Acute kidney injury (AKI) due to gentamicin nephrotoxicity is a significant concern in clinical medicine, particularly in patients receiving prolonged or high-dose gentamicin therapy. Gentamicin is an aminoglycoside antibiotic frequently used in the treatment of a range of bacterial infections. However, its use is associated with nephrotoxicity which can manifest as AKI. Due to this, it is crucial to diagnose promptly and manage treatment effectively. Ongoing studies are therefore focusing on non-protein-coding RNAs as potential biomarkers for AKI. Numerous microRNAs (miRNAs) have been implicated in gentamicin-induced nephrotoxicity and AKI. They participate in pathways associated with inflammation, cell death, and oxidative stress and each of these factors play critical roles in the development of gentamicin-induced kidney injury. Research studies have demonstrated changes in the expression levels of these miRNAs in response to gentamicin exposure both in vitro and in in vivo models, as well as in human clinical trials involving patients receiving gentamicin therapy. The dysregulation of these miRNAs correlates with the severity of kidney injury and may serve as sensitive biomarkers for early detection and monitoring of AKI induced by gentamicin.
To explore the effects and underlying mechanisms of Mdivi-1 on three common clinical models of acute kidney injury (AKI). Three common AKI cell models were constructed, classified into the control group (human renal tubular epithelial cells [HK-2] cells), the Iohexol group (HK-2 cells treated with Iohexol), the Genta group (HK-2 cells treated with Gentamicin), and the Cis group (HK-2 cells treated with Cisplatin). To explore the optimal protective concentration of Mdivi-1 for each AKI cell model, the experimental design consisted of the following seven groups: the control group (HK-2 cells cultured in medium), three injury groups (HK-2 cells subjected to Iohexol, Gentamicin, or Cisplatin), and the corresponding protection groups (with a certain concentration of Mdivi-1 added to each injury group). Cellular survival and apoptosis, reactive oxygen species (ROS) levels, and the expression of recombinant Sirtuin 3 (SIRT3) in each group were measured. Mitochondrial fission and fusion dynamics in cells were observed under an electron microscope. To explore relevant pathways, the changes in relevant pathway proteins were analyzed through Western blotting. The half maximal inhibitory concentration (IC50) values were 150.06 mgI/ml at 6 h in the Iohexol group, 37.88 mg/ml at 24 h in the Gentamicin group, and 13.48 microM at 24 h in the Cisplatin group. Compared with the control group, the three injury groups showed increased cell apoptosis rates and higher expressions of apoptotic proteins in HK-2 cells, with an accompanying decrease in cell migration. After the addition of corresponding concentrations of Mdivi-1, the optimal concentrations were 3 μM in the Iohexo-3 group, 1 microM in the Genta-1 group, and 5 μM in the Cis-5 group, HK-2 cells showed the highest survival rate, reduced apoptosis, decreased mitochondrial ROS and SIRT3 expression, and reduced mitochondrial fission and autophagy when compared with each injury group. Further verification with Western blot analysis after the addition of Mdivi-1 revealed a reduction in the expressions of mitochondrial fission proteins DRP1, Nrf2, SIRT3, Caspase-3, Jun N-terminal Kinase (JNK)/P-JNK, NF-kappaB, Bcl2, and autophagic protein P62, as well as reduced ROS levels. Mdivi-1 had protective effects on the three common AKI cell models by potentially reducing mitochondrial fission in cells and inhibiting the production of ROS through the mediation of the NF- B/JNK/SIRT3 signaling pathway, thereby exerting protective effects. Key words AKI, Cisplatin, Gentamicin, Iohexol, Mdivi-1.
- MeSH
- akutní poškození ledvin * metabolismus patologie farmakoterapie MeSH
- apoptóza účinky léků MeSH
- buněčné linie MeSH
- lidé MeSH
- MAP kinasový signální systém účinky léků fyziologie MeSH
- mitochondriální dynamika * účinky léků fyziologie MeSH
- NF-kappa B * metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- signální transdukce * účinky léků MeSH
- sirtuin 3 * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Hyperurikemie se vyskytuje u 60 % pacientů s chronickým onemocněním ledvin (CKD) a dna asi u 25 % těchto pacientů. I přes častý společný výskyt není vliv kyseliny močové na progresi onemocnění ledvin jednoznačně objasněn. O indika- cích k léčbě asymptomatické urikemie u pacientů s CKD se vedou spory. Převaha důkazů naznačuje, že asymptomatická hyperurikemie je pravděpodobně škodlivá, ale může se týkat zejména určitých podskupin pacientů, a to pacientů se systémovými depozity urátu, urátovou krystalurií nebo urolitiázou a pacientů s vysokou intracelulární hladinou kyseliny močové. Současné důkazy nepodporují nasazení inhibitorů xantinoxidázy ke zmírnění progrese CKD u pacientů s asymp- tomatickou hyperurikemií.
Hyperuricaemia occurs in 60% of patients with chronic kidney disease (CKD) and gout in about 25% of these patients. Despite the frequent co-occurrence, the influence of uric acid on the progression of kidney disease is not clearly understood. There is controversy over the indications for treatment of asymptomatic uricemia in patients with CKD. The preponderance of evidence suggests that asymptomatic hyperuricaemia is likely to be harmful, but may be particularly relevant to certain subgroups of patients, namely those with systemic crystal deposits, urate crystalluria or urolithiasis, and those with high intracellular uric acid levels. Current evidence does not support the deployment of xanthine oxidase inhibitors to ameliorate the progression of CKD in patients with asymptomatic hyperuricaemia.
- MeSH
- akutní poškození ledvin etiologie terapie MeSH
- chronická renální insuficience * diagnóza etiologie farmakoterapie MeSH
- hyperurikemie diagnóza farmakoterapie komplikace MeSH
- klinická studie jako téma MeSH
- kyselina močová krev MeSH
- lidé MeSH
- nemoci ledvin etiologie MeSH
- xanthinoxidasa antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
Kidney dysfunction often leads to neurological impairment, yet the complex kidney-brain relationship remains elusive. We employed spatial and bulk metabolomics to investigate a mouse model of rapid kidney failure induced by mouse double minute 2 (Mdm2) conditional deletion in the kidney tubules to interrogate kidney and brain metabolism. Pathway enrichment analysis of a focused plasma metabolomics panel pinpointed tryptophan metabolism as the most altered pathway with kidney failure. Spatial metabolomics showed toxic tryptophan metabolites in the kidneys and brains, revealing a connection between advanced kidney disease and accelerated kynurenine degradation. In particular, the excitotoxic metabolite quinolinic acid was localized in ependymal cells in the setting of kidney failure. These findings were associated with brain inflammation and cell death. Separate mouse models of ischemia-induced acute kidney injury and adenine-induced chronic kidney disease also exhibited systemic inflammation and accumulating toxic tryptophan metabolites. Patients with advanced chronic kidney disease (stage 3b-4 and stage 5) similarly demonstrated elevated plasma kynurenine metabolites, and quinolinic acid was uniquely correlated with fatigue and reduced quality of life. Overall, our study identifies the kynurenine pathway as a bridge between kidney decline, systemic inflammation, and brain toxicity, offering potential avenues for diagnosis and treatment of neurological issues in kidney disease.
- MeSH
- akutní poškození ledvin metabolismus chemicky indukované patologie MeSH
- chronická renální insuficience metabolismus patologie komplikace MeSH
- kynurenin * metabolismus MeSH
- kyselina chinolinová * toxicita metabolismus krev MeSH
- ledviny metabolismus patologie MeSH
- lidé MeSH
- metabolomika MeSH
- modely nemocí na zvířatech MeSH
- mozek * metabolismus patologie MeSH
- myši MeSH
- tryptofan * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: Circulating proenkephalin (PENK) is a stable endogenous polypeptide with fast response to glomerular dysfunction and tubular damage. This study examined the predictive value of PENK for renal outcomes and mortality in patients with acute coronary syndrome (ACS). METHODS: Proenkephalin was measured in plasma in a prospective multicentre ACS cohort from Switzerland (n = 4787) and in validation cohorts from the UK (n = 1141), Czechia (n = 927), and Germany (n = 220). A biomarker-enhanced risk score (KID-ACS score) for simultaneous prediction of in-hospital acute kidney injury (AKI) and 30-day mortality was derived and externally validated. RESULTS: On multivariable adjustment for established risk factors, circulating PENK remained associated with in-hospital AKI [per log2 increase: adjusted odds ratio 1.53, 95% confidence interval (CI) 1.13-2.09, P = .007] and 30-day mortality (adjusted hazard ratio 2.73, 95% CI 1.85-4.02, P < .001). The KID-ACS score integrates PENK and showed an area under the receiver operating characteristic curve (AUC) of .72 (95% CI .68-.76) for in-hospital AKI and .91 (95% CI .87-.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS achieved similarly high performance for in-hospital AKI (Zurich: AUC .73, 95% CI .70-.77; Czechia: AUC .75, 95% CI .68-.81; Germany: AUC .71, 95% CI .55-.87) and 30-day mortality (UK: AUC .87, 95% CI .83-.91; Czechia: AUC .91, 95% CI .87-.94; Germany: AUC .96, 95% CI .92-1.00), outperforming the contrast-associated AKI score and the Global Registry of Acute Coronary Events 2.0 score, respectively. CONCLUSIONS: Circulating PENK offers incremental value for predicting in-hospital AKI and mortality in ACS. The simple six-item KID-ACS risk score integrates PENK and provides a novel tool for simultaneous assessment of renal and mortality risk in patients with ACS.
- MeSH
- akutní koronární syndrom * mortalita krev MeSH
- akutní poškození ledvin * MeSH
- biologické markery * krev MeSH
- enkefaliny * krev MeSH
- hodnocení rizik metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- proteinové prekurzory * krev MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Acute kidney injury (AKI) is a consequence of several diseases that can severely damage kidney function. It is a frequent complication of hospitalization and very common in critically ill patients because of other serious illnesses, such as septic conditions. New diagnostic options, including renal biomarkers, may help in early diagnosis. Our study included 46 patients, 31 with AKI and 15 without AKI on admission. Blood samples were collected on the first, fourth, and seventh days of treatment, and in addition to basic biochemical parameters, neutrophil gelatinase-associated lipocalin (NGAL) levels in serum were also examined. Data from the first and seventh day were used for statistical analysis. On the first follow-up day, NGAL values were categorized according to an optimal cut-off value of 290 μg/l. We demonstrated that if NGAL levels were higher, the risk of renal injury increased approximately 16 times. Other results showed that NGAL levels were moderately correlated with serum creatinine (r = 0.613, p < 0.0001), procalcitonin (PCT) (r = 0.627, p < 0.0001), and AKI stage (r = 0.589, p < 0.0001). There was also a significant positive correlation with SOFA (Sequential Organ Failure Assessment) score (r = 0.395, p = 0.007). Early diagnosis and treatment are crucial in managing AKI and preventing further kidney damage. NGAL levels can increase within a few hours after injury, making it a useful tool for early AKI detection and diagnosis. Key words: Acute kidney injury, Biomarker, NGAL, Sepsis.
- MeSH
- akutní poškození ledvin * krev diagnóza MeSH
- biologické markery * krev MeSH
- dospělí MeSH
- kritický stav * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipokalin-2 * krev MeSH
- prediktivní hodnota testů MeSH
- senioři MeSH
- sepse * krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři 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: 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
Úvod: Akutní poškození ledvin (AKI – acute kidney injury) se vyskytuje u kriticky nemocných pacientů s výrazným dopadem na jejich morbiditu a mortalitu. Náhlé snížení renálních funkcí ovlivňuje činnost a funkci jiných orgánů, mezi jinými také střevo navozením střevní dysmikrobie, jež recipročně zhoršuje průběh AKI a může také vést k rozvoji chronické nefropatie. Cíl: Patofyziologie AKI, sepse a střevní dysmikrobie v kritickém stavu pacienta s dopadem na vývoj nemoci a jiné orgánové systémy s možnostmi jejího pozitivního ovlivnění nutričními opatřeními. Závěr: Kriticky nemocní pacienti zejména v septickém stavu komplikovaném AKI jsou náchylní ke komplikacím typu střevní dysmikrobie, sekundární sepse a imunodeficience. Léčba základního onemocnění a jeho komplikací spolu s nutriční podporou napomáhá ke zlepšení klinického stavu této skupiny nemocných.
Introduction: Acute kidney injury (AKI) occurs in critically ill patients with significant impact on their morbidity and mortality. The sudden reduction in renal function affects the function of other organs, comprising the intestine, inducing intestinal dysmicrobia, which reciprocally worsens the course of AKI and may also lead to the development of chronic nephropathy. Purpose: Pathophysiology of AKI, sepsis and intestinal dysmicrobia in a critical patient with impact on the development of the disease and other organ systems with possibilities of its positive influence by nutritional measures. Conclusion: Critically ill patients especially in septic status complicated by AKI are prone to complications such as intestinal dysmicrobia, secondary sepsis and immunodeficiency. Treatment of the underlying disease and its complications along with nutritional support helps to improve the clinical outcome of this group of patients.
- MeSH
- akutní poškození ledvin * komplikace patofyziologie MeSH
- dysbióza * etiologie mikrobiologie patologie MeSH
- lidé MeSH
- nutriční podpora MeSH
- péče o pacienty v kritickém stavu MeSH
- podvýživa etiologie terapie MeSH
- sepse patologie MeSH
- septický šok patologie MeSH
- uremické toxiny škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Hemolyticko-uremický syndrom (HUS) je formou trombotické mikroangiopatie. Je charakterizován akutním poškozením ledvin, neimunní Coombs negativní hemolytickou anemií a trombocytopenií. Typický HUS je závažné onemocnění, které se rozvíjí v návaznosti na průjmové onemocnění způsobené patogenními kmeny Escherichia coli s produkcí Shiga toxinů, jež lze prokázat kultivačně ve stolici. Jedná se o onemocnění, které postihuje převážně děti do 5 let věku. K nákaze dochází zejména po požití kontaminované potravy. V klinickém obrazu dominují bolesti břicha, často křečovité a doprovázené průjmem bez nebo s příměsí krve, ikterus a postižení ledvin, které se projeví hematurií, proteinurií a zvýšenými parametry funkce ledvin. Současně dochází k rozvoji různého stupně krvácivých projevů na kůži. Obávanou komplikací je postižení centrálního nervového systému. Důležité je včasné rozpoznání a léčba pacienta na jednotce intenzivní péče s možností provedení hemodialýzy.
Haemolytic-uraemic syndrome (HUS) is a form of thrombotic microangiopathy. It is characterised by acute kidney injury, non-immune Coombs-negative haemolytic anaemia, and thrombocytopenia. Typical HUS is a serious disease that develops as a consequence of diarrhoea caused by Shiga toxin-producing Escherichia coli (STEC) strains, which can be detected in a patient’s stool culture. The disease primarily affects preschool children. The infection occurs mostly through ingestion of STEC-contaminated food. The clinical course is dominated by abdominal pain often accompanied by cramps and diarrhoea with or without blood, icterus, and acute kidney injury with haematuria, proteinuria, and elevated kidney function parameters. At the same time, skin and mucosal bleeding of various extent occurs. central nervous system involvement may develop as a life-threatening complication. It is important to timely recognize and treat patients in an intensive care unit with the possibility of haemodialysis.
- MeSH
- akutní poškození ledvin diagnóza etiologie terapie MeSH
- dítě MeSH
- hemolyticko-uremický syndrom * diagnóza patofyziologie terapie MeSH
- infekce vyvolané Escherichia coli * diagnóza patologie MeSH
- lidé MeSH
- shiga toxiny toxicita MeSH
- trombotické mikroangiopatie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
