Vascular calcification is highly prevalent and associated with mortality in hemodialysis patients. However, extreme splanchnic arterial calcification in calciphylaxis with poor prognosis raises questions regarding the reliability of previous vascular calcification scoring methods. Therefore, this study aimed to examine the distribution characteristics of abdominal aortic branch calcification and identify a more reliable predictor of mortality in hemodialysis patients.

The cohort study included 237 hemodialysis patients. The distribution characteristics of abdominal aortic branch calcification were determined by quantifying the calcification volumes. The primary and secondary outcomes were all-cause mortality and new-onset cardiovascular events, respectively. We compared the prognostic values of abdominal aortic branch calcification and constructed a predictive nomogram model.

The prevalence of abdominal vascular calcification in hemodialysis patients was 95.36%, with the highest prevalence in the abdominal aorta (88.61%) and internal iliac artery (85.65%). During a median follow-up period of 3.92 years, 137 patients died. Internal iliac artery and mesenteric artery calcification showed the greatest predictive values for mortality. Internal iliac artery calcification and serum albumin level were independently associated with mortality in hemodialysis patients (p < .001). The nomogram model constructed with internal iliac artery calcification, serum albumin level, age, and comorbid cardiovascular disease was well discriminative, calibrated, and clinically applicable for predicting 3-year survival.

Abdominal aortic branch calcification, particularly internal iliac artery calcification, is a preferable prognostic predictor than abdominal aorta or coronary artery calcification in hemodialysis patients.

The benefits of ideal cardiovascular-health metrics (ICVHMs) in patients with renal insufficiency remain unclear. This study aimed to investigate ICVHM associations with prognosis in a renal insufficiency population.

The trial enrolled 29,682 participants from the US National Health and Nutrition Examination Survey (NHANES), 2007-2018, with mortality follow-up through December 31, 2019. Participants were divided into three groups based on estimated glomerular filtration rates. Cardiovascular health was assessed using new "Life's Essential 8" metrics. Cox regression analyses based on NHANES data were used to determine the associations between ICVHMs and cardiovascular mortality in patients with renal insufficiency.

During a mean follow-up of 6.58 years, ideal cardiovascular health (hazard ratio [HR] = 0.42; 95% confidence interval [CI]; 0.25-0.70) and ideal health behavior (HR = 0.53; 95% CI; 0.39-0.73) reduced cardiovascular mortality in participants with renal insufficiency. For each one ICVHM increment, a 25% reduction in cardiovascular mortality was recorded (95% CI; 0.69-0.82). When compared with participants with normal renal function, for those with mild renal insufficiency, the HR for cardiovascular mortality gradually decreased from 1.47 (95% CI; 0.85-2.52) in those who had ≤1 ICVHMs to 0.30 (95% CI; 0.12-0.77) in participants who had >6 ICVHMs.

From an ICVHM perspective, enhanced cardiovascular benefits were observed in individuals with renal insufficiency, coupled with a reduced risk of all-cause mortality. Furthermore, when compared with individuals with normal renal function, increased ICVHMs can mitigate adverse risks associated with renal impairment.

The role of regulatory CD8pos T cells (CD8pos Tregs) and cytotoxic CD8pos responder T cells (CD8pos Tresps) in maintaining stable graft function in kidney transplant recipients (KTR) remains largely unclear. The pathogenesis of graft deterioration in case of rejection involves the exhaustive differentiation of both CD8pos T cell subsets, but the causal mechanisms have not yet been identified.

In this study, we separately investigated the differentiation of CD8posTregs/Tresps in 134 stable KTR with no evidence of renal graft rejection, in 41 KTR diagnosed with biopsy-confirmed rejection at enrolment and in 5 patients who were unremarkable at enrolment, but developed rejection within three years of enrolment. We were investigating whether changed differentiation of CCR7posCD45RAposCD31pos recent thymic emigrant (RTE) cells via CD45RAnegCD31pos memory (CD31pos memory) cells (pathway 1), via direct proliferation (pathway 2), or via CCR7posCD45RA+CD31neg resting mature naïve (MN) cells (pathway 3) into CD45RAnegCD31neg memory (CD31neg memory) cells affects the CD8pos Treg/Tresp ratio or identifies a CD8pos Treg/Tresp subset that predicts or confirms renal allograft rejection.

We found that RTE Treg differentiation via pathway 1 was age-independently increased in KTR, who developed graft rejection during the follow-up period, leading to abundant MN Treg and central memory Treg (CM Treg) production and favoring a strongly increased CD8pos Treg/Tresp ratio. In KTR with biopsy-confirmed rejection at the time of enrolment, an increased differentiation of RTE Tregs into CCR7negCD45RAposCD31neg terminally differentiated effector memory (CD31neg TEMRA Tregs) and CD31pos memory Tregs was observed. CD31neg memory Treg production was maintained by alternative differentiation of resting MN Tregs, resulting in increased effector memory Treg (EM Treg) production, while the CD8pos Treg/Treg ratio was unaffected. An altered differentiation of CD8pos Tresps was not observed, shifting the Treg/Tresp ratio in favor of Tregs.

Our results show that exhaustive CD8pos Treg differentiation into CM Tregs may lead to future rejection, with a shift towards EM Treg production and an accumulation of CD31neg TEMRA Tregs in KTR with current rejection.

Chronic kidney disease - mineral bone disorder (CKD-MBD) is a syndrome that begins early in CKD, contributes to CKD-associated mortality, and includes components of FGF23 elevation, αklotho deficiency, CKD-stimulated vascular disease, and renal osteodystrophy. Hyperphosphatemia, occurring in later stages of CKD, is also driven by mechanisms of CKD-MBD, and has been shown to stimulate vascular calcification. In a mouse model of Alport CKD that is resistant to vascular calcification, we examine the effects of a high-phosphate Western-type diet on the CKD-MBD, and test whether the diet promotes induction of vascular calcification.

An X-linked Col4a5 deficient murine homolog of Alport Syndrome (CKD) and wild type (WT) littermates were fed an animal protein 1.2% high phosphate diet or a standard vegetable protein diet. At disease progression equivalent to CKD stage 4-5, we examined kidney histology for fibrosis, blood for BUN (marker of CKD), and markers of CKD-MBD disease progression, kidney tissue for klotho production, and aorta histology and tissue mRNA and protein analysis for vascular calcification.

The Western high Pi diet produced hyperphosphatemia in the CKD animals compared to WT and increased plasma PTH (1880 from 110 pg / ml), FGF23 c-term (670 from 120 pg / ml), and FGF23 intact (3780 from 280 pg / ml), and reduced kidney klotho mRNA and protein (57-67% reduction) (all p < 0.01). Referenced against the CKD animals fed vegetable-based diet, the Western high phosphate-fed CKD animals showed higher levels of plasma PTH and FGF23s. In the wild-type control mice with normal renal function, Western diet produced increased PTH, intact FGF23, and reduced renal klotho (all p <0.01). Vascular smooth muscle transdifferentiation and vascular calcification was not induced by Western high phosphate diet in this model of CKD.

Our results show that a Western-style high-phosphate diet advances elements of the CKD-MBD. Renal klotho, FGF23 and PTH are affected by diet even with normal kidney function, suggesting a need for early intervention in the management of phosphate homeostasis as a component of CKD therapy. Additionally, CKD, klotho, and FGF23 all are associated with early aging. Therefore, our findings suggest that a Western high Pi diet accelerates aging and would contribute to the systemic complications of CKD - cardiac disease, osteodystrophy, and vascular disease.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent significant public health challenges, linked to an elevated risk of cardiovascular disease (CVD) and influenced by socioeconomic disparities. This longitudinal study investigates the interplay between socioeconomic position (SEP), measured as educational level, CKD/ESRD and CVD using the syndemic framework.

We used data from the Piedmont Longitudinal Study to establish CKD and ESRD cohorts and to identify incident CVD between January 2013 and December 2017. The educational level was retrieved from census data. We applied an accelerated failure time model to explore the relationships between CKD/ESRD, CVD and educational level with all-cause mortality and emergency room (ER) acuity.

The CKD cohort included 44 220 individuals, with 12 341 deaths and 15 440 ER admissions. The ESRD cohort included 4021 subjects, experiencing 1303 deaths and 1640 ER admissions. After adjusting for confounders, the combination of CKD, low educational level and incident CVD was associated with increased all-cause mortality (time ratios (TR) 0.07, 95% CI 0.05 to 0.08) and ER acuity (TR 0.16, 95% CI 0.14 to 0.17) compared with those with higher education. Instead, patients with ESRD with incident CVD and high educational level had the highest increase in mortality (TR 0.08, 95% CI 0.05 to 0.14) and ER acuity (TR 0.20, 95% CI 0.1 to 0.30).

Patients with CKD with low educational levels and incident CVD may represent a 'syndemic', associated with higher mortality and ER acuity. Our study highlights a potential link between these conditions and socioeconomic disparities, suggesting the need for multifaceted approaches.

This study aimed to investigate the predictive ability of the neutrophil percentage-to-albumin Ratio (NPAR) concerning all-cause mortality and cardio-cerebrovascular mortality in patients undergoing peritoneal dialysis (PD).

We included a total of 807 PD patients from the Peritoneal Dialysis Center of the Second Affiliated Hospital of Soochow University between January 2009 and December 2019 in this study. Patients were categorized into three groups based on their baseline NPAR. The Kaplan-Meier method, multivariate Cox proportional hazard model, and Fine-Gray competing risk model were employed to examine the relationship between NPAR level and all-cause mortality and cardio-cerebrovascular mortality among PD patients. Furthermore, the ROC curve and calibration plots were utilized to compare the performance between NPAR and other conventional indicators.

The mean follow-up period was 38.2 months. A total of 243 (30.1%) patients passed away, with 128 (52.7%) succumbing to cardio-cerebrovascular diseases. The mortality rates of the Middle and High NPAR groups were significantly greater than that of the Low NPAR group (p < 0.001), and NPAR was independently associated with all-cause mortality and cardio-cerebrovascular mortality. Receiver Operating Characteristic (ROC) analysis indicated that the Area Under the Curve (AUC) of NPAR (0.714) was significantly superior to those of C-reactive protein (CRP) (0.597), neutrophil to lymphocyte ratio (NLR) (0.589), C-reactive protein to albumin ratio (CAR) (0.698) and platelet to lymphocyte ratio (PLR) (0.533).

NPAR served as an independent predictive marker for all-cause mortality and cardio-cerebrovascular mortality in PD patients. Moreover, NPAR demonstrated superior predictive potential compared to CRP, CAR, NLR, and PLR.

There is limited understanding of the optimal duration and dosage of pentoxifylline (PTX) therapy required to achieve significant reductions in atherosclerotic cardiovascular disease (ASCVD) risk, particularly in patients with diabetic kidney disease (DKD). This study aimed to evaluate the impact of long-term PTX therapy on the risk of ASCVD in patients with DKD who do not have pre-existing cardiovascular disease, while also exploring potential vascular protective mechanisms. This retrospective cohort study included data from Taiwan's Ministry of Health and Welfare's Health and Welfare Data Science Center. In 2008-2019, we identified and analyzed a specific sample of 129,764 patients with DKD without established cardiovascular disease. Participants were categorized according to their PTX treatment regimen. Short-term PTX users (<763 days) had a greater risk of developing ASCVD than non-PTX users. However, those who used PTX for >763 days (long-term PTX treatment) had a significantly lower risk of ASCVD, with a 47% lower cumulative incidence. A dose-dependent reduction in apoptosis was observed via Klotho treatment in cultured human aortic endothelial cells following PTX treatment. Long-term PTX treatment (24 h) caused a higher reduction in H2O2-induced reactive oxygen species production and cell apoptosis than short-term PTX treatment (2 h). In the DKD mice model experiments, PTX reduced the ASCVD risk by increasing the Klotho levels to inhibit endothelial cell damage. These findings suggest that the cardiovascular and renoprotective benefits of PTX may be extended to primary prevention strategies for people with DKD.

Planning for vascular access (VA) creation is essential in pre-dialysis patients although optimal timing for VA referral and placement is debatable. Guidelines suggest referral when eGFR is 15-20 mL/min/1.73 m2. This study aimed to validate the use of kidney failure risk equation (KFRE) in VA planning.

Retrospective analysis of all adult patients with CKD who were referred for first VA placement, namely AVF or AVG, at a tertiary center, between January 2018 and December 2019. The four-variable KFRE was calculated. Start of KRT, mortality, and VA placement were assessed in a 2-year follow-up. We used Cox regression to predict KRT start and calculated the ROC curve.

256 patients were included and 64.5% were male, mean age was 70.4 ± 12.9 years and mean eGFR was 16.09 ± 10.43 mL/min/1.73 m2. One hundred fifty-nine patients required KRT (62.1%) and 72 (28.1%) died in the 2-year follow-up. The KFRE accurately predicted KRT start within 2-years (38.3 ± 23.8% vs 17.6 ± 20.9%, p < 0.001; HR 1.05 95% CI (1.06-1.12), p < 0.001), with an auROC of 0.788 (p < 0.001, 95% CI (0.733-0.837)). The optimal KFRE cut-off was >20%, with a HR of 9.2 (95% CI (5.06-16.60), p < 0.001). Patients with KFRE ⩾ 20% had a significant lower mean time from VA consult to KRT initiation (10.8 ± 9.4 vs 15.6 ± 10.3 months, p < 0.001). On a sub-analysis of patients with an eGFR < 20 mL/min/1.73 m2, a KFRE ⩾ 20% was also a significant predictor of 2-year start of KRT, with an HR of 6.61 (95% CI (3.49-12.52), p < 0.001).

KFRE accurately predicted 2-year KRT start in this cohort of patients. A KFRE ⩾ 20% can help to establish higher priority patients for VA placement. The authors suggest referral for VA creation when eGFR < 20 mL/min/1.73 m2 and KFRE ⩾ 20%.

To identify and synthesise qualitative studies on barriers and facilitators perceived by dialysis patients in relation to self-care and disease management.

Systematic review of qualitative studies.

Qualitative study articles were extracted from PUBMED, MEDLINE, COCHRANE, WEB OF SCIENCE (WOS), CINAHL PsycINFO and EMBASE and electronic journals of the Spanish Society of Nephrology and Spanish Society of Nephrological Nursing until May 2022. Studies on barriers and/or facilitators affecting self-care and disease management expressed by people undergoing haemodialysis or peritoneal dialysis were included.

The SPICE (Setting, Perspective, Intervention, Comparison and Evaluation) strategy was used to develop issues and subissues through the thematic synthesis of the qualitative findings. GRADE-CERQual was used to evaluate the articles.

From 172 articles, 15 qualitative articles about barriers and facilitators perceived by patients concerning self-care and disease management were finally included. Identified eight facilitators and four barriers.

Patients perceived a significant number of barriers and facilitators. It is possible to identify which aspects facilitate self-management of their disease and to understand that the processes are individualised. This is why therapeutic strategies should be designed to foster the participation and empowerment of the person in the management of the disease.

Identifying the barriers and facilitators concerning the management of chronic kidney disease furnishes us with knowledge for individualised clinical practice and improved care processes.

This review is the first to synthesise barriers and facilitators in haemodialysis patients about the management of their disease and treatment. The results enable the proposal of improvements in the training of healthcare personnel, clinical practice guidelines and action protocols to improve the daily life and management of the disease by patients. No patient or public contribution due to this is a systematic review.

To evaluate the effect of multiple single cannulation technique on the complications of arteriovenous fistula.

A comprehensive literature search was conducted to investigate the impact of multiple single cannulation technique on the complications of arteriovenous fistula. The search was performed in both Chinese and English databases including Wanfang Medicine, China National Knowledge Infrastructure, Vip, Pubmed, Embase, and The Cochrane Library, with a search period up to December 20, 2023. Following literature screening and data extraction, the quality of the included studies was assessed using the Cochrane Bias Assessment Tool for Randomized Controlled Trials. Statistical analysis was performed using Review Manager version 5.3.

Thirteen papers, totaling 1299 patients, were included in the analysis. The experimental group consisted of 646 patients, while the control group had 595 patients. The meta-analysis revealed that the multiple single cannulation technique was more effective than rope ladder cannulation and buttonhole cannulation in reducing the incidence of angiomas (odds ratio [OR] = 0.19; 95% confidence interval [CI] = 0.10-0.35), stenosis (OR = 0.22; 95% CI 0.13-0.39), thrombosis (OR = 0.17; 95% CI = 0.07-0.39), and blood seepage (OR = 0.13; 95% CI = 0.08-0.21) of arteriovenous fistulas (P < .05). Additionally, it was found to increase the success rate of nurses' single cannulation (OR = 4.20; 95% CI = 1.78-9.95) of arteriovenous fistulas (P < .05).

Multiple single cannulation technique could effectively reduce the incidence of complications of arteriovenous fistula, improve the success rate of cannulation, prolong the life span of arteriovenous fistula, and prolong the survival cycle of hemodialysis patients.

Cardiovascular (CV) morbidity and mortality is high in patients with chronic kidney disease (CKD). Most patients reveal a high prevalence of CV risk factors such as diabetes or arterial hypertension and many have manifest cardiovascular disease (CVD), such as coronary artery disease and chronic heart failure with an increased risk of clinical events including sudden cardiac death. Diabetes mellitus and hypertension contribute to the development of CKD and the prevalence of CKD is in the range of 20-65% in diabetic and 30-50% in hypertensive patients. Therefore, prevention and optimal treatment of CV risk factors and comorbidities are key strategies to reduce CV risk and improve survival in CKD. Beyond common CV risk factors, patients with CKD are often physically inactive and have low physical function leading to subsequent frailty with muscle fatigue and weakness, sarcopenia and increased risk of falling. Consequently, the economic health burden of CKD is high, requiring feasible strategies to counteract this vicious cycle. Regular physical activity and exercise training (ET) have been shown to be effective in improving risk factors, reducing CVD and reducing frailty and falls. Nonetheless, combining ET and a healthy lifestyle with pharmacological treatment is not frequently applied in clinical practice. For that reason, this Clinical Consensus Statement reviews the current literature and provides evidence-based data regarding the role of ET in reducing CV and overall burden in patients with CKD. The aim is to increase awareness among cardiologists, nephrologists, and healthcare professionals of the potential of exercise therapy in order to encourage implementation of ET in clinical practice, eventually reducing CV risk and disease, as well as reducing frailty in patients with CKD G3-G5D.

The burden of chronic kidney disease (CKD) and its risk factors are projected to rise in parallel with the rapidly ageing global population. By 2050, the prevalence of CKD category G3-G5 may exceed 10% in some regions, resulting in substantial health and economic burdens that will disproportionately affect lower-income countries. The extent to which the CKD epidemic can be mitigated depends largely on the uptake of prevention efforts to address modifiable risk factors, the implementation of cost-effective screening programmes for early detection of CKD in high-risk individuals and widespread access and affordability of new-generation kidney-protective drugs to prevent the development and delay the progression of CKD. Older patients require a multidisciplinary integrated approach to manage their multimorbidity, polypharmacy, high rates of adverse outcomes, mental health, fatigue and other age-related symptoms. In those who progress to kidney failure, comprehensive conservative management should be offered as a viable option during the shared decision-making process to collaboratively determine a treatment approach that respects the values and wishes of the patient. Interventions that maintain or improve quality of life, including pain management and palliative care services when appropriate, should also be made available.

Cardiovascular disease (CVD) represents the primary cause of mortality in patients afflicted with end-stage renal disease and undergoing peritoneal dialysis (PD) treatment. Galectin-3 (Gal-3), a molecule known to exhibit a correlation with CVD mortality garners considerable interest. The objective of this study was to explore the potential association between serum Gal-3 levels and other CVD risk factors among PD patients.

In this cross-sectional study, a total of 114 PD patients with a minimum of 3 months of PD treatment were enrolled. Serum Gal-3 levels were quantified using an enzyme-linked immunosorbent assay. The data of patients with Gal-3 levels higher and lower than 26.744 pg/ml were compared using Mann-Whitney U tests or t tests. Pearson's correlation or Spearman's correlation analysis and multivariate regression were used to assess the associations between the known risk factors for CVD and Gal-3.

In comparison to the inter-group baseline data, the low Gal-3 group exhibited a higher glomerular filtration rate (GFR). Gal-3 levels correlate positively with PD duration, B-type natriuretic peptide (BNP), growth differentiation factor 15 (GDF-15), interventricular septal thickness in diastolic (IVST), and left ventricular mass index (LVMI). Conversely, Gal-3 exhibited a negative correlation with albumin levels. Multivariate linear regression analysis demonstrated a positive correlation between Gal-3 levels and BNP, GDF-15, PD duration, IVST and LVMI. Gal-3 levels were negatively correlated with albumin levels.

Gal-3 was strongly associated with BNP, GDF-15, IVST and LVMI in patients undergoing PD treatment. Prospective studies should be carried out to determine whether Gal-3 can be a promising biomarker in predicting increased risk of adverse cardiovascular events in PD patients.

This study aimed to evaluate the burden of kidney dysfunction (KD), assess socioeconomic inequalities, and project trends in the future.

Data on deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) were from Global Burden of Disease Study 2019. The Joinpoint regression model was utilized to analyze the temporal trend by the annual percentage change (APC). The slope index and concentration index were employed to evaluate cross-country disparities. The future trend was predicted using an age-period-cohort analysis.

In the past three decades, the death numbers of KD increased from 1,571,720 to 3,161,552, DALYs from 42,090,331 to 76,486,945, YLDs from 5,003,267 to 11,282,484, and YLLs from 37,087,065 to 65,204,461, respectively. The age-standardized rate (ASR) of deaths, DALYs, and YLLs exhibited a declining trend. The ASR of YLDs increased until 2017, then decreased. The slope index and concentration index for DALYs increased from 248.1 to 351.9 and from 40.70 to 57.8. In the future, the ASR of deaths, DALYs, YLDs, and YLLs will remain stable, while their numbers will continue to rise, except for YLLs.

The disease burden of KD remained serious. Tailored interventions should be developed based on national contexts.

Dilated cardiomyopathy (DCM), a primary myocardial disorder, manifests through the dilation of one or both ventricles, coupled with systolic and valvular dysfunction. Renal agenesis is a congenital condition characterized by the absence of one or both kidneys at birth. Unilateral renal agenesis, wherein one kidney is absent, can subtly evade detection due to the impressive adaptability of the remaining kidney, often preserving typical functionality. Nevertheless, when compounded with chronic kidney disease (CKD), the repercussions of renal agenesis become notably more pronounced. CKD and DCM represent two significant and interrelated clinical challenges, particularly in pediatrics. This case report examines the anesthesia management of a 10-year-old female with CKD and right renal agenesis complicated by DCM undergoing bilateral hemi-epiphysiodesis for genu valgum correction. It emphasizes the crucial role of a multidisciplinary approach in achieving favorable outcomes in patients undergoing non-cardiac surgery.

The global burden of cardiometabolic renal disease is increasing, particularly in underserved communities. Twinepidemic Inc.'s Galvanize Healthy Living program conducts community screenings, risk assessments, and educational interventions globally. We screened 1209 subjects for cardiovascular-kidney-metabolic syndrome, assessing their disease knowledge and self-confidence. Mean age was 50, with 65% females and 35% males. Imaging post-risk assessment revealed abnormalities: EKG (16%), echocardiogram (10%), carotid plaque (9%), ABI (2.5%), and eye exam (3.6%, including 8 retinopathies, 14 cataracts). New onset DM was found in 8%, prediabetes in 18.5%, High LDL in 4.2%, low HDL in 40.2%, high triglycerides in 13.1%, and abnormal BP in 38%. In addition, 18.2% were reclassified to a higher category of risk levels after imaging. Significant improvements in knowledge and self-empowerment (all p < 0.001) were seen after educational interventions. This study underscores early risk assessment's potential to enhance health outcomes globally for underserved populations, validating POC imaging and emphasizing the role of accessible care and education in patient engagement and empowerment.

This study aimed to assess the effectiveness of an electronic cannulation atlas in preventing and treating complications of arteriovenous fistula.

The observation group, consisting of 92 dialysis patients from July to December 2021, was managed with an electronic cannulation atlas. After 6 months, the incidence of complications such as stenosis, hematoma, thrombus, aneurysm, and cannulation failure was compared between the groups. Nurse satisfaction with the electronic cannulation atlas system was also assessed through a questionnaire.

The observation group had lower incidence rates of arteriovenous fistula stenosis, thrombus, aneurysm, and failure rate of cannulation compared to the control group, with statistically significant differences (p<0.05). The incidence rates of hematoa were similar in both groups, showing no significant difference (p>0.05). After 3 months of management, the incidence of arteriovenous fistula complications in the observation group was significantly lower than in the control group (p<0.05). Additionally, utilizing the electronic cannulation atlas system was found to increase nurses' job satisfaction.

The use of electronic cannulation atlas for the treatment of patients' arteriovenous fistula could effectively reduce the incidence of complications of patients' arteriovenous fistula, reduce the failure rate of cannulation, reduce the workload of nurses, and improve the job satisfaction of nurses.

Evidence has indicated that serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with coronary artery disease (CAD). The UA to HDL-C ratio (UHR) has recently drawn attention as a new predictor for metabolic syndrome, inflammation and atherosclerosis. However, the association between the UHR and CAD in nondialysis chronic kidney disease (CKD) patients is still unclear.

We retrospectively analysed 733 nondialysis patients with CKD stage 3-5 who received their first coronary artery angiography (CAG), including 510 participants with CAD. All laboratory indicators were collected within one week before CAG. The median UHR of CAD and non-CAD patients was 15.52% and 12.29%, respectively. In multivariate analysis, female patients with a high UHR were 4.7 times more at risk of CAD than those with a lower UHR. Meanwhile, the positive association of the UHR with the severity of coronary artery stenosis (CAS) persisted significantly in female CAD subjects but not in males. In addition, receiver operating characteristic (ROC) curves were constructed for CAD and severe CAS. The area under the curve (AUC) for the UHR was higher than that for UA and HDL-C alone in female patients [UHR (AUC): 0.715 for CAD and 0.716 for severe CAS].

An elevated UHR was independently related to an increased CAD risk and the severity of CAS in nondialysis female patients with CKD stage 3-5, and was more predictive of the onset of CAD and the severity of CAS than UA or HDL-C alone.

The Low Physical Activity Questionnaire (LoPAQ) was specifically developed to measure the low activity level observed in extremely inactive hemodialysis (HD) patients. This study aims to evaluate reliability and validity of Persian version of the LoPAQ.

This study was a cross sectional study, conducted in three HD centers in Iran. The LoPAQ was translated into Persian. After cultural adaptions, it was filled out by 120 HD patiens. Convergent validity, was evaluated by calculating the correlations among the Persian version of the LoPAQ and Persian version of the Community Healthy Adults Model Program for Seniors (CHAMPS) questionnaire, physical function scale of the SF-36 and physical function (Short Physical Performance Battery (SPPB) test) using Spearman's correlation coefficients. The test-retest reliability was analyzed using the intraclass correlation coefficient (ICC).

In total, 109 patients completed all of the questionnaires, took part in physical performance tests and had valid data. Their mean age was 64 ± 11 years, with a dialysis history of 31 ± 10 months. For total calories, there was a strong correlation between the Persian version of the LoPAQ and CHAMPS-measured physical activity (rho = 0.85, p < 0.001). In addition, the higher physical activity level reported by Persian version of the LoPAQ was also correlated with better self-reported physical function (rho = 0.7, p < 0.001) and better physical performance (rho = 0.67, p < 0.001). The ICC ranged from 0.65 to 0.78, indicating strong reliability.

The assessment of the validity and reliability of the Persian version of the questionnaire confirmed its suitability for evaluating the level of physical activity.

ClinicalTrials.gov Identifier: NCT05930964, Registered on 05/07/2023. Registered trial name: Validity and Reliability of Persian Version of Low Physical Activity Questionnaire (LoPAQ).

This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF 23, fetuin-A, sclerostin, and VC scores (Adragao method). Prevalence of VC was similar in both groups, but HD patients had more frequent VC scores ≥ 6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A and sclerostin levels were higher in pre-HD, while FGF 23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin, and no vitamin D treatment, while in HD patients with higher sclerostin, FGF 23 and urea, and lower iPTH. Conclusion: Biomarkers could be measurable indicators of biological processes underlying VC in CKD patients that may serve as a potential guide for considering personalized therapeutic approaches. Further studies are needed to elucidate the underlying pathways.

Chronic kidney disease (CKD) significantly increases cardiovascular risk and mortality, and the accumulation of uremic toxins in the circulation upon kidney failure contributes to this increased risk. We thus performed a screening for potential novel mediators of reduced cardiovascular health starting from dialysate obtained after hemodialysis of patients with CKD. The dialysate was gradually fractionated to increased purity using orthogonal chromatography steps, with each fraction screened for a potential negative impact on the metabolic activity of cardiomyocytes using a high-throughput MTT-assay, until ultimately a highly purified fraction with strong effects on cardiomyocyte health was retained. Mass spectrometry and nuclear magnetic resonance identified the metabolite mycophenolic acid-β-glucuronide (MPA-G) as a responsible substance. MPA-G is the main metabolite from the immunosuppressive agent MPA that is supplied in the form of mycophenolate mofetil (MMF) to patients in preparation for and after transplantation or for treatment of autoimmune and non-transplant kidney diseases. The adverse effect of MPA-G on cardiomyocytes was confirmed in vitro, reducing the overall metabolic activity and cellular respiration while increasing mitochondrial reactive oxygen species production in cardiomyocytes at concentrations detected in MMF-treated patients with failing kidney function. This study draws attention to the potential adverse effects of long-term high MMF dosing, specifically in patients with severely reduced kidney function already displaying a highly increased cardiovascular risk.

Chronic kidney disease leads to cardiac remodelling of multifactorial origin known as "uraemic cardiomyopathy", the reversibility of which after kidney transplantation (KT) remains controversial. Our objectives were to assess, in the modern era, changes in echocardiographic parameters following KT and identify predictive clinical and biological factors associated with echocardiographic changes.

One hundred six patients (mean age 48 ± 16, 73% male) who underwent KT at the University Hospital of Nancy between 2007 and 2018 were retrospectively investigated. Pre- and post-KT echocardiography findings (8.6 months before and 22 months after KT on average, respectively) were centralised, blind-reviewed and compared.

A majority of patients (60%) had either a left ventricular (LV) ejection fraction < 50%, at least moderately abnormal LV mass index or left atrial (LA) dilatation at pretransplanted echocardiography. After KT, LV remodelling and diastolic doppler indices did not significantly change whereas LA volume index (LAVI) increased (35.9 mL/m2 post-KT vs. 30.9 mL/m2 pre-KT, p = 0.006). Advancing age, cardiac valvular disease, delayed graft function, lower post-KT haemoglobin, and more severe post-KT hypertension were associated with higher LAVI after KT. Higher post-KT serum creatinine, more severe post-KT hypertension and lower pre-KT blood calcium levels were associated with a deterioration in LAVI after KT.

Adverse remodelling of the left atrial volume occurred after KT, predominantly in patients with lower pre-KT blood calcium, poorer graft function and post-KT hypertension. These results suggest that a better management of modifiable factors such as pre-KT hyperparathyroidism or post-KT hypertension could limit post-KT cardiac remodelling.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). As CKD progresses, CKD-specific risk factors, such as disordered mineral homeostasis, amplify traditional cardiovascular risk factors. Fibroblast growth factor 23 (FGF23) regulates mineral homeostasis by activating complexes of FGF receptors and transmembrane klotho co-receptors. A soluble form of klotho also acts as a 'portable' FGF23 co-receptor in tissues that do not express klotho. In progressive CKD, rising circulating FGF23 levels in combination with decreasing kidney expression of klotho results in klotho-independent effects of FGF23 on the heart that promote left ventricular hypertrophy, heart failure, atrial fibrillation and death. Emerging data suggest that soluble klotho might mitigate some of these effects via several candidate mechanisms. More research is needed to investigate FGF23 excess and klotho deficiency in specific cardiovascular complications of CKD, but the pathophysiological primacy of FGF23 excess versus klotho deficiency might never be precisely resolved, given the entangled feedback loops that they share. Therefore, randomized trials should prioritize clinical practicality over scientific certainty by targeting disordered mineral homeostasis holistically in an effort to improve cardiovascular outcomes in patients with CKD.

Data on angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (SV) in patients undergoing maintenance dialysis is scarce. Our study aimed to investigate the effect of SV on patients undergoing dialysis.

We retrospectively reviewed the data of end-stage kidney disease (ESRD) patients undergoing either peritoneal dialysis (PD) or hemodialysis (HD) in our center. A total of 51 patients receiving SV treatment were enrolled in the SV group. Another 51 age and sex-matched patients on dialysis without SV treatment were selected as the control group. All the patients were regularly followed up in the dialysis clinic. Their clinical, biochemical, and echocardiographic parameters were all recorded at baseline and during follow-up. The effect and safety of SV were further analyzed.

A total of 102 ESRD patients on dialysis (51 patients in the SV group and 51 patients in the control group) were finally enrolled. The median follow-up time was 349 days (interquartile range [IQR]: 217-535 days). The level of B-type natriuretic peptide (BNP) (median [IQR] before and after SV treatment: 596.35 pg/ml [190.6-1714.85] vs. 188.7 pg/ml [83.34-600.35], p < 0.001) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (median [IQR]: 6316.00 pg/ml [4552.00-28598.00] vs. 5074.00 pg/ml [2229.00-9851.00], p = 0.022) were significantly decreased after treatment with SV. The variant rate of left ventricular ejection fraction (LVEF) was significantly higher in the SV group compared to the control group, especially in the PD subgroup. No significant difference was found in other echocardiographic parameters between SV and control group. Subgroup analysis of the PD group showed an increase in daily PD ultrafiltration (median [IQR]: 400 ml/d [200-500] vs. 500 ml/d [200-850], p = 0.114) after SV treatment. Variant rate of overhydration (OH) measured by the body composition monitor (BCM) of the SV group were significantly different from the control group (median [IQR]: -13.13% [-42.85%-27.84%] vs. 0% [-17.95%-53.85%], p = 0.049). The rate of hyperkalemia was slightly higher but without significant difference before and after the introduction of SV (19.6% vs. 27.5%, p = 0.350). No event of hypotension and angioedema were observed.

SV might have a cardio-protective role in ESRD patients undergoing dialysis, especially in PD patients. Serum potassium should be monitored during the treatment.

Chronic kidney disease (CKD), especially diabetic CKD, is the condition that most increases the risk of lethal coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the underlying molecular mechanisms are unclear. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) regulate coronavirus cell entry and/or replication. We hypothesized that CKD may alter the expression of SCARF genes.

A literature search identified 34 SCARF genes of which we selected 21 involved in interactions between SARS-CoV/SARS-CoV-2 and host cells, and assessed their mRNA expression in target tissues of COVID-19 (kidneys, lungs, aorta and heart) in mice with adenine-induced CKD.

Twenty genes were differentially expressed in at least one organ in mice with CKD. For 15 genes, the differential expression would be expected to favor SARS-CoV-2 infection and/or severity. Of these 15 genes, 13 were differentially expressed in the kidney and 8 were validated in human CKD kidney transcriptomics datasets, including those for the most common cause of CKD, diabetic nephropathy. Two genes reported to protect from SARS-CoV-2 were downregulated in at least two non-kidney target organs: Ifitm3 encoding interferon-induced transmembrane protein 3 (IFITM3) in lung and Ly6e encoding lymphocyte antigen 6 family member 6 (LY6E) in aorta.

CKD, including diabetic CKD, is associated with the differential expression of multiple SCARF genes in target organs of COVID-19, some of which may sensitize to SARS-CoV-2 infection. This information may facilitate developing therapeutic strategies aimed at decreasing COVID-19 severity in patients with CKD.

Peritoneal dialysis (PD) is a current replacement therapy for end-stage kidney diseases (ESKDs). However, long-term exposure to PD fluids may lead to damage of the peritoneal membrane (PM) through mechanisms involving the activation of the inflammatory response and mesothelial-to-mesenchymal transition (MMT), leading to filtration failure. Peritoneal damage depends on a complex interaction among external stimuli, intrinsic properties of the PM, and subsequent activities of the local innate-adaptive immune system. Epigenetic drugs targeting bromodomain and extra-terminal domain (BET) proteins have shown beneficial effects on different experimental preclinical diseases, mainly by inhibiting proliferative and inflammatory responses. However the effect of BET inhibition on peritoneal damage has not been studied. To this aim, we have evaluated the effects of treatment with the BET inhibitor JQ1 in a mouse model of peritoneal damage induced by chlorhexidine gluconate (CHX). We found that JQ1 ameliorated the CHX-induced PM thickness and inflammatory cell infiltration. Moreover, JQ1 decreased gene overexpression of proinflammatory and profibrotic markers, together with an inhibition of the nuclear factor-κB (NF-κB) pathway. Additionally, JQ1 blocked the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and restored changes in the mRNA expression levels of NADPH oxidases (NOX1 and NOX4) and NRF2/target antioxidant response genes. To corroborate the in vivo findings, we evaluated the effects of the BET inhibitor JQ1 on PD patients' effluent-derived primary mesothelial cells and on the MeT-5A cell line. JQ1 inhibited tumor necrosis factor-α (TNF-α)-induced proinflammatory gene upregulation and restored MMT phenotype changes, together with the downmodulation of oxidative stress. Taken together, these results suggest that BET inhibitors may be a potential therapeutic option to ameliorate peritoneal damage.

Fixed-dose combination treatments reduce cardiovascular disease in primary prevention. We aim to explore whether those benefits differ in the presence of CKD.

We conducted an individual participant data meta-analysis in 18,162 participants on the efficacy and safety of treatment for the primary prevention of cardiovascular disease. Combination therapies consisted of at least two BP-lowering drugs and a statin, with or without aspirin versus placebo or minimal care. Here, we examine the differential effect of fixed-dose combination treatment on the risk of developing cardiovascular disease in participants with a low eGFR (<60 ml/min per 1.73 m 2 ; Chronic Kidney Disease Epidemiology Collaboration formula) compared with a normal eGFR (≥60 ml/min per 1.73 m 2 ). The primary composite outcome was time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization.

At baseline, the mean level of eGFR was 76 ml/min per 1.73 m 2 (SD 17). In total, 3315 (18%) participants had low eGFR at baseline. During a median follow-up of 5 years, among participants with normal eGFR, the primary outcome occurred in 232 (3%) participants in the treatment group compared with 339 (5%) in the control group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P < 0.001). In participants with low eGFR, the primary outcome occurred in 64 (4%) participants in the treatment group compared with 130 (8%) in the control group (hazard ratio, 0.49; 95% confidence interval, 0.36 to 0.66; P < 0.001; P for interaction 0.047). The relative risk reduction among participants with low eGFR was larger for combination strategies, including aspirin compared with treatments without aspirin. Apart from dizziness, other side effects did not differ between treatment and control groups, regardless of the stage of their kidney function.

A fixed-dose combination treatment strategy is effective and safe at preventing cardiovascular disease, irrespective of eGFR, but relative and absolute risk reductions are larger in individuals with low eGFR.

This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000251.mp3.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality. SARS-CoV-2 vaccines opened a new era, but patients with CKD (including kidney transplant, hemodialysis and peritoneal dialysis) were systematically excluded from pivotal clinical trials. The Spanish Society of Nephrology promoted the multicentric national SENCOVAC study aimed at assessing immunological responses after vaccination in patients with CKD. During the first year after vaccination, patients with non-dialysis CKD and those on hemodialysis and peritoneal dialysis presented good anti-Spike antibody responses to vaccination, especially after receiving the third and fourth doses. However, kidney transplant recipients presented suboptimal responses after any vaccination schedule (initial, third and fourth dose). Especially worrisome is the situation of a patients with a persistently negative humoral response that do not seroconvert after boosters. In this regard, monoclonal antibodies targeting SARS-CoV-2 have been approved for high-risk patients, although they may become obsolete as the viral genome evolves. The present report reviews the current status of SARS-CoV-2 vaccination in the CKD spectrum with emphasis on lessons learned from the SENCOVAC study. Predictors of humoral response, including vaccination schedules and types of vaccines, as well as the integration of vaccines, monoclonal antibodies and antiviral agents are discussed.

Chronic kidney disease of uncertain etiology (CKDu) is an emergent health concern, particularly in tropical farming communities in several global hotspots, including Sri Lanka. This particular nephropathy is characterized by a progressive decline in kidney function in the absence of conventional chronic kidney disease (CKD) risk factors such as diabetes mellitus, hypertension, and other identifiable kidney disorders. As it is almost asymptomatic at early stages, CKDu is mostly diagnosed at late stages with significant kidney damage. Hence, the identification of disease susceptibility and vulnerable communities at the earliest possible instances is highly important for the management of the disease.

We aimed to compare kidney health across three different farming communities in Sri Lanka to identify CKDu susceptibilities.

A cross-sectional study was performed with three selected farming communities: paddy farmers (PF; N = 581), sugarcane farmers (SF; N = 550), and vegetable farmers (VF; N = 244) in comparison with an age-matched control group of nonfarming (NF; N = 225) individuals. A medical examination was performed to investigate health status and medical history, whereas a urinalysis was performed to determine creatinine and albumin contents. Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR) were used for assessment of kidney function. CKDu susceptibility was determined based on eGFR, and urinary ACR adhering to the clinical practice guidelines in Sri Lanka.

The median (interquartile range [IQR]) eGFR levels of PF (85 mL/min/1.73 m2 [72-97]) and SF (93 mL/min/1.73 m2 [73-112]) were significantly lower than that of the NF group (103 mL/min/1.73 m2 [87-125]) (P < .0001), whereas eGFR of VF (100 mL/min/1.73 m2 [80-111]) was not significantly different compared with NF. The median (IQR) urinary ACR levels of the study groups, PF, SF, VF, and NF, were 0.59 (0.26-1.45), 0.46 (0.28-0.88), 0.45 (0.34-0.90), and 0.44 (0.34-1.02) mg/mmol, respectively. However, urinary ACR did not differ significantly across the study groups (P > .05). The prevalence of CKDu within PF (13.60%), SF (12.54%), and VF (6.67%) communities was significantly higher (P < .05) compared with the NF (2.67%). Of the total CKD cases, CKDu susceptible cases represented 73%, 69%, 50%, and 25% in PF, SF, VF, and NF, respectively, indicating a high risk of CKDu susceptibility among farming communities. Moreover, a noteworthy association of CKDu was observed with agrochemical exposure (odds ratio [OR] = 3.11, 95% confidence interval [CI] = 1.36-7.09). Concerning the farming practices, sugarcane farming showed the highest association with CKDu prevalence (OR = 3.40, 95% CI = 1.49-7.78).

Compared with the nonfarming group, a significant risk of CKDu was observed in the three farming communities, particularly among paddy and sugarcane farmers. Longitudinal epidemiological studies to identify vulnerable farming communities and associated risk factors are critically needed to develop effective management strategies against CKDu within farming communities.

Patients with kidney failure experience derangements of circulating markers of mineral metabolism and dysregulation of skeletal and cardiovascular physiology which results in high mortality rate in these patients. This study aimed to evaluate the effect of intradialytic exercise on regulation of these abnormalities in patients receiving chronic hemodialysis (HD).

In this randomized controlled trial conducted in an HD center in Iran, adult patients receiving chronic HD were randomized to intradialytic exercise (60 min) in the second hour of thrice weekly dialysis for 6 months (intervention) or no intradialytic exercise (control). The primary outcomes were serum calcium, serum phosphorous and parathyroid hormone levels. Secondary outcomes were serum alkaline phosphatase and calcium-phosphorous product.

The study included 44 participants randomized to intervention (n = 22) or control (n = 22). During the 6-month intervention period, significant between-group changes were observed in all primary and secondary outcomes between the intervention and control groups. Statistical analyses reveal a significant increase in serum calcium (P < 0.05) as well as a significant decrease in serum phosphorous, parathyroid hormone, alkaline phosphatase and calcium-phosphorous product (P < 0.05).

Intradialytic exercise performed for at least 60 min during thrice weekly dialysis sessions improves bone mineral metabolism in adult patients receiving HD. Further studies should focus on observing and comparing the effect of different types of exercise on bone mineral disorders and all-cause mortality in HD patients.

ClinicalTrials.gov Identifier: NCT04916743, Registered on 08/06/2021. Registered trial name: The Effect of Intradialytic Exercise on Calcium, Phosphorous and Parathyroid Hormone: A Randomized Controlled Trial.

Vascular calcification is an important risk factor for cardiovascular (CV) mortality in patients with chronic kidney disease (CKD). It is also a complex process involving osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) and abnormal deposition of minerals in the vascular wall. In an observational, multicenter European study, including 112 patients with CKD from Spain and 171 patients on dialysis from France, we used serum proteome analysis and further validation by ELISA to identify calprotectin, a circulating damage-associated molecular pattern protein, as being independently associated with CV outcome and mortality. This was confirmed in an additional cohort of 170 patients with CKD from Sweden, where increased serum calprotectin concentrations correlated with increased vascular calcification. In primary human VSMCs and mouse aortic rings, calprotectin exacerbated calcification. Treatment with paquinimod, a calprotectin inhibitor, as well as pharmacological inhibition of the receptor for advanced glycation end products and Toll-like receptor 4 inhibited the procalcifying effect of calprotectin. Paquinimod also ameliorated calcification induced by the sera of uremic patients in primary human VSMCs. Treatment with paquinimod prevented vascular calcification in mice with chronic renal failure induced by subtotal nephrectomy and in aged apolipoprotein E-deficient mice as well. These observations identified calprotectin as a key contributor of vascular calcification, and increased circulating calprotectin was strongly and independently associated with calcification, CV outcome, and mortality in patients with CKD. Inhibition of calprotectin might therefore be a promising strategy to prevent vascular calcification in patients with CKD.

Peer support has been associated with improved health-related outcomes (e.g., psychological well-being and treatment adherence) among patients with serious, chronic conditions, including kidney disease. Yet, there is little existing research evaluating the effects of peer support programs on health outcomes among patients with kidney failure being treated with kidney replacement therapy.

Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a systematic review using five databases to assess the effects of peer support programs on health-related outcomes (e.g., physical symptoms, depression) among patients with kidney failure undergoing kidney replacement therapy.

Peer support in kidney failure was assessed across 12 studies (eight randomized controlled trials, one quasi-experimental controlled trial, and three single-arm trials) with 2893 patients. Three studies highlighted the links between peer support and improved patient engagement with care, while one found peer support did not significantly impact engagement. Three studies showed associations between peer support and improvements in psychological well-being. Four studies underscored the effects of peer support on self-efficacy and one on treatment adherence.

Despite preliminary evidence of the positive associations between peer support and health-related outcomes among patients with kidney failure, peer support programs for this patient population remain poorly understood and underutilized. Further rigorous prospective and randomized studies are needed to evaluate how peer support can be optimized and incorporated into clinical care for this vulnerable patient population.

Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the "Treatise on Febrile Diseases" written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear.

In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors.

CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice. The insomnia related regulatory proteins, Orexin, Orexin R1, and Orexin R2 in the hypothalamus of CKD mice decreased significantly, while Orexin and its receptors increased remarkably after CLMD intervention. Following administration of CLMD, reduced neuron loss and improved learning as well as memory ability were observed in CKD mice. And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice.

Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study.

Diet-induced models of chronic kidney disease (CKD) offer several advantages, including clinical relevance and animal welfare, compared with surgical models. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. An increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction, and eventually CKD. Dahl-Salt-Sensitive (SS) rats are a common strain used to study hypertensive renal disease; however, the characterization of other diet-induced models on this background would allow for comparative studies of CKD within the same strain. In the present study, we hypothesized that SS rats on a low-salt, oxalate rich diet would have increased renal injury and serve as novel, clinically relevant and reproducible CKD rat models. Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks.Real-time PCR demonstrated an increased expression of inflammatory marker interleukin-6 (IL-6) (p < 0.0001) and fibrotic marker Timp-1 metalloproteinase (p < 0.0001) in the renal cortex of SS-OX rat kidneys compared with SS-NC. The immunohistochemistry of kidney tissue demonstrated an increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (p < 0.001). In addition, SS-OX rats displayed increased 24 h urinary protein excretion (UPE) (p < 0.01) as well as significant elevations in plasma Cystatin C (p < 0.01). Furthermore, the oxalate diet induced hypertension (p < 0.05). A renin-angiotensin-aldosterone system (RAAS) profiling (via liquid chromatography-mass spectrometry; LC-MS) in the SS-OX plasma showed significant (p < 0.05) increases in multiple RAAS metabolites including angiotensin (1-5), angiotensin (1-7), and aldosterone. The oxalate diet induces significant renal inflammation, fibrosis, and renal dysfunction as well as RAAS activation and hypertension in SS rats compared with a normal chow diet. This study introduces a novel diet-induced model to study hypertension and CKD that is more clinically translatable and reproducible than the currently available models.