BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS. METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 mg/d) or irbesartan (300 mg/d) for 8 weeks, followed by open-label sparsentan only. End points at week 8 were reduction from baseline in UP/C (primary) and proportion of patients achieving FSGS partial remission end point (FPRE) (UP/C: ≤1.5 g/g and >40% reduction [secondary]). RESULTS: Of 109 patients randomized, 96 received study drugs and had baseline and week 8 UP/C measurements. Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients did when all doses (45% versus 19%; P=0.006) or the 400 and 800 mg doses (47% versus 19%; P=0.01) were pooled for analysis. The FSGS partial remission end point was achieved in 28% of sparsentan-treated and 9% of irbesartan-treated patients (P=0.04). After 8 weeks of treatment, BP was reduced with sparsentan but not irbesartan, and eGFR was stable with both treatments. Overall, the incidence of adverse events was similar between groups. Hypotension and edema were more common among sparsentan-treated patients but did not result in study withdrawals. CONCLUSIONS: Patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan versus irbesartan. Sparsentan was safe and well tolerated.

• Klíčová slova
• angiotensin II, endothelin, focal segmental glomerulosclerosis, proteinuria, sparsentan,
• MeSH
• antagonisté endotelinového receptoru A aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• blokátory receptoru 1 pro angiotenzin II aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• dítě MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fokálně segmentální glomeruloskleróza farmakoterapie   moč   MeSH
• irbesartan aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kreatinin moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• proteinurie farmakoterapie   moč   MeSH
• senioři MeSH
• spirosloučeniny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• sulfonamidy aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté endotelinového receptoru A MeSH
• blokátory receptoru 1 pro angiotenzin II MeSH
• irbesartan MeSH
• kreatinin MeSH
• sparsentan MeSH Prohlížeč
• spirosloučeniny MeSH
• sulfonamidy MeSH

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.

• MeSH
• fokálně segmentální glomeruloskleróza genetika   MeSH
• lidé MeSH
• mutace MeSH
• nefrotický syndrom vrozené   genetika   patofyziologie   MeSH
• polymorfismus genetický MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

RATIONALE & OBJECTIVE: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years. STUDY DESIGN: Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years. SETTING & PARTICIPANTS: Patients with FSGS, excluding secondary FSGS. INTERVENTION: Sparsentan (200, 400, and 800 mg/d). OUTCOMES: Urinary protein-creatinine ratio, FSGS partial remission endpoint (urinary protein-creatinine ratio ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years. RESULTS: 109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during the double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95% CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of estimated glomerular filtration rate decline over the entire treatment period (-2.70 vs -6.56; P = 0.03) and in the first 2 years (-1.69 vs -6.46; P = 0.03). The most common treatment-emergent adverse events (>9 cases/100 patient-years) were headache, peripheral edema, upper respiratory infection, hyperkalemia, and hypotension. Peripheral edema and hypotension declined from year 1 (13.9% and 15.7% of patients, respectively) to ≤4% in years ≥2. There were no cases of heart failure and no patient deaths. LIMITATIONS: The open-label extension does not include a comparison group. CONCLUSIONS: Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.

There is substantial unmet clinical need for safe and effective treatments for focal segmental glomerulosclerosis (FSGS), a kidney lesion with varied causes. Sparsentan is being studied for treatment of FSGS and targets 2 important pathways (endothelin-1 and angiotensin II) that lead to the loss of kidney function. In the 8-week randomized, double-blind DUET study in patients with FSGS, sparsentan reduced the amount of protein in the urine better than irbesartan (a blood pressure medicine often used to treat FSGS). We examined long-term treatment with sparsentan over >4 years in the DUET open-label extension. We found sustained proteinuria reduction in patients who continued treatment with sparsentan and a consistent safety profile with no new or unexpected adverse effects.

• Klíčová slova
• FPRE, FSGS partial remission endpoint, eGFR slope, kidney function, open-label extension, proteinuria, randomized controlled clinical trial, sparsentan,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: An unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin-angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer-term treatment with sparsentan for FSGS are unknown. METHODS: In this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of ≤1.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy end point was the estimated glomerular filtration rate (eGFR) slope at the time of the final analysis. The change in eGFR from baseline to 4 weeks after the end of treatment (week 112) was a secondary end point. Safety was also evaluated. RESULTS: A total of 371 patients underwent randomization: 184 were assigned to receive sparsentan and 187 to receive irbesartan. At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan group (P = 0.009), a response that was sustained through 108 weeks. At the time of the final analysis at week 108, there were no significant between-group differences in the eGFR slope; the between-group difference in total slope (day 1 to week 108) was 0.3 ml per minute per 1.73 m2 of body-surface area per year (95% confidence interval [CI], -1.7 to 2.4), and the between-group difference in the slope from week 6 to week 108 (i.e., chronic slope) was 0.9 ml per minute per 1.73 m2 per year (95% CI, -1.3 to 3.0). The mean change in eGFR from baseline to week 112 was -10.4 ml per minute per 1.73 m2 with sparsentan and -12.1 ml per minute per 1.73 m2 with irbesartan (difference, 1.8 ml per minute per 1.73 m2; 95% CI, -1.4 to 4.9). Sparsentan and irbesartan had similar safety profiles, and the frequency of adverse events was similar in the two groups. CONCLUSIONS: Among patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan. (Funded by Travere Therapeutics; DUPLEX ClinicalTrials.gov number, NCT03493685.).

• MeSH
• biologické markery MeSH
• dítě MeSH
• dospělí MeSH
• fokálně segmentální glomeruloskleróza * komplikace   farmakoterapie   patofyziologie   MeSH
• hodnoty glomerulární filtrace MeSH
• indukce remise MeSH
• irbesartan * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kreatinin MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• proteinurie * farmakoterapie   etiologie   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• biologické markery MeSH
• irbesartan * MeSH
• kreatinin MeSH
• sparsentan MeSH Prohlížeč

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.

• Klíčová slova
• children, focal-segmental glomerulosclerosis, recurrence, renal transplantation, steroid-resistant nephrotic syndrome,
• MeSH
• dítě MeSH
• fokálně segmentální glomeruloskleróza prevence a kontrola   terapie   MeSH
• glukokortikoidy terapeutické užití   MeSH
• léková rezistence MeSH
• lidé MeSH
• nefrotický syndrom prevence a kontrola   terapie   MeSH
• pooperační komplikace prevence a kontrola   terapie   MeSH
• recidiva MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• transplantace ledvin * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• Názvy látek
• glukokortikoidy MeSH

The aim of the study was to characterize by molecular profiling two glomerular diseases: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) and to identify potential molecular markers of IgAN and FSGS progression. The expressions of 90 immune-related genes were compared in biopsies of patients with IgAN (n=33), FSGS (n=17) and in controls (n=11) using RT-qPCR. To identify markers of disease progression, gene expression was compared between progressors and non-progressors in 1 year follow-up. The results were verified on validation cohort of patients with IgAN (n=8) and in controls (n=6) using laser-capture microdissection, that enables to analyze gene expression separately for glomeruli and interstitium. In comparison to controls, patients with both IgAN and FSGS, had lower expression of BAX (apoptotic molecule BCL2-associated protein) and HMOX-1 (heme oxygenase 1) and higher expression of SELP (selectin P). Furthermore, in IgAN higher expression of PTPRC (protein-tyrosine phosphatase, receptor-type C) and in FSGS higher expression of BCL2L1 (regulator of apoptosis BCL2-like 1) and IL18 compared to control was observed. Validation of differentially expressed genes between IgAN and controls on another cohort using laser-capture microdissection confirmed higher expression of PTPRC in glomeruli of patients with IgAN. The risk of progression in IgAN was associated with higher expression EDN1 (endothelin 1) (AUC=0.77) and FASLG (Fas ligand) (AUC=0.82) and lower expression of VEGF (vascular endothelial growth factor) (AUC=0.8) and in FSGS with lower expression of CCL19 (chemokine (C-C motif) ligand 19) (AUC=0.86). Higher expression of EDN1 and FASLG along with lower expression of VEGF in IgAN and lower expression of CCL19 in FSGS at the time of biopsy can help to identify patients at risk of future disease progression.

• MeSH
• dospělí MeSH
• fokálně segmentální glomeruloskleróza genetika   patologie   MeSH
• IgA nefropatie genetika   patologie   MeSH
• kohortové studie MeSH
• ledviny metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prospektivní studie MeSH
• senioři MeSH
• stanovení celkové genové exprese metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease, characterized by progressive renal function deterioration, nephrotic proteinuria, and risk of chronic renal failure. We present long-term results of 5 patients with primary FSGS and recurrence of nephrotic proteinuria after renal transplantation treated with plasma exchange (PE) and immunoadsorption (IA). METHODS: We retrospectively investigated the relationship between the delay in initiation of the therapy and treatment outcomes, particularly achievement of remission of proteinuria. RESULTS: Remission occurred in all three patients who started PE/IA in interval 3-7 days after diagnosis of recurrence of FSGS. Remission was achieved after 3-4 weeks in two patients with 3 days of delay to the start of PE. The third patient (PE started with 7 days of delay) reached complete remission after 6 months of PE/IA treatment. All these patients had remission sustainable for a long time. The remaining two patients with 14 and 406 days of delay to PE treatment did not achieve remission sustainable for a long time. The two patients who did not achieve remission developed end-stage renal disease with graft loss (1 and 6.7 years after transplantation). Patients who achieved remission of proteinuria during PE/IA treatment have still functioning grafts (2.8, 9.7 and 3.8 years after renal transplantation). All these patients are still treated with PE/IA. CONCLUSIONS: The present 5 cases suggest that if recurrence of FSGS occurs, the probability of achieving remission is dependent on the early initiation of PE/IA therapy. Therefore, we suggest that PE/IA treatment might be started as soon as possible after recurrence of FSGS.

• MeSH
• časové faktory MeSH
• chronické selhání ledvin epidemiologie   MeSH
• dítě MeSH
• fokálně segmentální glomeruloskleróza patofyziologie   terapie   MeSH
• imunosorpční techniky MeSH
• indukce remise MeSH
• lidé MeSH
• mladiství MeSH
• plazmaferéza metody   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• proteinurie epidemiologie   etiologie   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• transplantace ledvin * MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Proteinuria has been recently shown to be an independent risk factor for the progression of chronic nephropathies, but the actual mechanisms by which urinary protein load damages renal tissue in humans remain unsolved. Using real-time RT-PCR method we evaluated intrarenal mRNA expression of various cytokines and chemokines in patients with biopsy-proven IgA nephropathy (IgAN, n=11), membranous nephropathy (MN, n=6) and focal and segmental glomerulosclerosis (FSGS, n=6) who exhibited proteinuria over 0.5 g/day. There was a significant positive correlation between the proteinuria extent and the intrarenal RANTES (regulated upon activation normal T cell expressed and secreted) mRNA expression in patients with IgAN, a similar trend was also observed in patients with MN and FSGS. There were no clear relationships between the proteinuria and intrarenal mRNA expression of tumor necrosis factor alpha, transforming growth factor beta1 and monocyte chemoattractant peptide-1. There were no differences in the pattern of cytokine mRNA expression between different glomerulopathies. In conclusion, our results support the hypothesis that lymphocytes, macrophages and their products provoke tissue injury in response to proteinuria independently of the nature of renal diseases in man.

• MeSH
• chemokin CCL5 genetika   MeSH
• chemokiny analýza   genetika   MeSH
• cytokiny analýza   genetika   MeSH
• dospělí MeSH
• exprese genu * MeSH
• fokálně segmentální glomeruloskleróza etiologie   genetika   metabolismus   MeSH
• IgA nefropatie etiologie   genetika   metabolismus   MeSH
• ledviny chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membranózní glomerulonefritida etiologie   genetika   metabolismus   MeSH
• messenger RNA analýza   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteinurie komplikace   genetika   metabolismus   MeSH
• senioři 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
• srovnávací studie MeSH
• Názvy látek
• chemokin CCL5 MeSH
• chemokiny MeSH
• cytokiny MeSH
• messenger RNA MeSH

Idiopathic focal segmental glomerulosclerosis (FSGS) is believed to be caused by a circulating permeability factor. FSGS recurrence is common after transplantation. The treatment is still a matter of debate; plasmapheresis (PE) and immunoadsorption (IA) are often used. We report on PE and IA in the treatment of two children with recurrent nephrotic proteinuria. Patient 1 was a 16-year-old girl who had recurrence of nephrotic proteinuria on the first day after transplantation (proteinuria-19 g/d). Primary immunosuppressive therapy was changed to high-dose cyclosporine and cyclophosphamide; plasmapheresis was started on day 4. Altogether we performed 53 PE and 38 IA procedures. During the first month, PE procedures were performed with no more than a 2-day interval between sessions, and the girl achieved partial remission (proteinuria 3 g/d). PE was then stopped. After 2 months, a relapse of heavy proteinuria occurred. This relapse was successfully treated again with intensified PE treatment. After achieving remission, a chronic PE regimen was started (PE once a week), similar to the previous series. The child remained in partial remission. Seven months after renal transplantation, she was switched from PE to IA, because of severe hypoproteinemia. Graft biopsy performed at 4 months showed effacement of the foot processes. At the present time she has a good graft function and 3 g/d proteinuria. Patient 2 was a 13-year-old girl with FSGS since 9 years. On the second day after renal transplantation she developed nephrotic proteinuria (proteinuria-14 g/d), which was treated with 39 PE and 16 IA treatments. She went into complete remission on the intensified PE regimen, had one relapse, and was switched to chronic IA. Graft biopsy performed at 2 weeks after transplantation showed effacement of the foot processes. At the present time she has good graft function and low proteinuria (0.3 g/d). In conclusion, intensified PE or IA treatments induced remission of recurrent nephrotic range proteinuria. Chronic PE or IA can maintain patients with frequent relapses in long-term remission.

• MeSH
• fokálně segmentální glomeruloskleróza chirurgie   MeSH
• imunosorpční techniky * MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• plazmaferéza * MeSH
• pooperační komplikace terapie   MeSH
• proteinurie terapie   MeSH
• recidiva MeSH
• transplantace ledvin * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunosupresiva MeSH

α-Actinin 4, encoded by ACTN4, is an F-actin crosslinking protein which belongs to the spectrin gene superfamily. It has a head-to-tail homodimer structure with three main domains. Mutations in ACTN4 are associated with idiopathic nephrotic syndrome (NS). However, until today only a few mutations have been described in this gene. We used genomic DNA of 48 patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) to screen for ACTN4 mutations by high-resolution melting analysis (HRM). Suspect samples were sequenced and compared with healthy controls. To investigate the prevalence and possible effect of some substitutions found in FSGS/MCD patients we also looked for these changes in patients with IgA nephropathy (IgAN) and membranous glomerulonephritis (MGN). We found 20 exonic and intronic substitutions in the group of 48 Czech patients. The substitution 2242A>G (p.Asn748Asp) is a candidate mutation which was identified in one patient but not in any of the 200 healthy controls. Exon 19 seems to be a variable region due to the amount of revealed polymorphisms. In this region we also found three unreported substitutions in IgAN patients, c.2351C>T (p.Ala784Val), c.2378G>A (p.Cys793Tyr) and c.2393G>A (p.Gly798Asp). These substitutions were not found in any tested healthy controls. To conclude, the ACTN4 mutations are not a frequent cause of FSGS/MCD in Czech adult patients. One new ACTN4 mutation has been identified.

• MeSH
• aktinin genetika   MeSH
• bodová mutace MeSH
• denaturace nukleových kyselin MeSH
• dospělí MeSH
• exony genetika   MeSH
• fokálně segmentální glomeruloskleróza epidemiologie   genetika   MeSH
• IgA nefropatie epidemiologie   genetika   MeSH
• introny genetika   MeSH
• konsenzuální sekvence MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoidní nefróza epidemiologie   genetika   MeSH
• membranózní glomerulonefritida genetika   MeSH
• missense mutace MeSH
• molekulární sekvence - údaje MeSH
• mutační analýza DNA MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• substituce aminokyselin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku 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
• ACTN4 protein, human MeSH Prohlížeč
• aktinin MeSH