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Circulation May 2024
PubMed: 38733145
DOI: 10.1161/CIRCULATIONAHA.124.069382 -
International Journal of Molecular... Apr 2024Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body... (Review)
Review
Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body in small amounts via the food chain. Many interesting disease details were published on the mechanistic steps, such as the generation of reactive oxygen species (ROS) and cuproptosis causing a copper dependent cell death. In the liver of patients with Wilson disease, also, increased iron deposits were found that may lead to iron-related ferroptosis responsible for phospholipid peroxidation within membranes of subcellular organelles. All topics are covered in this review article, in addition to the diagnostic and therapeutic issues of Wilson disease. Excess Cu primarily leads to the generation of reactive oxygen species (ROS), as evidenced by early experimental studies exemplified with the detection of hydroxyl radical formation using the electron spin resonance (ESR) spin-trapping method. The generation of ROS products follows the principles of the Haber-Weiss reaction and the subsequent Fenton reaction leading to copper-related cuproptosis, and is thereby closely connected with ROS. Copper accumulation in the liver is due to impaired biliary excretion of copper caused by the inheritable malfunctioning or missing ATP7B protein. As a result, disturbed cellular homeostasis of copper prevails within the liver. Released from the liver cells due to limited storage capacity, the toxic copper enters the circulation and arrives at other organs, causing local accumulation and cell injury. This explains why copper injures not only the liver, but also the brain, kidneys, eyes, heart, muscles, and bones, explaining the multifaceted clinical features of Wilson disease. Among these are depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser-Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, and arthralgia. In addition, Coombs-negative hemolytic anemia is a key feature of Wilson disease with undetectable serum haptoglobin. The modified Leipzig Scoring System helps diagnose Wilson disease. Patients with Wilson disease are well-treated first-line with copper chelators like D-penicillamine that facilitate the removal of circulating copper bound to albumin and increase in urinary copper excretion. Early chelation therapy improves prognosis. Liver transplantation is an option viewed as ultima ratio in end-stage liver disease with untreatable complications or acute liver failure. Liver transplantation finally may thus be a life-saving approach and curative treatment of the disease by replacing the hepatic gene mutation. In conclusion, Wilson disease is a multifaceted genetic disease representing a molecular and clinical challenge.
Topics: Humans; Hepatolenticular Degeneration; Copper; Iron; Ferroptosis; Reactive Oxygen Species; Liver; Animals
PubMed: 38731973
DOI: 10.3390/ijms25094753 -
Pediatric Research May 2024In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and... (Review)
Review
Neonatal somatic oxygenation and perfusion assessment using near-infrared spectroscopy : Part of the series on near-infrared spectroscopy by the European Society of Paediatric Research Special Interest Group "Near-Infrared Spectroscopy".
In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and multi-site applications in neonates. Assessing somatic oxygenation at various body locations in neonates may aid in the understanding of underlying pathophysiology of organ injury. Considering cerebral autoregulation may be active to protect the brain during systemic circulatory failure, peripheral somatic oxygenation may potentially provide an early indication of neonatal cardiovascular failure and ultimate hypoxemic injury to vital organs including the brain. Certain intestinal oxygenation patterns appear to be associated with the onset and course of necrotizing enterocolitis, whereas impaired renal oxygenation may indicate the onset of acute kidney injury after various types of hypoxic events. Peripheral muscle oxygenation measured at a limb may be particularly effective in the early prediction of shock in neonates. Using multi-site NIRS may complement current approaches and clinical investigations to alert for neonatal tissue hypoxemia, and potentially even guide management. However, somatic NIRS has its inherent limitations in regard to accuracy. Interpretation of organ-specific values can also be challenging. Last, currently there are limited prospective intervention studies, and clinical benefits need to be examined further, after the clarification of critical threshold-values. IMPACT: The assessment of somatic oxygenation using NIRS may contribute to the prediction of specific diseases in hemodynamically challenged neonates. Furthermore, it may give early warning signs for impending cardiovascular failure, and impaired cerebral circulation and oxygenation. We present a comprehensive overview of the literature on applications of NIRS to various somatic areas, with a focus on its potential clinical applicability, including future research directions. This paper will enable prospective standardized studies, and multicenter collaboration to obtain statistical power, likely to advance the field.
PubMed: 38730022
DOI: 10.1038/s41390-024-03226-z -
Annals of Surgical Oncology Jul 2024Renal function after left renal vein (LRV) ligation following en bloc resection of segmental inferior vena cava (IVC) and right kidney is understudied. We assessed the...
BACKGROUND
Renal function after left renal vein (LRV) ligation following en bloc resection of segmental inferior vena cava (IVC) and right kidney is understudied. We assessed the impact of LRV ligation on postoperative renal function following en bloc resection of segmental IVC and right kidney.
METHODS
We retrospectively reviewed 28 patients who underwent LRV ligation during en bloc resection of segmental IVC and right kidney. Patient demographics, tumor characteristics, intraoperative factors, complications, length of hospital and intensive care unit (ICU) stay, and patient survival were collected. Pre- and postoperative renal function was retrospectively analyzed.
RESULTS
Twenty patients underwent robot-assisted surgery and eight patients underwent open surgery. The median operative time was 162 min and estimated blood loss was 350 mL. Ten patients had normal renal function and 12 patients had an initial increase in creatinine but improved gradually. Six patients developed acute renal failure; five patients gradually recovered in 5-32 days after temporary hemodialysis. Renal replacement therapy significantly correlated with maximal anterior-posterior diameter of the LRV (p = 0.001). Complications were observed in 11 cases, four of which were Clavien-Dindo grades I-II. Thirteen patients were alive with no recurrence, nine patients were alive with metastasis, and six cases died during the follow-up period.
CONCLUSIONS
LRV ligation following en bloc resection of segmental IVC and right kidney is feasible, with no significant long-term impact on renal function. The maximum anterior-posterior diameter of the LRV is a reliable method for predicting renal replacement therapy in the absence of collateral circulation.
Topics: Humans; Vena Cava, Inferior; Male; Female; Renal Veins; Retrospective Studies; Middle Aged; Ligation; Kidney Neoplasms; Aged; Follow-Up Studies; Adult; Survival Rate; Nephrectomy; Postoperative Complications; Prognosis; Kidney; Robotic Surgical Procedures; Kidney Function Tests; Carcinoma, Renal Cell
PubMed: 38727768
DOI: 10.1245/s10434-024-15324-7 -
Frontiers in Nutrition 2024Chronic kidney disease (CKD) is a common public health problem, which is characterized as impairment of renal function. The associations between blood metabolites and...
BACKGROUND
Chronic kidney disease (CKD) is a common public health problem, which is characterized as impairment of renal function. The associations between blood metabolites and renal function remained unclear. This study aimed to assess the causal effect of various circulation metabolites on renal function based on metabolomics.
METHODS
We performed a two-sample Mendelian randomization (MR) analysis to estimate the causality of genetically determined metabolites on renal function. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, while summary-level data for creatinine-based estimated glomerular filtration rate (eGFR) or CKD occurrence were set the outcomes. Inverse variance weighted (IVW) was used for primary causality analysis and other methods including weight median, MR-egger, and MR-PRESSO were applied as complementary analysis. Cochran Q test, MR-Egger intercept test, MR-PRESSO global test and leave-one-out analysis were used for sensitivity analysis. For the identified metabolites, reverse MR analysis, linkage disequilibrium score (LDSC) regression and multivariable MR (MVMR) analysis were performed for further evaluation. The causality of the identified metabolites on renal function was further validated using GWAS data for cystatin-C-based eGFR. All statistical analyses were performed in R software.
RESULTS
In this MR analysis, a total of 44 suggestive associations corresponding to 34 known metabolites were observed. After complementary analysis and sensitivity analysis, robust causative associations between two metabolites (betaine and N-acetylornithine) and renal function were identified. Reverse MR analysis showed no causal effects of renal function on betaine and N-acetylornithine. MVMR analysis revealed that genetically predicted betaine and N-acetylornithine could directly influence independently of each other. The causal effects of betaine and N-acetylornithine were also found on cystatin-C-based eGFR.
CONCLUSION
Our study provided evidence to support the causal effects of betaine and N-acetylornithine on renal function. These findings required further investigations to conduct mechanism exploration and drug target selection of these identified metabolites.
PubMed: 38721027
DOI: 10.3389/fnut.2024.1371995 -
Resuscitation Plus Jun 2024Post-cardiac arrest (CA) shock is associated with multiple organ failure, including acute kidney injury, and is the leading cause of early death among patient...
BACKGROUND
Post-cardiac arrest (CA) shock is associated with multiple organ failure, including acute kidney injury, and is the leading cause of early death among patient successfully resuscitated from CA. Arginine-vasopressin (AVP) may be an interesting therapeutic alternative or complement to noradrenaline (NAD) to both control shock and preserve regional, especially renal, organ perfusions.
METHODS
18 swine (24-39 kg) were submitted to 14 min of ventricular fibrillation and cardio-pulmonary resuscitation. After return of spontaneous circulation (ROSC), animals randomly received either AVP, NAD or AVP-NAD combination for maintaining a targeted mean arterial pressure of 70 ± 5 mmHg for 6 h. Haemodynamic and biological parameters, including kidney function biomarkers and diuresis, were monitored throughout the follow-up.
RESULTS
Targeted mean arterial pressure was successfully obtained in the NAD ( = 6) and the AVP-NAD ( = 6) groups, but not in the AVP group ( = 6), where 4 animals died. As compared to NAD alone, renal blood flow (2.9 ± 1.15 4.36 ± 0.64 mL//kg/min in NAD and AVP-NAD groups) and diuresis were higher in the AVP-NAD group. This was associated with a reduction of carotid blood flow and a more severe metabolic acidosis during the first 3 h of follow-up in the AVP-NAD group as compared to NAD group.
CONCLUSION
Combination of AVP and NAD improved renal perfusion and diuresis but reduced carotid blood flow as compared to NAD alone in a porcine model of post-resuscitation syndrome. AVP alone failed to manage shock and led to mortality.
PubMed: 38716382
DOI: 10.1016/j.resplu.2024.100654 -
Chemosphere Jul 2024Per- and polyfluoroalkyl substances (PFAS) are a large class of stable toxic chemicals which have ended up in the environment and in organisms in significant...
Per- and polyfluoroalkyl substances (PFAS) are a large class of stable toxic chemicals which have ended up in the environment and in organisms in significant concentrations. Toxicokinetic models are needed to facilitate extrapolation of bioaccumulation data across PFAS congeners and species. For the present study, we carried out an inventory of accumulation processes specific for PFAS, deviating from traditional Persistent Organic Pollutants (POPs). In addition, we reviewed toxicokinetic models on PFAS reported in literature, classifying them according to the number of compartments distinguished as a one-compartment model (1-CM), two-compartment model (2- CM) or a multi-compartment model, (multi-CM) as well as the accumulation processes included and the parameters used. As the inventory showed that simple 1-CMs were lacking, we developed a generic 1-CM of ourselves to include PFAS specific processes and validated the model for legacy perfluoroalkyl acids. Predicted summed elimination constants were accurate for long carbon chains (>C6), indicating that the model properly represented toxicokinetic processes for most congeners. Results for urinary elimination rate constants were mixed, which might be caused by the exclusion of reabsorption processes (renal reabsorption, enterohepatic circulation). The 1-CM needs to be improved further in order to better predict individual elimination pathways. Besides that, more data on PFAS-transporter specific processes are needed to extrapolate across PFAS congeners and species.
Topics: Fluorocarbons; Humans; Bioaccumulation; Toxicokinetics; Persistent Organic Pollutants; Environmental Monitoring; Environmental Pollutants; Models, Biological
PubMed: 38714250
DOI: 10.1016/j.chemosphere.2024.142253 -
Clinical and Applied... 2024In unfractionated heparin (UFH) monitoring during extracorporeal circulation, the traditional measures of activated clotting time (ACT) or activated partial... (Observational Study)
Observational Study
In unfractionated heparin (UFH) monitoring during extracorporeal circulation, the traditional measures of activated clotting time (ACT) or activated partial thromboplastin time (APTT) may diverge, confounding anticoagulant adjustments. We aimed to explore the factors explaining this discrepancy in children and young adults. This retrospective observational study, conducted at an urban regional tertiary hospital, included consecutive pediatric patients who received UFH during extracorporeal circulation (continuous kidney replacement therapy or extracorporeal membrane oxygenation) between April 2017 and March 2021. After patients whose ACT and APTT were not measured simultaneously or who were also taking other anticoagulants were excluded, we analyzed 94 samples from 23 patients. To explain the discrepancy between ACT and APTT, regression equations were created using a generalized linear model (family = gamma, link = logarithmic) with ACT as the response variable. Other explanatory variables included age, platelet count, and antithrombin. Compared to APTT alone as an explanatory variable, the Akaike information criterion and pseudo-coefficient of determination improved from 855 to 625 and from 0.01 to 0.42, respectively, when these explanatory variables were used. In conclusion, we identified several factors that may explain some of the discrepancy between ACT and APTT in the routinely measured tests. Evaluation of these factors may aid in appropriate adjustments in anticoagulation therapy.
Topics: Humans; Heparin; Female; Male; Child; Retrospective Studies; Extracorporeal Circulation; Adolescent; Partial Thromboplastin Time; Child, Preschool; Young Adult; Adult; Infant; Anticoagulants; Blood Coagulation; Whole Blood Coagulation Time
PubMed: 38711321
DOI: 10.1177/10760296241252838 -
Medical Physics Jun 2024Assessing renal perfusion in-vivo is challenging and quantitative information regarding renal hemodynamics is hardly incorporated in medical decision-making while...
PURPOSE
Assessing renal perfusion in-vivo is challenging and quantitative information regarding renal hemodynamics is hardly incorporated in medical decision-making while abnormal renal hemodynamics might play a crucial role in the onset and progression of renal disease. Combining physiological stimuli with rubidium-82 positron emission tomography/computed tomography (Rb PET/CT) offers opportunities to test the kidney perfusion under various conditions. The aim of this study is: (1) to investigate the application of a one-tissue compartment model for measuring renal hemodynamics with dynamic Rb PET/CT imaging, and (2) to evaluate whether dynamic PET/CT is sensitive to detect differences in renal hemodynamics in stress conditions compared to resting state.
METHODS
A one-tissue compartment model for the kidney was applied to cardiac Rb PET/CT scans that were obtained for ischemia detection as part of clinical care. Retrospective data, collected from 17 patients undergoing dynamic myocardial Rb PET/CT imaging in rest, were used to evaluate various CT-based volumes of interest (VOIs) of the kidney. Subsequently, retrospective data, collected from 10 patients (five impaired kidney functions and five controls) undergoing dynamic myocardial Rb PET/CT imaging, were used to evaluate image-derived input functions (IDIFs), PET-based VOIs of the kidney, extraction fractions, and whether dynamic Rb PET/CT can measure renal hemodynamics differences using the renal blood flow (RBF) values in rest and after exposure to adenosine pharmacological stress.
RESULTS
The delivery rate (K) values showed no significant (p = 0.14) difference between the mean standard deviation (SD) K values using one CT-based VOI and the use of two, three, and four CT-based VOIs, respectively 2.01(0.32), 1.90(0.40), 1.93(0.39), and 1.94(0.40) mL/min/mL. The ratio between RBF in rest and RBF in pharmacological stress for the controls were overall significantly lower compared to the impaired kidney function group for both PET-based delineation methods (region growing and iso-contouring), with the smallest median interquartile range (IQR) of 0.40(0.28-0.66) and 0.96(0.62-1.15), respectively (p < 0.05). The K of the impaired kidney function group were close to 1.0 mL/min/mL.
CONCLUSIONS
This study demonstrated that obtaining renal K and RBF values using Rb PET/CT was feasible using a one-tissue compartment model. Applying iso-contouring as the PET-based VOI of the kidney and using AA as an IDIF is suggested for consideration in further studies. Dynamic Rb PET/CT imaging showed significant differences in renal hemodynamics in rest compared to when exposed to adenosine. This indicates that dynamic Rb PET/CT has potential to detect differences in renal hemodynamics in stress conditions compared to the resting state, and might be useful as a novel diagnostic tool for assessing renal perfusion.
Topics: Rubidium Radioisotopes; Positron Emission Tomography Computed Tomography; Humans; Hemodynamics; Male; Kidney; Female; Renal Circulation; Models, Biological; Middle Aged; Aged; Image Processing, Computer-Assisted; Retrospective Studies
PubMed: 38709908
DOI: 10.1002/mp.17080 -
The Journal of Vascular Access May 2024An accessible tool is required to analyze volume flow trends in arteriovenous fistulas for hemodialysis. Earlybird, an easy-to-place ultrasound Doppler device, has shown...
Assessment of volume flow rate in arteriovenous fistulas with a novel ultrasound Doppler device (earlybird): Trend analysis, comparison of methods, and inter- and intra-rater reliability.
BACKGROUND
An accessible tool is required to analyze volume flow trends in arteriovenous fistulas for hemodialysis. Earlybird, an easy-to-place ultrasound Doppler device, has shown comparable accuracy to duplex ultrasound. In this study, we compared volume flow measurements obtained with duplex ultrasound and the dilution technique to an enhanced earlybird device, featuring a dual Doppler probe system, eliminating the requirement for a known insonation angle.
METHODS
Nine patients with a distal radiocephalic arteriovenous fistula were monitored for 12 months with regular volume flow measurements. Correlation and inter- and intra-class reliability analyses were conducted.
RESULTS
An overall moderate correlation was observed between earlybird and duplex ultrasound or dilution technique (intraclass correlation coefficient = 0.606 (95% confidence interval 0.064, 0.721) and 0.581 (0.039, 0.739), respectively). Duplex ultrasound compared to dilution measurements, demonstrated an overall moderate correlation (0.725 (0.219, 0.843)). Correlation between earlybird and duplex ultrasound was stronger for the arteriovenous fistula (0.778 (0.016, 0.901)) than the brachial artery (0.381 (-0.062, 0.461)). For earlybird, inter-rater reliability was excellent for the arteriovenous fistula (0.907 (0.423, 0.930)) and poor for the brachial artery (0.430 (0.241, 0.716)). Duplex ultrasound showed a good inter-rater reliability (arteriovenous fistula: 0.843 (0.610, 0.871), brachial artery: 0.819 (0.477, 0.864)). The overall intra-rater reliability was good for duplex ultrasound (rater A: 0.893 (0.727, 0.911); rater B: 0.853 (0.710, 0.891)), while excellent for earlybird (rater A: 0.905 (0.819, 0.928); rater B: 0.921 (0.632, 0.969)).
CONCLUSION
We observed a weaker correlation in the measurements of volume flow rates in arteriovenous fistulas when obtained using earlybird compared to dilution technique, unlike the comparison between duplex ultrasound and the dilution technique. However, inter-rater reliability for the arteriovenous fistula was excellent with earlybird and good with duplex ultrasound, indicating the potential of earlybird as a tool for frequent measurements, enabling trend surveillance and predicting adverse outcomes.
PubMed: 38708835
DOI: 10.1177/11297298241250379