BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.

• MeSH
• antigeny nádorové MeSH
• dospělí MeSH
• karboanhydrasa IX metabolismus   genetika   MeSH
• karcinom z renálních buněk * patologie   metabolismus   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondriální DNA genetika   metabolismus   MeSH
• mitochondrie * metabolismus   patologie   genetika   MeSH
• mutace MeSH
• nádorový supresorový protein VHL genetika   metabolismus   MeSH
• nádory ledvin * patologie   metabolismus   genetika   MeSH
• respirační komplex II * metabolismus   genetika   MeSH
• senioři MeSH
• sukcinátdehydrogenasa genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is a rare malignancy posing significant diagnostic and management challenges. This review provides an overview of the evidence supporting various imaging modalities and offers insights into future innovations in UTUC imaging. RECENT FINDINGS: With the growing use of advancements in computed tomography (CT) technologies for both staging and follow-up of UTUC patients, continuous innovations aim to enhance performance and minimize the risk of excessive exposure to ionizing radiation and iodinated contrast medium. In patients unable to undergo CT, magnetic resonance imaging serves as an alternative imaging modality, though its sensitivity is lower than CT. Positron emission tomography, particularly with innovative radiotracers and theranostics, has the potential to significantly advance precision medicine in UTUC. Endoscopic imaging techniques including advanced modalities seem to be promising in improved visualization and diagnostic accuracy, however, evidence remains scarce. Radiomics and radiogenomics present emerging tools for noninvasive tumor characterization and prognosis. SUMMARY: The landscape of imaging for UTUC is rapidly evolving, with significant advancements across various modalities promising improved diagnostic accuracy, patient outcomes, and safety.

• MeSH
• karcinom z přechodných buněk * diagnóza   diagnostické zobrazování   terapie   patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• nádory ledvin diagnostické zobrazování   terapie   diagnóza   patologie   MeSH
• nádory močovodu diagnostické zobrazování   diagnóza   terapie   patologie   MeSH
• počítačová rentgenová tomografie metody   MeSH
• pozitronová emisní tomografie metody   MeSH
• staging nádorů MeSH
• urologické nádory diagnóza   diagnostické zobrazování   terapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: We aimed to evaluate the prognostic impact of renal insufficiency and fluctuation of glomerular filtration observed during hospitalization for heart failure (HF). METHODS: We followed 3,639 patients hospitalized for acute HF and assessed the mortality risk associated with moderate or severe renal insufficiency, either permanent or transient. RESULTS: After adjustment, severe renal failure defined as estimated glomerular filtration (eGFR) <30 mL/min indicates ≈60% increase in 5-year mortality risk. Similar risk also had patients with only transient decline of eGFR to this range. In contrast, we did not observe any apparent mortality risk attributable to mild/moderate renal insufficiency (eGFR 30-59.9 mL/min), regardless of whether it was transient or permanent. CONCLUSION: Even transient severe renal failure during hospitalization indicates poor long-term prognosis of patients with manifested HF. In contrast, only moderate renal insufficiency observed during hospitalization has no additive long-term mortality impact.

• MeSH
• hodnoty glomerulární filtrace MeSH
• hospitalizace MeSH
• ledviny MeSH
• lidé MeSH
• prognóza MeSH
• renální insuficience * komplikace   MeSH
• srdeční selhání * komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články 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

BACKGROUND: Nutrition plays a vital role in the outcome of critically ill children, particularly those with AKI. Currently, there are no established guidelines for children with AKI treated with continuous RRT (CRRT). A thorough understanding of the metabolic changes and nutritional challenges in AKI and CRRT is required. Our objective was to create clinical practice points for nutritional assessment and management in critically ill children with AKI receiving CRRT. METHODS: PubMed, MEDLINE, Cochrane, and Embase databases were searched for articles related to the topic. Expertise of the authors and a consensus of the workgroup were additional sources of data in the article. Available articles on nutrition therapy in pediatric patients receiving CRRT through January 2023. RESULTS: On the basis of the literature review, the current evidence base was examined by a panel of experts in pediatric nephrology and nutrition. The panel used the literature review as well as their expertise to formulate clinical practice points. The modified Delphi method was used to identify and refine clinical practice points. CONCLUSIONS: Forty-four clinical practice points are provided on nutrition assessment, determining energy needs, and nutrient intake in children with AKI and on CRRT on the basis of the existing literature and expert opinions of a multidisciplinary panel.

• MeSH
• akutní poškození ledvin * terapie   MeSH
• dítě MeSH
• konsensus MeSH
• kontinuální metody náhrady funkce ledvin * MeSH
• kritický stav terapie   MeSH
• lidé MeSH
• nutriční stav MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.

• MeSH
• diabetes mellitus * MeSH
• diabetická noha * MeSH
• diabetická retinopatie * MeSH
• diabetické nefropatie * etiologie   MeSH
• lidé MeSH
• obezita MeSH
• střevní mikroflóra * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy 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

Chronická obličková choroba sa u pacientov s alebo bez diabetes mellitus spája so zvýšeným rizikom hypoglykémie, hlavne dôsledkom poruchy glukoneogenézy a redukcie degradácie inzulínu v obličkách. Hypoglykémia sa často vyskytuje u hemodialyzovaných pacientov. Riziko hypoglykémie u týchto pacientov sa zvyšuje pri tesnej glykemickej kontrole pri liečbe inzulínom alebo perorálnymi antidiabetikami, použití dialyzačných roztokov bez glukózy a malnutrícii. V prevencii hypoglykémie u hemodialyzovaných pacientov s diabetes mellitus sa odporúča podávanie dialyzačných roztokov s koncentráciou glukózy v rozmedzí 5,5–11,1 mmol/l, individuálna titrácia dávky inzulínu a menej prísne cieľové hodnoty glykovaného hemoglobínu 7–8 % podľa DCCT v prípade opakovaných hypoglykémií.

Chronic kidney disease in patients with or without diabetes mellitus is associated with higher risk of hypoglycemia, mainly due to defect of kidney gluconeogenesis and reduction of renal insulin clearance. Hypoglycemia often occurs in patients on hemodialysis. Risk of hypoglycemia in these patients is increased in the case of strict glycemic control during treatment by insulin or oral antidiabetics, using of dialysate solutions without glucose and malnutrition. In prevention of hypoglycemia in hemodialyzed diabetic patients there is recommended using of dialysate solutions with glucose concentration 5.5–11.1 mM/L, individual titration of insulin dose and less strict goals of glycosylated hemoglobin values 7–8 % according to DCCT in the case of repeated hypoglycemias.

• MeSH
• chronická renální insuficience komplikace   terapie   MeSH
• diabetes mellitus MeSH
• dialýza ledvin * metody   škodlivé účinky   MeSH
• hypoglykemie etiologie   prevence a kontrola   MeSH
• inzulin metabolismus   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• uremie komplikace   MeSH
• Check Tag
• lidé MeSH

Empagliflozín je inhibítor sodíkovo-glukózového kotransportéra 2 (SGLT2i – Sodium-GLucose co-Transporter 2 inhibitor) primárne vyvinutý ako perorálne antidiabetikum. Postupne pribudli dôkazy z veľkých randomizovaných klinických štúdií pre multiorgánové benefity empagliflozínu výrazne presahujúce jeho glykémiu znižujúci efekt. V súčasnosti tak máme okrem diabetologickej indikácie aj indikáciu na terapiu srdcového zlyhávania a chronickej obličkovej choroby bez ohľadu na prítomnosť diagnózy diabetu. Tieto skutočnosti zapadajú do konceptu novokoncipovaného kardio-reno-metabolického (CRM – Cardio-Renal-Metabolic) syndrómu, ktorého včasné terapeutické ovplyvnenie práve liekmi ako empagliflozín má významné pozitívne efekty na zdravie celej populácie. V článku sú diskutované relevantné klinické štúdie a dáta z reálnej praxe (RWE – Real World Evidence) pre multiorgánové efekty a indikácie empagliflozínu a ich význam pre klinickú prax.

Empagliflozin is a sodium-glucose co-transporter 2 inhibitor (SGLT2i) primarily developed as an oral antidiabetic drug. Later on, evidence from large randomized controlled trials showed that empagliflozin has multiorgan benefits far exceeding its glucose lowering effects. At present empagliflozin has antidiabetic, cardiac and renal indications whereby the last two mentioned are independent on the presence of the diagnosis of diabetes. These data thus fit into the newly formulated concept of cardio-renal-metabolic (CRM) syndrome (or CKM – cardiovascular-kidney-metabolic syndrome). Targeted and early therapeutic intervention against CRM syndrome, with medications like empagliflozin, has profound positive effects on the health outcomes of the whole population. This article reviews the relevant clinical studies and real world evidence (RWE) data and their impact on clinical practice.

• Klíčová slova
• empagliflozin,
• MeSH
• benzhydrylové sloučeniny MeSH
• chronická renální insuficience diagnóza   farmakoterapie   MeSH
• diabetes mellitus farmakoterapie   MeSH
• glifloziny * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• glukosidy MeSH
• kardiorenální syndrom farmakoterapie   MeSH
• kardiovaskulární nemoci farmakoterapie   prevence a kontrola   MeSH
• lidé MeSH
• metabolický syndrom farmakoterapie   komplikace   MeSH
• nádory prevence a kontrola   MeSH
• srdeční selhání farmakoterapie   MeSH
• urolitiáza prevence a kontrola   MeSH
• Check Tag
• lidé MeSH