Publications by authors named "Xiaojiang Zhan"

26 Publications

  • Page 1 of 1

Hypomagnesemia Is a Risk Factor for Cardiovascular Disease- and Noncardiovascular Disease-Related Mortality in Peritoneal Dialysis Patients.

Blood Purif 2021 Apr 21:1-8. Epub 2021 Apr 21.

Department of Nephrology, Jiujiang No. 1 People's Hospital, Jiujiang, China.

Purpose: Recent research has shown that hypomagnesemia is associated with increased all-cause mortality in hemodialysis patients. However, the relationship between the long-term prognosis of peritoneal dialysis (PD) and the study is not yet clear. This study will analyze the effects of hypomagnesemia on all-cause, cardiovascular diseases (CVD), and non-CVD mortality in PD patients.

Method: In a retrospective cohort study, 1,004 samples were selected from 7 PD centers in China. Based on the baseline blood magnesium level at the beginning of stable dialysis, all patients were classified into blood magnesium <0.7 mmol/L group, 0.7-1.2 mmol/L group, and >1.2 mmol/L group (the end event was death). The Kaplan-Meier method was used to calculate the difference in cumulative survival rate; the Cox proportional hazard model was used to analyze the risk factors of all-cause, CVD, and non-CVD death causes.

Results: Cox multiple regression analysis results (reference comparison of 0.7-1.2 mmol/L group): patients with serum magnesium <0.7 mmol/L have a higher risk ratio of all-cause mortality (HR = 1.580, 95% CI: 1.222-2.042, p = 0.001), and it is also obvious after correction by multiple models (HR = 1.578, 95% CI: 1.196-2.083, p = 0.001). Subgroup analysis of the causes of death was as follows: CVD risk (HR = 1.628, 95% CI: 1.114-2.379, p = 0.012) and non-CVD risk (HR = 1.521, 95% CI: 1.011-2.288, p = 0.044). Further analysis of the causes of infection-related death in non-CVD is also significant (HR = 1.919, 95% CI: 1.131-3.1257, p = 0.016). On the other hand, the serum magnesium>1.2 mmol/L group had lower all-cause mortality after correction (HR = 0.687, 95% CI: 0.480-0.985, p = 0.041), and subgroup analysis of the cause of death had no statistical significance (p > 0.05).

Conclusions: Hypomagnesemia (serum magnesium <0.7 mmol/L) during stable dialysis in PD patients is a risk factor for CVD- and non-CVD-related mortality, especially infection-related death causes.
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http://dx.doi.org/10.1159/000514148DOI Listing
April 2021

PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway.

Diabetes Metab Syndr Obes 2021 25;14:355-366. Epub 2021 Jan 25.

Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China.

Introduction: Diabetic nephropathy (DN) is a metabolic disorder characterized by the accumulation of extracellular matrix (ECM). This study aims to investigate whether exists an interplay between poly (ADP-ribose) polymerase 1 (PARP-1) and sirtuin 1 (SIRT-1) in DN via AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) signaling pathway.

Methods: Eight-week-old male obese leptin-resistant (db/db) mice and nondiabetic control male C57BLKs/J (db/m) mice were used in this study. Body weight and blood glucose were evaluated after 6 h of fasting, which continues for 4 weeks. The kidney tissues were dissected for Western blot, immunofluorescence (IF) assay. Besides, PARP activity assay, MTT assay, NAD qualification, Western blot and IF were also performed to detect the level and relation of PARP-1 and SIRT-1 in mouse mesangial cells (MCs) with or without high glucose followed by inhibiting or elevating PARP-1 and SIRT-1, respectively.

Results: Western blotting shows PARP-1 and ECM marker fibronectin (FN) are upregulated while SIRT-1 is downregulated in db/db mice (p<0.05) or in mouse MCs with high glucose (p<0.05), which are significantly restored by PARP-1 inhibitor (PJ34) (p<0.05) and SIRT-1 lentiviral transfected treatment (p<0.05), or worsened by SIRT-1 inhibitor EX527 (p<0.05). PJ34 treatment (p < 0.05) or SIRT-1 overexpression (p < 0.05) could increase PGC-1α and p-AMPK levels, concomitant with down expression of FN, however, were reversed in the presence of EX527 (p<0.05).

Discussion: Our results suggest an important relationship between PARP-1 and SIRT-1 through AMPK-PGC-1α pathway, indicating a potential therapeutic method for DN.
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http://dx.doi.org/10.2147/DMSO.S291314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846827PMC
January 2021

High Neutrophil/Lymphocyte Ratio as an Independent Risk Factor for the First Occurrence of Stroke in Peritoneal Dialysis Patients.

Iran J Kidney Dis 2020 07;14(4):282-289

Department of Nephrology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Introduction: Though neutrophil/lymphocyte ratio (NLR) level appears to be related with stroke events in general population, its relationship with stroke in peritoneal dialysis (PD) patients is still uncertain. This study aims to investigate the association between NLR and the first occurrence of stroke in PD patients.

Methods: In this retrospective cohort study, 1507 PD patients were enrolled from four centers in China and stratified into tertiles of NLR levels. The incidence of the first occurrence of stroke was analyzed by Kaplan-Meier cumulative incidence curve among different NLR tertiles, competing risk analysis was used to calculate the incidence of the first occurrence of stroke in the presence of competing risk of other events, multivariable COX regression analysis was performed to estimate the hazard ratios (HRs) for the first occurrence of stroke, as well as forest plot was utilized to describe the relationship between NLR and the first occurrence of stroke in different subgroups.

Results: During follow-up, 84 new-onset stroke events were recorded. Kaplan-Meier cumulative incidence curves showed significant differences in the incidence of the first occurrence of stroke among three groups (log-rank test: P < .001). In competing risk analysis, the cumulative incidence curves for tertiles of NLR levels were highly significant for the first occurrence of stroke (P < .001), but they were not statistically different for the occurrence of other events. Compared to the lowest tertile of NLR level, the highest tertile was associated with increased risk of the first occurrence of stroke in the adjusted Cox model (HR = 2.39, 95% CI: 1.37 to 4.15; P < .05). As for forest plot, there was no interaction in all subgroups.

Conclusion: High NLR was an independent risk factor for the first occurrence of stroke in PD patients.
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July 2020

Serum C-reactive protein to albumin ratio and mortality associated with peritoneal dialysis.

Ren Fail 2020 Nov;42(1):600-606

Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Serum C-reactive protein to albumin ratio (CAR) was recently identified as a poor marker of prognosis among various populations. The current study aimed to examine the association between CAR and all-cause mortality among patients undergoing peritoneal dialysis (PD). A total of 758 patients with PD were included in this study during the period from 1 November 2005 to 28 February 2017 and followed up until 31 May 2017. The primary outcome was all-cause mortality. We used multivariate Cox proportional hazard models and Kaplan-Meier survival curves to assess the relationship between CAR and all-cause mortality in these patients. Among 758 participants, mean age was 49.1 ± 14.2 years, with 56% males and 18.6% prevalence of diabetes. Median CAR was 0.13 (interquartile range [IQR], 0.07-0.34). After 27 months (IQR, 14-40 months) of follow-up, 157 deaths had been reported. After adjusting for confounding factors, we found a significant association between serum CAR and all-cause mortality among those in the highest CAR group (hazard ratio 1.91, 95% confidence interval 1.05- 3.47,  = 0.034). In patients undergoing PD, an increase in serum CAR is independently associated with increased risk for all-cause mortality.
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http://dx.doi.org/10.1080/0886022X.2020.1783680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946068PMC
November 2020

Neutrophil to Lymphocyte Ratio Predicts Adverse Cardiovascular Outcome in Peritoneal Dialysis Patients Younger than 60 Years Old.

Mediators Inflamm 2020 20;2020:4634736. Epub 2020 May 20.

Department of Nephrology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Background: Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear.

Methods: From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR ≤ 2.74, 2.74 < NLR ≤ 3.96, and NLR > 3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups.

Results: During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR = 1.39, 95%CI = 1.01-1.93, = 0.046) and CVD mortality (HR = 1.81, 95%CI = 1.22-2.69, = 0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event ( < 0.001) and CVD mortality ( = 0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95%CI = 1.26 - 3.23, = 0.003) and CVD mortality was 2.98 (95%CI = 1.58 - 5.62, = 0.001) in the younger group (age < 60 years).

Conclusions: NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old.
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http://dx.doi.org/10.1155/2020/4634736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256716PMC
May 2020

Association between aminotransferase/alanine aminotransferase ratio and cardiovascular disease mortality in patients on peritoneal dialysis: a multi-center retrospective study.

BMC Nephrol 2020 06 1;21(1):209. Epub 2020 Jun 1.

Department of Nephrology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, No.600, Yi Shan Road, Shanghai, China.

Background: Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention.

Methods: A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model.

Results: Of eligible 1579 patients with a mean age of 49.3 ± 14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P = 0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR) = 1.50, 95% confidence index (CI) 1.09-2.07, P = 0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR = 1.43, 95%CI 1.08-2.41, P = 0.002).

Conclusions: PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.
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http://dx.doi.org/10.1186/s12882-020-01840-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268679PMC
June 2020

Monocyte to high-density lipoprotein ratio and cardiovascular events in patients on peritoneal dialysis.

Nutr Metab Cardiovasc Dis 2020 06 23;30(7):1130-1136. Epub 2020 Mar 23.

Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address:

Background And Aims: The monocyte to high-density lipoprotein cholesterol ratio (MHR) is associated with multiple cardiovascular diseases. However, the role of the MHR in predicting cardiovascular diseases in patients on peritoneal dialysis remains unclear.

Methods And Results: Eight hundred and eighty incident peritoneal dialysis patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Primary outcomes were cardiovascular events. Using the X-tile program, these patients were divided into three groups according to the MHR. Kaplan-Meier method and Cox regressions were used for survival analysis. During a median follow-up period of 26 months (interquartile range: 12-39 months), 139 cardiovascular events were recorded. After multiple adjustment, the high MHR group was associated with a 1.97-fold increase in the cardiovascular events hazard compared to that of the low group in the overall population (hazard ratio: 1.97; 95% CI, 1.19-3.28; P = 0.009). Subgroup analysis demonstrated that the association between the MHR and a higher risk of cardiovascular events was strongest in the subgroup of patients with diabetes (P for interaction = 0.004). In this subgroup, the high MHR group was found to be associated with a higher risk of cardiovascular events compared to the low group (hazard ratio: 7.69; 95% CI, 2.76-21.47).

Conclusion: This study suggests that the MHR is independently associated with the risk of cardiovascular events in patients undergoing peritoneal dialysis, and diabetes status can influence the association between the MHR and the risk of cardiovascular events.
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http://dx.doi.org/10.1016/j.numecd.2020.03.011DOI Listing
June 2020

The relationship between neutrophil-to-lymphocyte ratio and the first occurrence of pneumonia in peritoneal dialysis patients.

Clin Exp Nephrol 2020 Sep 25;24(9):770-778. Epub 2020 Apr 25.

Department of Nephrology, The Second Affiliated Hospital, Guangzhou Medical University, 250th, Chang Gang East Road, Guangzhou, 510260, China.

Background: Although neutrophil-to-lymphocyte ratio (NLR) is closely associated with pneumonia in the general population, its relationship is unclear in peritoneal dialysis (PD) patients.

Methods: This is a cohort study consisting of 739 PD patients and dividing into two groups. Kaplan-Meier curves were applied to observe the incidence of the first occurrence of pneumonia, competitive risk analysis was conducted to compare whether there was a significant difference in each NLR group in the presence of other competing events, multivariable COX regression analysis was used to evaluate the hazard ratios (HRs), as well as forest plot was used to analyze the relationship between NLR and the first occurrence of pneumonia in different subgroups.

Results: Of all the patients, 116 cases of first-time pneumonia were recorded. The first-time pneumonia incidence rate was 71.67/1000 patient-years in high NLR group, which was markedly higher than that of 45.81/1000 patient-years in low NLR group. Kaplan-Meier curves indicated significant differences in the incidence of the first occurrence of pneumonia between two groups (log-rank test p = 0.015). The competitive risk model suggested a significant difference in the cumulative incidence of first pneumonia between the two groups (p = 0.032). Compared to low NLR group, adjusted Cox model showed that high NLR group was associated with increased risk of pneumonia incidence (HR, 1.51; 95% CI 1.04-2.21; p = 0.031). Forest plot showed no interaction was found in subgroups.

Conclusions: The risk of pneumonia was significantly increasing in PD patients with high NLR, which may have a certain guiding significance for the clinic.
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http://dx.doi.org/10.1007/s10157-020-01894-9DOI Listing
September 2020

Monocyte/Lymphocyte Ratio and Cardiovascular Disease Mortality in Peritoneal Dialysis Patients.

Mediators Inflamm 2020 14;2020:9852507. Epub 2020 Feb 14.

Department of Nephrology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Objectives: The monocyte-to-lymphocyte ratio (MLR), as a new marker of the systemic inflammatory response, is associated with cardiovascular disease (CVD) mortality in the general population and hemodialysis patients. However, the association between the MLR and CVD mortality in peritoneal dialysis (PD) has received little attention.

Methods: In this multicenter retrospective cohort study, 1753 incident PD patients from November 1, 2005, to June 30, 2017, with a baseline MLR were enrolled. The primary endpoint was CVD mortality. The association of MLR with CVD mortality was assessed using a multivariable-adjusted Cox model and the Fine and Gray competing risk model.

Results: Of 1753 patients, the mean age was 51.1 ± 14.9 years, 56.9% of patients were male, and the Charlson comorbidity index was 4.29 ± 1.75. During the follow-up period of 31.2 ± 18.4 months, 368 patients died, of which 200 (54.3%) deaths were caused by CVD events. CVD mortality rates for the lowest, middle, and highest MLR tertiles were 70.6, 78.4, and 88.9 per 1000 patient-years, respectively ( < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log rank = 22.41, < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log rank = 22.41, < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log rank = 22.41, < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log rank = 22.41, < 0.001). After adjusting for confounding factors, the highest MLR tertile was significantly associated with a hazard ratio (HR) for CVD mortality of 1.45 (95% confidence interval, 1.13-2.51, = 0.016). The Fine and Gray method analysis showed that using all-cause mortality as competing risk, the highest MLR tertile remained an independent predictor of CVD mortality (HR = 1.39, 95% CI 1.10-2.47, = 0.021).

Conclusions: Higher MLR levels at the commencement of PD may be independently associated with increased CVD mortality in PD patients.
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http://dx.doi.org/10.1155/2020/9852507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048939PMC
January 2021

Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis.

Clin Gastroenterol Hepatol 2020 Oct 8;18(11):2526-2534.e9. Epub 2020 Jan 8.

Clinical Research, Celgene Corporation, Summit, New Jersey.

Background & Aims: New oral therapeutic agents are needed for patients with ulcerative colitis (UC) who are unresponsive or intolerant to conventional therapy.

Methods: We performed a double-blind, phase 2 trial of adults with active UC for 3 months or more who were naïve to biologic therapy or had been failed by, could not tolerate, or had contraindications to conventional therapies. The study was performed at 61 sites in 14 countries (screening from January 2015 through May 2017). Patients were randomly assigned to groups given apremilast 30 mg (n = 57), apremilast 40 mg (n = 55), or placebo (n = 58) twice daily for 12 weeks; patients were then randomly assigned to groups that received apremilast, 30 or 40 mg twice daily, for an additional 40 weeks. Endoscopies were performed and biopsies were collected during the screening phase, at week 12, and at week 52. Blood and fecal samples were also collected and analyzed throughout the study. The primary endpoint was clinical remission at week 12, defined as a total Mayo score of 2 or less, with no individual subscore above 1.

Results: Clinical remission was achieved at week 12 by 31.6% of patients in the 30 mg apremilast group and 12.1% of patients in the placebo group (P = .01). However, only 21.8% of patients in the 40 mg apremilast group achieved clinical remission at week 12 (P = .27 compared with placebo). Differences in clinical remission between the 30 mg and 40 mg apremilast groups were associated with differences in endoscopic improvement. Both apremilast groups had similar improvements from baseline in Mayo score components (stool frequency score, rectal bleeding score, physician's global assessment). The 30 mg and 40 mg apremilast groups had greater median percent reductions in C-reactive protein (measured by a high-sensitivity blood test) and fecal calprotectin through week 12 than the placebo group. At week 52, clinical remission was achieved by 40.4% of patients initially assigned to the apremilast 30 mg group and 32.7% of patients initially assigned to the apremilast 40 mg group. The most frequent apremilast-associated adverse events were headache and nausea.

Conclusions: Although the primary endpoint of clinical remission was not met in this phase 2 trial, a greater proportion of patients with active UC who received apremilast (30 mg or 40 mg) had improvements in clinical and endoscopic features, and markers of inflammation, at 12 weeks. Clinical remission was maintained to week 52 in up to 40% of patients who continued apremilast until that time point. ClinicalTrials.gov no: NCT02289417.
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http://dx.doi.org/10.1016/j.cgh.2019.12.032DOI Listing
October 2020

Mongersen (GED-0301) for Active Crohn's Disease: Results of a Phase 3 Study.

Am J Gastroenterol 2020 05;115(5):738-745

University of Amsterdam, Amsterdam, the Netherlands.

Introduction: The objective was to assess the efficacy and safety of GED-0301, an antisense oligodeoxynucleotide to Smad7, in active Crohn's disease (CD).

Methods: This phase 3, blinded study randomized patients (1:1:1:1) to placebo or 1 of 3 once-daily oral GED-0301 regimens: 160 mg for 12 weeks followed by 40 mg continuously or alternating placebo with 40 or 160 mg every 4 weeks through week 52.

Results: In all, 701 patients were randomized and received study medication before premature study termination; 78.6% (551/701) completed week 12, and 5.8% (41/701) completed week 52. The primary endpoint, clinical remission achievement (CD Activity Index score <150) at week 12, was attained in 22.8% of patients on GED-0301 vs 25% on placebo (P = 0.6210). At study termination, proportions of patients achieving clinical remission at week 52 were similar among individual GED-0301 groups and placebo. More placebo vs GED-0301 patients achieved endoscopic response (>50% decrease from baseline Simple Score for CD) at week 12 (18.1% vs 10.1%). Additional endoscopic endpoints were similar between groups at weeks 12 and 52. More placebo vs GED-0301 patients had clinical response (≥100-point decrease in the CD Activity Index score) at week 12 (44.4% vs 33.3%); at week 52, clinical response rates were similar. Adverse events were predominantly gastrointestinal and related to active CD, consistent with lack of clinical and endoscopic response to treatment. Two deaths occurred (GED-0301 total group) due to small intestinal obstruction and pneumonia; neither was suspected by the investigator to be treatment-related.

Discussion: GED-0301 did not demonstrate efficacy vs placebo in active CD.
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http://dx.doi.org/10.14309/ajg.0000000000000493DOI Listing
May 2020

Triglyceride to high-density lipoprotein cholesterol ratio is associated with increased mortality in older patients on peritoneal dialysis.

Lipids Health Dis 2019 Nov 15;18(1):199. Epub 2019 Nov 15.

Department of Nephrology, The First Affiliated Hospital of Nanchang University, 17# Yongwai Street, Nanchang, 330006, China.

Background: The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been suggested as a simple method to identify unfavorable cardiovascular (CV) outcomes in the general population. The aim of this study was to investigate the association between the TG/HDL-C ratio and all-cause and CV mortality in peritoneal dialysis (PD) patients.

Methods: We retrospectively analyzed patients on PD from November 1, 2005, to February 28, 2017, with a follow-up period lasting until May 31, 2017. The main outcomes were all-cause and CV mortality.

Results: Among the 973 PD patients, the mean age was 49.67 ± 14.58 (y). During a median follow-up period of 27.2 months (IQR = 13.4-41.5 months), 229 (23.5%) patients died, with 120 (12.3%) dying as a result of CV diseases. The median serum TG/HDL-C ratio was 1.11 (IQR = 0.71-1.80). In a multivariate Cox regression analysis, patients with higher TG/HDL-C ratio levels (tertile 3) had a higher incidence of CV mortality (adjusted HR = 2.12; 95% CI: 1.21-3.72; P = 0.009) and all-cause mortality (adjusted HR = 2.08; 95% CI: 1.37-3.14; P = 0.001) compared to patients in tertile 1. These associations persisted after excluding the patients who have already taken lipid-lowering medications. For older patients (> 60 years), each 1-unit higher baseline TG/HDL-C level was associated with a 48% (95% CI: 1.06-2.07; P = 0.021) increased risk of all-cause mortality and a 59% (95% CI: 1.03-2.45; P = 0.038) increased risk of CV mortality; however, this association was not observed in patients ≤60 years of age.

Conclusions: A higher serum TG/HDL-C ratio was an independent predictor of all-cause and CV mortality in PD patients. Furthermore, an elevated TG/HDL-C ratio was significantly associated with higher all-cause and CV mortality in older PD patients.
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http://dx.doi.org/10.1186/s12944-019-1147-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858755PMC
November 2019

Serum lipoprotein(a) and risk of hemorrhagic stroke among incident peritoneal dialysis patients: a large study from a single center in China.

Ren Fail 2019 Nov;41(1):800-807

Department of Respiration, The First Affiliated Hospital of Nanchang University , Nanchang , China.

This retrospective study investigated whether baseline serum lipoprotein(a) (Lp(a)) may predict subsequent stroke in patients under chronic peritoneal dialysis (PD). Eight hundred and sixty incident PD patients, treated from 1 November 2005 to 28 February 2017, were enrolled, and followed until discontinuation of PD, death, or 31 May 2017. Hemorrhagic or ischemic stroke was the primary outcome. The population was stratified by baseline serum Lp(a) tertile. The risk of each stroke subtype was analyzed using the Cox proportional hazard models. Adjustments were made for: age; gender; history of stroke and hypertension; systolic blood pressure; lipid-lowering, antiplatelet and antihypertensive medications; laboratory profiles including hemoglobin, serum albumin, calcium, triglyceride, total and low-density lipoprotein cholesterol; and apolipoprotein A1. Among the 860 participants, 19.3% and 4.1% had diabetes mellitus and a history of stroke, respectively. The median baseline serum Lp(a) was 328 (172-585) mg/L. After 28 (14-41) months of follow-up, 33 (3.84%) and 12 (1.40%) patients developed hemorrhagic and ischemic stroke, respectively. Participants in the highest Lp(a) tertile had a significantly lower risk of hemorrhagic stroke compared with those in the lowest tertile (hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1-0.86;  = .026); the rates of ischemic stroke were comparable among the tertiles. Each 10 mg/L rise in serum Lp(a) was associated with a 2% (95% CI 0.96-1;  = .033) lower risk of hemorrhagic stroke. Among patients with incident PD, a higher serum Lp(a) level may predict a lower risk of hemorrhagic stroke.
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http://dx.doi.org/10.1080/0886022X.2019.1659151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746282PMC
November 2019

Intrarenal microRNA signature related to the fibrosis process in chronic kidney disease: identification and functional validation of key miRNAs.

BMC Nephrol 2019 08 27;20(1):336. Epub 2019 Aug 27.

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, China.

Background: Though the roles of microRNAs (miRNAs) in renal diseases have been extensively investigated, a thorough screening and comparison of miRNAs among different types of chronic kidney disease (CKD) has never been performed.

Methods: The intrarenal miRNAs were profiled from fresh kidney tissues of patients with biopsy-proven minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS) and diabetic nephropathy (DN) by using microarray. Commonly dysregulated miRNAs were validated by real-time PCR using paraffin-embedded renal tissues from all three types of CKD patients as well as mouse unilateral ureteral obstruction (UUO) model. Two novel miRNAs were selected and annotations of their target genes were performed using GO and KEGG pathway enrichment analysis. Biological functions of three two candidate miRNAs were explored in TGF-β1-induced cell model using human kidney proximal tubular cells (HK-2).

Results: The kidney biopsy samples of three disease types represent different levels of damage and fibrosis, which were the mildest in MCD, moderate in FSGS, and the most severe in DN. 116 miRNAs were identified to be commonly dysregulated, including 40 up-regulated and 76 down-regulated in CKD tissues as compared with healthy donor kidney biopsy tissues. Two novel miRNAs, hsa-miR-3607-3p and hsa-miR-4709-3p, were verified as consistently differentially expressed among all three types of patient samples as well as in mouse model. In vitro, hsa-miR-3607-3p was repressed while hsa-miR-4709-3p was induced by TGF-β1 treatment. Inhibition of hsa-miR-3607-3p or overexpression of hsa-miR-4709-3p promoted TGF-β1-induced migration and F-actin assembling in HK-2 cells, which are characteristics of epithelial-mesenchymal transition (EMT). Further study identified that ITGB8 and CALM3 were the bona fide target genes of hsa-miR-3607-3p and hsa-miR-4709-3p respectively.

Conclusions: The present identify a unique miRNAs profile that probably relates to the common fibrosis process of CKD. Results of our study suggest that hsa-miR-3607-3p and hsa-miR-4709-3p may represent as promising therapeutic targets against kidney fibrosis.
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http://dx.doi.org/10.1186/s12882-019-1512-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712721PMC
August 2019

Serum alkaline phosphatase levels correlate with long-term mortality solely in peritoneal dialysis patients with residual renal function.

Ren Fail 2019 Nov;41(1):718-725

a Department of Nephrology, The First Affiliated Hospital of Nanchang University , Nanchang , China.

Increased serum alkaline phosphatase (ALP) is predictive of a higher mortality in patients with end-stage renal disease. However, it remains unknown whether residual renal function (RRF) influences the outcome-association of serum ALP among peritoneal dialysis (PD) patients. A total of 650 incident PD patients receiving PD catheter implantation in an institute between 1 November 2005 and 28 February 2017 were retrospectively enrolled. These patients were divided into groups with and without RRF (RRF and non-RRF groups) and those with serum ALP levels in tertiles. The Kaplan-Meier method and multivariate Cox proportional hazard models were used to analyze their outcomes based on RRF and serum ALP levels. These 650 patients had a mean age of 49.4 ± 14.0 years old, their median ALP level was 74 U/L (interquartile range (IQR): 59-98). After 28-month (IQR: 14-41) follow-up, 80 patients in RRF group and 40 patients in non-RRF group died. PD patients with the highest serum ALP tertile had significant lower survival ( = .014), when compared to other patients in the RRF group. However, this relationship was not observed in patients in the non-RRF group. After multivariate adjustment, in the RRF group, patients with the highest ALP tertile had a significantly higher risk of mortality (hazard ratio (HR): 2.26, 95% confidence interval (CI): 1.06-4.82,  = .034). Each 10-U/L increase in ALP level was associated with a 4% (HR: 1.04, 95% CI: 1.00-1.08,  = .045) higher mortality risk. Higher serum ALP level is associated with increased mortality solely in PD patients with RRF.
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http://dx.doi.org/10.1080/0886022X.2019.1646662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713195PMC
November 2019

Comparison of risk of stroke in patients treated with peritoneal dialysis and hemodialysis: a systematic review and meta-analysis.

Ren Fail 2019 Nov;41(1):650-656

a Department of Nephrology , The First Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China.

Accumulating evidence has demonstrated that dialysis patients are at increased risk for stroke. However, the impact of dialysis modalities on stroke risk remains controversial. We conducted a systematic review and meta-analysis to determine the effect of peritoneal dialysis (PD) and hemodialysis (HD) on stroke risk. A systematic search of PubMed, EMBASE, and Web of Science was performed to identify articles comparing the stroke outcomes of dialysis patients. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and synthesized to examine stroke outcomes, including ischemic stroke, hemorrhagic stroke, and overall stroke. The search yielded five studies composed of 1,219,245 patients that were evaluated in the final analysis. The results showed that PD was associated with a lower risk for hemorrhagic stroke compared with HD (HR = 0.78; 95% CI: 0.69-0.88;  < 0.001). For ischemic stroke, the results showed that PD was associated with a higher risk compared with HD among the non-Asian patients (HR = 1.13; 95% CI: 1.05-1.23;  = 0.002), but there were no significant differences between PD and HD for the Asian patients. Similarly, there were no significant differences between the effects of the PD and HD approaches on overall stroke risk. We observed that PD patients were less likely to develop hemorrhagic stroke than HD patients, and the risk for ischemic stroke was significantly higher for PD patients than for HD patients among the non-Asian patients. However, our findings could be biased due to the heterogeneity of the included studies.
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http://dx.doi.org/10.1080/0886022X.2019.1632210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691832PMC
November 2019

Relationship between serum bilirubin levels and mortality in patients on peritoneal dialysis.

Ren Fail 2019 Nov;41(1):532-539

a Department of Nephrology , The First Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China.

Studies have shown that the serum total bilirubin (TBil) is associated with the mortality of the general population and of hemodialysis patients. However, few studies have examined the associations of the direct bilirubin (DBil) and indirect bilirubin (IBil) with the mortality of peritoneal dialysis (PD) patients. This was a retrospective cohort study. Clinical and laboratory data were collected from 740 PD patients. The primary endpoint was 5-year all-cause mortality. Survival analysis was performed using the Kaplan-Meier method with the log-rank test. The mortality hazard ratio was evaluated using Cox regression models. Among the 740 PD patients, the mean age was 49.9 ± 15.0 years, 54.9% were men, and 20.3% had diabetes. During the median follow-up period of 28 months (interquartile range, 14-41 months), 178 patients died. Kaplan-Meier analysis revealed that all-cause mortality was higher in the patients in the higher TBil group than in the lower TBil group (25.6% vs. 18.3%,  = .017) and in patients in the higher IBil group than in the lower IBil group (24.3% vs. 19%,  = .026). Multivariate analysis showed that compared with the lower TBil group, the 5-year mortality risk was higher in the higher TBil group (HR = 1.69, 95% CI: 1.11-2.56,  = .014). Similarly, there was a 56% higher risk of 5-year mortality in the higher IBil group than in the lower IBil group (HR = 1.56, 95% CI: 1.04-2.34,  = .032). However, no such associations were observed between the DBil and the mortality risk. The baseline serum TBil and IBil levels were significantly associated with 5-year all-cause mortality among PD patients.
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http://dx.doi.org/10.1080/0886022X.2019.1628062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598530PMC
November 2019

Novel long non-coding RNA AV310809 promotes TGF-β1 induced epithelial-mesenchymal transition of human peritoneal mesothelial cells via activation of the Wnt2/β-catenin signaling pathway.

Biochem Biophys Res Commun 2019 05 30;513(1):119-126. Epub 2019 Mar 30.

Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China. Electronic address:

Peritoneal fibrosis (PF) is a crucial cause of the loss of peritoneal function in patients with peritoneal dialysis. To better understand the underlying mechanism of PF, we selected AV310809, which is one of the most highly upregulated lncRNA in fibrotic peritoneal tissue, for functional analysis. We used co-expression analysis to explore the potential relationship between AV310809 and coding genes. qPCR, WB and IF were applied to evaluate the expression and localization of AV310809, epithelial markers and proteins involved in the Wnt2/β-catenin signaling pathway. The interaction between AV310809 and β-catenin was examined using an RNA pulldown assay. The expression level of AV310809 was upregulated in fibrotic peritoneum and TGF-β1 induced EMT in HPMCs. Ectopic overexpression of AV310809 promoted EMT and activated the Wnt2/β-catenin signaling pathway. Furthermore, we demonstrated that AV310809 could interact with β-catenin and blocking β-catenin inhibited the augmentation of EMT by AV310809. These findings indicated that AV310809 promoted TGF-β1-induced EMT in HPMCs through the activation of the Wnt2/β-catenin signaling pathway, possibly by targeting β-catenin. We suggest that AV310809 may be a new therapeutic target for the management of peritoneal dialysis-associated PF.
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http://dx.doi.org/10.1016/j.bbrc.2019.03.071DOI Listing
May 2019

MiR-200a ameliorates peritoneal fibrosis and functional deterioration in a rat model of peritoneal dialysis.

Int Urol Nephrol 2019 May 19;51(5):889-896. Epub 2019 Mar 19.

Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Peritoneal fibrosis is recognised as the main cause of the technical failure of peritoneal dialysis (PD), and currently, there are no specific and effective anti-fibrosis therapies. We have found that miR-200a is down-regulated in a rat model of PD-related peritoneal fibrosis (PF) and could inhibit transforming growth factor beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells by target ZEB1/2. However, its treatment role in vivo is still largely unclear. In this study, we examined the therapeutic potential for miR-200a on PD-related PF in a rat model of PD induced by daily infusion of 4.25% dextrose-containing dialysate. Male Sprague-Dawley rats were divided into four groups: control group, PD group, PD + miR-agomir-NC group, and PD + miR-200a-agomir group (n = 5 in each group). MiR-200a agomir was delivered into the peritoneum by intra-peritoneal injection on days 10 and 20 after PD. We found that treatment with miR-200a agomir significantly reduced the collagen volume fraction (CVF) of the peritoneum and prevented peritoneal dysfunction. The up-regulation of the EMT marker (decreased E-cadherin and increased α-smooth muscle actin) and extracellular matrix (fibronectin and collagen I) was significantly ameliorated by miR-200a in the PD + miR-200a-agomir group. Furthermore, we demonstrated that miR-200a inhibition of PF in vivo was associated with the suppression of ZEB1 and 2, which were proved to be the target of miR-200a in our previous study. In conclusion, results from the present study suggest that treatment with miR-200a may represent a novel and effective therapy for PD-related PF.
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http://dx.doi.org/10.1007/s11255-019-02122-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499761PMC
May 2019

Celastrol antagonizes high glucose-evoked podocyte injury, inflammation and insulin resistance by restoring the HO-1-mediated autophagy pathway.

Mol Immunol 2018 12 12;104:61-68. Epub 2018 Nov 12.

Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China. Electronic address:

Diabetic nephropathy (DN) contributes to end-stage renal disease and kidney dysfunction with a proverbial feature of podocyte injury. Inflammation and insulin resistance is recently implicated in the pathogenesis of diabetic kidney injury. Celastrol exerts critical roles in inflammatory diseases and injury progression. However, its function and mechanism in DN remains elusive. Here, celastrol dose-dependently restored podocyte viability under high glucose (HG) conditions, but with little cytotoxicity in podocyte. Preconditioning with celastrol counteracted HG-evoked cell apoptosis, LDH release, ROS production and podocyte depletion. Additionally, HG-elevated high transcripts and secretions of pro-inflammatory cytokines were reversed following celastrol treatment, including IL-1β, TNF-α, IL-6. Simultaneously, the inhibitory effects of HG on insulin-triggered glucose uptake and nephrin expression were overturned after celastrol exposure. Intriguingly, celastrol restored HG-induced deficiency of autophagy pathway. Nevertheless, blocking the autophagy signaling by its antagonist 3-MA muted celastrol-protected against HG-evoked cell injury, inflammation and insulin resistance. Importantly, celastrol enhanced heme oxygenase-1 (HO-1) expression in HG-stimulated podocytes. Notably, HO-1 cessation depressed autophagy pathway activation and subsequently blunted beneficial effects of celastrol on HG-exposed podocytes. These finding suggest that celastrol may protect against HG-induced podocyte injury, inflammation and insulin resistance by restoring HO-1-mediated autophagy pathway, implying a promising therapeutic strategy against DN.
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http://dx.doi.org/10.1016/j.molimm.2018.10.021DOI Listing
December 2018

Apolipoprotein B/apolipoprotein A1 ratio and mortality among incident peritoneal dialysis patients.

Lipids Health Dis 2018 May 17;17(1):117. Epub 2018 May 17.

Department of Nephrology, The First Affiliated Hospital of Nanchang University, 17# yongwai street, Nanchang, 330006, Jiangxi, China.

Background: To investigate the association between the ratio of apolipoprotein B (apo B) / apolipoprotein A1 (apo A1) with all-cause mortality and cardiovascular events in peritoneal dialysis (PD) patients.

Methods: Eight hundred and sixty incident PD patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Outcomes were all-cause mortality and cardiovascular events. Associations between the apo B/apo A1 ratio with all-cause mortality and cardiovascular events were evaluated using multivariable-adjusted Cox models.

Results: Of the 860 patients, the mean age was 49.9 ± 14.5 years, 57.6% were men, and 19.3% were diabetic patients. The median apo B/apo A1 ratio was 0.65 (range: 0.22-2.24). During a median follow-up period of 27 months (interquartile range, 13 - 41 months), 202 deaths, and 145 cardiovascular events were recorded. After adjustment for age, sex, body mass index, diabetes, cardiovascular disease, systolic blood pressure, total Kt/V, estimated glomerular filtration rate, hemoglobin level, neutrophil to lymphocyte ratio and albumin, triglyceride, and cholesterol, as well as the use of lipid-lowering agents, the highest apo B/apo A1 ratio tertile was significantly associated with a hazard ratio for all-cause mortality of 1.60 (95% CI: 1.02 to 2.49, P = 0.040) and for cardiovascular events of 2.04 (95% CI: 1.21 to 3.44, P = 0.008).

Conclusion: An increased apo B/apo A1 ratio was independently associated with all-cause mortality and cardiovascular events in PD patients.
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http://dx.doi.org/10.1186/s12944-018-0771-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960196PMC
May 2018

MiR-200a negatively regulates TGF-β-induced epithelial-mesenchymal transition of peritoneal mesothelial cells by targeting ZEB1/2 expression.

Am J Physiol Renal Physiol 2018 06 10;314(6):F1087-F1095. Epub 2018 Jan 10.

Department of Nephrology, The First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi , China.

Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells was recognized as the key process of peritoneal fibrosis, which is a major cause of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unknown. In this study, we found that miR-200a was significantly downregulated in peritoneal tissues with fibrosis in a rat model of PD. In vitro, transforming growth factor (TGF)-β-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in human peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR-200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2), suggesting a close link between miR-200a and ZEB1/2 in TGF-β-induced EMT. It was further demonstrated that miR-200a was able to bind to the 3'UTR of ZEB1/2, and overexpression of miR-200a blocked TGF-β-induced upregulation of ZEB1/2 and, therefore, inhibited EMT and collagen expression. In contrast, overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression in HMPCs. In conclusion, miR-200a could negatively regulate TGF-β-induced EMT by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS indicates the therapeutic potential of miR-200a as a treatment for peritoneal fibrosis associated with PD.
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http://dx.doi.org/10.1152/ajprenal.00566.2016DOI Listing
June 2018

Effects of Mongersen (GED-0301) on Endoscopic and Clinical Outcomes in Patients With Active Crohn's Disease.

Gastroenterology 2018 01 25;154(1):61-64.e6. Epub 2017 Aug 25.

Icahn School of Medicine at Mount Sinai, New York, New York.

GED-0301 is an antisense oligodeoxynucleotide with a sequence complementary to the Smad7 mRNA transcript. Smad7 is a negative regulator of transforming growth factor-β, which is increased in the intestinal mucosa of patients with active Crohn's disease (CD). We randomly assigned 63 CD patients to 4-, 8-, or 12-week treatment groups receiving oral GED-0301 (160 mg/day). The primary objective was to determine GED-0301's effect on endoscopic CD measures; secondary objectives included effects on clinical activity. Endoscopic improvement was observed in 37% of participants with evaluable endoscopy results at week 12. At week 12, 32% (4 weeks), 35% (8 weeks), and 48% (12 weeks) of patients receiving GED-0301 were in remission (CD activity index score <150); corresponding reductions from baseline in mean CD activity index scores were -124, -112, and -133 points. No new safety signals were observed. These findings support a GED-0301 benefit in active CD. ClinicalTrials.gov no: NCT02367183.
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http://dx.doi.org/10.1053/j.gastro.2017.08.035DOI Listing
January 2018

Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3).

Ann Rheum Dis 2016 Jun 20;75(6):1065-73. Epub 2016 Jan 20.

Combined Rheumatology Practice, University of New South Wales, Kogarah, New South Wales, Australia.

Objective: To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.

Methods: Patients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks.

Results: At week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%; p=0.0295 and p<0.0001, respectively), and mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (-0.20) versus placebo (-0.07; p=0.0073). In patients with baseline psoriasis body surface area involvement ≥3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%; p=0.0098) at week 16. At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment. Most adverse events were mild to moderate in severity; the most common were diarrhoea, nausea, headache and upper respiratory tract infection.

Conclusions: Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. Apremilast was generally well tolerated and demonstrated an acceptable safety profile.

Trial Registration Number: NCT01212770.
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http://dx.doi.org/10.1136/annrheumdis-2015-207963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893110PMC
June 2016

Prevalence and risk factors of CKD in Chinese patients with periodontal disease.

PLoS One 2013 7;8(8):e70767. Epub 2013 Aug 7.

Department of Periodontology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, China.

Background: Periodontal disease is common among adults and is associated with an increasing risk of chronic kidney disease (CKD). We aimed to investigate the prevalence and risk factors of CKD in patients with periodontal disease in China.

Methods: In the current cross-sectional study, patients with periodontal disease were included from Guangdong Provincial Stomatological Hospital between March 2011 and August 2011. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), the presence of albuminuria, or hematuria. All patients with periodontal disease underwent a periodontal examination, including periodontal probing pocket depth, gingival recession, and clinical attachment level by Florida Probe. They completed a questionnaire and had blood and urine samples taken. The adjusted prevalence of indicators of kidney damage was calculated and risk factors associated with CKD were analyzed.

Results: A total of 1392 patients with periodontal disease were invited to participate this study and 1268 completed the survey and examination. After adjusting for age and sex, the prevalence of reduced eGFR, albuminuria, and hematuria was 2.7% (95% CI 1.7-3.7), 6.7% (95% CI 5.5-8.1) and 10.9% (95% CI 9.2-12.5), respectively. The adjusted prevalence of CKD was 18.2% (95% CI 16.2-20.3). Age, male, diabetes, hypertension, history of CKD, hyperuricemia, and interleukin-6 levels (≥7.54 ng/L) were independent risk factors for reduced eGFR. Female, diabetes, hypertension, history of CKD, hyperuricemia, high level of cholesterol, and high sensitivity C-reactive protein (hsCRP) (≥ 1.03 mg/L) and TNF-α levels (≥ 1.12 ng/L) were independently associated with an increased risk of albuminuria. Female, lower education (
Conclusions: 18.2% of Chinese patients with periodontal disease have proteinuria, hematuria, or reduced eGFR, indicating the presence of kidney damage. Whether prevention or treatment of periodontal disease can reduce the high prevalence of CKD, however, remains to be further investigated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070767PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737364PMC
August 2014

Comparisons of methods for analysis of repeated binary responses with missing data.

J Biopharm Stat 2011 May;21(3):371-92

Late Development Statistics, Merck Research Laboratories, North Wales, Pennsylvania, USA.

It is important yet challenging to choose an appropriate analysis method for the analysis of repeated binary responses with missing data. The conventional method using the last observation carried forward (LOCF) approach can be biased in both parameter estimates and hypothesis tests. The generalized estimating equations (GEE) method is valid only when missing data are missing completely at random, which may not be satisfied in many clinical trials. Several random-effects models based on likelihood or pseudo-likelihood methods and multiple-imputation-based methods have been proposed in the literature. In this paper, we evaluate the random-effects models with full- or pseudo-likelihood methods, GEE, and several multiple-imputation approaches. Simulations are used to compare the results and performance among these methods under different simulation settings.
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http://dx.doi.org/10.1080/10543401003687129DOI Listing
May 2011