Recent advances in the involvement of epigenetics in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease that manifests as skin rash, arthritis, lymphadenopathy, and multiple organ lesions. Epigenetics, including DNA methylation, histone modification, and non-coding RNA regulation, mainly affect the function and characteristics of cells through the regulation of gene transcription or translation. Increasing evidence indicates that there are a variety of complex epigenetic effects in patients with SLE, which interfere with the differentiation and function of T, and B lymphocytes, monocytes, and neutrophils, and enhance the expression of SLE-associated pathogenic genes. This paper summarizes our currently knowledge regarding pathogenesis of SLE, and introduces current advances in the epigenetic regulation of SLE from three aspects: immune function, inflammatory response, and lupus complications. We propose that epigenetic changes could be used as potential biomarkers and therapeutic targets of SLE.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Development of a sensitive ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of nine active compounds in rat plasma and its application to a pharmacokinetic study after administration of Viscum coloratum extracts.

A simple, specific, and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous quantification of nine compounds including a new compound, rhamnazin-3-Ο-ß-D-(6″-ß-hydroxy-ß-methyglutaryl)-ß-D-glucoside-4'-Ο-ß-D-glucoside, in rat plasma using baicalin as an internal standard. The plasma samples were pretreated and extracted by protein precipitation with 0.2% formic acid in acetonitrile. The analytes were separated on a Thermo Syncronis C18 column by gradient elution with a mobile phase consisting of acetonitrile and 0.1% aqueous formic acid at a flow rate of 0.25 mL/min. The detection of the analytes was performed on an electrospray ionization interface operating in positive-ion and multiple reaction monitoring acquisition modes. The calibration curves of these analytes showed good linearity (r > 0.99) within the test ranges. The lower limit of quantification ranged from 0.4 to 20.1 ng/mL for the analytes. The intra- and interday precision and accuracy were all within ±15%, and the recoveries were higher than 80.0%. The validated method was successfully applied to a pharmacokinetic study of the nine flavonoids after administration of the Viscum coloratum extracts by intravenous injection.

Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies.

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.

Efficacy and safety of Abelmoschus manihot for primary glomerular disease: a prospective, multicenter randomized controlled clinical trial.

BACKGROUND: Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. STUDY DESIGN: Prospective, open-label, multicenter, randomized, controlled, clinical trial. SETTING & PARTICIPANTS: From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. INTERVENTIONS: A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50mg/d. The duration of intervention was 24 weeks. OUTCOMES & MEASUREMENTS: The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. RESULTS: Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of -508, -376, and -545 mg/d, respectively (P=0.003 for A manihot vs losartan and P<0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P>0.05), and there were no severe adverse events in any group. LIMITATIONS: Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. CONCLUSIONS: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

Prevalence of human papillomavirus infection in esophageal and cervical cancers in the high incidence area for the two diseases from 2007 to 2009 in Linzhou of Henan Province, Northern China.

The etiological role of human papillomavirus (HPV) in cervical cancer has been well established. However, it is inconclusive whether HPV plays the same role in esophageal carcinogenesis. In this study, we detected HPV infection in 145 frozen esophageal tissues, including 30 normal epithelium (ENOR), 37 dysplasia (DYS) and 78 invasive squamous cell carcinoma (ESCC), and in 143 frozen cervical tissues composed of 30 normal epithelium (CNOR), 38 intraepithelial neoplasia (CIN) and 75 invasive squamous cell carcinoma (CSCC). The patients and symptom-free subjects enrolled in this study were from a high-incidence area for both ESCC and CSCC, Linzhou City, Northern China, from 2007 to 2009. The HPV infection analysis was conducted by using an HPV GenoArray Test Kit. We found that the high-risk HPV types accounted for more than 90 % of the HPV-positive lesions of esophagus and cervix tissues. The prevalence of high-risk HPV types increased significantly during the progression of both esophageal and cervical carcinogenesis (positive rate in esophageal tissues: 33 % ENOR, 70 % in DYS and 69 % in ESCC; positive rate in cervical tissues: 27 % in CNOR, 82 % in CIN and 88 % in CSCC; P < 0.001, respectively). Infection with the high-risk HPV types increased the risk for both DYS and ESCC by 4-fold (DYS vs. ENOR: OR = 4.73, 95 %CI = 1.68-13.32; ESCC vs. ENOR: OR = 4.50, 95 %CI = 1.83-11.05) and increased the risk for both CIN and CSCC by 12-fold and 20-fold (CIN vs. CNOR: OR = 12.18, 95 %CI = 3.85-38.55; CSCC vs. CNOR: OR = 20.17, 95 %CI = 6.93-58.65), respectively. The prevalence of high-risk types in ESCC patients was lower than that in CSCC patients (P = 0.005) and was significantly associated with the degree of ESCC tumor infiltration (P = 0.001). HPV 16 was the most prevalent subtype in both esophageal and cervical tissues. Single HPV infection increased significantly along with the progression of ESCC and maintained a high level in cervical tissues, regardless of whether they were CNOR or CSCC tissues. Our results showed that infection with HPV, especially the high-risk types, was positively associated with both esophageal and cervical cancers, suggesting that HPV also plays a role in the etiology of ESCC in the high-incidence area.

Corrigendum: Effectiveness, safety, and treatment pattern of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia: interim analysis from a multicenter, prospective, real-world study (Actualize Study).

[This corrects the article DOI: 10.3389/fphar.2024.1398953.].

[Preparation and characterization of upconversion phosphor based on AlF3-YbF3 : Er3+].

In the present paper, AlF3-YbF3 : Er3+ was prepared by high temperature solid phase reaction, and the concentration effect of Er3+ on luminous intensity of phosphors was studied. The crystal structures of the phosphors were characterized by means of X-ray diffraction (XRD), and the upconversion luminescence properties of phosphor were studied by fluorescence emission spectra. Upon 980 nm excitation, when the Er3+ concentration was fixed to be 0.7 mol%, the maximum red emission intensities can be obtained in the sample. Furthermore, the research results showed that the fitted slope for red transition emission was 2.24, indicating that red emission is due to a two-photon excitation process.

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis with headache and kidney involvement at presentation and with arthralgia at relapse: A case report.

BACKGROUND: Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis (AAV) experience different manifestations at the initial onset and relapse. However, such cases of different initial and relapse manifestations have not been reported in myeloperoxidase (MPO)-AAV patients. CASE SUMMARY: A 52-year-old woman was admitted to our hospital because of headache. Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria, serum creatinine of 243 µmol/L, anti-MPO antibody titer of > 400 RU/mL, and positive perinuclearantineutrophil cytoplasmic antibody. Renal biopsy showed pauci-immune crescentic glomerulonephritis. The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality. Therefore, MPO-AAV was diagnosed. Corticosteroids, plasmapheresis, and cyclophosphamide as induction therapy and mycophenolate mofetil (MMF) as maintenance therapy were administered. The patient's headache disappeared; serum creatinine returned to normal; complete remission of microscopic hematuria and proteinuria was observed. Anti-MPO antibody titer reached normal limits after immunosuppressive treatment. Twenty-five months after stopping the immunosuppressive treatment, the patient relapsed with arthralgia, without neurological or renal involvement. The patient's arthralgia improved after treatment with prednisone and MMF. CONCLUSION: We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement. However, relapse presented with only arthralgia, which was completely different from the initial manifestations. This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission, when clinical manifestations at relapse are different from those at onset. Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.

Mortality and associated risk factors between young and elderly maintenance haemodialysis patients: a multicentre retrospective cohort study in China.

OBJECTIVES: Mortality and associated risk factors in young and elderly haemodialysis patients with end-stage kidney disease (ESKD) have not been well examined in China. Therefore, we aimed to assess the all-cause mortality and risk factors associated with all-cause mortality between young and elderly haemodialysis patients in China. DESIGN: A population-based multicentre retrospective cohort study. SETTING: Using the Dialysis Initiation based on Fuzzy mathematics Equation study data, patients with ESKD undergoing maintenance haemodialysis from 24 centres in China from 1 January 2008 to 30 September 2015. PARTICIPANTS: 1601 enrolled patients with ESKD were categorised into young group (18-44 years old) and elderly (≥60 years old) group. OUTCOME MEASURES: The primary outcome was all-cause mortality. We estimated overall survival using a log-rank test. Cox proportional hazard regression analysis was implemented to identify risk factors and HR associated all-cause mortality. RESULTS: During a mean follow-up of 48.17±25.59 months, of the 1601 subjects, 319 (19.92%) patients death, including 64 (9.97%) in young group and 255 (26.59%) in elderly group, respectively. The cumulative survival in elderly group was lower than young group (Log Rank tests=63.31, p<0.001). Multivariate Cox proportional hazards analysis showed the cardiovascular disease (HR, 2.393; 95% CI 1.532 to 3.735; p<0.001), cerebrovascular disease (HR, 2.542; 95% CI 1.364 to 4.739; p=0.003) and serum albumin<3.5 g/dL (HR, 1.725; 95% CI 1.091 to 2.726; p=0.020) at the haemodialysis initiation were associated with increased risk of all-cause mortality in elderly groups; however, the cardiovascular disease only was associated with increased risk of all-cause mortality in young groups. CONCLUSIONS: The all-cause mortality of elderly haemodialysis patients were higher than young haemodialysis patients in China. Identified risk factors associated all-cause mortality may inform development of age-appropriate treatment, intervention strategies and improve survival prognosis of this unique population.

Lower starting dose of roxadustat in non-dialysis-dependent chronic kidney disease patients with anaemia: a study protocol for a randomised, multicentre, open-label study.

INTRODUCTION: Roxadustat is a first-in-class oral therapy that treats chronic kidney disease (CKD) anaemia with the benefit of a novel mechanism of action that consistently corrects and maintains haemoglobin (Hb) across the spectrum of non-dialysis-dependent (NDD) CKD anaemia with an acceptable safety profile. METHODS AND ANALYSIS: This is a randomised, control, open-label, multicentre trial. About 250 adult Chinese participants with stage 3-5 CKD NDD in approximately 30 centres will be enrolled, randomly assigned in a 1:1 ratio, to receive a 16-week treatment and 4-week follow-up. The interventions for study arm are <60 kg: 50 mg TIW and ≥60 kg: 70 mg TIW; for control arm, <60 kg: 70 mg TIW and ≥60 kg: 100 mg TIW. The primary endpoint is the mean change in haemoglobin level from baseline to average over weeks 12-16. Secondary endpoints are to assess the proportion of subjects achieving an average Hb level of 100 to 120 g/L over weeks 12-16, the Hb variability, the rescue therapy requirement between two groups and the safety in two groups. The exploratory objectives are expected to evaluate the rate and time of Hb response, times of dose adjustment, the proportion of subjects with rapid Hb rise, overshooting during the treatment between two different starting dose groups, and subgroup analyses. ETHICS AND DISSEMINATION: The Medical Ethics Committee of Chinese PLA General Hospital has approved this study (No. S2020-523-05) and will be performed in accordance with the Declaration of Helsinki. Participant consent will be obtained in writing. Results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2100045359.

Anti-phospholipase A2 receptor-associated membranous nephropathy with human immunodeficiency virus infection treated with telitacicept: A case report.

BACKGROUND: The co-occurrence of Anti-phospholipase A2 receptor-associated membranous nephropathy (anti-PLA2R-MN) and human immunodeficiency virus (HIV) infection is a rare clinical scenario, presenting significant challenges in terms of management and treatment. CASE SUMMARY: A 32-year-old Chinese male diagnosed with HIV infection presented with a clinical history of proteinuria persisting for over two years. A kidney biopsy demonstrated subepithelial immune complex deposition and a thickened glomerular basement membrane, indicative of stage I-II membranous nephropathy. Immunofluorescence staining revealed granular deposition of PLA2R (3+) along the glomerular capillary loops, corroborated by a strongly positive anti-PLA2R antibody test (1:320). Initial treatment involving losartan potassium, rivaroxaban, tacrolimus, and rituximab was discontinued due to either poor effectiveness or the occurrence of adverse events. Following a regimen of weekly subcutaneous injections of telitacicept (160 mg), a marked decline in the 24 h urine protein was observed within a three-month period, accompanied by a rise in serum albumin level. No significant reductions in peripheral blood CD3+CD4+T and CD3+CD8+T cell counts were detected. The patient's physical and psychological conditions showed significant improvements, with no adverse events reported during the treatment course. CONCLUSION: Telitacicept might offer a potential therapeutic avenue for patients diagnosed with anti-PLA2R-MN concomitant with HIV infection.

Positive association of serum FUT8 activity with renal tubulointerstitial injury in IgA nephropathy patients.

BACKGROUND: α-1,6 Fucosyltransferase (FUT8) appears to play an essential role in the pathogenesis of renal fibrosis. However, it remained unknown whether FUT8 also contributed to renal fibrosis in immunoglobulin A nephropathy (IgAN). In the present study, we explored the association of serum FUT8 activity with renal tubulointerstitial injury in IgAN patients. METHODS: Serum FUT8 activity was measured in 135 IgAN patients and 68 healthy controls from January 2016 to December 2018. The relationships of serum FUT8 activity with clinical and pathological features were analyzed. RESULTS: Relative to healthy controls, IgAN patients had significantly higher serum FUT8 activity and upregulation of renal FUT8 protein (p < .05). Among IgAN patients, there was a positive correlation of serum FUT8 activity with renal FUT8 protein expression (p < .05). Multivariable logistic regression analyses showed that serum FUT8 activity was significantly associated with serum creatinine and eGFR (p < .05). Based on a cut-off value determined from ROC curve analysis, we divided IgAN patients into a low serum FUT8 activity group (≤12.2 pmol/h/mL, n = 40) and a high serum FUT8 activity group (>12.2 pmol/h/ml, n = 95). The high serum FUT8 activity group had a higher Oxford T score, increased inflammatory cell infiltration, more severe fibrosis and poor renal function (p < .05). CONCLUSION: Serum FUT8 activity was positive association with renal tubulointerstitial injury in IgAN patients.

Association between kidney and cardiac diastolic function in Chinese subjects without overt disease: correlation with ageing and inflammatory markers.

BACKGROUND: Age-related changes in kidney structure and function have been well documented. This study aimed to assess the relationship between declines of normal ageing-related kidney function and cardiac diastolic function in a healthy Chinese population. MATERIALS AND METHODS: A total of 852 healthy adults aged 30-98 years were enrolled and divided into four groups according to quartiles of estimated glomerular filtration rate (eGFR) and cystatin C (CYSC). Cardiac diastolic function was measured by ratio of peak velocity of early filling to peak velocity of atrial filling (E/A), which was derived by B-mode echocardiography. Lower E/A was defined as measures under the 25th percentile of sample distribution (0·784). RESULTS: Age was significantly associated with eGFR (r = -0·102, P < 0·01), CYSC (r = 0·544, P < 0·01) and E/A (r = -0·381, P < 0·01). Binary logistic regression analysis revealed that second, third and fourth quartile groups of CYSC and fourth quartile of eGFR were significantly associated with lower E/A in an unadjusted model. However, these associations were lost after full adjustment. CONCLUSIONS: Our results confirm that ageing is a major factor contributing to declines in both kidney and cardiac diastolic function in a healthy population. Adjustment for covariates, however, showed that normal ageing-related declines in kidney function and cardiac diastolic function are not independently linked.

The Impact of Inflammatory Immune Reactions of the Vascular Niche on Organ Fibrosis.

Inflammation is a type of defense response against tissue damage, and can be mediated by lymphocytes and macrophages. Fibrosis is induced by tissue injury and inflammation, which leads to an increase in fibrous connective tissue in organs and a decrease in organ parenchyma cells, finally leading to organ dysfunction or even failure. The vascular niche is composed of endothelial cells, pericytes, macrophages, and hematopoietic stem cells. It forms a guiding microenvironment for the behavior of adjacent cells, and mainly exists in the microcirculation, including capillaries. When an organ is damaged, the vascular niche regulates inflammation and affects the repair of organ damage in a variety of ways, such as via its angiocrine function and transformation of myofibroblasts. In this paper, the main roles of vascular niche in the process of organ fibrosis and its mechanism of promoting the progress of fibrosis through inflammatory immunoregulation are summarized. It was proposed that the vascular niche should be regarded as a new therapeutic target for organ fibrosis, suggesting that antifibrotic effects could be achieved by regulating macrophages, inhibiting endothelial-mesenchymal transition, interfering with the angiocrine function of endothelial cells, and inhibiting the transformation of pericytes into myofibroblasts, thus providing new ideas for antifibrosis drug research.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.

[Epidemiology of anticoagulation for hemodialysis patients: survey of 842 cases in seven hemodialysis centers].

OBJECTIVE: To investigate the anticoagulant methods and characters of hemodialysis patients in hospitals of Grade III Level A. METHODS: A questionnaire survey was conducted in 7 hemodialysis centers of class 3 first level general hospital in Beijing, Shenyang, Harbin, and Dalian, on the hemodialysis status, primary diseases, anticoagulation methods, and complications. RESULTS: 808 of the 842 patients (95.9%) underwent hemodialysis, and 34 patients (4.1%) were subjected to hemodialysis filtration. 606 hemodialysis patients (74.9%) used heparin as the anticoagulant, and the doses and using method were different among different centers. 223 patients (26.5%) used low molecular weight heparin (LMWH) with different kinds, doses and using methods. The underlying diseases included diabetes (15.1%), hypertension (9.4%), and other diseases (75.5%). There was no significant difference in the dosage of heparin among different diseases, while the dosage of LMWH was lower for the diabetes and hypertension patients. 171 patients (20.3%) had hemorrhagic tendency, and 67 patients (20.3%) suffered from thrombus. The dosage of heparin was lower in the patients with hemorrhagic tendency while no difference was found in the dosages of LMWH among the patients with different diseases. Antiplatelet agents were co-administrated in 172 hemodialysis patients (20.4%). The percentages of co-administration of antiplatelet for patients with thrombus and hemorrhagic tendency were 14% and 12.8% respectively. The dosages of heparin and LMWH were higher in the patients with co-administration than those without co-administration. Coagulation marker examination was conducted in only 385 patients (45.7%), and no difference in the frequency of coagulation marker examination was found among the patients with hemorrhagic tendency, thrombus, and other diseases. CONCLUSION: Heparin is the main anticoagulant in hemodialysis. The anticoagulant methodology in hemodialysis is still empirical without clotting monitor and standard for usage of anticoagulants.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Calcium-Polystyrene Sulfonate Decreases Inter-Dialytic Hyperkalemia in Patients Undergoing Maintenance Hemodialysis: A Prospective, Randomized, Crossover Study.

Hyperkalemia is a life-threatening emergency in maintenance hemodialysis (MHD) patients. This clinical trial investigated the efficacy and safety of calcium-polystyrene sulfonate (Ca-PS) in MHD patients with interdialytic hyperkalemia. A total of 58 hemodialysis patients with hyperkalemia (≥5.5 mol/L) were selected and administered either a 3-week Ca-PS (3 × 5 g/day) or a blank control following the model of a prospective, randomized, crossover clinical trial with a 1-week washout period. All patients were followed up for another 3 weeks for safety evaluations. The primary outcome was the magnitude of the change in serum potassium levels. The secondary outcomes were electrocardiography (ECG) changes and treatment safety (volume overload, electrolyte imbalance). Compared with the control group, Ca-PS treatment significantly reduced serum potassium levels (P <0.01). More patients in the Ca-PS group had lower serum potassium levels than the safety level of <5.5 mmol/L (32% for control vs. 61% for Ca-PS, P <0.01). Peaked T-wave occurred less frequently in patients in the Ca-PS group (13.8% for Ca-PS vs. 31.03% for control, P <0.01). In addition, Ca-PS reduced serum phosphorus levels with no effects on serum levels of calcium and sodium, fluid volume, blood pressure, or interdialytic weight gain. Ca-PS treatment decreases serum levels of potassium and phosphorus in MHD patients with interdialytic hyperkalemia. Ca-PS does not induce volume overload or disrupt electrolyte balance.

Effect of Conversion to CTLA4Ig on Tacrolimus-Induced Diabetic Rats.

BACKGROUND: The effect of conversion to cytotoxic T lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig) treatment on tacrolimus (TAC)-induced renal dysfunction is well known, but its effect on TAC-induced diabetes mellitus (DM) is still undetermined. In the present study, we tested the diabetogenicity of CTLA4Ig and evaluated the effect of conversion to CTLA4Ig treatment on TAC-induced diabetic rats. METHODS: We tested diabetogenicity of CTLA4Ig by escalating doses (0.25, 0.5, 1, 2, and 4 mg/kg weekly) for 4 weeks. In the conversion study, we administered TAC (1.5 mg/kg) for 3 weeks and confirmed TAC-induced DM by intraperitoneal glucose tolerance test. Thereafter, TAC administration was continued, withdrawn, or replaced by CTLA4Ig treatment (1 or 2 mg/kg) for additional 3 weeks. The effect of CTLA4Ig on TAC-induced DM in vivo and in vitro was evaluated by assessing pancreatic islet function, histopathology, oxidative stress, apoptosis, and macrophage infiltration. RESULTS: Intraperitoneal glucose tolerance test in the CTLA4Ig groups did not differ from the control group. In addition, plasma insulin level, glucose-induced insulin secretion, and islet viability were not different between the CTLA4Ig and control groups. In the conversion study, TAC withdrawal ameliorated pancreatic islet dysfunction compared with the TAC group, and conversion to CTLA4Ig further improved pancreatic islet function compared with the TAC withdrawal group. TAC-induced oxidative stress, apoptotic cell death, and infiltration of macrophages decreased with TAC withdrawal, and CTLA4Ig conversion further reduced those values. In the in vitro study, CTLA4Ig decreased TAC-induced pancreatic islet cell death and reactive oxygen species production. CONCLUSIONS: CTLA4Ig was not diabetogenic, and conversion to CTLA4Ig reduced TAC-induced pancreatic islet injury.