faktory terapeutické užití   MeSH
• imunosupresiva škodlivé účinky   MeSH
• lidé MeSH
• lipoidní nefróza * farmakoterapie   MeSH
• nefrotický syndrom MeSH
• recidiva MeSH
• rituximab terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• imunologické faktory MeSH
• imunosupresiva MeSH
• rituximab MeSH

Blood filtration and formation of primary urine in the kidney glomerulus is provided by a specialized membrane called slit diaphragm located between well-branched pedicels of podocytes. Actually, the slit diaphragm is a protein supercomplex, whose disruption can cause failure of renal filtration, and patients usually manifest nephrotic syndrome. Recently, familial forms of nephrotic syndrome have been described which arise from malfunction of mutated proteins making up the slit diaphragm. In 2005 it was found that one of the proteins present in this complex was non-selective cation channel TRPC6. The aim of this work was to screen mutations and polymorphisms of the TRPC6 gene in a group of 64 Czech patients with nephrotic syndrome and subsequently, on the basis of these data, evaluate the role of mutations in the TRPC6 gene in Czech population. The analysis was performed by the PCR method followed by direct sequencing and high-resolution melting method. We have not identified any mutations in our group of patients. Two additional single nucleotide polymorphisms - p.P15S and p.A404V - were detected along with nucleotide changes that did not result in amino acid changes and with a few intronic changes. P.P15S heterozygotes were more frequent in patients with steroid-resistant FSGS than in steroid- sensitive patients (29 % versus 12.1 %). To conclude, we did not find any probable disease-causing mutation in the TRPC6 gene in the cohort of 64 Czech patients. The p.P15S polymorphism might have some influence on the therapeutic response of FSGS patients.

• MeSH
• dospělí MeSH
• fokálně segmentální glomeruloskleróza genetika   MeSH
• kationtové kanály TRPC genetika   MeSH
• kationtový kanál TRPC6 MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoidní nefróza genetika   MeSH
• mladý dospělý MeSH
• mutace MeSH
• mutační analýza DNA * MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• kationtové kanály TRPC MeSH
• kationtový kanál TRPC6 MeSH
• TRPC6 protein, human MeSH Prohlížeč

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.

• MeSH
• biopsie MeSH
• elektronová mikroskopie MeSH
• IgA nefropatie diagnóza   patologie   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• lipoidní nefróza diagnóza   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Fifty-eight needle biopsies of the kidneys with the light microscopical diagnosis of so-called minimal glomerular lesions were subjected to ultrastructural evaluation. The series contained children and adults under 25 years of age with the mean age of 16.9 years. The most frequent findings were those of the glomerular epithelia: vacuolation and swelling of their cytoplasm in 72.8%, microvilloustransformation in 13.6%. Endothelial lesions were less frequent: swelling and vacuolation of their cytoplasm occurred in 46.6%. The most important ultrastructural lesions appeared to be the mesangial ones. Focal increase in the mesangial matrix was seen in 44.8% and small intralobular scars in 13.6%. True focal increase in mesangial cells was rare (6.9%). The formation of duplicatures of the basement membranes in the glomeruli was exceptional (3.6%). Another important ultrastructural finding was a focal thickening of the basement membrane in a larger number of cases (32.3%). Deposits were found rarely (7 cases, 12.1%) most of them occurring in the mesangium. The cellularity of the glomeruli did not exceed the normal range.

• MeSH
• biopsie MeSH
• glomerulus ultrastruktura   MeSH
• lidé MeSH
• lipoidní nefróza patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

• MeSH
• chronická nemoc MeSH
• glomerulonefritida farmakoterapie   moč   MeSH
• lidé MeSH
• lipoidní nefróza farmakoterapie   moč   MeSH
• methylprednisolon aplikace a dávkování   škodlivé účinky   MeSH
• proteinurie MeSH
• rozvrh dávkování léků MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• methylprednisolon MeSH

BACKGROUND: Mutations in INF2 are frequently responsible for focal segmental glomerulosclerosis (FSGS), which is a common cause of end stage renal disease (ESRD); additionally, they are also connected with Charcot-Marie-Tooth neuropathy. INF2 encodes for inverted formin 2. This protein participates in regulation of the dynamics of the actin cytoskeleton, involving not only the polymerisation, but also the depolymerisation of filaments. The present study is the first mutational analysis of INF2 done in the Czech Republic. METHODS: Mutational analysis of INF2 was performed on 109 patients (mean age at onset 41.44 ± 18.91 years) with FSGS or minimal change disease (MCD); and also in 6 patients without renal biopsy who had already developed chronic kidney disease (CKD)/ESRD at the time of diagnosis. We used high resolution melting method (HRM), with subsequent Sanger sequencing, in suspect samples from HRM analysis. The HRM method is an effective method for the screening of large cohorts of patients. RESULTS: Two pathogenic mutations (p.Arg214His and p.Arg218Gln) were detected in INF2. The first (p.Arg214His) was identified in the FSGS patient with a positive family history. The second mutation (p.Arg218Gln) was found in two brothers with ESRD of unknown etiology. The most frequent sequence change was the substitution p.P35P, the incidence of which corresponded with the frequencies available in the ExAC Browser and gnomAD Browser databases. This analysis also detected different exonic and intronic changes that probably did not influence the phenotype of the included patients. CONCLUSIONS: The INF2 mutational screening is useful in familial FSGS cases as well as in patients with an unknown cause for their ESRD, but with a positive family history. INF2 seems to be not only the cause of FSGS, but also of ESRD of unknown etiology. Our study has confirmed that the HRM analysis is a very useful method for the identification of single nucleotide substitutions.

• Klíčová slova
• End stage renal disease, Focal segmental glomerulosclerosis, High resolution melting method, INF2, Minimal change disease,
• MeSH
• Charcotova-Marieova-Toothova nemoc genetika   metabolismus   MeSH
• chronické selhání ledvin genetika   metabolismus   MeSH
• dospělí MeSH
• exony genetika   MeSH
• fenotyp MeSH
• fokálně segmentální glomeruloskleróza genetika   metabolismus   MeSH
• forminy MeSH
• introny genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• mikrofilamentové proteiny genetika   metabolismus   MeSH
• mutace genetika   MeSH
• mutační analýza DNA metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• forminy MeSH
• INF2 protein, human MeSH Prohlížeč
• mikrofilamentové proteiny MeSH

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.

• Klíčová slova
• AAV, ANCA, C3, FSGS, IgA nephropathy, IgA vasculitis, KDIGO, MPGN, anti-GBM, complement, evidence-based, glomerular diseases, glomerulonephritis, guideline, infection-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, nephrotic syndrome, systematic review,
• MeSH
• dítě MeSH
• dospělí MeSH
• glomerulonefritida * diagnóza   terapie   MeSH
• IgA nefropatie * diagnóza   terapie   MeSH
• ledviny MeSH
• lidé MeSH
• lipoidní nefróza * MeSH
• membranózní glomerulonefritida * diagnóza   farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• směrnice pro lékařskou praxi MeSH

In mantle cell lymphoma (MCL), minimal residual disease (MRD) is an indicator of the disease outcome. Quantitative methods used so far do not provide a suitable molecular marker in 30-70% patients with MCL (depending on the technique used). We tested cyclin D1 as a marker for quantitative MRD monitoring. The real-time PCR of cyclin D1 mRNA was performed in 144 bone marrow (BM) specimens including 95 BMs from MCL patients, 39 BMs from patients with other B-cell non-Hodgkin's lymphomas and 10 BMs from healthy volunteer donors. In 73 BMs obtained from 20 MCL patients we examined the cyclin D1 level during the treatment and follow-up period. We detected a cyclin D1 overexpression exclusively in BMs infiltrated with MCL, including minimal residual infiltration. Dynamics of cyclin D1 correlated with the patient's clinical status in 69/73 BMs. Individual monitoring of patients during the disease course showed cyclin D1 quantitative changes accompanying either the disease relapse or a successful treatment response or the disease-free survival (remission) and it showed a predictive significance. Cyclin D1 detection is a promising approach for the quantitative MRD monitoring in MCL patients, and the individual monitoring of the cyclin D1 dynamics represents a suitable indicator of the disease course.

• MeSH
• cyklin D1 genetika   metabolismus   MeSH
• dospělí MeSH
• kostní dřeň metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk diagnóza   metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• polymerázová řetězová reakce MeSH
• prediktivní hodnota testů MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• reziduální nádor diagnóza   metabolismus   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklin D1 MeSH
• messenger RNA MeSH
• nádorové biomarkery MeSH

• MeSH
• aktivace lymfocytů * MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• lipoidní nefróza imunologie   MeSH
• lymfocyty klasifikace   imunologie   MeSH
• mladiství MeSH
• předškolní dítě MeSH
• tvorba rozet MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

BACKGROUND: We describe data on 10,472 renal biopsies gathered by the Czech Registry of Renal Biopsies over a period of 18 years. METHODS: We assessed the main demographic, clinical and histological data of individuals who underwent renal biopsies of native kidneys in 31 centers in the Czech Republic (population 10.3 million) during the period 1994-2011. RESULTS: We evaluated 10,472 renal biopsies: males 57.8%, children (≤15 years) 13.6%, elderly (>60 years) 19.1%. The most frequent biopsy-proven diseases were primary (55.7%) and secondary (29.1%) glomerulonephritides (GN). Tubulointerstitial nephritis (TIN) was observed in 3.4 % and vascular diseases in 4.1%. The samples were non-diagnostic in 4.2%. Among primary GN the most frequent diagnoses were IgA nephropathy (IgAN) (37.4%), membranous GN (MGN) (13%) and focal segmental glomerulosclerosis (FSGS) (12.6%). Among secondary GN, systemic lupus erythematosus (SLE) represented 23.2%, hereditary diseases 19.8% and necrotizing vasculitis (NV) 19.4%. Among adults, mild renal insufficiency [serum creatinine (SCr) 111-200 μmol/l] was present in 24.7%, advanced renal insufficiency (SCr 201-400 μmol/l) in 15.3, and 12.3% of patients had SCr > 400 μmol/l. The most common diseases in patients with nephrotic proteinuria were minimal change disease (MCD) (39.7%) among children, IgAN (26.2%) in adults aged 16-60 years and amyloidosis (42.7%) among the elderly. The mean annual incidence (per million population) was: primary GN 30.9, secondary GN 18.1, IgAN 11.6, MGN 4.0, SLE 4.0, FSGS 3.9, MCD 3.4, NV 3.2, diabetic nephropathy 2.3, thin basement membrane glomerulopathy 2.0, mesangioproliferative GN 1.9, and TIN 1.9. Ultrasound needle guidance was used in 66.8%. The frequency of serious complications (symptomatic hematoma, gross hematuria, blood transfusion) was approximately 3.2%. CONCLUSIONS: This report provides representative population-based data on native biopsy-proven renal diseases in the Czech Republic. Over the 18 years of nationwide biopsy survey, we noted an increase of the mean age of renal biopsy cases, an increasing proportion of elderly, and a cardinal change in biopsy technique towards ultrasonography needle guidance.

• MeSH
• amyloidóza patologie   MeSH
• chronická renální insuficience patologie   MeSH
• dědičná nefritida patologie   MeSH
• diabetické nefropatie epidemiologie   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• glomerulonefritida epidemiologie   patologie   MeSH
• incidence MeSH
• kojenec MeSH
• ledviny patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoidní nefróza epidemiologie   patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nekróza epidemiologie   etiologie   patologie   MeSH
• nemoci ledvin epidemiologie   patologie   MeSH
• předškolní dítě MeSH
• registrace MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ultrazvukem navigovaná biopsie škodlivé účinky   MeSH
• vaskulitida komplikace   epidemiologie   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH