BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective:By summarizing and analyzing the results of the inter-laboratory quality evaluation of hematoxylin-eosin(HE)staining organized by the Pathological Equipment Branch of Chinese Medical Equipment Association,to timely identify problems and summarize experience,and to improve the level of HE staining and the ability of inter-laboratory quality control management in medical institutions.Methods:The results of the national routine pathology HE staining inter-laboratory quality evaluation sponsored by the Pathology Equipment Branch of the China Medical Equipment Association in 2022 and 2023 were collected,and the grades,tissue types and evaluation results of the evaluation units participating in the inter-laboratory quality evaluation of HE staining were statistically analyzed.Results:In 2022,a total of 165 evaluation units participated in the inter-laboratory quality evaluation of HE staining with valid results,and 156 in 2023.HE stained tissue types included uterine tissue,gastrointestinal tissue,lung tissue,and breast tissue.The qualified rates of HE staining of the participating units in 2023 were 82.42％(136/165),which was higher than that of 90.38％(141/156)in 2022,the difference was statistically significant(x2=4.30,P＜0.05).There was no statistically significant difference in the staining pass rate of the tertiary hospitals participating in the evaluation in 2023 compared with that in 2022(P＞0.05).The qualified rates of secondary hospitals and non-public medical institutions were 100％and 92.37％,respectively,which were higher than those in 2022,the difference was statistically significant(x2=3.91,5.93,P＜0.05).The qualified rates of inter-laboratory quality evaluation of uterine tissue,gastrointestinal tissue,lung tissue and breast tissue evaluated in 2023 were 92.31％(144/156),91.03％(142/156),91.03％(142/156)and 91.67％(143/156),respectively,which were higher than those in 2022,the differences between uterine tissue and gastrointestinal tissue in two-year evaluation were statistically significant(x2=6.33,5.93,P＜0.05).There was no statistically significant difference in the two-year evaluation between lung tissue and breast tissue(P＞0.05).Conclusion:The continuous participation of medical institutions in the inter-laboratory quality evaluation activities of HE staining can improve the quality of routine pathological HE staining,improve the level of pathological technicians,and reduce the staining differences caused by different unit properties and specimen types.

Objective To investigate the efficacy of leflunomide combined with prednisone in the induction therapy of proliferative lupus nephritis (LN).Methods A prospective,multicenter,randomized controlled clinical trial was conducted in patients with biopsy-proved proliferative lupus nephritis recruited from 15 renal centers from 2013 to 2015.Patients were randomized to two groups.Oral leflunomide or intravenous cyclophosphamide was given to patients in each group.Both groups received a tapering course of oral prednisone therapy.All patients were followed up for 24 weeks.The blood biochemistry,urine index,clinical curative effect and adverse reaction were recorded and analyzed statistically.Results A total of 100 patients were enrolled in this clinical trial,including 48 patients in leflunomide group and 52 patients in cyclophosphamide group.After 24 weeks,the overall response rate was 79％ (95％ CI 67％-90％) in the leflunomide group and 69％ (95％ CI 56％-82％) in the cyclophosphamide group.23％ (95％CI 11％-35％) of patients in leflunomide group showed complete remission compared with 27％ (95％CI 24％-30％) in cyclophosphamide group (P=0.35).The levels of 24-hr urine protein excretion,SLEDAI and anti-dsDNA antibody titers were decreased in patients treated with leflunomide group after 24-weeks treatment.And the levels of serum albumin and complement 3 after treatment were significantly higher compared with these before treatment.There was also no significant difference in changes of 24-hr urine protein excretion,SLEDAI score,anti-dsDNA antibody titers,serum albumin and complement C3 levels after treatment between two groups.Incidence of adverse events did not differ between the leflunomide and cyclophosphamide group.Conclusions Leflunomide combined with prednisone showed same efficacy compared with cyclophosphamide as induction therapy for lupus nephritis.Leflunomide might be an useful medicine in the induction therapy of lupus nephritis.

Objective Idiopathic membranous nephropathy(IMN)is a common cause of nephrotic syndrome in adults,and the prognosis of IMN varies among individuals. The aim of this study was to investigate the prognosis and risk factors,especially the prognostic indicators in kidney patholo?gies for IMN. Methods Patients diagnosed as IMN by renal biopsy from January 2006 to December 2011 were collected and those who finished at least 12 months of follow?up were enrolled in this study. The clinical and renal pathological indicators were collected and the correlation between the pathological indicators and the prognosis was analyzed. Results Totally 137 patients were enrolled in this study,18 patients(13.14%)reached the follow up ending point(defined as eGFR<30 mL/min). The prognosis of kidney function was poor in IMN patients with interstitial fibrosis,tubular atrophy and severe vascular sclerosis and those who were older at disease onset and demonstrated to have higher MAP,poorer renal function,intersti?tial fibrosis,tubular atrophy and worse vascular sclerosis. Conclusion Renal pathological characteristics during renal biopsy were correlated with the renal prognosis of IMN. Severe interstitial fibrosis,tubular atrophy and vascular sclerosis were identified as risk factors for the poor prognosis of re?nal function in IMN patients.

AIM: To investigate the correlation of hepatitis B virus X protein (HBx) with renal tubular epithelialcell apoptosis in hepatitis B virus-associated glomerulonephritis (HBVGN) and the possible signaling mechanism. METHODS: The activation of JAK2/STAT3 signal pathway and the expression of apoptosis -related proteins in humankindey proximal tubular epithelial cells (HK-2 cells) were determined by Western blotting after transfection with HBx eukaryoticexpression vector.The cell proliferation was observed by CCK-8 assay.The cell apoptosis was analyzed by the imagingof HO33342 staining, transmission electron microscopy and flow cytometry with Annexin V /PI double staining.RESULTS:After transfection of the target gene HBx, the expression levels of both p-JAK2 and p-STAT3 were significantly increased.At the same time, the cell proliferation was obviously inhibited, and the apoptotic rate was increased.After incubationwith AG490, the JAK2/STAT3 signal pathway was partially blocked, and the cell apoptosis induced by HBx was reduced. CONCLUSION: HBx up-regulates the activation of JAK2/STAT3 signal pathway to induce renal tubular epithelialcell apoptosis, which is possibly involved in the pathogenic mechanism that HBV directly damages nephridial tissue .

Objective To analyze the occurrence and clinical features of chronic kidney disease (CKD) in the ICU patients and identify the possible risk factors.Methods A retrospective study was performed in 2281 ICU patients enrolled from Shengjing hospital between January 2007 and December 2010,in which 1860 cases had complete data and were followed-up,the other 421 cases were excluded for the reasons of dying,suffering from CKD originally,lacking complete data and missing.The cases were divided into CKD and non-CKD groups according to SCODRED and CKD diagnosis standards.Assessment was performed to screen risk factors of CKD.Results There were obvious differences between CKD and non-CKD groups at age,pregnancy,AKI and liver function (P ＜0.05).The CKD's annual morbidity rate of ICU patients was 20％-30％,and the incidence showed an increasing trend with time.Age,pregnancy,AKI,APACHE-Ⅱ score,invasive diagnosis and treatment,mechanical ventilation,organ failure and kidney-hurt drugs were risk factors for CKD in the ICU patients.Conclusions The morbidity rate of CKD in the ICU patients is high,and the number of CKD patients show an increasing trend with time.Age,APACHE-Ⅱ score ＞ 15,the number of failed organs ≥2,the variety of kidney-hurt drug≥2,pregnancy,AKI,the number of invasive diagnosis and treatment≥3,mechanical ventilation are independent risk factors of CKD in the ICU patients.

Objective To investigate the effect of aliskiren on type 2 diabetic nephropathy in db/db mice.Methods Eight-week old db/db and db/m mice were subjected to right nephrectomy to hasten the development of diabetic nephropathy.At age of 16 weeks,they were divided into four groups:db/m group (normal control),db/db group ( diabetic control),db/db+ A3 group (db/db mice treated with aliskiren 3 mg·kg-1d-1) and db/db+A25 group (db/db mice treated with aliskiren 25 mg kg-1 d-1).Body weight,blood glucose,glycosylated hemoglobin,proteinuria and systolic blood pressure were measured before and after treatment.After treatment,renal histological examination by PAS staining,TGF-β1 and PAI-1 protein by ELISA,expression of ColⅣ and FN protein by immunofluorescence,mRNA expression of TGF-β1,PAI-1,ColⅣ,FN and renin by real time PCR,renin activity and angiotensin Ⅱ level by radioimmunoassay were performed.Results Treatment for 4 weeks of aliskiren at a dose of 25 mg kg-1 d-1 markedly decreased urinary albumin excretion,glomerulosclerosis and suppressed synthesis of TGF-β1,PAI-1,Col Ⅳ,FN without inducing significantl change in systolic blood pressure,compared to those of db/db group (all P＜0.05).Aliskiren also suppressed renin activity and angiotensin Ⅱ level in renal cortex (all P＜0.05).Conclusion Aliskiren protects against type 2 diabetic nephropathy.

Objective To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. Methods A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was chosed as controlled drug. The duration of treatment was 7-14 days in both groups. Results A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for perprotocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS)population were 79.7% and 77.4%, the effective rates were 95.2% and 96. 7%, and the bacterial clearance were 96. 7% and 97. 5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety.The drug adverse events occurred both in 10. 1%, and drug adverse reactions accurred in 7. 8% and 7.9%patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prologation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P＞0.05).Conclusions Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.

Objective To investigate whether sodium ferulate（SF）can prevent contrast-induced renal injury in chronic renal insufficiency patients and its possible mechanism.Methods Eighty-six patients with chronic renal insufficiency,whose serum creatinine（Scr）levels ranged from 132 μmol/L to 358 μmol/L were randomly divided into control group（saline 100 ml iv drip）and SF treatment group（treatment group,saline 100 ml ＋ 0.3 g SF iv drop）based on sufficient hydration.Patients were treated with the above-mentioned protocols at 3 h be-fore the administration of contrast medium and in the following 3 days,Scr,plasma malondialdehyde（MDA）and urine nitric oxide（NO）were measured before angiography and on the third day after angiography.Results The incidence rate of contrast-induced nephropathy（CIN）in control group was significantly higher than that in treatment group（P 〈 0.05）.The contrast medium increased Scr levels and plasma MDA,and decreased urine NO excretion,while SF treatment attenuated the above changes（P 〈 0.05）.Conclusion The preventive effect of SF on con-trast-induced renal injury might be associated with its suppressive effect on endothelin,increasing renal production of NO and anti-oxydation.

Objective To investigate the efficacy and the adverse effect of mycophenolate mofetil(MMF)in HBV associated glomerulonephritis.Methods Twenty patients with HBV-GN diagnosed by renal biopsy were treated with MMF.The initial dosage of MMF was 1.5 g/d.The dosage was reduced to 1.0 g/d when 24 h excretion of urinary protein decreased to 0.5 g/d.Blood routine test,hepatic and renal function,plasma albumin,serum triglyceride and cholesterol,24 h urinary protein excretion,HBV DNA were performed before and after 2,3,6,9 months' treatment.Results Twenty-four-hour urinary protein excretion was significantly reduced by the treatment with mycophenolate mofetil(P