Research Progress on Cognitive Frailty in Older Adults with Chronic Kidney Disease.

BACKGROUND: As the medical challenges posed by the ageing population become increasingly severe, the proportion of older people among patients with chronic kidney disease (CKD) is increasing every year. SUMMARY: The prevalence of frailty in patients with CKD is significantly higher than that in the general population, and older patients are also a high-risk group for frailty and cognitive impairment. Cognitive frailty, as an important subtype of frailty, is a syndrome characterised by cognitive dysfunction caused by physiological factors, excluding Alzheimer's disease and other types of dementia. It is characterised by the coexistence of physical frailty and cognitive impairment. Previous studies have mainly focused on cognitive impairment, and there is limited research on cognitive frailty, particularly in older patients with CKD. KEY MESSAGES: This article provides a comprehensive review of the concept, epidemiology, screening methods, prevention, and treatment measures and possible pathogenesis of cognitive frailty in patients with CKD.

Analysis of m6A-regulated genes and subtype classification in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE). N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, the roles of m6A regulators in LN are not fully demonstrated. METHODS: We downloaded the kidney tissue transcriptome dataset of LN patients and normal controls from the GEO database and extracted the expression levels of m6A regulators. We constructed and compared Random Forest (RF) and Support Vector Machine (SVM) models, and subsequently selected featured genes to develop nomogram models. The m6A subtypes were identified based on significantly differentially expressed m6A regulators, and the m6A gene subtypes were identified based on m6A-associated differential genes, and the two m6A modification patterns were comprehensively evaluated. RESULTS: We obtained the GSE32591 and GSE112943 datasets from the GEO database, including 78 LN samples and 36 normal control samples. We extracted the expression levels of 20 m6A regulators. By RF analysis we identified 7 characteristic m6A regulators and constructed nomogramh models with these 7 genes. We identified two m6A subtypes based on these seven important m6A regulators, and the immune cell infiltration levels of the two subtype clusters were significantly different. We identified two more m6A gene subtypes based on m6A-associated DEGs. We calculated the m6A scores using the principal component analysis (PCA) algorithm and found that the m6A scores of m6A cluster A and gene cluster A were lower than those of m6A cluster B and gene cluster B. In addition, we found that the levels of inflammatory factors were also significantly different between m6A clusters and gene clusters. CONCLUSION: This study confirms that m6A regulators are involved in the LN process through different modes of action and provide new diagnostic and therapeutic targets for LN.

Clinicopathological characteristics and outcomes of PLA2R related idiopathic membranous nephropathy in patients with seronegative PLA2R antibodies.

BACKGROUND: Idiopathic membranous nephropathy (IMN) with deposits of phospholipase A2 receptor (PLA2R) antigen in glomerular tissue (GAg+) but no circulating serum PLA2R antibody (SAb-) has been reported. However, little is known about the clinicopathological characteristics and prognosis of this subtype. METHODS: A total of 74 IMN patients with GAg + identified by kidney biopsy were enrolled in this study. We categorized patients into two groups based on the presence or absence of serum PLA2R antibody. Data on clinical features, pathological features, and outcomes were collected. Kaplan-Meier analysis of complete remission (CR) and partial remission (PR) comparing SAb-/GAg + and SAb+/GAg + patients. Cox proportional hazards models was used to examine factors associated with CR and PR. RESULTS: Among 74 IMN patients, 14 were SAb-/GAg+. Compared with SAb+/GAg + patients, SAb-/GAg + patients presented with higher levels of albumin, lower levels of cholesterol and low density lipoprotein cholesterol (all p < .01), but similar pathological manifestations of kidney biopsy. Multivariate logistic analyses indicated that low albumin (0.79 [95%CI: 0.66-0.95], p = .01) and high cholesterol (1.81 [95%CI: 1.02-3.19], p = .04) were correlated with seropositivity of PLA2R antibody. SAb-/GAg + patients exhibited a significantly higher probability of CR (p = .03) than patients who were SAb+/GAg+. However, no difference was found in the PR rate. Cox regression analyses showed that compared to SAb+/GAg + patients, SAb-/GAg + was more predictive of complete remission (4.28 [95%CI: 1.01-18.17], p = .04). CONCLUSION: IMN with PLA2R staining on kidney biopsy but without serum PLA2R antibody has milder clinical manifestations and a better prognosis.

Integrative analysis of the association between circadian rhythm and lupus nephritis.

Background: Lupus nephritis (LN) is an autoimmune nephropathy associated with systemic lupus erythematosus. Circadian rhythms are involved in the development of several diseases, especially inflammation-related diseases, but their relationship with LN is unclear. Methods: This was an integrative bioinformatics study. The expression profile from glomeruli, tubular interstitium and renal whole tissue samples was used to assess the expression levels and relevance of circadian rhythm-related genes. To screen for circadian rhythm-related signatures, we employed the LASSO and SVM-RFE algorithms. A consensus clustering algorithm was used to classify LN patients into two circadian rhythm patterns (cluster A and cluster B). We made immune cell infiltration analysis. We used the weighted gene co-expression network analysis (WGCNA) algorithm to identify cluster-specific differentially expressed genes. Nephroseq data were used to observe the relationship between genes and renal function. Results: We found more significant differences in circadian rhythm-related gene expression in LN glomeruli compared with tubulointerstitial and whole-kidney tissues. We established a circadian rhythm-related signature consisting of eight genes that can easily distinguish LN from healthy individuals. Patients in cluster A were associated with B-cell-dominated immunity, whereas patients in cluster B were associated with T-cell-dominated immunity. As most of the patients with proliferative LN combined with membranous LN belonged to cluster B, patients in cluster B may have more severe renal pathology compared with patients in cluster A. Fifteen circadian rhythm-related genes associated with LN and LN typing were screened using the WGCNA algorithm, with COL1A2 and DOCK2 associated with renal prognosis. Conclusions: This study found that circadian rhythms are associated with the occurrence of LN, providing new ideas for the development of new LN treatment options from the perspective of circadian rhythms.

Mean Platelet Volume/Platelet Count Ratio as a Predictor of Both Incidence and Prognosis of Acute Ischemic Stroke in Hemodialysis Patients.

Purpose: This study aimed to explore whether the mean platelet volume/platelet count ratio (MPR) has predictive value for the occurrence and prognosis of acute ischemic stroke (AIS) in hemodialysis patients. Patients and Methods: A total of 402 patients undergoing maintenance hemodialysis were screened and 259 were enrolled in this study. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the predictive power of the models. The patients enrolled in this study were divided into three groups based on the tertiles of the MPR value (Q1, Q2, and Q3). Kaplan-Meier curves were used to investigate the association between the MPR and AIS-free survival in hemodialysis patients. Chi-square analysis was performed to explore the association between the MPR and AIS outcomes in hemodialysis patients. And the AIS outcome was assessed using the modified Rankin Scale (mRS). Results: MPR had a predictive value for the occurrence of AIS (AUC=0.814) in hemodialysis patients with a high sensitivity and specificity. AIS-free survival rates in the MPR Q1, MPR Q2, and MPR Q3 groups were 0.930, 0.701, and 0.360, respectively. The proportion of patients with good outcomes (mRS 0-2) was significantly greater among patients in the MPR Q1-Q2 group than in the MPR Q3 group (0.844 vs 0.745, p <0.001). Conclusion: The MPR can be used as a good predictor of AIS in patients undergoing hemodialysis. Patients on hemodialysis with increased MPR levels had a higher incidence of AIS and poorer functional outcomes than those with low MPR levels.

Prevalence and associated factors of cognitive frailty in older patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is prevalent in older adults. In the aging CKD population, cognitive frailty is more common, but its prevalence and associated risk factors need to be further investigated. METHODS: This is a cross-sectional study that enrolled patients aged ≥ 60 years with a diagnosis of CKD from January 2018 to February 2021. Patients were assessed for frailty and cognition with the FRAIL and the Mini-Mental State Examination (MMSE) scales and were divided into the cognitive frailty and non-cognitive frailty groups. Risk factors for cognitive frailty were identified by univariate and multivariate logistic regression analyses. A prediction model for cognitive frailty was built and a nomogram was plotted. The performance of the nomogram was evaluated by using a concordance index (C-index) and calibration plots. RESULTS: A total of 1015 older patients with CKD were enrolled, among whom 607 (59.8%) were males and 408 (40.2%) were females, with an age ranging from 60 to 98 years, and an cognitive frailty prevalence of 15.2%. The prevalence of cognitive frailty varied among the CKD stages 1-5, with rates of 4.7%, 7.5%, 13.8%, 18.5%, and 21.4%, respectively. Multivariate logistic regression analysis showed that age (OR = 1.11, 95%CI 1.08-1.14, p < 0.001), depression (OR = 2.52, 95%CI 1.54-4.11, p < 0.001), low social support (OR = 2.08, 95%CI 1.28-3.39, p = 0.003), Charlson comorbidity index (CCI) (OR = 1.92, 95%CI 1.70-2.18, p < 0.001), eGFR (OR = 0.98, 95%CI 0.96-0.99, p < 0.001) and albuminuria (OR = 5.93, 95%CI 3.28-10.74, p < 0.001) were independent risk factors affecting the association with cognitive frailty in older patients with CKD. A nomogram for assessing cognitive frailty was established and well-calibrated with a C-index of 0.91 (95%CI 0.89-0.94). CONCLUSIONS: The prevalence of cognitive frailty was higher in older patients having CKD. Advanced age, comorbidity, depression, low social support, eGFR and albuminuria were independent risk factors for CKD accompanied with cognitive frailty.

The impact of palliative care education and training program on the resident physicians.

BACKGROUND: Due to the advancements in medicine coupled with the aging population, palliative care has become widely needed. In many countries, medical students are trained in palliative care in their postgraduate courses. However, palliative care education is not available as an independent course or standardized training for residents in China. METHODS: This parallel randomized controlled trial was conducted in the Department of Internal Medicine, Beijing Chao-yang Hospital, Capital Medical University, between June 2016 and August 2017. The aim of the study was to explore the impact of the palliative care education and training program on 72 residents who were trained in standardization and were randomly divided into experimental and control groups at the ratio 1:1. The experimental group received resident physician standardized training and palliative care training program, while the control group received only standardized training. Standardized training included training in humanistic medical skills. The two groups were tested after training. A questionnaire survey was carried out to analyze the effect of palliative care education in humanistic medical skills. RESULTS: The total score of humanistic medical skills assessment of residents in the experimental group was higher compared to the control group (82.92±8.39 vs. 77.36±7.41, t =2.978, P=0.004). The experimental group performed better in terms of medical skills and the ability to care for dying patients. CONCLUSIONS: Palliative care education and training program should be required for residents as it is very useful. The purpose of palliative care education is to translate the knowledge in practice, truly implement the idea of palliative care, and relieve patients of terminal discomfort. The educational promotion of palliative care is of great value in China.

Main Risk Factors Related to Activities of Daily Living in Non-Dialysis Patients with Chronic Kidney Disease Stage 3-5: A Case-Control Study.

INTRODUCTION: Elderly people are at increased risk of falls, disability and death due to reduced functional reserve, decline in multiple systems functions, which affects their activities of daily living (ADL) and eventually develop into frailty. The ADL assessment is conducive to early detection to avoid further serious situations. Previous studies on patients' activities of daily living with chronic kidney disease (CKD) are mainly focused on dialysis patients. Little information is available on non-dialysis patients. PATIENTS AND METHODS: A total of 303 elderly patients with CKD stage 3-5 who were admitted to our hospital were selected. ADL evaluation was performed on patients at admission, with Barthel index (BI) as the evaluation tool. They were divided into two groups based on BI (≥60 and <60). Demographic information, lifestyle and clinical profile were collected. The risk factors related to ADL were analyzed by univariate and multivariate models. RESULTS: The data of 303 patients enrolled in this study were analyzed. The average age of patients was 84.48± 7.14 years and 62.05% were male. There were 88 patients (29.04%) in BI <60 group and 215 patients (70.96%) in the BI ≥60 group. The average age of subjects in the two groups was 87.47 ± 5.85 years and 83.26± 7.28 years, respectively. On univariate analysis, ADL impairment was associated with many factors, such as age, body mass index, blood lipid, heart rate, smoking history, Charlson comorbidity index (CCI), hemoglobin, serum albumin, BNP, eGFR, etc. Multivariate logistic regression showed that age (OR 1.08, 95% CI 1.00-1.17, P=0.0390), Charlson comorbidity index (OR 4.75, 95% CI 1.17-19.30, P=0.0295), and serum albumin (OR 0.80, 95% CI 0.70-0.92, P=0.0012) were the independent risk factors of ADL impairment. CONCLUSION: Decline of ADL in CKD patients was independently correlated with age, Charlson comorbidity index and serum albumin. ADL and its influential factors in the elderly CKD patients deserve further attention.

Individualized intervention for frail non-dialysis elderly patients with chronic kidney disease: protocol for a randomized controlled trial.

BACKGROUND: Frailty describes an age-related clinical state and can be regarded as a predictive factor for fall, disability, hospitalization, and death in the elderly. Previous studies proved that frailty could be reversed or attenuated by multi-disciplinary intervention. However, only a few studies have been performed in non-dialysis patients with chronic kidney disease. METHODS: A randomized parallel controlled trial will be conducted to compare an individualized intervention according to the consequence of the comprehensive geriatric assessment with routine treatment. A total of 242 individuals aged ≥65 years, who fulfill the Fried Phenotype of frailty and have chronic kidney disease stage 3-5 without dialysis will be recruited from the Department of Nephrology and Department of Internal Medicine, Beijing Chaoyang Hospital, Capital Medical University. The participants will be followed-up for 30 days and 12 months. DISCUSSION: This protocol would be established to examine the efficiency of targeted intervention for frailty. If a positive consequence could be obtained, a novel treatment for frail elderly patients with chronic kidney disease who have never undergone dialysis can be carried out in routine clinical practice. TRIAL REGISTRATION: The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR-IOR-17013429 on November 17, 2017.

Relationship between Cellular Immunity Changes and Prognosis in Elderly Patients with Sepsis.

OBJECTIVE: To detect relationship between cellular immunity changes and prognosis in elderly patients with sepsis. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: General Department and Emergency Care Unit, Beijing Chaoyang Hospital, Beijing, China, from January to December 2016. METHODOLOGY: Patients who had infection were included in this study, and divided into two groups; those with sepsis and no sepsis. One hundred and forty-one healthy volunteers were chosen to enroll in this study just as a control (control group). Patients were excluded if they were younger than 18 years of age; had hematological or immunological disease; had uncontrolled diabetes; and pretreated with immunosuppressive agents. Patients were further grouped according to age, their T lymphocyte subsets were compared, and their acute physiology and chronic health evaluation II (APACHE II) scores were compared. The 28-day re-hospitalisation rate was followed-up, and the effects of T lymphocyte subsets and APACHE II scores on this rate were statistical analysed. RESULTS: Out of the 687 patients, 350 patients had sepsis (sepsis group), and 337 patients had no sepsis (non-sepsis group). The age of these patients ranged from 19-96 years. CD3+T, CD4+T, CD8+T and natural NK cells were significantly lower in the elderly population, (p< 0.01). CD3+T, CD4+T, CD8+T and NK cells were significantly lower in the sepsis group, compared with patients in the non-sepsis group and control group; and the differences were statistically significant (p<0.05), while APACHE II score was significantly higher (p<0.01). In the sepsis group, compared with the non-elderly population, CD3+T, CD4+T and NK cells were significantly lower in the elderly population; and the differences were statistically significant (p<0.05), while APACHE II score was significantly higher (p<0.05). The 28-day re-hospitalisation rate was associated with CD3+T, CD4+T, CD8+T cells and APACHE II scores (p<0.05). CONCLUSION: CD3+T, CD4+T, CD8+T cells and APACHE II scores can be used as independent predictors of the 28-day re-hospitalisation rate.

Simultaneous occurrence of splenic diffuse large B cell lymphoma and gastrointestinal stromal tumor in the stomach: a case report.

BACKGROUND: Although the primary malignant spleen tumor is relatively rare, lymphoma is the most common splenic malignancy. It can have quite different clinical manifestations that usually lead to relatively poor outcomes, and thus early and accurate diagnosis are of utmost importance. CASE PRESENTATION: The present study reports a case of a 67-year-old female with high fever, abnormal spleen (diagnosed by PET/CT) and no obvious lymph node enlargement. After being subjected to splenectomy, the patient was diagnosed with splenic diffuse large B cell lymphoma coexisting with gastrointestinal stromal tumor in the stomach. CONCLUSIONS: To our knowledge, splenic lymphoma accompanied by gastrointestinal stromal tumor in the stomach is rarely reported. This case report discusses the diagnosis and case management of a patient referring to the existing literature.

The expression of microRNA-23a regulates acute myocardial infarction in patients and in vitro through targeting PTEN.

Cardiovascular disease is responsible for one of the highest rates of fatality worldwide. The present study investigated the presence and influence of microRNA (miRNA)-23a in the regulation of acute myocardial infarction (AMI). A total of 6 patients with AMI and 6 normal volunteers without myocardial disease were included, and blood samples were taken to analyze the expression of miRNA­23a by reverse transcription­quantitative polymerase chain reaction. miRNA­23a expression in patients with AMI was downregulated compared with the normal group. In H9C2 cells treated with H2O2, upregulation of miRNA­23a expression increased the superoxide dismutase, glutathione and catalase activity levels, and suppressed the malonaldehyde activity level, as determined by ELISA. Western blot analysis and a caspase­3 substrate assay demonstrated that upregulation of miRNA­23a expression suppressed the Bcl­2­associated X (Bax)/Bcl­2 protein expression ratio, caspase­3 activity level and tumor suppressor p53 (p53) protein expression in H2O2­induced H9C2 cells. Furthermore, downregulation of phosphatase and tensin homolog (PTEN), by the PTEN inhibitor bpV(HOpic), increased miRNA­23a expression and suppressed the Bax/Bcl­2 protein expression ratio, caspase­3 activity level and p53 protein expression in H2O2­induced H9C2 cells. Therefore, the results of the present study indicate that the expression of miRNA­23a may regulate AMI through targeting PTEN in patients and in vitro, and PTEN/miRNA­23a may therefore be potential targets for the clinical treatment of AMI.

Blood pressure circadian rhythms and adverse outcomes in type 2 diabetes patients diagnosed with orthostatic hypotension.

AIMS/INTRODUCTION: Patients with diabetes frequently develop orthostatic hypotension (OH). The present study was designed to examine the relationship of blood pressure (BP) circadian rhythms and outcomes in diabetes with OH. MATERIALS AND METHODS: In the present study, 173 inpatients with type 2 diabetes were enrolled. Patients were divided into an OH group and a non-OH group according to the BP changes detected in the supine and standing position. Then, 24-h ambulatory BP was monitored. Patients were followed up for an average of 45 ± 10 months post-discharge. Outcomes - death and major adverse cardiac and cerebrovascular events, including heart failure, myocardial infarction and stroke - were recorded. RESULTS: There were 61 patients (35.26%) in the OH group and 112 patients (64.74%) in the non-OH group. In the OH group, the night-time systolic BP and night-time diastolic BP were higher, the blood BP rhythms were predominantly of the riser type (67.21%). OH was as an independent marker of riser type circadian rhythm (adjusted odds ratio 4.532, 95% confidence interval 2.579-7.966). In the OH group, the incidence rates of mortality, and major adverse cardiac and cerebrovascular events were increased significantly compared with those in the non-OH group (11.48 vs 2.68%, P = 0.014; 37.70 vs 8.93%, P < 0.01). CONCLUSIONS: In patients who had type 2 diabetes diagnosed with OH, the BP circadian rhythm usually showed riser patterns, and they had increased rates of mortality, and major adverse cardiac and cerebrovascular events.

Vitamin D Level is Associated with Increased Left Ventricular Mass and Arterial Stiffness in Older Patients with Impaired Renal Function.

BACKGROUND Impaired renal function is common among older patients. Deficiency of vitamin D is a frequent phenomenon among patients with impaired renal function, who are likely to develop cardiovascular diseases. This study aimed to explore the association of 25 (OH) D levels with left ventricular mass and arterial stiffness in older patients with impaired renal function. MATERIAL AND METHODS Based on their admission estimate glomerular filtration rate (eGFR), 273 inpatients (≥65 years) were allocated into a normal eGFR group (≥60 ml/min) and an impaired eGFR group (<60 ml/min). The 25 (OH) D levels were measured and the left ventricular mass index (LVMI) was estimated. Pulse wave velocity (PWV) was used to explore arterial stiffness. RESULTS The 25 (OH) D levels of patients in the impaired eGFR group were significantly lower than in the normal eGFR group [(11.92±6.01) µg/L vs. (18.14±8.07) µg/L, p<0.05). LVMI and PWV were both significantly higher in the impaired eGFR group than in the normal eGFR group [(104.89±33.50) g/m2 vs. (92.95±18.95) g/m2, P<0.05; (15.99±3.10) m/s vs. (13.62±2.90) m/s, P<0.05]. After adjusting for age, sex, eGFR, cardiovascular risk factors, serum calcium, and iPTH levels, the inverse association between LVMI and 25 (OH) D, PWV, and 25 (OH) D were statistically significant. CONCLUSIONS Vitamin D level is lower in older patients with impaired renal function. Lower vitamin D levels were correlated with higher left ventricular mass and increased arterial stiffness in older patients.

Analysis of Clinically Relevant Factors for Pulmonary Hypertension in Maintenance Hemodialysis Patients.

BACKGROUND Pulmonary hypertension (PH) is common in patients with maintenance hemodialysis (MHD) and is associated with high mortality. This study analyzed clinically relevant factors for pulmonary hypertension in MHD patients and the effect of serum pentraxin3 (PTX3) in the pathogenesis of PH to provide the basis for early diagnosis and treatment of MHD patients with PH. MATERIAL AND METHODS This study included 60 MHD patients (group A) and 30 healthy controls (group B). Group A was further divided into PH and non-PH groups. Clinical characteristics, auxiliary examination results and serum PTX3 level of the PH and non-PH groups were compared. Binary logistic regression was used to assess the risk factors for PH in MHD patients. ROC curve was applied to evaluate the diagnostic value of PTX3 in PH. RESULTS The incidence rate of PH in MHD patients was 50%, and most presented as mild to moderate. Compared with the non-PH group, patients in PH group presented significantly longer atrial diameter, right ventricular diameter and main pulmonary artery diameter (P<0.05), as well as higher PTX3 and NT-proBNP level. Atrial diameter and PTX3 level were the risk factors for PH in MHD patients. AUC of PTX3 was 0.721 (95%CI: 0.590-0.851, P=0.003). CONCLUSIONS The prevalence of PH was higher in MHD patients and mostly presented as mild to moderate. Such patients often developed heart structural changes and cardiac ultrasound was highly recommended. Serum PTX3 level was significantly elevated and could be used as a marker of PH in MHD patients.

Osteoporosis biomarkers act as predictors for diagnosis of chronic renal insufficiency in elder patients.

Chronic renal insufficiency and osteoporosis have become very common among old people in China. Hyperparathyroidism caused by renal insufficiency would result in turbulence of bone metabolism and unbalance between serum calcium and phosphorus. The aim of this study is to investigate the BMD, PTH, CT and 25(OH)-Vit's significance for screening and diagnosing chronic renal insufficiency. In this study, seventy cases with chronic renal insufficiency from Jun. 2010 to Oct. 2013 were selected as the observation group. Meanwhile, another 70 volunteers with normal renal functions were set as the control group. The level of BMD, PTH, CT and 25(OH)-Vit were detected by using ELISA assay. DPX bone density meters (UNIGAMMA X-RAY PLUS) were used for the detection of BMD. The results indicated that BMD levels of the proximal femur (include Troch, Shaft, Total, Neck, Ward) and lumbar vertebra in the observation group were significantly lower while the PTH and CT were significantly higher compared with the control group (P<0.05). A positive correlation was identified between the serum creatinine (Scr) concentrations and CT, PTH, while the correlation with 25(OH)-Vit was considered to be negative. In conclusion, the BMD, PTH, CT, and 25 (OH)-Vit would provide reference in diagnosing and treatment for chronic renal insufficiency. These indexes would be important clinical significance for screening and early diagnose of osteoporosis in these patients.

Correlation of high-sensitivity C-reactive protein and carotid plaques with coronary artery disease in elderly patients.

The aim of this study was to explore the correlation of high-sensitivity C-reactive protein (hs-CRP) and carotid plaques with the severity of coronary artery disease (CAD). A total of 140 patients with angina who underwent coronary angiography were selected and divided into a single-vessel disease group (n=11), double-vessel disease group (n=18), multi-vessel disease group (n=71) and control group (n=40). Color Doppler ultrasound was applied to measure the intima-media thickness (IMT) of the common carotid artery (CCA) and carotid bifurcation, and to record the location and number of carotid plaques. The serum hs-CRP level was also determined. Compared with the control and single-vessel disease groups, the multi-vessel disease group showed significantly higher IMT of the CCA (P<0.05). The serum hs-CRP level was highest in the multi-vessel disease group (P<0.01). The hs-CRP level and carotid plaque characteristics were found to correlate closely with the severity of CAD. Therefore, they may be used to improve the prediction of CAD severity in elderly patients.

Interleukin-13 promotes expression of Alix to compromise renal tubular epithelial barrier function.

The epithelial barrier dysfunction plays a critical role in a number of kidney diseases. The mechanism is unclear. Alix is a protein involving in protein degradation in epithelial cells. This study aims to investigate that interleukin (IL)-13 inhibits Alix to compromise the kidney epithelial barrier function. In this study, the murine collecting duct cell line (M-1) was cultured in Transwell inserts to investigate the significance of Alix in compromising the epithelial barrier functions. T cell (Teff cells) proliferation assay was employed to assess the antigenicity of ovalbumin (OVA) that was transported across the M-1 monolayer barrier. The results showed that M-1 cells express Alix. Exposure to interleukin (IL)-13 markedly decreased the expression of Alix in M-1 cells, which compromised the M-1 monolayer barrier functions by showing the increases in the permeability to OVA. Over-expression of Alix abolished the IL-13-induced M-1 monolayer barrier dysfunction. Knockdown of Alix significantly increased M-1 monolayer permeability. The OVA collected from the Transwell basal chambers induced the OVA-specific T cell proliferation. We conclude that IL-13 compromises M-1 epithelial barrier functions via inhibiting Alix expression.

Blood dendritic cell levels associated with impaired IL-12 production and T-cell deficiency in patients with kidney disease: implications for post-transplant viral infections.

Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL-12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8(+) T-cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3(+) INF-γ responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T-cell level/function, which may explain the known correlation of CD8(+) T-cell lymphopenia with deficient post-transplant antiviral responses.

Brain natriuretic peptide and copeptin levels are associated with cardiovascular disease in patients with chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). We explored the relationship between CVD, plasma brain natriuretic peptide (BNP) and copeptin in non-dialysis patients with chronic kidney disease (CKD). METHODS: BNP and copeptin were measured using ELISA in 86 non-dialysis patients with different degrees of CKD and in 20 control patients. The effects of BNP, copeptin levels and other biochemical indices on carotid ultrasound echocardiography and CVD history were determined using correlation analysis. RESULTS: BNP and copeptin levels were significantly higher in the CKD group than in the control group. Both indices increased progressively, in parallel with the decline in glomerular filtration rate (GFR). BNP levels were (184.25 ± 65.18) ng/L in early phase CKD, (975.245 ± 354.09) ng/L in middle phase CKD, and (1463.51 ± 614.92) ng/ml in end phase CKD compared with levels of (101.56 ± 42.76) ng/L in the control group (all P < 0.01). Copeptin levels in the middle phase ((20.36 ± 9.47) pmol/L) and end phase groups ((54.26 ± 18.23) pmol/L were significantly higher than in the control group ((9.21 ± 2.64) pmol/L; both P < 0.01). There was no difference in copeptin levels between early phase CKD ((10.09 ± 5.23) pmol/L) and control patients. Stepwise multiple regression analysis identified GFR, intima-media thickness (IMT), left ventricular hypertrophy (LVH), and previous history of CVD as independent risk factors for elevated BNP and copeptin levels. CONCLUSION: BNP and copeptin appear to provide sensitive biological markers for the evaluation of atherosclerosis in non-dialysis patients with CKD.