YKL-40 (chitinase-3-like protein 1) serum levels are associated with abdominal aortic calcification in hemodialysis patients.

BACKGROUND: Vascular calcification (VC) is highly prevalent and predicts cardiovascular mortality in dialysis patients. The mechanisms are still unclear. Inflammation is a well-known inducer of VC. YKL-40 has been suggested as a novel biomarker of inflammation and has been demonstrated to be associated with cardiovascular mortality in hemodialysis patients. This study aims to evaluate the relationship between serum YKL-40 and VC in hemodialysis (HD) patients. METHODS: A total of 109 HD patients and 31 healthy controls were enrolled in the study from September 2014 to December 2014. We evaluated the abdominal aortic calcification (AAC) score by plain X-ray films of the abdomen and measured serum YKL-40 concentrations using enzyme-linked immunosorbent assay. We also examined the relationship between YKL-40 levels and AAC scores in HD patients. RESULTS: Serum YKL-40 levels in HD patients were significantly higher than those in healthy controls [199.8 (144.8, 288.7) vs. 71.9 (52.8, 89.3) ng/ml; P < 0.001]. There was a tendency that YKL-40 levels in diabetic hemodialysis patients were higher than those in nondiabetic patients [217.8 (155.3, 335.8) vs. 192.9 (135.9, 274.4) ng/ml; P = 0.093]. A significant positive correlation was found between serum YKL-40 level and AAC score in these patients (r = 0.410, P = 0.003). Multiple regression analysis showed that Ln(YKL-40) was independently associated with AAC score in HD patients (P = 0.044). CONCLUSION: This study showed high serum YKL-40 concentrations in chronic HD patients and that YKL-40 was independently associated with increased AAC in hemodialysis patients.

Higher serum trimethylamine N-oxide (TMAO) levels are associated with increased visceral fat in hemodialysis patients.

BACKGROUND: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has emerged as a new potentially important cause of increased atherosclerosis and cardiovascular risk in chronic kidney disease (CKD) patients. However, the possible causes whereby TMAO potentiates atherosclerosis development remain poorly defined. The strong association between gut microbiota and obesity suggested that the TMAO pathway may be linked to the pathogenesis of obesity. MATERIALS AND METHODS: A total of 184 hemodialysis (HD) patients and 38 healthy controls were enrolled in the study from March 2019 to May 2019. We evaluated visceral fat area (VFA) by anthropometric measurement and measured serum TMAO concentrations using liquid chromatography/differential ion mobility spectrometry tandem mass spectrometry. We also examined the relationship between TMAO levels and visceral fat accumulation. RESULTS: TMAO level was markedly higher in HD patients than in control subjects (5.80 (3.96, 9.46) vs. 0.18 (0.11, 0.32) µg/mL, p < 0.01), and its level in diabetic HD patients was significantly higher than in nondiabetic patients (6.93 (4.67, 11.40) vs. 5.25 (3.78, 8.02) µg/mL, p < 0.01). A significant positive correlation was found between serum TMAO level and VFA in these patients (r = 0.282, p = 0.005). Multiple regression analysis showed that Ln(TMAO) was independently associated with Ln(VFA) in HD patients (p = 0.008). CONCLUSION: Our results showed that there was a significant positive correlation between serum TMAO levels and visceral fat in HD patients, which suggested that TMAO may predict cardiovascular risk through increased visceral fat.

Longitudinal association between dietary protein intake and survival in peritoneal dialysis patients.

BACKGROUND: Decreased dietary protein intake (DPI) may lead to protein-energy malnutrition and may be associated with increased mortality risk. We hypothesized that longitudinal changes in dietary protein intake have independent associations with survival in peritoneal dialysis (PD) patients. METHODS: 668 stable PD patients were selected in the study from January 2006 to January 2018 and were followed up until December 2019. Their three-day dietary records were collected at the baseline (the sixth month after PD) and thereafter every 3 months for two and a half years. The latent class mixed models (LCMM) were used to identify subgroups of PD patients with similar longitudinal trajectories of DPI. The relation between DPI (baseline and longitudinal data) and survival was examined using Cox model to estimate death hazard ratios. Meanwhile, different formulae were used to assess nitrogen balance. RESULTS: The results showed that baseline DPI ≤ 0.60g/kg/day was associated with the worst outcome in PD patients. Patients with DPI 0.80-0.99g/kg/day and DPI ≥ 1.0g/kg/day both presented positive nitrogen balance; patients with DPI 0.61-0.79g/kg/day presented obviously negative nitrogen balance. Longitudinal association between time-dependent DPI and survival was found in PD patients. The consistently low DPI' (0.61-0.79g/kg/d) group was correlated with increased death risk as compared with the 'consistently median DPI' group (0.80-0.99g/kg/d, HR = 1.59, p = 0.008), whereas there was no difference in survival between 'consistently median DPI' group and 'high-level DPI' group (≥1.0 g/kg/d, p > 0.05). CONCLUSION: Our study revealed that DPI ≥ 0.8 g/kg/day was beneficial to the long-term outcome for the PD population.

A modified renal risk score for Chinese patients with antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: The renal risk score (RRS) is a useful tool to predict end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to validate the predictive performance of RRS and to further modify this model in Chinese AAV patients. METHODS: Two hundred and seventy-two patients diagnosed with AAV confirmed by renal biopsies were retrospectively enrolled from a single center. The RRS was calculated based on 3 categorical variables, i.e., the proportion of normal glomeruli, the proportion of interstitial fibrosis and tubular atrophy (IF/TA), and eGFR at biopsy, classifying these patients into low-, medium-, and high-risk groups. In addition, a modified model was developed based on the RRS and was further validated in another independent cohort of 117 AAV patients. The predictive performance of each model was evaluated according to discrimination and calibration. RESULTS: Patients were classified by the RRS into low- (26.5%), medium- (46.7%), and high-risk (26.8%) groups, with 120-month renal survival rates of 93.3%, 57.2%, and 18.4%, respectively (P < 0.001). The RRS showed good discrimination but less satisfactory calibration. Therefore, a modified model with improved discrimination and calibration was developed in Chinese AAV patients, with eGFR, proportion of normal glomeruli (both as continuous variables), and IF/TA (< 25%, 25-50%, > 50%) included. Internal and external validation of the modified model were performed. Finally, an online risk prediction tool was developed based on the modified model. CONCLUSIONS: The RRS was an independent predictor of ESRD of AAV patients. The modified model could predict the probability of ESRD for AAV patients with improved performance in Chinese AAV patients.

5-Hydroxymethylcytosine profiles in plasma cell-free DNA reflect molecular characteristics of diabetic kidney disease.

Background: Diabetic kidney disease (DKD), one of the main complications of diabetes mellitus (DM), has become a frequent cause of end-stage renal disease. A clinically convenient, non-invasive approach for monitoring the development of DKD would benefit the overall life quality of patients with DM and contribute to lower medical burdens through promoting preventive interventions. Methods: We utilized 5hmC-Seal to profile genome-wide 5-hydroxymethylcytosines in plasma cell-free DNA (cfDNA). Candidate genes were identified by intersecting the differentially hydroxymethylated genes and differentially expressed genes from the GSE30528 and GSE30529. Then, a protein interaction network was constructed for the candidate genes, and the hub genes were identified by the MCODE and cytoHubba algorithm. The correlation analysis between the hydroxymethylation level of the hub genes and estimated glomerular filtration rate (eGFR) was carried out. Finally, we demonstrated differences in expression levels of the protein was verified by constructing a mouse model of DKD. In addition, we constructed a network of interactions between drugs and hub genes using the Comparative Toxicogenomics Database. Results: This study found that there were significant differences in the overall distribution of 5hmC in plasma of patients with DKD, and an alteration of hydroxymethylation levels in genomic regions involved in inflammatory pathways which participate in the immune response. The final 5 hub genes, including (CTNNB1, MYD88, CD28, VCAM1, CD44) were confirmed. Further analysis indicated that this 5-gene signature showed a good capacity to distinguish between DKD and DM, and was found that protein levels were increased in renal tissue of DKD mice. Correlation analysis indicated that the hydroxymethylation level of 5 hub genes were nagatively correlated with eGFR. Toxicogenomics analysis showed that a variety of drugs for the treatment of DKD can reduce the expression levels of 4 hub genes (CD44, MYD88, VCAM1, CTNNB1). Conclusions: The 5hmC-Seal assay was successfully applied to the plasma cfDNA samples from a cohort of DM patients with or without DKD. Altered 5hmC signatures indicate that 5hmC-Seal has the potential to be a non-invasive epigenetic tool for monitoring the development of DKD and it provides new insight for the future molecularly targeted anti-inflammation therapeutic strategies of DKD.

The history of peritoneal dialysis in China: past, present and future trends.

Peritoneal dialysis (PD) was introduced in China more than 60 years ago and has grown continuously since then. Now China leads the first of the world in number of patients on PD. In this manuscript a brief review of the history of peritoneal dialysis in China is presented; this includes a description of pioneers and their important contributions, discussion of peritoneal dialysate, the technique of the use of Tenckhoff catheter, the use of continuous ambulatory peritoneal dialysis (CAPD) and dialysis registration. Current ongoing PD research activities among Chinese PD academicians are also discussed. Finally, we present four areas of future focus: 1) the promotion of PD in rural areas where PD use is still very limited due to the lack of PD awareness and education; 2) PD quality management and continuous quality improvement (CQI) program particularly focusing on PD adequacy and patient rehabilitation; 3) development and enforcement of national standards on PD management; 4) multi-center studies to compare the benefits of PD and hemodialysis (HD) that should include survival, rehabilitation and cost-effectiveness.

Psycho-social and educational interventions for enhancing adherence to dialysis in adults with end-stage renal disease: A meta-analysis.

AIMS AND OBJECTIVES: To examine the influence of psycho-social and educational interventions on improving adherence to dialysis for patients with end-stage renal disease. BACKGROUND: Adherence to the complex regimen is poor, contributing to avoidable hospitalisation and morbidity. Psycho-social and educational interventions may be beneficial coping strategies. DESIGN: Systematic literature review and meta-analysis were conducted. METHODS: We conducted a systematic search of 8 databases from their inceptions to 16 January 2019 to identify relevant articles. Only randomised controlled trials (RCTs) were included in the analysis. The PRISMA checklist was used. RESULTS: A total of forty RCTs were included to evaluate the effect. The aggregated results of the studies showed that psycho-social and educational interventions elevated adherence rate in both peritoneal dialysis (PD) and haemodialysis (HD) patients. For physiological and biochemical indicators, meta-analysis revealed that significant post-treatment effects were evident for interdialytic weight gain (IDWG), IDWG/dry weight, serum potassium, phosphate, creatinine and blood urea nitrogen (BUN), except for albumin. In particular, subgroup analysis indicated that only the interventions carried out individually exerted significant combined effect for lowering IDWG. As for subjective measures, meta-analysis also revealed small but significant combined effects. CONCLUSIONS: The results of this meta-analysis suggest that psycho-social and educational interventions were associated with significant effects on adherence in patients receiving dialysis regimen. RELEVANCE TO CLINICAL PRACTICE: The analysis suggests that psycho-social and educational interventions should be considered as effective strategies for enhancing adherence to dialysis in adults with end-stage renal disease. The potential utility of these interventions should focus on how best to promote individually implementation in clinical practice.

The history of hemodialysis in China.

The technique of hemodialysis was introduced into China more than 50 years ago; and both research and use of clinical hemodialysis began in mid-1960s to late-1960s. A brief review of the history of hemodialysis in China is presented here, including a brief description of pioneers and their contributions, local development and use of dialyzers, hemodialysis machines, and vascular access, and dialysis management and logistics.

Infection-Related Hospitalizations in Home Hemodialysis Patients.

INTRODUCTION AND AIMS: Infection is an important cause of hospitalization and death in patients receiving hemodialysis (HD). Few studies have examined infection-related hospitalizations in home HD (HHD) population. The purpose of this study was to examine the scope of infections and the effect of HHD modality (daily home HD (DHD) and conventional home HD (CHD)) on infection-related hospitalizations in HHD patients. METHODS: The study was performed in a large cohort of HHD patients. Infection-related hospitalizations during July 1, 2005, and August 30, 2010, were abstracted from the centralized computer system. Data on demographics, dialysis vintage and dialysis modality were analyzed. RESULTS: One hundred sixty-five patients were included. During a median follow-up of 5 years, infection-related hospitalizations were observed in approximately 35.8% of all hospitalizations, which was the first cause for hospitalization. Rates of non-access-related infections were observed to be higher than that of access-related infections (1.7:1). Rates (per 100 person-years) of soft-tissue infection, pneumonia and sepsis ranged from 0.85 to 1.82 in patients on HHD. Meanwhile, access-related infection was the main cause for access-related hospitalizations (34.8%). Cox regression analysis showed that the usage of different dialysis modalities was not associated with a high risk for infection-related hospitalizations in HHD patients. CONCLUSIONS: Infection-related hospitalization occurred frequently in HHD patients. A broad range of infections, many unrelated to dialysis access, resulted in hospitalization in this population. HHD modalities were not associated with infection-related hospitalizations in HHD patients.

Effects of beta-blocker use on volume status in hemodialysis patients.

BACKGROUND: Removal and control of excess fluid with dialysis is considered critical for protection against cardiovascular sequelae. Antihypertensive agents including beta-blockers may influence hemodynamics, which may limit fluid removal during hemodialysis (HD). METHODS: Fifty chronic HD patients underwent bioimpedance measurement before and after a midweek dialysis session. Data on volume status, blood pressure, antihypertensive medications, and bioimpedance were analyzed. RESULTS: Patients in the high-volume status group used a significantly higher percentage of beta-blockers than patients in the low-volume status group (54.2 vs. 19.2%, respectively, p = 0.01). Multivariable regression revealed that the use of beta-blockers was independently positively associated with fluid overload (p < 0.05). Intradialytic muscle cramping occurred more often in the beta-blocker group than the control group (44.4 vs. 12.5%, respectively, p = 0.02). CONCLUSIONS: Our results suggest that the use of beta-blockers was associated with fluid overload in HD patients, and patients being treated with them experienced more intradialytic muscle cramping during dialysis.

Effect of multi-dimensional education on disease progression in pre-dialysis patients in China.

BACKGROUND: There is an increasing body of evidence showing that educational interventions aiming at empowering patients are successful in chronic disease management. The aim of this study was to conduct an evaluation of the systematic effectiveness of a multi-dimensional education intervention program in a group of pre-dialysis chronic kidney disease (CKD) patients. In addition, we investigated whether the outcome of the program was related with the amount of education. METHODS: We collected data retrospectively from 302 patients with CKD stages 3, 4, and 5, who were followed up from February 2006 to March 2008. The patients were divided into long-time education group and short-time education group depending on the number of provided hours of education. Survival analysis was undertaken to see if the progression of the kidney function differed between these two groups. RESULTS: The percentage of patients receiving long-time education was highest with severe degree of impairment of renal function (45.5%, 61.3%, and 66.7% in CKD stages 3, 4, and 5 groups, respectively). In a multivariate regression analysis, adjusting for age, gender, Charlson comorbidity index, and other traditional risk factors of renal failure, such as smoking, hypertension, and renal function (glomerular filtration rate), the length of time until a decline of renal function by 25% was noted and was significantly shorter in the short-time education group as compared to the long-time education group (p = 0.0334). CONCLUSION: Multi-component structured empowerment intervention is effective in pre-dialysis CKD patients and may lead to a delay in the progression of kidney disease.

Sex difference in the prevalence of left ventricular hypertrophy in dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important, independent negative predictor of cardiovascular morbidity and mortality in the general population and in dialysis patients. Previous studies suggest a sex dimorphism in the prevalence of LVH; however, this issue has never been approached in dialysis patients. METHODS: This study enrolled 237 prevalent dialysis patients: 49 on hemodialysis (HD) and 188 on peritoneal dialysis (PD) from a single center. LVH was defined by echocardiography measurements, which were normalized to body surface area (BSA) and height(2.7), respectively. RESULTS: The mean ages in HD and PD patients were 60 +/- 14 and 60 +/- 13 years, with a median dialysis vintage of 43 and 20 months, respectively. Although there was no significant difference in age, diabetes, proportion of uncontrolled hypertension, antihypertensive medication and blood pressure between male and female patients within each dialysis modality, the prevalence of LVH (whether indexed to BSA or height(2.7)) was consistently higher in females than in males. When these patients were divided into LVH or non-LVH groups, a significant difference in sex distribution was observed between the two groups (62.0% vs. 41.0% when the BSA-indexed standard was used, p < 0.01; 62.8% vs. 37.1% when the height(2.7)-indexed standard was used, p < 0.001). In logistic regression analysis, female sex was identified as a risk factor of LVH (odds ratio, OR = 2.48, 95% confidence interval, CI = 1.33-4.59; when BSA-indexed LVH was treated as dependent variable, and OR = 4.05, 95% CI = 1.96-8.38, when height(2.7)-indexed LVH was treated as dependent variable) even after adjustment for age, diabetes, blood pressure and antihypertensive medication. CONCLUSION: This study showed that the prevalence of LVH determined by echocardiography was significantly higher in female dialysis patients than in male dialysis patients. Compared with males, female patients had a 2.5- to 4-fold higher risk to develop LVH even after adjustment for other potential confounding factors, which may indicate that elderly females in the uremic scenario are more prone to develop LVH than elderly males.

Stepwise increase in the prevalence of isolated systolic hypertension with the stages of chronic kidney disease.

BACKGROUND: Hypertension is common in patients with chronic kidney disease (CKD), and isolated systolic hypertension (ISH) accounts for most patients with inadequate blood pressure (BP) control. However, it remains unclear whether the prevalence of ISH would increase with the advancement of CKD. METHODS: CKD patients of stages 3, 4 and 5 were recruited (n = 324). Based on office systolic BP (SBP) and diastolic BP (DBP), they were classified into any of the four hypertensive subtypes: normotension (SBP/DBP <140/90 mmHg), isolated diastolic hypertension (IDH, SBP <140 mmHg and DBP >or=90 mmHg), ISH (SBP >or=140 mmHg and DBP <90 mmHg) and systolic-diastolic hypertension (SDH, SBP/DBP >or=140/90 mmHg). RESULTS: The control rate was 45.7% at stage 3, which decreased with the advancement of CKD (control rate was 51.9%, 40.4% and 38.6% in stage 3, 4 and 5, respectively; P < 0.05). The prevalence of IDH changed from 5.0% to 5.3% and 0% from stage 3 to 4 and 5, while there was no significant change in the prevalence of SDH (15.0%, 14.9% and 15.7% at stage 3, 4 and 5, respectively). There was a stepwise increase in the prevalence of ISH with the stages of CKD (it was 28.1%, 39.4% and 45.7% in stage 3, 4 and 5, respectively). Logistic regression showed that age and CKD stages [compared with stage 3, stage 4 and 5 had 2.57 (95% CI 1.04-6.33) and 3.68 (95% CI 1.09-12.47) folds higher risk to develop ISH, respectively] were independent predictors of ISH. CONCLUSION: The prevalence of ISH increased correspondingly with advanced stages of CKD, which may partially contribute to the increased cardiovascular mortality during the progress of CKD.

Volume overhydration is related to endothelial dysfunction in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: In dialysis patients, volume overhydration is common and is related to increased risk of cardiovascular morbidity and mortality. However, it remains unclear whether volume overload imposes those detrimental effects through endothelial dysfunction. METHODS: In this cross-sectional study, 81 stable patients on continuous ambulatory peritoneal dialysis in a single center were recruited. Volume status was evaluated by extracellular water, assessed by bioimpedance analysis, and normalized to individual height (nECW). Endothelial function was estimated by endothelial-dependent flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. RESULTS: There were 37 male and 44 female patients (mean age 61 +/- 12 years, dialysis vintage 20 +/- 23 months). FMD in female patients was significantly higher than that in male patients (9.17% +/- 6.23% vs 6.31% +/- 5.01%, p < 0.05). FMD was negatively correlated with weight (r = -0.308, p < 0.01), body mass index (r = -0.242, p < 0.05), systolic blood pressure (r = -0.228, p < 0.05), ECW (r = -0.404, p < 0.001), and nECW (r = -0.418, p < 0.001). No correlation was found between FMD and other variables. In multiple stepwise regression analysis, calcium x phosphate product (beta = 0.422, p < 0.001), nECW (beta = -0.343, p < 0.01), and dialysis vintage (beta = -0.237, p < 0.05) were independent determinants of FMD (adjusted R(2) = 0.327 for this model). CONCLUSION: There was independent correlation between index of volume status and FMD, and higher nECW was related to worse endothelial function. The results of this study may help us understand the underlying mechanism of volume overhydration leading to increased cardiovascular morbidity and mortality in dialysis patients.

A survey of chronic kidney disease in a large hospital in China.

BACKGROUND: Chronic kidney disease (CKD) has emerged as a serious public health problem worldwide. How a CKD program should be organized, though, is still unknown. Therefore, we conducted a study to investigate the burden of CKD in a large university hospital and explore the possible approaches to care CKD appropriately in China. METHODS: This is a retrospective cohort study of all new cases of CKD in a large hospital determined by a persistently increased serum creatinine (SCr) level (>1.47 mg/dL, >130 umol/L for more than three months) measured in the hospital laboratory. An abbreviate MDRD equation was used to estimate GFR from initial SCr values. RESULTS: There was a large CKD population in the hospital. In all, 1,006 cases had definite chronic kidney disease. Excepting the nephrology department, CKD patients were distributed in 18 disciplines and departments, with the focus on outpatient department and emergency department. In total, 1,257 cases were suspicious of CKD, who had only one or two tests of serum creatinine without detailed follow-up data. Furthermore, when SCr level is higher than 442 umol/L, there were 129 cases with only one test result. CONCLUSION: CKD is a great burden in the hospital. Multidiscipline cooperation based on outpatient, emergency department, and good follow-up system establishments are necessary for appropriate CKD care. Future work is needed to explore how to organize a good CKD management program to advance the care of patients with CKD.

The role of erythrocytes phosphatidylserine exposure in anemia in peritoneal dialysis patients.

BACKGROUND: An increased red blood cell (RBC) phosphatidylserine (PS) exposure in uremic patients was found that could promote macrophage recognition and decrease RBC survival time. Furthermore, a reduced red cell life span was found to contribute anemia in patients with renal failure. It is therefore possible to hypothesize that increased PS externalization of RBC may influence renal anemia. The present study preliminarily explored the role of erythrocytes' PS exposure in anemia in uremic patients. METHOD: Erythrocyte PS exposure was measured in 67 stable patients on continuous ambulatory peritoneal dialysis (CAPD). An investigation was conducted in the relationship between the level of erythrocyte PS exposure and hemoglobin concentration. A flow-cytometric assay based on FITC-Annexin V was used to measure the PS exposure of erythrocytes. RESULTS: An inverse correlation was found between the percentage of PS-positive RBCs and hemoglobin concentration (r = -0.2601, p < 0.05). Logistic regression analysis revealed that the percentage of PS-positive RBCs was identified as a risk factor for anemia (Hazards ratio = -0.421, p < 0.05). CONCLUSION: This study found that elevated PS exposure in erythrocytes might be a risk factor for anemia and contribute to the development of anemia in peritoneal dialysis patients.