Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hoc analysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months. PEXIVAS was a randomized controlled trial recruiting 691 patients with ANCA-associated glomerulonephritis, of whom 349 underwent PLEX and 342 received no-PLEX. The primary outcomes of this post hoc study of PEXIVAS were change in estimated glomerular filtration rate (eGFR) from baseline and recovery of kidney function (defined as eGFR increase of 15ml/min/1.73m2 or more). Baseline eGFR was 21.7 ± 20.3 and 20.6 ± 18.7 ml/min/1.73m2 in the PLEX and no-PLEX groups, respectively. Mean improvements in eGFR at weeks two, four, and eight after initiation of therapy were greater for the PLEX vs. the no-PLEX groups. The greatest significant difference in recovery of kidney function in the PLEX compared to the no-PLEX groups was at week four (relative risk (RR): 1.41; 95% confidence interval:1.09-1.82). Increased eGFR or recovery of kidney function at week four were significantly associated with lower risk for end-stage kidney disease at week 52 (RR: 0.96: 0.95-0.97, and RR: 0.29: 0.16-0.52; respectively). Neither changes in eGFR nor recovery of kidney function differed by reduced- compared to standard-dose glucocorticoid group. Overall, our study indicates that PLEX improves early kidney function in patients with ANCA-associated glomerulonephritis.

• MeSH
• ANCA-asociované vaskulitidy * patofyziologie   terapie   farmakoterapie   komplikace   imunologie   diagnóza   MeSH
• dospělí MeSH
• glomerulonefritida * patofyziologie   imunologie   terapie   krev   MeSH
• glukokortikoidy * terapeutické užití   aplikace a dávkování   MeSH
• hodnoty glomerulární filtrace * MeSH
• ledviny * patofyziologie   účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obnova funkce MeSH
• senioři MeSH
• výměna plazmy * MeSH
• výsledek terapie 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
• randomizované kontrolované studie MeSH

• MeSH
• ANCA-asociované vaskulitidy komplikace   terapie   MeSH
• glomerulonefritida * etiologie   terapie   MeSH
• IgA nefropatie farmakoterapie   MeSH
• lidé MeSH
• nefritida při lupus erythematodes farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Akútna pyelonefritída patrí medzi časté bakteriálne infekcie v detskom veku. pre pediatrov je obávanou infekciou pre riziko vzniku akútnych komplikácií ako urosepsa alebo neskorých komplikácii ako chronická obličková choroba a hypertenzia. správny manažment detských pacientov s akútnou pyelonefritídou významne redukuje riziko vzniku možných komplikácií a preto mu v dnešnej dobe venujeme zvýšenú pozornosť.

Acute pyelonephritis is a common bacterial infection in childhood. it is a concerning infection for pediatricians due to the risk of acute complications, such as urosepsis, or long-term complications, like chronic kidney disease and hypertension. proper management of pediatric patients with acute pyelonephritis significantly reduces the risk of potential complications, which is why it receives increased attention today.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• cefalosporiny druhé generace farmakologie   terapeutické užití   MeSH
• diagnostické zobrazování metody   MeSH
• dítě * MeSH
• infekce močového ústrojí etiologie   farmakoterapie   MeSH
• lidé MeSH
• pyelonefritida * diagnóza   etiologie   farmakoterapie   MeSH
• Check Tag
• dítě * MeSH
• lidé MeSH

A20/Tnfaip3, an early NF-κB response gene and key negative regulator of NF-κB signaling, suppresses proinflammatory responses. Its ubiquitinase and deubiquitinase activities mediate proteasomal degradation within the NF-κB pathway. This study investigated the involvement of A20 signaling alterations in podocytes in the development of kidney injury. The phenotypes of A20Δpodocyte (podocyte-specific knockout of A20) mice were compared with those of control mice at 6 months of age to identify spontaneous changes in kidney function. A20Δpodocyte mice presented elevated serum urea nitrogen and creatinine levels, along with increased accumulation of inflammatory cells-neutrophils and macrophages-within the glomeruli. Additionally, A20Δpodocyte mice displayed significant podocyte loss. Ultrastructural analysis of A20 podocyte-knockout mouse glomeruli revealed hypocellularity of the glomerular tuft, expansion of the extracellular matrix, podocytopenia associated with foot process effacement, karyopyknosis, micronuclei, and podocyte detachment. In addition to podocyte death, we also observed damage to intracapillary endothelial cells with vacuolation of the cytoplasm and condensation of nuclear chromatin. A20 expression downregulation and CRISPR-Cas9 genome editing targeting A20 in a podocyte cell line confirmed these findings in vitro, highlighting the significant contribution of A20 activity in podocytes to glomerular injury pathogenesis. Finally, we analyzed TNFAIP3 transcription levels alongside genes involved in apoptosis, anoikis, NF-κB regulation, and cell attachment in glomerular and tubular compartments of kidney biopsies of patients with various renal diseases.

• MeSH
• cytoskelet * metabolismus   MeSH
• glomerulonefritida * patologie   metabolismus   genetika   MeSH
• glomerulus patologie   metabolismus   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši knockoutované * MeSH
• myši MeSH
• NF-kappa B metabolismus   MeSH
• podocyty * metabolismus   patologie   MeSH
• signální transdukce MeSH
• TNFAIP3 * metabolismus   genetika   MeSH
• zánět * patologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: To determine differences in the blood innate gene expression signatures of systemic lupus erythematosus (SLE) patients across various organ manifestations and disease activity, with a focus on lupus nephritis (LN) and central nervous system (CNS) involvement. METHODS: Toll-like receptor family (TLR 1-10) mRNA expression was investigated in peripheral blood mononuclear cells from patients with SLE (n = 74) and healthy controls (n = 34). We compared patients with histologically confirmed active LN or neuropsychiatric systemic lupus erythematosus (NPSLE) with patients without these symptoms. The expression of TLR mRNA was determined by RT‒qPCR using a high-throughput SmartChip Real-Time-qPCR system (WaferGen). Multivariate analysis and nonparametric statistics were used for data analysis to assess the associations between TLRs and disease activity and severity. RESULTS: TLR4 (0.044 vs. 0.081, p = 0.012) was upregulated and TLR10 (0.009 vs. 0.006, p = 0.0007) was downregulated in the whole cohort of SLE patients compared to healthy controls. A comparison of the active LN group with participants without kidney involvement revealed increased expression of TLR2 (0.078 vs. 0.03, p = 0.009), and TLR5 (0.035 vs. 0.017, p = 0.03). Moreover, a significant difference was observed in TLR9 expression between inactive LN and the control group (0.014 vs. 0.009, p = 0.01), together with borderline correlation in TLR2 expression (0.04 vs. 0.03, p = 0.06). Receiver operating characteristic (ROC) curve analysis revealed that TLR1 and TLR2 expression were the best potential diagnostic markers for active LN. The NPSLE group showed upregulation of TLR1 (0.088 vs. 0.048, p = 0.01), TLR4 (0.173 vs. 0.066, p = 0.0003) and TLR6 (0.087 vs. 0.036, 0.007). Our correlation analysis supported the close relationships among the expression of individual TLRs in the whole lupus cohort and its subgroups. CONCLUSION: Our study revealed differences in TLR expression between a lupus cohort and healthy controls. Additionally, our analysis provides insight into specific TLR expression in cases with severe organ manifestations, such as LN and NPSLE. The multiple mutual relationships of TLRs demonstrate the activation of innate immunity in SLE and suggest promising targets for future therapies or diagnostics.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nefritida při lupus erythematodes * genetika   krev   MeSH
• systémový lupus erythematodes krev   genetika   MeSH
• toll-like receptory * genetika   biosyntéza   MeSH
• vaskulitida centrálního nervového systému při lupus erythematodes * krev   genetika   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

Tubulointersticiální nefritida (TIN) je běžná příčina akutního poškození ledvin. Vzhledem k nespecifickým příznakům a laboratorním nálezům je často stanovení diagnózy pozdní. Léky indukovaná TIN je nejčastější forma, vzácnější etiologie jsou systémová onemocnění a infekce. Při správném provedení anamnézy a časném odstranění rizikové terapie dochází ke spontánní úpravě u mnoha pacientů bez nutnosti extenzivního vyšetřování a imunosupresivní terapie. Část pacientů však vyžaduje biopsii ledviny a podrobnější vyšetření s cílem vypátrat etiologii onemocnění. Kortikoidy jsou lékem volby u pacientů s akutní TIN, u kterých nedochází ke spontánní úpravě stavu po odstranění vyvolávající noxy. U pacientů s chronickou TIN se imunosuprese zpravidla neindikuje, indikovaná je pouze terapie komplikací spojených s chronickým onemocnění ledvin s cílem zpomalit progresi onemocnění.

Tubulointersticial nephritis (TIN) is a frequent cause of acute kidney injury. Establishing the diagnosis is often delayed due to its nonspecific symptoms and results of laboratory methods. Drug-induced TIN is the most frequent form of TIN, followed by systemic diseases, and infections. Spontaneous resolution often occurs without the need for extensive examination or treatment, especially when a thorough medical history is obtained and the medication associated with TIN is discontinued early. However, kidney biopsy, along with extensive examinations, is sometimes necessary to determine the etiology of TIN. Patients with acute TIN who do not show spontaneous improvement after removal of causative insult are treated with corticosteroids, whereas immuno­suppressive treatment is usually not indicated for those with chronic TIN. In such cases, management focuses primarily on treating complications of chronic kidney disease, aiming to slow disease progression.

• MeSH
• akutní poškození ledvin diagnóza   etiologie   terapie   MeSH
• dítě MeSH
• idiopatické střevní záněty komplikace   MeSH
• intersticiální nefritida * diagnóza   etiologie   terapie   MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1. METHODS: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. RESULTS: Surveys were emailed to 637 individuals, with responses from 89 ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). CONCLUSIONS: Individuals with ADTKD-MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.

• MeSH
• COVID-19 * mortalita   genetika   MeSH
• dospělí MeSH
• intersticiální nefritida genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mucin 1 * krev   MeSH
• mutace * MeSH
• registrace MeSH
• SARS-CoV-2 genetika   MeSH
• senioři MeSH
• uromodulin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Úvod: Cílem studie bylo určit rozsah renálního poškození podle gradingu 99mTc-DMSA scanu u dětí s vezikoureterálním refluxem (VUR) III. stupně, který je částí odborné veřejnosti považován spolu s VUR I. a II. stupně za nízkostupňový. Metody: Celkem bylo vyšetřeno 132 pacientů (56 chlapců a 76 dívek ve věku 6 měsíců až 11 let) s diagnózou VUR různého stupně 6 měsíců po akutní pyelonefritidě. Statická scintigrafie ledvin byla provedena 2 hodiny po i.v. podání 18–80 MBq 99mTc-DMSA. Stanovení stupně postižení ledvin bylo provedeno podle počtu postižených segmentů ledviny (0–12) na základě gradingu 99mTc-DMSA G0-G4 (Mattoo et al), s naší modifikací stupně G4. V každé postižené ledvině byl hodnocen počet patologických segmentů/jizev. Průměr hodnot v rámci každého stupně VUR byl vyhodnocen pomocí Studentova t-testu. Výsledky: Hodnoceno celkem 201 ledvin s VUR, významně vyšší počet jizev byl prokázán u VUR III. stupně než u zbylých nízkostupňových stupňů (2,88 vs. 1,58, p = 0,002). Na druhou stranu, ve srovnání se IV. stupněm VUR, se jednalo o nevýznamně nižší hodnotu (2,88 vs. 3,51, p = 0,08). Ve srovnání s VUR IV. a V. stupně byla hodnota statisticky významně nižší (3,99 vs. 2,88, p = 0,004). Závěr: VUR III. stupně je spojen s vyšším rozsahem parenchymových změn (podle 99mTc-DMSA gradingu) ve srovnání s VUR I. a II. stupně. 99mTc-DMSA grading může demaskovat závažnější případy VUR III. stupně, který proto doporučujeme vyčlenit a hodnotit jako samostatný stupeň. Korespondující autorka: MUDr. Daniela Chroustová, Ph.D. Ústav nukleární medicíny VFN a 1. LF UK Praha U nemocnice 5 128 08 Praha 2

Introduction: The aim of this study was to determine the risk of renal damage in children diagnosed with vesico-ureteral reflux (VUR) grade III, which is generally considered as a low-grade VUR, according to the occurrence of renal changes using the 99mTc-DMSA scan grading. Methods: A total of 132 patients with VUR were examined (56 boys, 76 girls aged 6 months -11 years) 6 months after acute pyelonephritis with. Static renal scintigraphy was performed 2 h after i.v. administration of 18-80 MBq 99mTc-DMSA. Determination of the degree of kidney involvement according to the 99mTc-DMSA grading G0-G4 (Mattoo et al) was based on the number of affected segments (0-12). The number of pathological segments/scars was assessed in each involved kidney. Mean values within each VUR grade were evaluated using Student’s t-test. Results: 200 kidneys were evaluated. VUR III. grade demonstrated significantly higher value of scars (2.88 vs 1.58, p = 0.002) than the remaining low-risk grades I and II. On the other hand, when compared with high-risk grade IV, the value was not significantly lower (2,88 vs. 3,51, p = 0,08). In comparing VUR III. with VUR IV.-V. grades, there was a significantly higher number of scars in high-grade VUR. (3.99 vs. 2.88, p = 0.004). Conclusion: VUR III. grade is associated with a higher extend of parenchymal changes (according to 99mTc-DMSA grading) compared to low grades VUR I. and II. 99mTc-DMSA grading can unmask more severe cases of VUR III. degree, which we therefore recommend separating and evaluating as a separate degree.

• MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• nemoci ledvin diagnostické zobrazování   klasifikace   patologie   MeSH
• předškolní dítě MeSH
• pyelonefritida diagnóza   etiologie   prevence a kontrola   MeSH
• radioisotopová scintigrafie klasifikace   metody   MeSH
• renální insuficience diagnostické zobrazování   diagnóza   etiologie   klasifikace   MeSH
• retrospektivní studie MeSH
• technecium 99mTc dimerkaptojantarová kyselina * analýza   metabolismus   MeSH
• vezikoureterální reflux * diagnostické zobrazování   diagnóza   klasifikace   komplikace   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.

• MeSH
• amyloidóza * MeSH
• apolipoproteiny A * MeSH
• chronická renální insuficience * diagnóza   genetika   komplikace   MeSH
• intersticiální nefritida * diagnóza   genetika   komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN. METHODS: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records. RESULTS: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) μmol/L in the conservatively managed group versus 374 (249-558) μmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001). CONCLUSIONS: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.

• MeSH
• dialýza ledvin * škodlivé účinky   MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• intersticiální nefritida * farmakoterapie   diagnóza   MeSH
• kreatinin MeSH
• ledviny patologie   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH