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Objective The aim of this study was to evaluate the efficacy and side effects of sacubitril/valsartan in the treatment of patients with chronic kidney disease(CKD)at stage 5 with resistant hypertension,and to explore the cardiovascular benefits and security of medical in the patients.Methods Patients with CKD5 resistant hypertension diagnosed and treated in the First Affiliated Hospital of Guangxi Medical University from September 2020 to March 2022 were selected and divided into the observation group(treated with routine treatment of kidney disease at end-stage and sacubitril/valsartan)and control group(include droutine treatment of renal disease at end-stage and ACEI or ARB drugs)according to treatment strategy.The patients in both two groups were treated with adequate dialysis treatment and conventional drug treatment of renal disease at end-stage.The patients were followed up for at least 3 months,the clinical efficacy of three months after treated with sacubitril/valsartan was observed,and the efficacy indicators and security indicators and adverse cardiovascular events were observed,the occurrence of adverse effects during the period of drug use were compared with the control group.Results A total of 110 patients were included in this study and there were 55 cases in each group.There were no significant differences in gender,age,age of dialysis,etiology,dialysis mode and blood pressure between the two groups(P>0.05).The Systolic blood pressure(SBP),diastolic blood pressure(DBP),b-type urinary natriuretic peptide precursor(Pro-BNP)and cardiac function grade in the observation group after treatment was significantly decreased compared with before treatment.The left ventricular ejection fraction(LVEF)and the ratio of LVEF<50%in the observation group was significantly reduced after treatment(P<0.05).SBP,DBP and Pro-BNP decreased 3 months after treatment compared with the baseline before treatment,and improved significantly in the first month after treatment(P<0.05).The decrease of DBP and BNP before and after treatment was significantly different between the two groups,and the decrease of DBP and BNP was more significant in the observation group(P<0.05).The difference of LVEF and left ventricular end diastolic diameter(LVEDD)between the two groups before and after treatment was statistically significant,and the improvement was more obvious in the observation group(P<0.05).There were no significant differences in the safety indicators of serum potassium,estimated glomerular filtration rate(eGFR)and liver function between two groups before and after treatment(P>0.05).In terms of adverse reactions,only 1 case in the control group developed hyperkalemia within 3 months of follow-up,and no hypotension or other adverse reactions occurred in the two groups.Conclusions The treatment of patients with CKD stage 5 hypertension with sacubitril/valsartan has obvious cardiovascular benefits.Sacubitril/Valsartan has efficacy in lowering blood pressure,improving cardiac function and reducing volume load,with less adverse events and higher safety than control group.

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Background: Cognitive decline exists in the chronic kidney disease (CKD) population and is particularly severe in patients with stage 5 CKD, but the mechanisms underlying this relationship are unclear. Structural-functional coupling, an integrated measure that combines functional and structural networks, offers the possibility of exploring changes in network relationships in patients with stage 5 CKD. This study aimed to investigate the brain network topology and structural-functional coupling characteristics in patients with non-dialysis-dependent stage 5 CKD (CKD 5ND) and the correlation between network changes and cognitive scores. Methods: We prospectively performed diffusion tensor and resting-state functional magnetic resonance (rs-fMRI) imaging on 40 patients with CKD 5ND disease and 47 healthy controls (HCs). Graph theory analysis of functional and structural connectivity (SC) was performed. Small-world properties and network efficiency properties were calculated, including characteristic path length (Lp), clustering coefficient (Cp), normalized clustering coefficient (Gamma), normalized characteristic path length (Lambda), small-worldness (Sigma), global efficiency (Eglob), and local efficiency (Eloc). The SC-functional connectivity (FC) coupling characteristics and the association between Montreal Cognitive Assessment (MoCA) scores and graph-theoretical features were analyzed. Results: For SC, the Sigma (P=0.009), Cp (P=0.01), Eglob (P<0.001), and Eloc (P=0.01) were significantly lower in patients with CKD 5ND than in HCs, while Lp (P<0.001) and Lambda (P<0.001) were significantly higher in the patients than in the HCs. For FC, the Sigma (P=0.008), Gamma (P=0.009), Eglob (P=0.04), and Eloc (P<0.0001) were lower in patients with CKD 5ND than in HCs; however, the Lp (P=0.02) was higher in the patients than in the HCs. SC-SC coupling (P<0.001) was greater in patients with CKD 5ND than in HCs. The structural (Cp, Eloc, Eglob) and functional network parameters (Sigma, Gamma, Eglob) of the patients with CKD 5ND were positively correlated with MoCA scores; however, the Lp of both structural and functional networks was negatively correlated with MoCA scores. Conclusions: All patients with CKD 5ND included in the study exhibited changes in their structural and functional brain network topology closely related to mild cognitive impairment. SC-SC coupling was elevated in the patients compared with that in the controls. This may provide vital information for understanding and revealing the underlying mechanisms of cognitive impairment in patients with CKD 5ND.

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Aim To study the prevalence of frailty in patients with chronic kidney disease stage 5 (CKD5) and to assess coexisting factors associated with frailty in chronic kidney disease. Patients and methods We studied the prevalence of frailty in CKD5 patients from November 2021 to November 2022. CKD5 patients over 18 years of age were included. Patients on maintenance hemodialysis and CKD5 patients on pre-dialysis care were included. Patients with active infection and significant morbidity were excluded. We performed a history and clinical examination and recorded laboratory data. We performed frailty assessments using modified Fried's criteria. Frailty was defined based on previously validated Fried's criteria, which included 1. Slowness, 2. Weakness, 3. Unintentional weight loss, 4. Exhaustion, 5. Low physical activity. A patient is considered frail if three or more components are present. We evaluated the prevalence of frailty in pre-dialysis and dialysis care participants and the association of frailty with coexisting factors. Results Of the 139 patients, 84 were on thrice-weekly hemodialysis, and 55 were on pre-dialysis care. We found the prevalence of frailty to be 41%. The prevalence of frailty was similar in patients on pre-dialysis care and hemodialysis. The prevalence of frailty in hemodialysis patients and those in pre-dialysis care was 43% and 40%, respectively. The prevalence of frailty among the elderly (over 55) was 82%. The prevalence of frailty among diabetes patients was 75%. Factors with a statistically significant association with frailty included old age (p < 0.005), native kidney disease (p < 0.005), edema (p < 0.001), intradialytic hypotension (p = 0.002), and various comorbidities like diabetes (p < 0.001), heart failure (p < 0.001), coronary artery disease (p = 0.001), and cerebrovascular accidents (p = 0.016). We observed no significant association with the duration of chronic kidney disease (CKD) (p = 0.458), duration of dialysis (p = 0.838), or body mass index (BMI) (p = 0.267). The most commonly reported frailty components were exhaustion (61.9%), low physical activity (61.2%), and weak handgrip (55.4%). Conclusion Frailty is a marker of increased vulnerability to adverse outcomes. A significant proportion, 41% of CKD5 patients, are frail. Dialysis does not affect the prevalence of frailty in CKD5 patients. Old age, native kidney disease, edema, intradialytic hypotension, and comorbidities like diabetes, heart failure, coronary artery disease, and cerebrovascular accident are significantly associated with frailty in CKD5 patients. CKD patients with those conditions should receive special care to reduce the development of frailty.

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This study aimed to investigate the topological characteristics of the resting-state functional network and the underlying pathological mechanism in nondialysis patients with stage 5 chronic kidney disease (CKD5 ND). Eighty-five subjects (21 patients with CKD5 ND, 32 patients with CKD on maintenance hemodialysis (HD), and 32 healthy controls (HCs)) underwent laboratory examinations, neuropsychological tests, and brain magnetic resonance imaging. The topological characteristics of networks were compared with a graph-theoretical approach, and correlations between neuropsychological scores and network properties were analyzed. All participants exhibited networks with small-world attributes, and global topological attributes were impaired in both groups of patients with CKD 5 (ND and HD) compared with HCs (p < 0.05); these impairments were more severe in the CKD5 ND group than in the HD group (p < 0.05). Compared with the HC group, the degree centrality of the CKD5 ND group decreased mainly in the basal ganglia and increased in the bilateral orbitofrontal gyrus, bilateral precuneus, and right cuneus. Correlation analysis showed that the degree of small-worldness, normalized clustering coefficients, and Montreal Cognitive Assessment (MoCA) scores were positively correlated and that characteristic path length was negatively correlated with these variables in patients with CKD5 ND. The nodal efficiency of the bilateral putamen (r = 0.53, p < 0.001 and r = 0.47, p < 0.001), left thalamus (r = 0.37, p < 0.001), and right caudate nucleus (r = 0.28, p = 0.01) was positively correlated with MoCA scores. In conclusion, all CKD5 ND patients exhibited changes in functional network topological properties and were closely associated with mild cognitive impairment. More interestingly, the topological property changes in CKD5 ND patients were dominated by basal ganglia areas, which may be more helpful to understand and possibly reveal the underlying pathological mechanisms of cognitive impairment in CKD5 ND.

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PURPOSE: Patients suffering from chronic kidney disease (CKD) are in general at high risk for severe coronavirus disease (COVID-19) but dialysis-dependency (CKD5D) is poorly understood. We aimed to describe CKD5D patients in the different intervals of the pandemic and to evaluate pre-existing dialysis dependency as a potential risk factor for mortality. METHODS: In this multicentre cohort study, data from German study sites of the Lean European Open Survey on SARS-CoV-2-infected patients (LEOSS) were used. We multiply imputed missing data, performed subsequent analyses in each of the imputed data sets and pooled the results. Cases (CKD5D) and controls (CKD not requiring dialysis) were matched 1:1 by propensity-scoring. Effects on fatal outcome were calculated by multivariable logistic regression. RESULTS: The cohort consisted of 207 patients suffering from CKD5D and 964 potential controls. Multivariable regression of the whole cohort identified age (> 85 years adjusted odds ratio (aOR) 7.34, 95% CI 2.45-21.99), chronic heart failure (aOR 1.67, 95% CI 1.25-2.23), coronary artery disease (aOR 1.41, 95% CI 1.05-1.89) and active oncological disease (aOR 1.73, 95% CI 1.07-2.80) as risk factors for fatal outcome. Dialysis-dependency was not associated with a fatal outcome-neither in this analysis (aOR 1.08, 95% CI 0.75-1.54) nor in the conditional multivariable regression after matching (aOR 1.34, 95% CI 0.70-2.59). CONCLUSIONS: In the present multicentre German cohort, dialysis dependency is not linked to fatal outcome in SARS-CoV-2-infected CKD patients. However, the mortality rate of 26% demonstrates that CKD patients are an extreme vulnerable population, irrespective of pre-existing dialysis-dependency.

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BACKGROUND: Carbapenem-induced neurotoxicity is an unusual side effect, with seizure being the most commonly reported symptom. Among the carbapenems, imipenem-cilastin is classically associated with the most severe neurotoxicity side effects. Carbapenem is mainly excreted by the kidney and its half-life is significantly increased in patients with chronic kidney disease (CKD). Therefore, dose adjustment is necessary in such patients. Ertapenem-associated neurotoxicity is increasingly being reported in CKD patients, but rarely seen in patients with recommended dose adjustment. CASE PRESENTATION: We report a case of a 56-year-old male patient with chronic kidney disease 5 on dialysis(CKD 5D). The patient presented with a history of fever, chills and rigours during a session of haemodialysis (HD). He was diagnosed with Enterobacter cloacae catheter-related blood stream infection and was started on ertapenem. After 13 days of ertapenem, he experienced an acute confusional state and progressed to having auditory and visual hallucinations. His blood investigations and imaging results revealed no other alternative diagnosis. Hence a diagnosis of ertapenem-induced neurotoxicity was made. He had complete resolution of symptoms after 10 days' discontinuation of ertapenem. CONCLUSION: Our case draws attention to the risk of potentially serious toxicity of the central nervous system in HD patients who receive the current recommended dose of ertapenem. It also highlights that renal dosing in CKD 5D patients' needs to be clinically studied to ensure antibiotic safety.

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Introduction: With the advent of endovascular technique and the emergence of vascular surgery as a separate branch distinct from general surgery, there is a decrease in exposure of open vascular technique to general surgery resident. Vascular access surgery is a vascular subspecialty area and not all residents get similar exposure during training, and this has implications if one becomes a vascular consultant in the future and have to undertake access surgery. There is no established protocol or duration, following which a surgical resident can be named as "trained" in vascular anastomosis. Our study tries to address the aforementioned problems; in particular the actual training that a general surgery resident needs in vascular access. Objective: To study and compare the outcomes of AV Fistula surgeries, created by "trained" general surgical residents and consultant. Method: A single-institution retrospective cohort study comparing two groups of cohorts: trained residents (group A) and consultant (group B). Study has been done in accordance with the standards of ICMJE and registered with the Clinical Trial Registry of India. (CTRI/2021/12/038581). Result: Out of 238 patients recruited, 157 underwent surgery in group 'A' (the trained residents performing arteriovenous fistula surgery) and 81 underwent surgery in group 'B' (by consultant of general surgery). Clinical maturation noted after 8 weeks was 83.4% (131/157) in group A and 90.1% (73/81) in group 'B'; (p = 0.113). The mean duration of surgery in group 'A' was 99.8 ± 18.2 min and group 'B' was 56.2 ± 10.4 min; (p value < 0.0001). Conclusion: A structured training in vascular anastomosis provided to the newly recruited residents in general surgery for 6 months lead to outcomes that were comparable with the consultants.

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The centrosome lacks microtubule (MT)-nucleation activity in differentiated neurons. We have previously demonstrated that MTs were nucleated at the cytoplasm of mouse neurons. They are supposed to serve seeds for MTs required for dendrite growth. However, the factors that activate the cytoplasmic γ-tubulin ring complex (γTuRC) are unknown. Here we report an alternative splicing isoform of cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CKD5RAP2) as a candidate for the cytoplasmic γTuRC activator. This isoform lacked exon 17 and was expressed predominantly in the brain and testis. The expression was transient during the development of cortical neurons, which period coincided with the period we reported cytoplasmic MT nucleation. This isoform resulted in a frameshift and generated truncated protein without a centrosomal localization signal. When this isoform was expressed in cells, it localized diffusely in the cytoplasm. It was co-immunoprecipitated with γ-tubulin and MOZART2, suggesting that it can activate cytosolic γTuRCs. After cold-nocodazole depolymerization of MTs and subsequent washout, we observed numerous short MTs in the cytoplasm of cells transfected with the cDNA of this isoform. The isoform-overexpressing cells exhibited an increased amount of MTs and a decreased ratio of acetylated tubulin, suggesting that MT generation and turnover were enhanced by the isoform. Our data suggest the possibility that alternative splicing of CDK5RAP2 induces cytoplasmic nucleation of MTs in developing neurons.

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PURPOSE: To evaluate the potential ethnic differences of ferric pyrophosphate citrate (FPC, Triferic) in healthy subjects and patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) and identify covariates that may influence pharmacokinetics (PK) of FPC. METHODS: Data were collected from 2 Asian and 4 non-Asian clinical studies involving healthy subjects and CKD-5HD patients. Three population PK models were developed: M1 for intravenous (IV) administration of FPC in healthy subjects; M2 for dialysate administration of FPC in CKD-5HD patients; M3 for pre-dialyzer administration of FPC in CKD-5HD patients. All the models were fitted to concentration versus time data of FPC using the nonlinear mixed effect approach with the NONMEM® program. All statistical analyses were performed using SAS version 9.4. RESULTS: In total, 26 Asians and 65 non-Asians were included in the final model analysis database. Forty healthy subjects were administered FPC via intravenous (IV) route and 51 patients with CKD-5HD via dialysate (N = 50) and pre-dialyzer blood circuit administration (N = 51). The PK parameters of FPC IV were similar. The population PK model showed good parameter precision and reliability as shown by model evaluation, and no relevant influence of ethnicity on PK parameters was observed. In healthy subjects, the maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) decreased with increase in lean body mass (LBM) and the average serum total iron at 6 h before the baseline period (Feav), whereas, in both patient populations, Cmax and AUC decreased with increase in LBM and decrease in Febaseline. Other factors such as gender, age, Feav, and ethnicity had no influence on PK exposures in patients. The influence of LBM on PK exposures in patients was smaller than that in healthy subjects (ratio of AUC0-24 for the 5th [68 kg] and 95th [45 kg] patient's LBM was almost 1). The influence of Feav and LBM on PK exposures was < 50%. CONCLUSION: The population pharmacokinetics model successfully described the PK parameters of FPC in healthy subjects and CKD-5HD patients and were comparable between Asian and non-Asian populations.

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Death from stage 5 chronic kidney disease (CKD 5) in childhood or adolescence is rare, but something that all paediatric renal physicians and most paediatricians will encounter. In this paper, we present the literature on three key areas of palliative care practice essential to good clinical management: shared decision-making, advance care planning, and symptom management, with particular reference to CKD 5 where kidney transplant is not an option and where a decision has been made to withdraw or withhold dialysis. Some areas of care, particularly with regard to symptom management, have not been well-studied in children and young people (CYP) with CKD 5 and recommendations with regard to drug choice and dose modification are based on adult literature, known pharmacokinetics, and clinical experience.

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Objectives: Chronic kidney disease (CKD) strongly affects patients' health-related quality of life (HRQoL), mostly in the advanced stages of CKD. Health literacy (HL) may affect this association, in particular for some aspects of HRQoL. The aim of this study is to compare the profiles of HRQoL in dialyzed patients with varying HL. Methods: We obtained data on HL using the Health Literacy Questionnaire (HLQ) and on HRQoL using the Kidney Disease Quality of Life - Short Form (KDQoL-SF 1.3) in a multicentre cross-sectional study in 20 dialysis clinics in Slovakia (n = 542; mean age = 63.6 years; males: 60.7%). We compared HRQoL for three HL groups using ANOVA and the Kruskal-Wallis test. Results: Patients with low HL reported worse HRQoL than patients with moderate and high HL. The greatest differences between HL groups were found in the scales Effect of kidney disease, Cognitive function, Quality of social interaction, Social support, Dialysis staff encouragement, Patient satisfaction, Physical functioning, Pain, Emotional well-being and Social function. p-values in all cases were <0.001. Conclusion: Patients with low HL have a worse HRQoL in several domains than patients with a higher HL. Increasing HL capacities and better supporting patients with low HL should thus be given priority to support their HRQoL and at least maintain its level.

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BACKGROUND: This study aims to develop a method to estimate the potential of preemptive kidney transplantation (PKT) by identifying patients who were transplanted after a dialysis period (non-preemptive kidney transplantation (NPKT)) despite being medically suitable for PKT. METHODS: All children (< 18 years old) starting kidney replacement therapy (KRT) in France, between 2010 and 2016 and transplanted before December 31, 2017, were included. A propensity score (PS) of receiving PKT was estimated by multivariate logistic regression based on recipient medical characteristics. Healthcare use during the 24 months prior to KRT initiation was extracted from the French National Health Insurance database, and a pre-KRT follow-up of more than 18 months was considered sufficient to allow preemptive transplantation. RESULTS: Among 643 patients who started KRT, 149 (23.2%) were preemptively transplanted. Using PS stratification, among 391 NPKT patients, we identified 145 patients (37%) suitable for PKT, according to clinical characteristics. Mean age was 12.3 years, 67% were males, and 56% had urological abnormalities. Among those 145 patients, we identified 79 NPKT patients who started on dialysis despite early referral to a nephrologist (more than 18 months prior to KRT initiation). CONCLUSIONS: This method estimates a potential of 228 (149 + 79) PKT (35%) among pediatric patients in France. A similar method could be used in adults or in other countries. Estimation of the rate of patients with CKD stage 5 medically suitable for PKT will be of interest for health policy makers when setting up objectives for improvement in preemptive kidney transplant access.

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Chronic kidney disease stage 5 (CKD5) dialysis patients who stay long term in uremic environment often exhibit several, poorly defined, immune impairments. In this study, we assessed peripheral virus-specific effector/memory cells and subpopulations of T, B and DC cells using ELISPOT and FACS methods in 74 low-risk kidney transplant candidates without anti-HLA antibodies, prior to transplantation in pre-emptive (never experienced dialysis) and dialysis cohorts. There was difference in circulating marginal zone B cells (MZB) (IgDhighCD27high) between dialysis patients and those receiving kidney grafts pre-emptively (P = .002). Patients treated on dialysis >12 months had also 4.2-fold greater risk of increased absolute numbers of MZB (95%CI:1.6-11.2; P = .004). There were no other differences in B-, T- and DC-cell subsets. Numbers of effector/memory T cells reactive to major opportunistic virus-specific antigens (CMV, BKV and EBV) were not affected by dialysis. Non-sensitised dialysis-treated patients displayed significantly more circulating MZB compared to those CKD5 patients that had never undergone dialysis therapy.

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Effective vascular access (VA) is an essential condition for providing hemodialysis, affecting patients' health outcomes. We aim to explore how health literacy (HL) as a non-clinical factor is associated with the decision-making process regarding VA type selection. Using data from 20 dialysis centers across Slovakia (n = 542, mean age = 63.6, males = 60.7%), the association of HL with type of VA (arteriovenous fistula (AVF) vs. central venous catheter (CVC)) was analyzed using a logistic regression model adjusted for sociodemographic characteristics and comorbidity. Sociodemographic data and data on nine domains of HL were collected by questionnaire. Data on VA and comorbidity were obtained from a medical records. Patients with a greater ability to engage with healthcare providers (odds ratio (OR): 1.34; 95% confidence interval (CI): 1.00-1.78), those with a better ability to navigate the healthcare system (OR: 1.41; 95% CI: 1.08-1.85), those more able to find good health information (OR: 1.52; 95% CI: 1.15-2.03), and those who understand it well enough to know what to do (OR: 1.52; 95% CI: 1.12-2.06) are more likely to have AVF. Patients' HL is associated with the type of VA; therefore, it should be considered in the decision-making process regarding the selection of the type of VA, thereby informing strategies for improving patients' HL and doctor-patient communication.

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OBJECTIVE: Current treatment options for patients with stage 5 chronic kidney disease before dialysis (predialysis CKD-5) are determined by individual circumstances, economic factors, and the doctor's advice. This study aimed to explore the plasma metabolic traits of patients with predialysis CKD-5 compared with maintenance hemodialysis (HD) and peritoneal dialysis (PD) patients, to learn more about the impact of the dialysis process on the blood environment. METHODS: Our study enrolled 31 predialysis CKD-5 patients, 31 HD patients, and 30 PD patients. Metabolite profiling was performed using a targeted metabolomics platform by applying an ultra-high-performance liquid chromatography-tandem mass spectrometry method, and the subsequent comparisons among all three groups were made to explore metabolic alterations. RESULTS: Cysteine metabolism was significantly altered between predialysis CKD-5 patients and both groups of dialysis patients. A disturbance in purine metabolism was the most extensively changed pathway identified between the HD and PD groups. A total of 20 discriminating metabolites with large fluctuations in plasma concentrations were screened from the group comparisons, including 2-keto-D-gluconic acid, kynurenic acid, s-adenosylhomocysteine, L-glutamine, adenosine, and nicotinamide. CONCLUSION: Our study provided a comprehensive metabolomics evaluation among predialysis CKD-5, HD, and PD patients, which described the disturbance of metabolic pathways, discriminating metabolites and their possible biological significances. The identification of specific metabolites related to dialysis therapy might provide insights for the management of advanced CKD stages and inform shared decision-making.

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OBJECTIVE: To study the prevalence, etiology, and outcome of acute pancreatitis (AP) in kidney transplant and stage 5 chronic kidney disease (CKD) populations in comparison to a non-CKD cohort. PATIENTS AND METHODS: Using the Nationwide Inpatient Sample database, we identified patients with acute pancreatitis as the primary discharge diagnosis, after which propensity scores were used to create 2 cohorts of patients: 1 with CKD (n=13,425) and 1 without CKD (n=13,425). The CKD group was subsequently subdivided into dialysis-independent stage 5 CKD (n=690), dialysis-dependent stage 5 CKD (n=11,415), and kidney transplant recipients (n=1320). Patients younger than 18 years old, those who received a kidney transplant during the incident admission, and pancreas transplant recipients were excluded. RESULTS: The adjusted odds ratios (ORs) of AP were comparable between the no CKD, stage 5 CKD, and kidney transplant populations. Adjusted inpatient mortality was highest in patients with dialysis-dependent stage 5 CKD (OR, 2.72; 95% CI, 2.2-3.3; P<.01), followed by kidney transplant recipients (OR, 2.29; 95% CI, 1.12-4.51; P=.02), compared to the non-CKD group. Patients with stage 5 CKD experienced higher rates of shock and intensive care unit admission and had more prolonged and costly hospitalizations than the non-CKD group (P<.01 for all). Hypercalcemia was the most common cause of AP in both dialysis-dependent and dialysis-independent patients with stage 5 CKD, while viral and drug-induced pancreatitis were more prevalent in the transplant recipients. CONCLUSION: Despite comparable adjusted prevalence of AP among the stage 5 CKD, transplant, and non-CKD populations, mortality, morbidity, and resource utilization were higher in the patients with stage 5 CKD and transplant recipients. Hypercalcemia is the most common cause of AP in the stage 5 CKD population irrespective of dialysis requirement.

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[Objective]To discuss the clinical experiences and unique views of professor CHEN Hongyu in treating chronic kidney disease at the fifth stage (non-dialysis).[Method]To analyze the professor CHEN Hongyu's understanding about the pathogenesis of chronic kidney disease and her academic point of view that treating from spleen and kidney. To sum up the clinical experiences in treating CKD5 (non-dialysis) according to invigorating the spleen and kidney, and analyze typical clinical case. [Result] Professor CHEN Hongyu considers that the root cause of CKD is the spleen and kidney deficiency and often accompanied by pathogenic dampness or blood stasis or turbidity toxin. Also rheumatic is an important risk factor for prompting disease activity and protracted course, which is easy to cause kidney deficiency, renal bi and is usually poor for the prognosis. Professor CHEN Hongyu considers protecting spleen and stomach and invigorating the spleen and kidney as the fundamental law, making good use of application of modern technology, emphasizing the combination of macro and micro, treatment based on syndrome differentiation,which has obvious curative effect to remit or eliminate clinical symptoms in patients with chronic renal disease, beneficial to delay the progress of the renal function and improve life quality.[Conclusion] Professor CHEN Hongyu 's experience in treating chronic kidney disease fifth stage(non-dialysis) is worth learning and spreading.

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UNLABELLED: Recent studies have implicated epigenetic remodeling in brain reward regions following psychostimulant or stress exposure. It has only recently become possible to target a given type of epigenetic remodeling to a single gene of interest, and to probe the functional relevance of such regulation to neuropsychiatric disease. We sought to examine the role of histone modifications at the murine Cdk5 (cyclin-dependent kinase 5) locus, given growing evidence of Cdk5 expression in nucleus accumbens (NAc) influencing reward-related behaviors. Viral-mediated delivery of engineered zinc finger proteins (ZFP) targeted histone H3 lysine 9/14 acetylation (H3K9/14ac), a transcriptionally active mark, or histone H3 lysine 9 dimethylation (H3K9me2), which is associated with transcriptional repression, specifically to the Cdk5 locus in NAc in vivo We found that Cdk5-ZFP transcription factors are sufficient to bidirectionally regulate Cdk5 gene expression via enrichment of their respective histone modifications. We examined the behavioral consequences of this epigenetic remodeling and found that Cdk5-targeted H3K9/14ac increased cocaine-induced locomotor behavior, as well as resilience to social stress. Conversely, Cdk5-targeted H3K9me2 attenuated both cocaine-induced locomotor behavior and conditioned place preference, but had no effect on stress-induced social avoidance behavior. The current study provides evidence for the causal role of Cdk5 epigenetic remodeling in NAc in Cdk5 gene expression and in the control of reward and stress responses. Moreover, these data are especially compelling given that previous work demonstrated opposite behavioral phenotypes compared with those reported here upon Cdk5 overexpression or knockdown, demonstrating the importance of targeted epigenetic remodeling tools for studying more subtle molecular changes that contribute to neuropsychiatric disease. SIGNIFICANCE STATEMENT: Addiction and depression are highly heritable diseases, yet it has been difficult to identify gene sequence variations that underlie this heritability. Gene regulation via epigenetic remodeling is an additional mechanism contributing to the neurobiological basis of drug and stress exposure. In particular, epigenetic regulation of the Cdk5 gene alters responses to cocaine and stress in mouse and rat models. In this study, we used a novel technology, zinc-finger engineered transcription factors, to remodel histone proteins specifically at the Cdk5 gene. We found that this is sufficient to regulate the expression of Cdk5 and results in altered behavioral responses to cocaine and social stress. These data provide compelling evidence of the significance of epigenetic regulation in the neurobiological basis of reward- and stress-related neuropsychiatric disease.

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BACKGROUND: Primary membranous nephropathy is associated with variable clinical course ranging from spontaneous remission to slow progression to end stage renal failure. Achieving remission confers better renal survival in primary membranous nephropathy (PMN). Longer term outcomes such as patient survival and relapse of active disease remain poorly understood. METHODS: We performed a retrospective study of 128 consecutive adult patients diagnosed with biopsy proven PMN at a single UK centre between 1980 and 2010. These patients were followed prospectively over a median of 128 months. We assessed impact of persistent disease and relapse on Stage 5 chronic kidney disease (CKD-5) and patient survival and present longer term cumulative incidences of different end points. RESULTS: One hundred patients achieved partial remission (PartRem) and 28 patients did not achieve remission (NoRem). Nine per cent of patients achieving first remission developed CKD-5 and 75% of those with NoRem developed CKD-5 [hazard ratio (HR) 0.07, 95% confidence interval 0.03-0.19). Relapse following PartRem occurred in 31 patients (31%) during follow-up and was significantly associated with progression to CKD-5. Progression to CKD-5 was strongly associated with death (47 versus 6%, HR 23.4; P < 0.01). Cumulative incidence at 15 years following first presentation included: death, 14%; CKD-5, 28%; and relapse 40% (in patients who achieved first remission). CONCLUSIONS: Our data strongly suggest that mortality in PMN is seen in patients with disease progression to CKD-5. Achieving remission is strongly associated with improved renal survival after first presentation and following relapse. We suggest that patients who achieve remission should be followed up in longer term, and better strategies to help improve outcomes are needed in clinical practice.

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INTRODUCTION: The options available to CKD 5 patients with donor shortage due to incompatibilities is to either get enlisted in cadaver transplant program or opt for three other alternatives viz; ABO-incompatible transplant (ABO-I), ABO-incompatible transplant with Rituximab (ABO-R) or paired-kidney exchange transplant (PKE). At our institute we have performed ABO-I, ABO-R and PKE transplants and we are presenting the results of these transplants performed at our institution. Here, we report our experiences of living donor kidney transplantation in highly sensitized patients. OBJECTIVE: To review the options available to CKD 5 patients with incompatible donor. MATERIALS AND METHODS: Between January 2008 and June 2011, 7 PKE, 26 ABO-I and 7 ABO-R transplants were carried out at our institute. Evaluation of both the recipients and donors involved biochemical, serological and radiological investigations. In case of PKE, recipients were operated simultaneously in different operation theaters. In ABO-I splenectomy was done while in ABO-R was given. Post-transplant the recipient management protocol remained the same. Expenditure following each transplant was calculated. RESULTS: The graft and patient survival of ABO-I, ABO-R and PKE transplants 12-18 months after transplant were 78.9%:80%, 85.7%:85.7% and 100%:100%, respectively. CONCLUSIONS: The inclusion of Rituximab in the transplant protocol appears promising. The existing donor shortage could be addressed by encouraging other options like PKE. The limiting factor for ABO-R and PKE transplants is time and cost, respectively. The decision depends on the informed consent between the patient and the nephrologists.