BACKGROUND: In patients with multiple myeloma (MM) free light chain-induced cast nephropathy is a serious complication associated with poor survival. High-cut-off (HCO) hemodialysis can reduce the amount of serum free light chains (sFLC), but data on its impact on clinical outcome is limited and contradictory. To gain further insights we collected real world data from two major myeloma and nephrology centers in Austria and the Czech Republic. METHODS: Sixty-one patients with MM and acute kidney injury, who were treated between 2011 and 2019 with HCO hemodialysis and bortezomib-based MM therapy, were analyzed. RESULTS: The median number of HCO hemodialysis sessions was 11 (range 1-42). Median glomerular filtration rate at diagnosis was 7 ± 4.2 ml/min/1.73m2. sFLC after the first HCO hemodialysis decreased by 66.5% and by 89.2% at day 18. At 3 and 6 months, 26 (42.6%) and 30 (49.2%) of patients became dialysis-independent. CONCLUSION: The widely used strategy combining HCO hemodialysis and bortezomib-based antimyeloma treatment is dissatisfactory for half of the patients undergoing it and clearly in need of improvement.

• Klíčová slova
• Acute kidney injury, Bortezomib, Cast nephropathy, High-cut-off (HCO) hemodialysis, Multiple myeloma,
• MeSH
• akutní poškození ledvin * diagnóza   terapie   MeSH
• bortezomib škodlivé účinky   MeSH
• dialýza ledvin škodlivé účinky   MeSH
• lehké řetězce imunoglobulinů MeSH
• lidé MeSH
• mnohočetný myelom * komplikace   diagnóza   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bortezomib MeSH
• lehké řetězce imunoglobulinů MeSH

OBJECTIVE: The aim of this study is to draw attention to a nosological unit called thrombotic microangiopathy (TMA). This syndrome represents a serious pathological condition characterized by microangiopathic haemolytic anemia (MAHA), thrombocytopenia and various organ dysfunction. Patients are most often presented with symptoms of the HELLP syndrome but if the clinical picture is not restituted within 48-72 hours after delivery, other TMAs should be considered. SETTING: Department of Obstetrics and Gynecology, 1st Medical Faculty and General Teaching Hospital Prague; Clinic of Nephrology, 1st Medical Faculty and General Teaching Hospital Prague; Department of Obstetrics and Gynecology, Regional Hospital Kolín. DESIGN: Review article and case reports. METHODS: Review of the literature and description of two cases of TMA. CONCLUSION: The authors present a basic overview of the issue of TMA, which requires interdisciplinary cooperation of obstetricians, anesthesiologists, nephrologists and hematologists. In the second part of the article, we present two TMA case reports and finally show the differential diagnostic and therapeutic scheme as agreed by the authorities in the field.

• Klíčová slova
• HELLP syndrome, acute fatty liver of pregnancy, atypical hemolytic uremic syndrome, eculizumab, hemolytic uremic syndrome, thrombotic microangiopathy, thrombotic thrombocytopenic purpura,
• MeSH
• kardiovaskulární komplikace v těhotenství diagnóza   terapie   MeSH
• lidé MeSH
• těhotenství MeSH
• trombotická trombocytopenická purpura MeSH
• trombotické mikroangiopatie diagnóza   terapie   MeSH
• týmová péče o pacienty MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

Immunoglobulin light chain amyloidosis (AL amyloidosis - ALA) is a monoclonal gammopathy characterized by presence of aberrant plasma cells producing amyloidogenic immunoglobulin light chains. This leads to formation of amyloid fibrils in various organs and tissues, mainly in heart and kidney, and causes their dysfunction. As amyloid depositing in target organs is irreversible, there is a big effort to identify biomarker that could help to distinguish ALA from other monoclonal gammopathies in the early stages of disease, when amyloid deposits are not fatal yet. High throughput technologies bring new opportunities to modern cancer research as they enable to study disease within its complexity. Sophisticated methods such as next generation sequencing, gene expression profiling and circulating microRNA profiling are new approaches to study aberrant plasma cells from patients with light chain amyloidosis and related diseases. While generally known mutation in multiple myeloma patients (KRAS, NRAS, MYC, TP53) were not found in ALA, number of mutated genes is comparable. Transcriptome of ALA patients proves to be more similar to monoclonal gammopathy of undetermined significance patients, moreover level of circulating microRNA, that are known to correlate with heart damage, is increased in ALA patients, where heart damage in ALA typical symptom.Key words: amyloidosis - plasma cell - genome - transcriptome - microRNA.

• MeSH
• biologické markery analýza   MeSH
• lidé MeSH
• plazmatické buňky patologie   MeSH
• primární amyloidóza krev   genetika   MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• volné cirkulující nukleové kyseliny MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• biologické markery MeSH
• volné cirkulující nukleové kyseliny MeSH

OBJECTIVE: ST2, a member of the interleukin-1 receptor family, is selectively expressed on Th2 cells and mediates important Th2 functions. IL-33 is a specific ligand of ST2. The aim of the study was to determine whether serum levels of soluble ST2 (sST2) or IL-33 predict activity of the disease in patients with ANCA-associated vasculitides (AAV). METHODS: 139 AAV patients and 62 controls were studied. IL-33 and sST2 in the blood were measured with a commercially available ELISA. RESULTS: Newly diagnosed AAV patients had higher sST2 levels than controls (P < 0.01). Levels of sST2 were significantly higher in active newly diagnosed AAV patients than in patients with remission (P < 0.001). IL-33 levels were higher in AAV patients than in the control groups (P = 0.002). However, serum IL-33 levels were not increased in patients with active AAV compared to patients in remission. IL-33 levels were higher in patients with granulomatosis with polyangiitis than in patients with microscopic polyangiitis (P = 0.012). CONCLUSIONS: Serum sST2, but not serum IL-33, may be a marker of activity in AAV patients.

• MeSH
• ANCA-asociované vaskulitidy imunologie   MeSH
• dospělí MeSH
• interleukin 33 krev   MeSH
• interleukin-1 receptor-like 1 protein MeSH
• lidé středního věku MeSH
• lidé MeSH
• receptory buněčného povrchu krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• IL1RL1 protein, human MeSH Prohlížeč
• IL33 protein, human MeSH Prohlížeč
• interleukin 33 MeSH
• interleukin-1 receptor-like 1 protein MeSH
• receptory buněčného povrchu MeSH

Rituximab (RTX) was reported effective in ANCA-associated vasculitis (AAV). We aimed to evaluate clinical efficacy of RTX in AAV along with its impact on immunological parameters. Eighteen RTX-treated AAV patients (M/F 11/7; median age 37.5; 15× PR3-ANCA, 3× MPO-ANCA; 16× relapsing/refractory, 2× first-line therapy) were enrolled. Clinical response, ANCA, total serum IgG levels and cellular immunity parameters were examined. The patients were followed up (FU) for a median of 26 months (range 3-82, 15 for ≥6 months). All patients achieved B cell depletion (lasting 3-24 months). No significant increase was noted in T cell or NK cell subpopulations. At 6 months, partial remission was achieved in 5/15 patients (33 %) and complete in 8 (53 %). The median prednisone dose (30..10 mg/d) and ANCA levels (17.2..2.7 IU/mL) decreased (p < 0.01). RTX retreatment was used in nine (8× pre-emptive, 1× relapse). Six patients relapsed (none of the pre-emptively treated). Three patients died of infection. IgG levels at 3 months decreased compared to baseline (9.0 vs 5.7 g/L, p < 0.01). Higher percentage of HLA-DR+CD3+ cells and lower percentage of CD4+CD45RA+ naive T cells persisted during FU. IFN-γ production increased at 6 months compared to baseline (27.3 vs 41.5 %). No significant change was noted in the intracellular IL-10 and IL-12 production. RTX helped to lower the glucocorticosteroids dose and withdraw cytotoxic drugs in most AAV patients. Hypogammaglobulinaemia was common but well tolerated. Peripheral circulating T cells remained activated despite B cell depletion.

• MeSH
• ANCA-asociované vaskulitidy farmakoterapie   imunologie   MeSH
• buněčná imunita účinky léků   MeSH
• dospělí MeSH
• humorální imunita účinky léků   MeSH
• imunoglobulin G krev   MeSH
• imunologické faktory farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myší monoklonální protilátky farmakologie   terapeutické užití   MeSH
• rituximab MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• 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
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobulin G MeSH
• imunologické faktory MeSH
• myší monoklonální protilátky MeSH
• rituximab MeSH

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

• Klíčová slova
• Lupus nephritis, cyclosporine A, systemic lupus erythematosus, treatment,
• MeSH
• cyklofosfamid škodlivé účinky   MeSH
• cyklosporin škodlivé účinky   MeSH
• imunosupresiva škodlivé účinky   MeSH
• lidé MeSH
• následné studie MeSH
• nefritida při lupus erythematodes farmakoterapie   patologie   MeSH
• proliferace buněk účinky léků   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• renální insuficience chemicky indukované   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cyklofosfamid MeSH
• cyklosporin MeSH
• imunosupresiva MeSH

The complete renal artery embolization is an alternative to surgical nephrectomy in seriously ill patients. Iatrogenic embolization can be used in many different conditions. Refractory nephrotic syndrome represents a very rare indication for embolization. Complete renal artery embolization has usually been complicated by postembolization syndrome (PES) which is characterized by flank pain and fever. Possible immunologic contribution to the PES leads some authors to the administration of corticosteroids to the patients undergoing embolization. We report here a cohort of 13 patients undergoing complete embolization of total 21 kidneys due to refractory nephrotic syndrome non-responding to the various specific treatment regimes. We treated our patients undergoing renal artery embolization according to special protocol containing combination of antibiotic drugs and corticosteroids (CS) to diminish PES and evaluated its influence to the cytokine production. The incidence of PES was less frequent and milder in comparison with the historical group of patients. Significant decrease in plasma levels of tumor necrosis factor α during first post-embolization day (8.37 pre- vs. 5.74 pg/ml post-embolization, P=0.0002) could partially explain the reduction of PES symptoms. The procedure was not complicated by severe complications and represents an elegant alternative to surgical procedure. The accurate timing of the embolization remains a controversial point in this intervention.

• MeSH
• arteria renalis * MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nefrotický syndrom mortalita   terapie   MeSH
• paliativní péče * MeSH
• terapeutická embolizace škodlivé účinky   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
• Názvy látek
• cytokiny MeSH
• glukokortikoidy MeSH

Proteinuria is one of the main symptoms of renal impairment. It may manifest itself as a small amount of albumin in the urine (microalbuminuria) or as the nephrotic syndrome. Testing strips results should be considered as preliminary; a negative result does not exclude renal disease. At present, proteinuria is assessed as a total protein waste in the urine collected over 24 hours with up to 150 mg/day being considered a norm. Lately, the protein (albumin) to creatinine ratio in a sample of morning urine is being preferred (protein/creatinine ratio - PCR or albumin/creatinine ratio - ACR). More detailed nephrological examination should be performed if these reach pathological values (PCR > 15 mg/mmol a ACR > 3.5 mg/mmol). These assessments are not burdened by the same variability of values as with the 24-hour urine collection. A number of studies provided evidence on the role of proteinuria (as well as microalbuminuria) in accelerating a decline in glomerular filtration as well as its role as a risk factor of total and cardiovascular mortality. Therefore, this issue should receive appropriate attention and patients who are in a higher risk of renal impairment should be intentionally sought. These include diabetics, patients with heart disease, hypertension and patients with known personal or family history of renal disease. Only when a renal disease (and proteinuria is a clear symptom) is detected in time, targeted or symptomatic treatment can by initiated to slow down or even halt the disease progression to end stage renal disease. Despite this, more than 1/3 of patients entering chronic dialysis treatment have not been monitored. This significantly increases their morbidity and mortality, particularly within the first year of dialysis. General practitioners as well as internal medicine specialists, cardiologists and diabetologists play a fundamental role in screening of the high risk population.

• MeSH
• lidé MeSH
• nemoci ledvin diagnóza   moč   MeSH
• primární zdravotní péče * MeSH
• proteinurie etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

Vascular endothelial growth factor is an important mediator in maintaining normal kidney functions. In addition, several lines of evidence show that up-regulation of this mediator in glomeruli may be associated with or may directly cause renal dysfunction. We tried to assess the influence of the -2578 C/A and -1154 G/A polymorphisms in the regulatory region of the vascular endothelial growth factor gene upon progression of three primary chronic glomerulonephritides (minimal change disease/focal and segmental glomerulosclerosis, membranous nephropathy, immunoglobulin A nephropathy). We studied a cohort of 213 patients compared to 311 unrelated healthy controls. Analysis of the C/A polymorphism of vascular endothelial growth factor revealed an increased prevalence of CC genotype in the minimal change disease/focal and segmental glomerulosclerosis group in comparison with the other groups. A balanced distribution of G and A alleles among the respective types of chronic glomerulonephritides was shown in the analysis of -1154 G/A polymorphism. Finally, we have not proved any significant influence of the polymorphisms at positions -2578 C/A and -1154 G/A of the vascular endothelial growth factor gene promoter on the progression of chronic glomerulonephritides even though our study suggests a negative effect of CC genotype of -2578 C/A polymorphism on the clinical course of minimal change disease/focal segmental glomerulosclerosis.

• MeSH
• chronická nemoc MeSH
• dospělí MeSH
• genotyp MeSH
• glomerulonefritida genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický genetika   MeSH
• progrese nemoci MeSH
• vaskulární endoteliální růstový faktor A genetika   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
• Názvy látek
• vaskulární endoteliální růstový faktor A MeSH

Patients with renal diseases associated with salt-losing tubulopathies categorized as Gitelman and classic form of Bartter syndrome have undergone genetic screening for possible mutation capture in two different genes: SLC12A3 and CLCNKB. Clinical symptoms of these two diseases may overlap. Patients with clinical symptoms of antenatal form of Bartter syndrome were screened for mutations in two different genes: KCNJ1 and SLC12A1. The aim was to establish genetic mutation screening of Bartter/Gitelman syndrome and to confirm the proposed diagnosis. We have identified seven different causative mutations in the SLC12A3 gene, four in the CLCNKB gene, two in the SLC12A1 gene, and none in the KCNJ1 gene. Nine of these mutations are novel. In one case, genetic analysis led to re-evaluation of diagnosis between the Gitelman and classic form of Bartter syndrome.

• MeSH
• Bartterův syndrom genetika   MeSH
• chloridové kanály genetika   MeSH
• draslíkové kanály dovnitř usměrňující genetika   MeSH
• Gitelmanův syndrom genetika   MeSH
• ledviny MeSH
• lidé MeSH
• membránové transportní proteiny genetika   MeSH
• mutace * MeSH
• receptory léků genetika   MeSH
• rodina nosičů rozpuštěných látek 12, člen 1 MeSH
• rodina nosičů rozpuštěných látek 12, člen 3 MeSH
• sodík-draslík-chloridové symportéry genetika   MeSH
• symportéry genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chloridové kanály MeSH
• CLCNKB protein, human MeSH Prohlížeč
• draslíkové kanály dovnitř usměrňující MeSH
• KCNJ1 protein, human MeSH Prohlížeč
• membránové transportní proteiny MeSH
• receptory léků MeSH
• rodina nosičů rozpuštěných látek 12, člen 1 MeSH
• rodina nosičů rozpuštěných látek 12, člen 3 MeSH
• SLC12A1 protein, human MeSH Prohlížeč
• SLC12A3 protein, human MeSH Prohlížeč
• sodík-draslík-chloridové symportéry MeSH
• symportéry MeSH