-
JACC. Advances Dec 2023Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications.
BACKGROUND
Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications.
OBJECTIVES
The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients.
METHODS
COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression.
RESULTS
Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; < 0.0001) and were in more advanced physiological stage ( = 0.032) and NYHA functional class ( = 0.01), had lower baseline oxygen saturation ( = 0.0001), and more frequently had a history of atrial arrhythmia ( < 0.0001), previous hospitalization for heart failure ( < 0.0007), and were more likely hospitalized for COVID-19 ( < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; < 0.0001) were independently associated with increased risk of TE/bleeding complications.
CONCLUSIONS
ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.
PubMed: 38938489
DOI: 10.1016/j.jacadv.2023.100701 -
Renal Failure Dec 2024Chronic kidney disease (CKD) poses a significant public health challenge globally while impacting patients' physical function and quality of life. Addressing the issues...
Effects of a combined aerobic and core stabilization exercise training program on functional capacity, pain, and health-related quality of life in hemodialysis and kidney transplant patients.
BACKGROUND
Chronic kidney disease (CKD) poses a significant public health challenge globally while impacting patients' physical function and quality of life. Addressing the issues of physical inactivity and pain management is essential during treatment to improve health-related quality of life. The present study investigated the effect of an aerobic training program with core stabilization exercises for hemodialysis (HD) patients on a transplant waiting list and renal transplant (RTx) patients.
METHODS
A total of 45 patients with CKD were included in the 12-week study: 25 patients receiving HD (12 HD treatment group, 13 HD control group) and 20 patients with RTx (9 RTx treatment group, 11 RTx control group). Functional capacity was measured using the 6-min walk test, pain was measured using the visual analog scale, and health-related quality of life was measured using the Kidney Disease Quality of Life-Short Form 12 questionnaire. Nonparametric statistical tests were performed at a significance level of 0.05.
RESULTS
Both the HD and RTx treatment groups showed significantly reduced times for the 6-min walking test ( = 0.002 and = 0.008, respectively), significantly reduced pain severity ( = 0.002 and = 0.008, respectively), and significantly improved quality of life scores ( = 0.006 and = 0.041, respectively) by the end of the study compared with control groups.
CONCLUSION
Based on the results, structured exercise programs could be effective therapies in CKD management. Therefore, health providers should promote their integration into routine care practices to enhance patient outcomes and well-being.
Topics: Humans; Quality of Life; Male; Female; Renal Dialysis; Middle Aged; Kidney Transplantation; Exercise Therapy; Adult; Renal Insufficiency, Chronic; Exercise; Aged; Pain Management; Walk Test; Pain Measurement; Surveys and Questionnaires
PubMed: 38938194
DOI: 10.1080/0886022X.2024.2370439 -
Critical Care (London, England) Jun 2024The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of...
BACKGROUND
The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of differences in sepsis pathophysiology between women and men, sex is currently not being considered in the SOFA score. We aimed to investigate potential sex-specific differences in organ dysfunction, as measured by the SOFA score, in patients with sepsis or septic shock and explore outcome associations.
METHODS
Retrospective analysis of sex-specific differences in the SOFA score of prospectively enrolled ICU patients with sepsis or septic shock admitted to one of 85 certified Swiss ICUs between 01/2021 and 12/2022.
RESULTS
Of 125,782 patients, 5947 (5%) were admitted with a clinical diagnosis of sepsis (2244, 38%) or septic shock (3703, 62%). Of these, 5078 (37% women) were eligible for analysis. A statistically significant difference of the total SOFA score on admission was found between women (mean 7.5 ± SD 3.6 points) and men (7.8 ± 3.6 points, Wilcoxon rank-sum p < 0.001). This was driven by differences in the coagulation (p = 0.008), liver (p < 0.001) and renal (p < 0.001) SOFA components. Differences between sexes were more prominent in younger patients < 52 years of age (women 7.1 ± 4.0 points vs men 8.1 ± 4.2 points, p = 0.004). No sex-specific differences were found in ICU length of stay (women median 2.6 days (IQR 1.3-5.3) vs men 2.7 days (IQR 1.2-6.0), p = 0.13) and ICU mortality (women 14% vs men 15%, p = 0.17).
CONCLUSION
Sex-specific differences exist in the SOFA score of patients admitted to a Swiss ICU with sepsis or septic shock, particularly in laboratory-based components. Although the clinical meaningfulness of these differences is unclear, a reevaluation of sex-specific thresholds for SOFA score components is warranted in an attempt to make more accurate and individualised classifications.
Topics: Humans; Female; Male; Organ Dysfunction Scores; Intensive Care Units; Middle Aged; Aged; Retrospective Studies; Sepsis; Shock, Septic; Switzerland; Sex Factors; Prospective Studies; Adult
PubMed: 38937819
DOI: 10.1186/s13054-024-04996-y -
BMC Nephrology Jun 2024To investigate the expression and significance of Fractalkine (CX3CL1, FKN) in serum and renal tissue of myeloperoxidase and anti-neutrophil cytoplasmic antibody...
OBJECTIVE
To investigate the expression and significance of Fractalkine (CX3CL1, FKN) in serum and renal tissue of myeloperoxidase and anti-neutrophil cytoplasmic antibody associated vasculitis (MPO-AAV) rats.
METHODS
Thirty Wistar-Kyoto (WKY) rats were randomly divided into: Control group, MPO-AAV group (400 µg/kg MPO mixed with Freund's complete adjuvant i.p), MPO-AAV + Anti-FKN group (400 µg/kg MPO mixed with Freund's complete adjuvant i.p), anti-FKN group (1 µg/ rat /day, i.p) after 6 weeks. MPO-AAV associated glomerulonephritis model was established by intraperitoneal injection of MPO + Freund's complete adjuvant with 10 mice in each group. The concentration of MPO-ANCA and FKN in serum was detected by Enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to detect pathological changes of kidney tissue. Western blot and immunofluorescence staining were used to detect the expression and localization of FKN protein in kidney tissue. Renal function test indicators: 24-hour urinary protein (UAER), blood urea nitrogen (BUN), serum creatinine (Scr). The expression levels of p65NF-κB and IL-6 was detected by Immunohistochemical assays.
RESULTS
Compared with the control group, the serum MPO-ANCA antibody expression level in the MPO-AAV group was significantly increased (P < 0.01), and the contents of UAER, BUN and Scr were significantly up-regulated at 24 h (P < 0.01). Compared with the control group, the glomeruli in the MPO-AAV group had different degrees of damage, infiltration of inflammatory cell, and membrane cell hyperplasia and renal tubule edema. Compared with the control group, rats in the MPO-AAV group had significantly higher levels of FKN in serum and renal tissues (P < 0.01), and high expression of p65NF-κB and IL-6 in renal tissues (P < 0.01) (P < 0.05), whereas anti-FKN reversed the expression of the above factors. In MPO-AAV renal tissue, FKN was mainly expressed in the cytoplasm of renal tubular epithelial cells and glomerular podocytes. In addition, the contents of 24 h UAER, BUN and Scr of renal function in MPO-AAV rats were significantly decreased (P < 0.01) and the damage of renal tissue was significantly ameliorated after the administration of antagonistic FKN.
CONCLUSION
FKN may play a key role in the pathogenesis of MPO-AAV associated glomerulonephritis.
Topics: Animals; Chemokine CX3CL1; Glomerulonephritis; Rats; Peroxidase; Rats, Inbred WKY; Male; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Kidney; Antibodies, Antineutrophil Cytoplasmic; Transcription Factor RelA
PubMed: 38937701
DOI: 10.1186/s12882-024-03565-3 -
BMC Nephrology Jun 2024Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt...
BACKGROUND
Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt metabolism but are cumbersome to perform. We assessed urinary sodium (U-Na) concentration in spot urine samples and investigated the correlation with 24h U-Na excretion and concentration in CKD patients under nephrological care. Further, we studied the role of CKD stage and diuretics and evaluated the performance of commonly used formulas for the prediction of 24h U-Na excretion from spot urine samples.
METHODS
One hundred eight patients of the German Chronic Kidney Disease (GCKD) study were included. Each participant collected a 24h urine and two spot urine samples within the same period. The first spot urine sample (AM) was part of the second morning urine. The second urine sample was collected before dinner (PM). Patients were advised to take their medication as usual without changing dietary habits. U-Na concentrations in the two spot urine samples and their average ((AM + PM)/2) were correlated with U-Na concentration and total Na excretion in the 24h urine collections. Correlations were subsequently studied after stratification by CKD stage and diuretic intake. The usefulness of three commonly applied equations to estimate 24h U-Na excretion from spot urine samples (Kawasaki, Tanaka and Intersalt) was determined using Bland-Altman plots, analyses of sensitivity, specificity, as well as positive (PPV) and negative predictive values (NPV).
RESULTS
Participants (42 women, 66 men) were on average (± SD) 62.2 (± 11.9) years old, with a mean serum creatinine of 1.6 (± 0.5) mg/dl. 95% had arterial hypertension, 37% diabetes mellitus and 55% were on diuretics. The best correlation with 24h U-Na total excretion was found for the PM spot U-Na sample. We also found strong correlations when comparing spot and 24h urine U-Na concentration. Correction of spot U-Na for U-creatinine did not improve strength of correlations. Neither CKD stage, nor intake of diuretics had significant impact on these correlations. All examined formulas revealed a significant mean bias. The lowest mean bias and the strongest correlation between estimated and measured U-Na excretion in 24h were obtained using the Tanaka-formula. Also, application of the Tanaka-formula with PM U-Na provided best sensitivity, specificity, PPV and NPV to estimate U-Na excretion > 4g/d corresponding to a salt consumption > 10g/d.
CONCLUSION
U-Na concentration of spot urine samples correlated with 24h U-Na excretion especially when PM spot U-Na was used. However, correlation coefficients were relatively low. Neither CKD stage nor intake of diuretics appeared to have an influence on these correlations. There was a significant bias for all tested formulas with the Tanaka-formula providing the strongest correlation with measured 24h U-Na excretion. In summary, using spot urine samples together with the Tanaka-formula in epidemiological studies appears feasible to determine associations between approximate salt intake and outcomes in CKD patients. However, the usefulness of spot-urine samples to guide and monitor salt consumption in individual patients remains limited.
Topics: Humans; Female; Male; Renal Insufficiency, Chronic; Middle Aged; Sodium; Aged; Urine Specimen Collection; Diuretics; Predictive Value of Tests; Urinalysis; Adult
PubMed: 38937680
DOI: 10.1186/s12882-024-03639-2 -
BMC Nephrology Jun 2024Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with...
BACKGROUND
Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with sarcoidosis is rare and membranous nephropathy (MN) is cited as the most common. The association between the two diseases remained unclear. This article reported a case of co-occurrence of sarcoidosis and anti-PLA2R-associated MN, to provide a possible relationship between these two entities.
CASE PRESENTATION
A 61-year-old Chinese Han woman with a history of sarcoidosis was admitted to our hospital for nephrotic syndrome. Her sarcoidosis was diagnosed according to the adenopathy observed on the computed tomography scan and the biopsy of lymph nodes. The MN presented with nephrotic syndrome with a PLA2R antibody titer of 357RU/ml, and the final diagnosis was based on a renal biopsy. The patient's sarcoidosis was remitted after treatment with prednisone. One year later MN was diagnosed, and she was treated with prednisone combined with calcineurin inhibitors, based on a full dose of renin-angiotensin system (RAS) inhibitor. The patient's sarcoidosis had been in remission while the MN was recurrent, and her renal function deteriorated to end-stage renal disease 6 years later due to discontinuation of immunosuppression. A genetic test led to the identification of the HLA-DRB1*0301 and HLA-DRB1*150 genes associated with both sarcoidosis and MN, which provides a new possible explanation of the co-occurrence of these two diseases.
CONCLUSION
This case suggested for the first time a potential genetic connection between idiopathic MN and sarcoidosis which needs further studies in the future.
Topics: Humans; Glomerulonephritis, Membranous; Female; Middle Aged; Receptors, Phospholipase A2; Sarcoidosis; Genetic Predisposition to Disease; Autoantibodies
PubMed: 38937663
DOI: 10.1186/s12882-024-03649-0 -
Scientific Reports Jun 2024Malnutrition and pain are common in patients with chronic kidney disease who undergo hemodialysis. Although both pain and malnutrition are associated with increased...
Malnutrition and pain are common in patients with chronic kidney disease who undergo hemodialysis. Although both pain and malnutrition are associated with increased morbidity and mortality, few studies have explored the correlation between pain and nutritional status. This study aimed to investigate the factors associated with pain intensity in patients undergoing hemodialysis, focusing on the risk of malnutrition. This was a cross-sectional study conducted at a regional dialysis center in a large tertiary hospital. Convenience sampling was used to recruit adult patients who had undergone hemodialysis for more than three months. An interviewer-administered questionnaire was used to gather sociodemographic and clinical data related to dialysis status, comorbidities, and body mass index (BMI). Pain severity and pain interference with functioning domains of the Brief Pain Index (BPI) were used to assess pain, and the malnutrition inflammation score (MIS) was used to assess nutritional status. Descriptive and inferential statistics were used to report the findings. The data were analyzed using the 25th version of the Statistical Package for the Social Sciences (IBM-SPSS) software. Of the final sample of 230 patients, 63.0% were males and 37.0% were females, with an average age of 58.3 years. Almost one-third of the participants had a BMI within the normal range (33.9%), and nearly one-third had a BMI within the underweight range (33.9%). Slightly more than half had a normal nutritional status or mild malnutrition (54.8%), while just under half had moderate or severe malnutrition (45.2%). The prevalence of pain was 47.0%. At the multivariate level, the severity of pain was associated with malnutrition (p < 0.001). Pain interference with function was associated with marital status (p = 0.045), number of comorbidities (p = 0.012), and malnutrition (p < 0.001). The MIS was positively correlated with both the severity of pain and the interference score. Pain and malnutrition were found to be prevalent in patients undergoing hemodialysis. Pain severity was associated with malnutrition, and pain interference was associated with malnutrition, marital status, and the number of comorbidities. Hemodialysis treatment should follow a patient-tailored approach that addresses pain, nutritional status, and associated chronic conditions. In addition, pain assessment and management should be included in the curriculum of nephrology training programs.
Topics: Humans; Female; Male; Renal Dialysis; Malnutrition; Middle Aged; Prevalence; Pain; Cross-Sectional Studies; Aged; Nutritional Status; Body Mass Index; Adult; Risk Factors; Renal Insufficiency, Chronic; Surveys and Questionnaires
PubMed: 38937541
DOI: 10.1038/s41598-024-65603-2 -
Scientific Reports Jun 2024Moderately elevated albuminuria (30-300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have...
Moderately elevated albuminuria (30-300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have reported a relationship between moderately elevated albuminuria and triglyceride (TG) levels. Therefore, we aimed to evaluate the relationship between the urine albumin-to-creatinine ratio (UACR) and total cholesterol (TC), TG, and high-density lipoprotein C (HDL-C) levels. We analyzed data from 19,340 patients from the 2011-2014 and 2019-2020 from the Korea National Health and Nutrition Examination Surveys. Multivariate linear regression analysis showed that the UACR was positively associated with TC and TG levels and negatively associated with HDL-C levels in both Korean women and men. These results were reanalyzed according to the degree of proteinuria (normal, moderately elevated albuminuria, and severely elevated albuminuria (≥ 300 mg/g)). We found a positive relationship between UACR and TC and TG levels, but a negative association with HDL-C levels, except for TC (moderately elevated albuminuria) and HDL-C (moderately elevated albuminuria) in Korean men and TC (severely elevated albuminuria), TG (severely elevated albuminuria), and HDL-C (normal range albuminuria) in Korean women. The correlation between albuminuria and lipid profiles became more evident as albuminuria shift from normal to the severely elevated albuminuria. Thus our multivariate linear regression analysis showed that lipid profiles (TG, TC, and HDL-C levels) were associated with the UACR.
Topics: Humans; Female; Male; Albuminuria; Middle Aged; Creatinine; Republic of Korea; Adult; Triglycerides; Cholesterol, HDL; Aged; Lipids; Nutrition Surveys; Cholesterol; Biomarkers
PubMed: 38937496
DOI: 10.1038/s41598-024-65037-w -
Molecular Biomedicine Jun 2024Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in...
Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.
Topics: Animals; Mice; Fibrosis; Disease Progression; Single-Cell Analysis; Gene Expression Profiling; Renal Insufficiency, Chronic; Mice, Knockout; Nerve Tissue Proteins; Membrane Proteins; Kidney; Transcriptome; Reactive Oxygen Species; Epithelial-Mesenchymal Transition; Disease Models, Animal; Mitochondria
PubMed: 38937317
DOI: 10.1186/s43556-024-00187-x -
Biomedicine & Pharmacotherapy =... Jun 2024Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue...
Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue fibrosis and chronic kidney disease due to interstitial fibroblast activation and tissue repair failures that lack direct treatments. After an AKI episode, surviving renal tubular cells undergo cycles of dedifferentiation, proliferation and redifferentiation while fibroblast activity increases and then declines to avoid an exaggerated extracellular matrix deposition. Appropriate tissue recovery versus pathogenic fibrotic progression depends on fine-tuning all these processes. Identifying endogenous factors able to affect any of them may offer new therapeutic opportunities to improve AKI outcomes. Galectin-8 (Gal-8) is an endogenous carbohydrate-binding protein that is secreted through an unconventional mechanism, binds to glycosylated proteins at the cell surface and modifies various cellular activities, including cell proliferation and survival against stress conditions. Here, using a mouse model of AKI induced by folic acid, we show that pre-treatment with Gal-8 protects against cell death, promotes epithelial cell redifferentiation and improves renal function. In addition, Gal-8 decreases fibroblast activation, resulting in less expression of fibrotic genes. Gal-8 added after AKI induction is also effective in maintaining renal function against damage, improving epithelial cell survival. The ability to protect kidneys from injury during both pre- and post-treatments, coupled with its anti-fibrotic effect, highlights Gal-8 as an endogenous factor to be considered in therapeutic strategies aimed at improving renal function and mitigating chronic pathogenic progression.
PubMed: 38936192
DOI: 10.1016/j.biopha.2024.116923