SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 μ mol/L=0, K1: 250-450 μ mol/L=4, K2: >450 μ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.

• MeSH
• ANCA-asociované vaskulitidy * diagnóza   MeSH
• atrofie MeSH
• fibróza MeSH
• kreatinin MeSH
• ledviny MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• protilátky proti cytoplazmě neutrofilů * MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• IgA nefropatie * farmakoterapie   MeSH
• imunoglobulin A MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

V populaci diabetiků 2. typu je častěji než v běžné populaci diagnostikováno jak srdeční selhání, tak i chronické onemocnění ledvin (CKD). Screening CKD musí směřovat k časnému záchytu onemocnění s cílem zvrátit, nebo alespoň významně zpomalit jeho průběh a oddálit přechod do selhání ledvin s nutností chronické dialyzační anebo transplantační léčby. Finerenon je nesteroidní, selektivní antagonista mineralokortikoidního receptoru. Efekty finerenonu u nemocných s diabetem 2. typu byly zkoumány ve velkých registračních klinických studiích fáze III FIDELIO-DKD, FIGARO-DKD a následně v jejich sdružené analýze FIDELITY. Na základě výsledků publikovaných prospektivních randomizovaných kontrolovaných studií s finerenonem je jeho použití u pacientů s CKD a diabetem 2. typu zmíněno v několika recentních doporučeních. Zástupci expertního panelu zahrnujícího Českou nefrologickou společnost, Českou diabetologickou společnost ČLS JEP, Českou internistickou společnost ČLS JEP a Českou kardiologickou společnost v souladu s recentními mezinárodními doporučeními považují finerenon za jeden z pilířů léčby pacientů s chronickým onemocněním ledvin a diabetem 2. typu pro jeho nefroprotektivní a kardioprotektivní účinky.

Both heart failure and chronic kidney disease (CKD) are detected more often in the type 2 diabetic population than in the general population. CKD screening should focus on its early detection to reverse, or at least significantly slow down its course and delay stage 5 CKD with the need for chronic dialysis or transplant treatment. Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist. The effects of finerenone in patients with type 2 diabetes were investigated in the large registration phase III clinical trials FIDELIO-DKD, FIGARO-DKD and subsequently in their pooled analysis FIDELITY. Based on the results of published prospective randomized controlled trials with finerenone, its use in patients with CKD and type 2 diabetes is mentioned in several recent recommendations. Representatives of an expert panel including the Czech Nephrological Society, the Czech Diabetological Society, the Czech Internal Medicine Society and the Czech Cardiology Society, in accordance with recent international recommendations, consider finerenone to be one of the pillars of the treatment of patients with chronic kidney disease and type 2 diabetes for its nephroprotective and cardioprotective effects.

• Klíčová slova
• finerenon,
• MeSH
• chronická renální insuficience * farmakoterapie   prevence a kontrola   MeSH
• diabetes mellitus 2. typu * farmakoterapie   komplikace   MeSH
• dialýza ledvin MeSH
• komplikace diabetu farmakoterapie   MeSH
• lidé MeSH
• naftyridiny farmakologie   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé MeSH

OBJECTIVES: This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS: Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS: A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS: In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.

• MeSH
• ANCA-asociované vaskulitidy * farmakoterapie   epidemiologie   komplikace   MeSH
• granulomatóza s polyangiitidou * farmakoterapie   epidemiologie   komplikace   MeSH
• lidé MeSH
• mikroskopická polyangiitida * farmakoterapie   epidemiologie   MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• registrace MeSH
• správnost dat MeSH
• ukládání a vyhledávání informací MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. Clinical manifestations of IgAN vary from asymptomatic with microscopic or intermittent macroscopic haematuria and stable kidney function to rapidly progressive glomerulonephritis. IgAN has been proposed to develop through a 'four-hit' process, commencing with overproduction and increased systemic presence of poorly O-glycosylated galactose-deficient IgA1 (Gd-IgA1), followed by recognition of Gd-IgA1 by antiglycan autoantibodies, aggregation of Gd-IgA1 and formation of polymeric IgA1 immune complexes and, lastly, deposition of these immune complexes in the glomerular mesangium, leading to kidney inflammation and scarring. IgAN can only be diagnosed by kidney biopsy. Extensive, optimized supportive care is the mainstay of therapy for patients with IgAN. For those at high risk of disease progression, the 2021 KDIGO Clinical Practice Guideline suggests considering a 6-month course of systemic corticosteroid therapy; however, the efficacy of systemic steroid treatment is under debate and serious adverse effects are common. Advances in understanding the pathophysiology of IgAN have led to clinical trials of novel targeted therapies with acceptable safety profiles, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, as well as blockade of complement components.

• MeSH
• galaktosa MeSH
• IgA nefropatie * diagnóza   MeSH
• imunoglobulin A MeSH
• imunokomplex MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Onemocnění IgA nefropatie (IgAN) je celosvětově nejčastější primární glomerulonefritida. Zásadní úlohu v patogenezi IgAN představují imunokomplexy, které jsou složené z galaktóza-deficitního imunoglobulinu A1 (Gd-IgA1) a autoprotilátek proti Gd-IgA1. Ukládají se v mezangiu glomerulů, kde vyvolávají komplementem zprostředkovaný zánět, který může vyústit ke zhoršení funkce ledvin až k renálnímu selhání. Nová léčba je cílena na imunopatogenezi IgAN, včetně ovlivnění tvorby Gd-IgA1 imunitními buňkami. Tento článek se zabývá terapeutickým potenciálem perorálního budesonidu s cíleným uvolňováním pro léčbu IgAN, který byl prokázán v klinické studii fáze III (NefIgArd).

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The key role in the pathogenesis of IgAN play the immune complexes, composed of galactose-deficient immunoglobulin A1 (Gd-IgA1) and Gd-IgA1 autoantibodies, deposited in mesangial area of glomeruli, where they induce complement-mediated inflammation that may result in the progression of kidney function to end stage kidney failure. New treatment options are aimed at immunopathogenesis of IgAN including the activity of Gd-IgA1 producing immune cells. This article reviews the therapeutic potential of targeted-release formulation of oral budesonide for the treatment of IgAN which was demonstrated by the phase III clinical trial (NefIgArd).