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Brain and Behavior Jun 2024To assess changes in neurovascular coupling (NVC) by evaluating the relationship between cerebral perfusion and brain connectivity in patients with end-stage renal...
PURPOSE
To assess changes in neurovascular coupling (NVC) by evaluating the relationship between cerebral perfusion and brain connectivity in patients with end-stage renal disease (ESRD) undergoing hemodialysis versus in healthy control participants. And by exploring brain regions with abnormal NVC associated with cognitive deficits in patients, we aim to provide new insights into potential preventive and therapeutic interventions.
MATERIALS AND METHODS
A total of 45 patients and 40 matched healthy controls were prospectively enrolled in our study. Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Arterial spin labeling (ASL) was used to calculate cerebral blood flow (CBF), and graph theory-based analysis of results from resting-state functional magnetic resonance imaging (rs-fMRI) was used to calculate brain network topological parameters (node betweenness centrality [BC], node efficiency [Ne], and node degree centrality [DC]). Three NVC biomarkers (CBF-BC, CBF-Ne, and CBF-DC coefficients) at the whole brain level and 3 NVC biomarkers (CBF/BC, CBF/Ne, and CBF/DC ratios) at the local brain region level were used to assess NVC. Mann-Whitney U tests were used to compare the intergroup differences in NVC parameters. Spearman's correlation analysis was used to evaluate the relationship among NVC dysfunctional pattern, cognitive impairment, and clinical characteristics multiple comparisons were corrected using a voxel-wise false-discovery rate (FDR) method (p < .05).
RESULTS
Patients showed significantly reduced global coupling coefficients for CBF-Ne (p = .023) and CBF-BC (p = .035) compared to healthy controls. Coupling ratios at the local brain region level were significantly higher in patients in 33 brain regions (all p values < .05). Coupling ratio changes alone or accompanied by changes in CBF, node properties, or both CBF and node properties were identified. In patients, negative correlations were seen between coupling ratios and MoCA scores in many brain regions, including the left dorsolateral superior frontal gyrus, the bilateral median cingulate and paracingulate gyri, and the right superior parietal gyrus. The correlations remained even after adjusting for hemoglobin and hematocrit levels.
CONCLUSION
Disrupted NVC may be one mechanism underlying cognitive impairment in dialysis patients.
Topics: Humans; Male; Female; Middle Aged; Magnetic Resonance Imaging; Neurovascular Coupling; Kidney Failure, Chronic; Cognitive Dysfunction; Brain; Adult; Cerebrovascular Circulation; Renal Dialysis; Neuroimaging; Aged; Prospective Studies; Mental Status and Dementia Tests; Nerve Net
PubMed: 38923330
DOI: 10.1002/brb3.3598 -
JAMA Network Open Jun 2024Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to...
IMPORTANCE
Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care.
OBJECTIVE
To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023.
EXPOSURES
Demographics, lifestyle factors, comorbidities, medications, and laboratory results.
MAIN OUTCOMES AND MEASURES
Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit.
RESULTS
Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment.
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.
Topics: Humans; Diabetes Mellitus, Type 2; Female; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Aged; Guideline Adherence; Practice Guidelines as Topic; Mass Screening; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; United States; Glomerular Filtration Rate
PubMed: 38922613
DOI: 10.1001/jamanetworkopen.2024.18808 -
Critical Care Explorations Jul 2024COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked...
IMPORTANCE
COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point.
OBJECTIVES
To better understand mechanisms of acute kidney injury in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19.
DESIGN, SETTING, AND PARTICIPANTS
The COVID-19 Host Response and Outcomes study prospectively enrolled patients admitted to ICUs in Washington State with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival.
MAIN OUTCOMES AND MEASURES
We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance.
RESULTS
At ICU admission, the mean age was 55 ± 16 years; 45% required mechanical ventilation; and the mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater occurrence of MAKE (relative risk 1.70; 95% CI, 1.05-2.74) and a 741% greater occurrence of KRT (relative risk 7.41; 95% CI, 1.69-32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and estimated glomerular filtration rate (eGFR) increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group.
CONCLUSIONS
Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction and reduced eGFR despite similar degrees of kidney injury.
Topics: Humans; COVID-19; Middle Aged; Critical Illness; Male; Acute Kidney Injury; Female; Prospective Studies; Aged; Hepatitis A Virus Cellular Receptor 1; SARS-CoV-2; Adult; Biomarkers; Kidney Tubules; Creatinine; Intensive Care Units; Washington; Epidermal Growth Factor; Renal Replacement Therapy
PubMed: 38922318
DOI: 10.1097/CCE.0000000000001109 -
Arquivos Brasileiros de Cardiologia 2024Identifying risk factors in cardiovascular surgery assists in predictability, resulting in optimization of outcomes and cost reduction.
BACKGROUND
Identifying risk factors in cardiovascular surgery assists in predictability, resulting in optimization of outcomes and cost reduction.
OBJECTIVE
This study aimed to identify preoperative and intraoperative risk predictors for prolonged hospitalization after coronary artery bypass grafting (CABG) surgery in the state of São Paulo, Brazil.
METHODS
A cross-sectional analysis using data from the REPLICCAR II database, a prospective, consecutive, multicenter registry that included CABG surgeries performed between August 2017 and July 2019. The primary outcome was a prolonged hospital stay (PHS), defined as a postoperative period exceeding 14 days. Univariate and multivariate logistic regression analyses were performed to identify the predictors with significance set at p <0.05.
RESULTS
The median age was 63 (57-70) years and 26.55% of patients were female. Among the 3703 patients analyzed, 228 (6.16%) had a PHS after CABG, with a median hospital stay of 17 (16-20) days. Predictors of PHS after CABG included age >60 years (OR 2.05; 95% CI 1.43-2.87; p<0.001); renal failure (OR 1.73; 95% CI 1.29-2.32; p <0.001) and intraoperative red blood cell transfusion (OR 1.32; 95% CI 1.07-2.06; p=0.01).
CONCLUSION
Age >60 years, renal failure, and intraoperative red blood cell transfusion were independent predictors of PHS after CABG. The identification of these variables can help in multiprofessional strategic planning aimed to enhance results and resource utilization in the state of São Paulo.
Topics: Humans; Female; Coronary Artery Bypass; Male; Middle Aged; Length of Stay; Aged; Risk Factors; Cross-Sectional Studies; Age Factors; Renal Insufficiency; Brazil; Blood Transfusion; Risk Assessment; Prospective Studies
PubMed: 38922261
DOI: 10.36660/abc.20230769 -
Toxins May 2024Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be... (Review)
Review
Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be related to traditional risk factors and CKD-specific factors that accelerate atherosclerosis and vascular calcification in CKD patients. The accumulation of uremic toxins is a significant factor in CKD-related systemic disorders. Basic research suggests that indoxyl sulfate (IS), a small protein-bound uremic toxin, is associated with macrophage dysfunctions, including increased oxidative stress, exacerbation of chronic inflammation, and abnormalities in lipid metabolism. Strategies to mitigate the toxicity of IS include optimizing gut microbiota, intervening against the abnormality of intracellular signal transduction, and using blood purification therapy with higher efficiency. Further research is needed to examine whether lowering protein-bound uremic toxins through intervention leads to a reduction in CVD in patients with CKD.
Topics: Indican; Humans; Atherosclerosis; Macrophages; Animals; Uremia; Renal Insufficiency, Chronic; Uremic Toxins; Gastrointestinal Microbiome; Oxidative Stress
PubMed: 38922148
DOI: 10.3390/toxins16060254 -
Toxins May 2024Both physical inactivity and disruptions in the gut microbiome appear to be prevalent in patients with chronic kidney disease (CKD). Engaging in physical activity could... (Review)
Review
Both physical inactivity and disruptions in the gut microbiome appear to be prevalent in patients with chronic kidney disease (CKD). Engaging in physical activity could present a novel nonpharmacological strategy for enhancing the gut microbiome and mitigating the adverse effects associated with microbial dysbiosis in individuals with CKD. This narrative review explores the underlying mechanisms through which physical activity may favorably modulate microbial health, either through direct impact on the gut or through interorgan crosstalk. Also, the development of microbial dysbiosis and its interplay with physical inactivity in patients with CKD are discussed. Mechanisms and interventions through which physical activity may restore gut homeostasis in individuals with CKD are explored.
Topics: Gastrointestinal Microbiome; Humans; Renal Insufficiency, Chronic; Dysbiosis; Exercise; Animals
PubMed: 38922137
DOI: 10.3390/toxins16060242 -
Marine Drugs Jun 2024Cadmium (Cd) is a toxic heavy metal that causes nephrosis, including acute kidney injury. To prevent and treat acute kidney injury (AKI) following Cd exposure, a...
Cadmium (Cd) is a toxic heavy metal that causes nephrosis, including acute kidney injury. To prevent and treat acute kidney injury (AKI) following Cd exposure, a tripeptide, Ser-Arg-Pro (SRP), from L. was employed, and its potential efficacy in AKI was assessed. Oral administration of SRP significantly alleviated Cd-induced kidney damage, leading to improved renal function and the attenuation of structural abnormalities. A network pharmacology analysis revealed the potential of SRP in renal protection by targeting various pathways, including mitogen-activated protein kinase (MAPK) signaling, inflammatory response, and apoptosis pathways. Mechanistic studies indicated that SRP achieves renal protection by inhibiting the activation of MAPK pathways (phosphorylation of p38, p56, ERK, and JNK) in the oxidative stress cascade, suppressing inflammatory responses (iNOS, Arg1, Cox2, TNF-α, IL-1β, and IL-6), and restoring altered apoptosis factors (caspase-9, caspase-3, Bax, and Bcl-2). Hence, SRP has the potential to be used as a therapeutic agent for the treatment of Cd-induced nephrotoxicity.
Topics: Animals; Acute Kidney Injury; Apoptosis; Mice; Cadmium; Oxidative Stress; Male; Oligopeptides; MAP Kinase Signaling System; Kidney; Inflammation; Disease Models, Animal; Network Pharmacology
PubMed: 38921597
DOI: 10.3390/md22060286 -
Frontiers in Immunology 2024Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain... (Observational Study)
Observational Study
BACKGROUND
Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients.
METHODS
In a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI). After correcting for multiple testing, adjustments for comorbidities and demographics were performed on the statistically significant markers.
RESULTS
Of the 92 markers tested, circulating levels of fibroblast growth factor 23 (FGF-23) and interleukin-15 receptor alpha (IL15RA), both involved in renal disease, were significantly correlated with 6-month mortality (27.5% overall) after correcting for multiple testing. The incidence of postoperative AKI (25.4%) was strongly associated with 6-month mortality, odds ratio = 10.57; 95% CI [2.76-40.51], and with both markers plus estimated glomerular filtration rate (eGFR)- cystatin C (CYSC) but not eGFR-CRE. The effect of these markers on mortality was significantly mediated by their effect on postoperative AKI.
CONCLUSION
High postoperative mortality in frail hip fracture patients is highly correlated with preoperative biomarkers of renal function in this pilot study. The effect of preoperative circulating levels of FGF-23, IL15RA, and eGFR-CYSC on 6-month mortality is in part mediated by their effect on postoperative AKI. Creatinine-derived preoperative renal function measures were very poorly correlated with postoperative outcomes in this group.
Topics: Humans; Hip Fractures; Male; Female; Biomarkers; Aged; Fibroblast Growth Factor-23; Aged, 80 and over; Acute Kidney Injury; Prospective Studies; Postoperative Complications; Fibroblast Growth Factors; Glomerular Filtration Rate; Inflammation; Preoperative Period
PubMed: 38919625
DOI: 10.3389/fimmu.2024.1372079 -
Frontiers in Endocrinology 2024The Oxidative Balance Score (OBS), which quantifies the balance between antioxidants and pro-oxidants influenced by diet and lifestyle, is crucial given oxidative...
BACKGROUND
The Oxidative Balance Score (OBS), which quantifies the balance between antioxidants and pro-oxidants influenced by diet and lifestyle, is crucial given oxidative stress's significant role in Chronic Kidney Disease (CKD). This study aims to determine the association between OBS and CKD using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018.
METHODS
We analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. OBS was constructed from a detailed array of 20 factors, including dietary nutrients and lifestyle behaviors. The relationship between OBS and CKD risk was evaluated using weighted logistic regression models, adjusted for potential confounders, with a generalized additive model (GAM) examining non-linear associations. Subgroup analyses and interaction effects across diverse demographic and clinical groups, along with sensitivity analyses, were performed to validate the findings.
RESULTS
Among 32,120 participants analyzed, 4,786 were identified with CKD. Fully adjusted weighted logistic regression analysis revealed that each unit increase in OBS was associated with a 2% reduction in CKD prevalence [OR: 0.98 (0.98-0.99), P < 0.001]. Higher OBS quartiles were significantly correlated with a decreased CKD risk [Q4 . Q1: OR: 0.82 (0.68-0.98), P = 0.03; P for trend = 0.01]. The GAM and smoothed curve fit indicated a linear relationship between OBS and the risk of CKD. Stratified and sensitivity analyses further substantiated the inverse relationship between OBS and CKD prevalence.
CONCLUSIONS
Our findings from the NHANES data affirm a significant inverse association between OBS and CKD risk in the U.S. population, underscoring the role of optimizing dietary and lifestyle factors in managing CKD risk. These results advocate for incorporating OBS considerations into CKD prevention and treatment strategies.
Topics: Humans; Renal Insufficiency, Chronic; Nutrition Surveys; Female; Male; Middle Aged; Oxidative Stress; Adult; Aged; Life Style; Diet; Cross-Sectional Studies; Prevalence; Risk Factors; Antioxidants; United States
PubMed: 38919480
DOI: 10.3389/fendo.2024.1396465 -
BMC Nephrology Jun 2024There is still a very high morbidity and mortality rate for patients undergoing peritoneal dialysis (PD). The advanced lung cancer inflammation index (ALI) has been...
BACKGROUND
There is still a very high morbidity and mortality rate for patients undergoing peritoneal dialysis (PD). The advanced lung cancer inflammation index (ALI) has been demonstrated to be associated with the prognosis in multiple types of cancers. Like in cancer, systemic chronic low-grade inflammation is one of the distinguishing features of PD patients. Therefore, we aimed to investigate the relationships between the ALI and all-cause and cardiovascular disease (CVD) mortality in PD patients.
METHODS
Patients who started PD at Shaoxing People's Hospital between 1 January 2013 and 31 December 2020 (n = 277) were recruited and followed up until 1 July 2023. They were divided into high-ALI group and low-ALI group according to the median of ALI. Kaplan-Meier curves and multivariate Cox regression analyses were used to assess the associations between the ALI and all-cause and CVD mortality. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated to determine the predictive power of the ALI for all- cause and CVD mortality.
RESULTS
During the median follow-up of 40.50 months (interquartile range, 26.42-59.77 months), a total of 55 patients died, 31 of whom died due to CVD. Kaplan-Meier curves revealed that patients in the low-ALI group had significantly lower cumulative and cardiovascular cumulative survival rates than did those in the high-ALI group (all P < 0.001). After we corrected for confounders, the risk of all-cause and CVD mortality was significantly greater in the low-ALI group than in the high-ALI group [hazard ratio (HR) 1.944, 95% confidence interval (CI) 1.068-3.540, P = 0.030, and HR 2.672, 95% CI 1.188-6.009, P = 0.017, respectively]. The predictive value of ALI (AUC = 0.708, 95% CI 0.630-0.786, P < 0.001) for all-cause mortality was superior to albumin (AUC = 0.644, 95% CI 0.556-0.726, P < 0.001), body mass index (AUC = 0.581, 95% CI 0.496-0.659, P = 0.069) and neutrophil-to-lymphocyte ratio (AUC = 0.675, 95% CI 0.596-0.754, P < 0.001).
CONCLUSION
A lower ALI is an independent risk factor for all-cause and cardiovascular mortality in PD patients. The ALI may be an effective indicator for predicting outcomes in PD patients.
Topics: Humans; Male; Female; Middle Aged; Peritoneal Dialysis; Inflammation; Lung Neoplasms; Cardiovascular Diseases; Aged; Cause of Death; Adult; Kaplan-Meier Estimate; Kidney Failure, Chronic; ROC Curve; Prognosis
PubMed: 38918730
DOI: 10.1186/s12882-024-03645-4