Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

Effects of Entry Grades on Students' Academic Performance Under Homogeneous Educational Resources.

Background: A minor difference in college entrance examination scores can result in vastly different educational resources in China, so it has been debated whether it is the difference in the student population or the difference in educational resources that causes the difference in medical graduates. We aimed to evaluate the effects of entry grades on students' academic performance under homogeneous educational resources. Methods: Students in grade 2016 with 13-point difference in the average admission scores of 2 medicine schools in Sun Yat-sen University were educated in mixed classes and were taught with the same educators during the 5 years of undergraduate period. The grades, graduation, and postgraduate enrollment rates of the students were compared between the two campuses. Results: The average admission scores for Shenzhen Campus (SZC) students are 13 points lower than those of Guangzhou North Campus (GZNC) (613 points vs 626 points). After 5 years of homogeneous education, comparing the GZNC students with the SZC students, there were no significant differences in the average total score (80.2 ± 4.6 vs 80.0 ± 5.6, P = 0.691), the average compulsory course (78.9 ± 3.4 vs 78.4 ± 6.1, P = 0.438), the average core course score (78.8 ± 7.4 vs 78.7 ± 5.0, P=0.860) and the average clerkship score (85.1 ± 7.2 vs 84.6 ± 2.7, P=0.275). However, the completion rate for SZC was higher than for GZNC (93.94% vs 86.27%, P=0.009). There was no statistical difference in postgraduate enrolment between the two institutions (P=0.758). Conclusion: Given the same educational resources, more medical students with lower entrance scores completed their studies and achieved the same percentage of postgraduate acceptance. This finding suggests that a key component of improving the quality of medical higher education in China may be to further rationalize the allocation of high-quality educational resources, rather than to pursuing students with high entrance examination scores.

1. Undergraduates from two medical schools with different average admission scores were educated with the same resources during the 5-year undergraduate period. After 5 years of homogeneous education, more students with lower entrance scores completed their studies and achieved the same percentage of postgraduate acceptance. 2. The key to improving educational quality is to optimize educational resources, not just to recruit high-scoring students.

Differences of clinicopathological characteristics and outcomes of IgA nephropathy patients with and without nephrotic syndrome.

PURPOSE: To evaluate the differences in clinicopathological features and outcomes of IgA nephropathy (IgAN) patients with and without nephrotic syndrome. METHODS: In this retrospective cohort study, IgAN patients from January 2006 to December 2011 in the First Affiliated Hospital of Sun Yat-sen University were enrolled and followed up to Dec 31, 2013. Logistic and Cox regression were conducted to evaluate the associated factors of nephrotic syndrome (NS) and its relation with outcomes of creatinine doubling and progression to end-stage kidney disease (ESKD). RESULTS: A total of 1413 patients with IgAN were enrolled in this study, 57 (4.0%) of whom exhibited NS. Meanwhile, 13 (22.8%) of NS IgAN patients had minimal change disease (MCD). Logistic regression showed that more presence of hypertension, less glomerular sclerosis, less tubular atrophy/interstitial fibrosis, and lower density of IgA deposition in mesangial region were significantly associated with NS IgAN that were independent of age and gender. In addition, a total of 921 patients (890 with non-NS IgAN and 31 with NS IgAN) were followed up to Dec 31, 2013. After adjusting for age, sex, baseline estimated glomerular rate, hypertension and hemoglobin, no significant difference was observed in outcomes of serum creatinine doubling and ESKD between patients with or without NS IgAN. CONCLUSIONS: Prevalence of NS IgAN patients was 4.0%, and 22.8% of them had MCD. Patients with NS IgAN had more severe clinical but less severe pathological features. However, outcomes of serum creatinine doubling and ESKD were not significantly different between patients with or without NS IgAN.

Comparative analysis between the safety and efficacy of oral corticosteroids versus corticosteroids pulse therapies in IgA nephropathy.

OBJECTIVE: This study retrospectively compared the safety and efficacy of oral corticosteroid therapy (OCT) and corticosteroid pulse therapy (CPT) in the treatment of IgA nephropathy. METHODS: One ninety-two patients were diagnosed with IgA nephropathy and had an estimated glomerular filtration rate > 15mL/min/1.73m2 and 24-h urine protein level of 0.75-3.5g. Patients were divided into CPT and OCT groups according to the treatment protocol. The differences in the efficacy and safety between the two groups were assessed by logistic regression analysis and propensity score matching. RESULTS: Significant differences at baseline, including 24-h urine protein level and eGFR, were observed between the two groups. Logistic regression analysis indicated that the remission rate increased significantly, while the incidences of total adverse events and infections decreased in CPT group compared with the OCT group after adjusting the potential confounding factors. Forty-seven pairs of subjects are matched by using propensity score matching with similar baseline data. The results indicate that the total remission rate and complete remission rate were significantly higher, while the incidences of total adverse events were lower (p = 0.008) in the CPT group than in the OCT group. The subgroup analysis showed that CPT group was more likely to achieve remission in patients with initial 24-h urine protein levels falling into the range of 2-3.5 g and Oxford Classification of S1 or C1/2 (p < 0.05). CONCLUSION: Among patients with IgA nephropathy and 24-h urine protein levels of 0.75-3.5g, CPT may be more effective than OCT in reducing urinary protein levels and improving renal function with a lower incidence of adverse events.

Mediation of serum albumin in the association of serum potassium with mortality in Chinese dialysis patients: a prospective cohort study.

BACKGROUND: The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration. METHODS: This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities. RESULTS: A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7 ±â€Š14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ±â€Š0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found ( P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation. CONCLUSIONS: Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.

Clinical characteristics and outcomes of antibiotic-associated encephalopathy in patients with end-stage kidney disease.

OBJECTIVE: End-stage kidney disease (ESKD) patients have a higher risk of antibiotic-associated encephalopathy (AAE) than other patients. We aimed to evaluate the prevalence, risk factors and outcomes of AAE in ESKD patients. METHOD: A retrospective study of ESKD patients treated with intravenous antibiotics in our hospital from Jan. 1, 2006, to Dec. 31, 2015 was performed. AAE was diagnosed by the modified Delphi method. Control individuals were randomly selected from the remaining patients who did not exhibit neurologic symptoms. Logistic regression analysis was used to identify risk factors for AAE as well as the association between AAE and outcome. RESULT: A total of 2104 patients were included in the study. The prevalence of AAE in our study was 4.4% (92/2104). The multivariate logistic regression analysis revealed that anuria (OR = 8.04, 95% CI: 4.13-15.65, p < 0.001), history of central nervous system disorder (OR = 3.03, 95% CI: 1.21-7.56, p = 0.018) and hypoalbuminemia (OR= 1.87, 95% CI: 1.01-3.47, p = 0.046) were independent factors associated with AAE in ESKD patients. After adjustment for confounders, AAE was associated with composite outcomes of in-hospital mortality and treatment withdrawal (OR = 4.36, 95% CI: 2.09-9.10, p < 0.001). CONCLUSION: The prevalence of AAE was 4.4% in ESKD patients and varied among different antibiotics. Anuria, history of central nervous system disorder and hypoalbuminemia were associated with AAE in ESKD patients. AAE is associated with worse outcomes in ESKD patients.

Association of Ratio of Apolipoprotein B to Apolipoprotein A1 With Survival in Peritoneal Dialysis.

Background: Although the ratio of apolipoprotein B (apo B) to apolipoprotein A1 (apo A1) (apo B/apo A1) seems to be associated with mortality in hemodialysis (HD) patients, the association of apo B/apo A1 ratio with death remains not clear in peritoneal dialysis (PD) patients. Aims: The study targets to examine the relationship of apo B/apo A1 ratio with survival in patients receiving PD treatment. Methods: In this single-center prospective observational cohort study, we enrolled 1,616 patients receiving PD treatment with a median follow-up time of 47.6 months. We used a multivariable Cox proportional hazards model to examine the relationship between apo B/apo A1 ratio and cardiovascular (CV) and all-cause mortality. The association of apo B/apo A1 ratio with atherosclerotic and non-atherosclerotic CV mortality was further evaluated by competing risk regression models. Results: During the follow-up, 508 (31.4%) patients died, 249 (49.0%) died from CV events, of which 149 (59.8%) were atherosclerotic CV mortality. In multivariable models, for 1-SD increase in apo B/apo A1 ratio level, the adjusted hazard ratios for CV and all-cause mortality were 1.26 [95% confidence interval (CI), 1.07-1.47; P = 0.005] and 1.20 (95% CI, 1.07-1.35; P = 0.003), respectively. The adjusted subdistribution hazard ratios for atherosclerotic and non-atherosclerotic CV mortality were 1.43 (95% CI, 1.19-1.73; P < 0.001) and 0.85 (95% CI, 0.64-1.13; P = 0.256), respectively. For quartile analysis, patients in quartile 4 had higher CV, all-cause, and atherosclerotic CV mortality compared with those in quartile 1. Moreover, apo B/apo A1 ratio had a diabetes-related difference in CV, all-cause, and atherosclerotic CV mortality. Conclusion: Elevated apo B/apo A1 ratio level was significantly associated with CV, all-cause, and atherosclerotic CV mortality in patients undergoing PD. Moreover, the association was especially statistically significant in patients with diabetes.

Serum Phosphorus and Albumin in Patients Undergoing Peritoneal Dialysis: Interaction and Association With Mortality.

Hyperphosphatemia and hypoalbuminemia confer worse clinical outcomes, whether these risk factors interact to predispose to mortality is unclear. In this prospective cohort study, 2,118 patients undergoing incident continuous ambulatory peritoneal dialysis (CAPD) were enrolled and categorized into four groups based on the changing point regarding mortality at 1.5 mmol/L for serum phosphorus and 35 g/L for serum albumin. Risks of all-cause and cardiovascular mortality were examined independently and interactively in overall and subgroups. There was no association between serum phosphorus with all-cause and cardiovascular mortality, but significant interactions (p = 0.02) between phosphorus and albumin existed in overall population. Patients in subgroup with high phosphorus and low albumin were at greater risk of all-cause (HR 1.95, 95%CI 1.27-2.98, p = 0.002) but not cardiovascular mortality (HR 0.37, 95%CI 0.10-1.33, p = 0.13), as compared to those with low phosphorus and high albumin. In contrast, patients with both low parameters had a higher risk of all-cause (HR 1.75, 95%CI 1.22-2.50, p = 0.002) and cardiovascular mortality (HR 1.92, 95%CI 1.07-3.45, p = 0.03). Notably, an elevated risk of both all-cause and cardiovascular mortality was observed in those with low serum albumin, irrespective of phosphorus levels, suggesting low albumin may be useful to identify a higher-risk subgroup of patients undergoing CAPD with different serum phosphorus levels.

Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Association between urinary VEGFA and renal pathology of IgA nephropathy patients.

BACKGROUND: Renal biopsy remains the golden standard for diagnosing and monitoring IgA nephropathy (IgAN). Vascular endothelial growth factor A (VEGFA) was crucial for the survival of glomerular cells. Our aim was to screen the expression pattern of urinary, circulating and renal VEGFA in IgAN patients to reveal their relationship with renal pathology and outcomes. METHODS: Baseline VEGFA levels were determined with ELISA, real-time PCR and immunohistochemistry. Associations between VEGFA expression and clinical-pathological parameters, and renal outcomes were evaluated. RESULTS: Compared with healthy controls, urinary VEGFA level was obviously elevated in IgAN patients (76.19 ± 63.67 pg/mg Cr vs 146.67 ± 232.71 pg/mg Cr, p = 0.0291) and not correlated with serum VEGFA level. Baseline urinary VEGFA was significantly associated with gender and tubular atrophy/interstitial fibrosis by stepwise multivariate regression analysis. Urinary VEGFA was higher in male patients accompanied with higher serum creatinine, larger proportion of hypertension and recurrent hematuria than in female patients. In the kidney of IgAN patients, VEGFA were robustly expressed in the parietal epithelial cells, podocytes, mesangial cells and tubular epithelial cells. After a follow-up duration of 38.53 ± 27.14 months, IgAN patients with higher urinary VEGFA level were found to have a poorer renal outcome of renal replacement therapy (HR = 1.027, p = 0.037) or composite outcome (HR = 1.023, p = 0.039) after adjusting for confounders. CONCLUSIONS: Increased urinary VEGFA might reflect certain renal pathology and, although not fully specific, still could be served as a valuable noninvasive indicator in predicting renal progression of IgAN.

Non-high-density lipoprotein cholesterol and mortality among peritoneal dialysis patients.

BACKGROUND: The association between non-high-density lipoprotein cholesterol (non-HDL-C) and mortality in patients undergoing peritoneal dialysis (PD) is unclear. OBJECTIVE: The aim of this study was to evaluate the association of non-HDL-C with cardiovascular (CV) and all-cause mortality in PD patients. METHODS: We conducted a prospective cohort study. A total of 1,616 incident PD patients from a single PD center in South China were followed for a median of 47.6 months. The independent association of non-HDL-C with CV and all-cause mortality was evaluated by a Cox regression analysis. RESULTS: During the follow-up period, 508 (31.4%) patients died, of which 249 (49.0%) were due to CV events. Atherosclerotic CV mortality accounted for 59.8% of CV mortality. In multivariable models, for 1-SD increase in non-HDL-C level, the hazard ratios (HRs) for CV and all-cause mortality were 1.52  [95% confidence interval (CI), 1.32-1.75; P < 0.001)] and 1.24 (95% CI, 1.12-1.39; P < 0.001), respectively. Furthermore, non-HDL-C was positively associated with atherosclerotic CV mortality (HR, 1.29; 95% CI, 1.09-1.52; P = 0.004) but not associated with nonatherosclerotic CV mortality (HR, 0.79; 95% CI, 0.59-1.05; P = 0.108). The quartile analyses showed a similar pattern to the continuous variable analyses of non-HDL-C levels for CV and all-cause mortality but did not demonstrate statistical significance for atherosclerotic or nonatherosclerotic CV mortality. CONCLUSION: An elevated non-HDL-C level was independently associated with an increased risk of CV mortality, especially atherosclerotic CV mortality, and all-cause mortality in incident PD patients.

Association between monocyte count to high-density lipoprotein cholesterol ratio and mortality in patients undergoing peritoneal dialysis.

BACKGROUND AND AIMS: Previous studies had demonstrated that elevated monocyte count to high-density lipoprotein cholesterol ratio (MHR), a novel marker of inflammation, was associated with higher cardiovascular events and mortality in patients with pre-dialysis chronic kidney disease, diabetes, and coronary heart disease. However, the association between MHR and mortality in patients undergoing peritoneal dialysis (PD) has received little attention. The aim of this study was to investigate the association between MHR and all-cause and cardiovascular mortality in PD patients. METHODS AND RESULTS: In this single center retrospective cohort study, PD patients who had catheter insertion in our PD center from January 1, 2006 to December 31, 2016 were enrolled. All patients were divided into three groups according to the tertiles of baseline MHR levels and followed up until December 31, 2018. The associations of MHR levels with all-cause and cardiovascular mortality were assessed by using Cox proportional hazards models. Of 1584 patients, mean age was 46.02 ± 14.65 years, 60.1% were male, and 24.2% had diabetes. The mean MHR level was 0.39 ± 0.23. During a median follow up time of 45.6 (24.6-71.8) months, 349 patients died, and 181 deaths were caused by cardiovascular disease. After adjusting for confounders, the highest MHR tertile was significantly associated with all-cause and cardiovascular mortality with a hazard ratio of 1.43 (95%CI = 1.06-1.93, P = 0.019), 1.54 (95%CI = 1.01-2.35, P = 0.046), respectively. CONCLUSION: Higher MHR level was an independent risk factor for all-cause and cardiovascular mortality in PD patients.

Elevated Serum Trimethylamine N-Oxide Levels Are Associated with Mortality in Male Patients on Peritoneal Dialysis.

BACKGROUND: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. METHODS: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. RESULTS: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8-61.0) µM. During a median follow-up of 63.7 months (IQR, 43.9-87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01-1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07-1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02-1.94; p = 0.038) in men but not in women. CONCLUSIONS: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.

Prevalence, risk factors and impact on outcomes of 30-day unexpected rehospitalization in incident peritoneal dialysis patients.

BACKGROUND: Rehospitalization is a major problem for end stage renal disease (ESRD) populations. However, researches on 30-day unexpected rehospitalzation of incident peritoneal dialysis (PD) patients were limited. This study aimed to investigate the prevalence, risk factors and impact on outcomes of 30-day unexpected rehospitalization in incident PD patients. METHODS: This was a retrospective cohort study. Patients who accepted PD catheter implantation in our centre from Jan 1, 2006 to Dec 31, 2013 and regular follow-up were included. The demographic characteristics, laboratory parameters, and rehospitalization data were collected and analyzed. The primary outcome was all-cause mortality, and the secondary outcomes included cardiovascular disease (CVD) mortality and technical failure. RESULTS: Totally 1632 patients (46.9 ± 15.3 years old, 60.1% male, 25.6% with diabetes) were included. Among them, 149 (9.1%) had a 30-day unexpected rehospitalization after discharge. PD-related peritonitis (n = 48, 32.2%), catheter malfunction (n = 30, 20.1%) and severe fluid overload (n = 19, 12.8%) were the top three causes for the rehospitalization. Multivariate logistic regression analysis showed that length of index hospital stays [Odds ratio (OR) =1.02, 95% confidence interval (CI) 1.00-1.03, P = 0.036) and hyponatremia (OR = 1.85, 95% CI 1.06-3.24, P = 0.031) were independently associated with the rehospitalization. Multivariate Cox regression analysis indicated that 30-day rehospitalization was an independent risk factor for all-cause mortality [Hazard ratio (HR) =1.52, 95% CI 1.07-2.16, P = 0.019) and CVD mortality (HR = 1.73, 95% CI 1.03-2.90, P = 0.038). CONCLUSIONS: The prevalence of 30-day unexpected rehospitalization for incident PD patients in our centre was 9.1%. The top three causes for the rehospitalization were PD-related peritonitis, catheter malfunction and severe fluid overload. Thirty-day unexpected rehospitalization increased the risk of all-cause mortality and CVD mortality for PD patients.

Risk factors and outcomes of cardiovascular disease readmission within the first year after dialysis in peritoneal dialysis patients.

BACKGROUND: In the first year of dialysis, patients are vulnerable to cardiovascular disease (CVD) hospitalization, but knowledge regarding the risk factors and long-term outcomes of cardiovascular readmission within the first year after dialysis in incident continuous ambulatory peritoneal dialysis (CAPD) patients is limited. METHODS: This retrospective cohort study was conducted in incident CAPD patients. The demographic characteristics, laboratory parameters, and CVD readmission were collected and analyzed. The primary outcome was all-cause mortality, and the secondary outcomes included CVD mortality, infection-related mortality and technique failure. A logistic regression was used to identify the risk factors associated with CVD readmission within the first year after dialysis. Cox proportional hazards models were used to evaluate the association between CVD readmission and the outcomes. RESULTS: In total, 1589 peritoneal dialysis (PD) patients were included in this study, of whom 120 (7.6%) patients had at least one episode of CVD readmission within the first year after dialysis initiation. Advanced age, CVD history, and a lower level of serum albumin were independently associated with CVD readmission. CVD readmission within the first year after dialysis was significantly associated with all-cause (HR 2.66, 95%CI 1.91-3.70, p < 0.001) and CVD (HR 3.42, 95%CI 2.20-5.31, p < 0.001) mortality, but not infection-related mortality or technique failure, after adjusting for confounders. CONCLUSIONS: Our findings suggest that an advanced age, a history of CVD, and a lower level of serum albumin were independently associated with CVD readmission. Moreover, CVD readmission was associated with all-cause and cardiovascular mortality in incident CAPD patients.

Vitamin D (1,25-(OH)2D3) Improves Endothelial Progenitor Cells Function via Enhanced NO Secretion in Systemic Lupus Erythematosus.

It has been proven that vitamin D was decreased and function of circulating endothelial progenitor cells (EPCs) was injured in systemic lupus erythematosus (SLE) patients. However, the effect of vitamin D on the function of EPCs in vitro and its mechanism need further study. Therefore, we investigated whether vitamin D improved the function of EPCs in vitro. The peripheral blood mononuclear cells of the participants were isolated from SLE patients and control subjects and cultured to EPCs. After the EPCs were treated with vitamin D (1,25-(OH)2D3), we evaluated the number, migratory and proliferative activities, and nitric oxide (NO) production of EPCs in vitro and detected vascular endothelial function by flow-mediated dilatation (FMD). We found that vitamin D in a dose-dependent manner improved number and migratory and proliferative activities of EPCs from SLE patients. Additionally, vitamin D upregulated NO production from EPCs in vitro. A significant correlation between the FMD and plasma NO level was found. There was also a correlation between number, migration, and proliferation of EPCs and NO production. Thus, the present findings indicated that vitamin D improved the function of EPCs from SLE patients via NO secretion.

Rationale and design for Lowering-hyperUricaemia treatment on cardiovascular outcoMes In peritoNeal diAlysis patients: a prospective, multicentre, double-blind, randomised controlled trial (LUMINA).

INTRODUCTION: The prevalence of hyperuricaemia in peritoneal dialysis patients is quite high. Studies have demonstrated a correlation between hyperuricaemia and cardiovascular disease and treatment of hyperuricaemia reportedly reduces cardiovascular risk in patients with chronic kidney disease. However, whether hyperuricaemia treatment benefits cardiovascular outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is not yet known. METHODS AND ANALYSES: This prospective, multicentre, double-blind, randomised controlled trial was designed to evaluate the effects of hyperuricaemia treatment on cardiovascular event risk in CAPD patients. Based on a power of 80%, with type I error α=0.05, two-sided test and 1:1 parallel control study, considering a dropout rate of 20%, a total of 548 eligible patients are expected to be randomly assigned to either the hyperuricaemia treatment group (febuxostat) or control group (placebo). ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University and the ethics committees of other participating institutions. Written informed consent will be obtained from potential trial participants or authorised surrogates.The findings of the study will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT03200210. 25 June 2017. The trial was started on 13 July 2017, and is expected to end by 31 December 2022. Till 20 Jan 2020, a total of 548 patients have been recruited. PROTOCOL VERSION: The protocol version number and date are YLT-1604-V2.0 and 15 December 2016.

Plasma fibrinogen and mortality in patients undergoing peritoneal dialysis: a prospective cohort study.

BACKGROUND: Plasma fibrinogen is significantly associated with cardiovascular (CV) events and mortality in the general population. However, the association between plasma fibrinogen and mortality in patients undergoing peritoneal dialysis (PD) is unclear. METHODS: This was a prospective cohort study. A total of 1603 incident PD patients from a single center in South China were followed for a median of 46.7 months. A Cox regression analysis was used to evaluate the independent association of plasma fibrinogen with CV and all-cause mortality. Models were adjusted for age, sex, smoking, a history of CV events, diabetes, body mass index, systolic blood pressure, hemoglobin, blood platelet count, serum potassium, serum albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, estimated glomerular filtration rate, antiplatelet agents and lipid-lowering drugs. RESULTS: The mean age was 47.4 ± 15.3 years, 955 (59.6%) patients were male, 319 (19.9%) had a history of CV events, and 410 (25.6%) had diabetes. The average plasma fibrinogen level was 4.12 ± 1.38 g/L. Of the 474 (29.6%) patients who died during follow-up, 235 (49.6%) died due to CV events. In multivariable models, the adjusted hazard ratios (HRs) for quartile 1, quartile 3, and quartile 4 versus quartile 2 were 1.18 (95% confidence interval [CI], 0.72-1.95, P = 0.51), 1.47 (95% CI, 0.93-2.33, P = 0.10), and 1.78 (95% CI, 1.15-2.77, P = 0.01) for CV mortality and 1.20 (95% CI, 0.86-1.68, P = 0.28), 1.29 (95% CI, 0.93-1.78, P = 0.13), and 1.53 (95% CI, 1.12-2.09, P = 0.007) for all-cause mortality, respectively. A nonlinear relationship between plasma fibrinogen and CV and all-cause mortality was observed. CONCLUSIONS: An elevated plasma fibrinogen level was significantly associated with an increased risk of CV and all-cause mortality in patients undergoing PD.

Elevated Osteoprotegerin Concentration Predicts Increased Risk of Cardiovascular Mortality in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Studies have shown inconsistent results regarding the association between osteoprotegerin (OPG) concentration and cardiovascular mortality in patients with chronic kidney disease (CKD). This systematic review and meta-analysis aims to investigate the association between OPG concentration and cardiovascular mortality in patients with CKD. METHODS: Between January 1970 and February 2020, the PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies investigating the association between OPG concentration and cardiovascular mortality in patients with CKD. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated using random effects models. RESULTS: In total, 10 studies comprising 2,120 patients (including 1,723 receiving dialysis) with CKD were included. The included studies were considered to be of fair to high quality. Patients in the highest OPG concentration group had a significantly higher risk of cardiovascular mortality (4 studies; adjusted HR, 2.05; 95% CI, 1.39-3.00) than patients in the low OPG concentration group. An increase of 1 pmol/L in OPG concentration was associated with a 4% increased risk of cardiovascular mortality (6 studies; adjusted HR, 1.04; 95% CI, 1.02-1.07). CONCLUSION: Elevated OPG concentrations are associated with an increased risk of cardiovascular death in patients with CKD.