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 To investigate the labeling of dialysis-related information in the instructions of drugs for systemic use in patients with end-stage renal disease undergoing hemodialysis,and to provide reference for further standardization and im-provement of drug instructions.Methods Collected the information on pharmacokinetics and drug dose adjustment in hemodi-alysis patients with end-stage renal disease from the instructions of chemicals and biologics used systemically in XuanWu hospital's formulary from January to March 2023.Classified and compared the labeling rates of the corresponding information of the originally developed drugs and generic drugs,imported drugs and domestic drugs;Drugs eliminated by non-renal route,or with mo-lecular weight≥5 000,or binding rate of plasma protein ≥ 60％,or drug distribution volume＞360L were classified as"non-dialysis group",and other drugs were classified as"dialysis group",compared the labeling rate of corresponding information of drugs in"dialysis group"and"non-dialysis group";and compared the labeling rate and content with relevant information in Lexicomp and Micromedex.Results Among the 930 drug instructions,the labeling rates of drug dialysis clearance,drug adjustment,and ex-plicit drug adjustment plan were 16.67％,25.16％,and 24.52％.There was no significant difference in the labeling rate of dialysis-related information between original and generic drugs,and imported and domestic drugs.There was a significant difference in the labeling rate of dialysis-related information between the"dialyzable group"and the"non-dialyzable group"(P＜0.01).The differ-ence in the labeling rate of dialysis related information between the investigated drug instructions and the corresponding drugs in Lexicomp or Micromedex was statistically significant(P＜0.01).Conclusion Attention should be paid to the lack of informa-tion and unclear labeling of hemodialysis patients with end-stage renal disease in the drug instructions by relevant departments.

Objective To investigate the labeling of dialysis-related information in the instructions of drugs for systemic use in patients with end-stage renal disease undergoing hemodialysis,and to provide reference for further standardization and im-provement of drug instructions.Methods Collected the information on pharmacokinetics and drug dose adjustment in hemodi-alysis patients with end-stage renal disease from the instructions of chemicals and biologics used systemically in XuanWu hospital's formulary from January to March 2023.Classified and compared the labeling rates of the corresponding information of the originally developed drugs and generic drugs,imported drugs and domestic drugs;Drugs eliminated by non-renal route,or with mo-lecular weight≥5 000,or binding rate of plasma protein ≥ 60％,or drug distribution volume＞360L were classified as"non-dialysis group",and other drugs were classified as"dialysis group",compared the labeling rate of corresponding information of drugs in"dialysis group"and"non-dialysis group";and compared the labeling rate and content with relevant information in Lexicomp and Micromedex.Results Among the 930 drug instructions,the labeling rates of drug dialysis clearance,drug adjustment,and ex-plicit drug adjustment plan were 16.67％,25.16％,and 24.52％.There was no significant difference in the labeling rate of dialysis-related information between original and generic drugs,and imported and domestic drugs.There was a significant difference in the labeling rate of dialysis-related information between the"dialyzable group"and the"non-dialyzable group"(P＜0.01).The differ-ence in the labeling rate of dialysis related information between the investigated drug instructions and the corresponding drugs in Lexicomp or Micromedex was statistically significant(P＜0.01).Conclusion Attention should be paid to the lack of informa-tion and unclear labeling of hemodialysis patients with end-stage renal disease in the drug instructions by relevant departments.

The silent lung that occurs during the perioperative period is characterized by rapid onset,rapid progression,and high mortality.This article reports a case of a 62-year-old patient with a left lower lung nodule who underwent lower lung segmentectomy under thoracoscopy and was assisted with tracheal intubation using rocuronium.21 minutes after the first administration,the patient presented with increased airway pressure,difficult ventilation,a"steel lung"feel,and symptoms similar to silent lung.Subsequently,80 mg of methylprednisolone and 50 μg of epinephrine(in divided doses)were injected intravenously,but no relief was observed,and the blood oxygen saturation decreased to 38％.In this case,after giving another 1 mg of epinephrine,the airway pressure gradually decreased to 33 cmH2O,and the blood oxygen saturation gradually increased.Considering that airway spasm might be caused by multiple intubation stimulations,additional rocuronium bromide was added to allow for reintubation.However,the patient again experienced increased airway pressure and difficulty in ventilation prior to intubation.The clinical pharmacist conducted a correlation evaluation of this adverse event and considered the result as possible.The mechanism,rescue and prevention of silent lung induced by rocuronium was also discussed in the case report.A thorough anesthesia assessment should be conducted prior to surgery,and an appropriate anesthesia induction plan should be formulated.Once an adverse event occurs,it should be promptly identified and treated.

A 50-year-old male patient was scheduled to undergo epiglottic mass resection under general anesthesia due to an epiglottic cyst. Before anesthesia induction, the patient received dexamethasone, methylprednisolone, midazolam, and ondansetron by intravenous injectionin sequence. After 2 minutes, the patient complained of palpitations, abdominal spasmodic pain, cyanosis of the lips, and patchy changes in the skin on the chest and body. The electrocardiogram monitor showed a heart rate of 175 beats per minute, but his cuff blood pressure cannot be measured. His blood oxygen saturation was 0.76, and he did not respond to the call afterwards. Oxygen through a face mask and pressure ventilation, intravenous injection of 20 mg of esmolol twice were given immediately. The patient′s consciousness recovered, the heart rate gradually decreased to 60 beats per minute (sinus rhythm), and the blood pressure increased to 74/50 mmHg. Continuous IV pumping of norepinephrine 8 μg/min was given. After 25 minutes, the patient′s bedside electrocardiogram showed atrial fibrillation with ventricular differential conduction, myocardial injury or acute myocardial infarction, and QT interval prolongation. Then intravenous injection of furosemide 40 mg was given, his above symptoms were improved,his blood pressure recovered to 110-120/70 mmHg, blood oxygen saturation was 1.00, the skin spots on his chest and body disappeared, and his abdominal pain was alleviated. Anesthesiologists and pharmacists evaluated the patient′s adverse reactions and considered that there was a high possibility of type I Kounis syndrome caused by the combination of glucocorticoids, midazolam, and ondansetron.

With the spread of hemodialysis therapy and the continuous breakthrough of kidney transplantation technology, the survival period of patients with end-stage renal disease is prolonged, and malignant tumor has become one of the main causes for hospitalization and death of patients on hemodialysis and undergoing kidney transplantation. Due to the particularity of pharmacokinetics in patients on dialysis and the long-term maintenance immunosuppressive therapy in kidney transplant patients, many aspects need to be considered and balanced in these patients when they need anti-tumor drug treatments. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, and systematically answers many clinical questions about anticancer drug therapy in patients on hemodialysis and underwent kidney transplantation in the second chapter. This article interprets this part to provide references for the anti-tumor drug treatments of patients on dialysis and after kidney transplantation in China.

A 50-year-old male patient was scheduled to undergo epiglottic mass resection under general anesthesia due to an epiglottic cyst. Before anesthesia induction, the patient received dexamethasone, methylprednisolone, midazolam, and ondansetron by intravenous injectionin sequence. After 2 minutes, the patient complained of palpitations, abdominal spasmodic pain, cyanosis of the lips, and patchy changes in the skin on the chest and body. The electrocardiogram monitor showed a heart rate of 175 beats per minute, but his cuff blood pressure cannot be measured. His blood oxygen saturation was 0.76, and he did not respond to the call afterwards. Oxygen through a face mask and pressure ventilation, intravenous injection of 20 mg of esmolol twice were given immediately. The patient′s consciousness recovered, the heart rate gradually decreased to 60 beats per minute (sinus rhythm), and the blood pressure increased to 74/50 mmHg. Continuous IV pumping of norepinephrine 8 μg/min was given. After 25 minutes, the patient′s bedside electrocardiogram showed atrial fibrillation with ventricular differential conduction, myocardial injury or acute myocardial infarction, and QT interval prolongation. Then intravenous injection of furosemide 40 mg was given, his above symptoms were improved,his blood pressure recovered to 110-120/70 mmHg, blood oxygen saturation was 1.00, the skin spots on his chest and body disappeared, and his abdominal pain was alleviated. Anesthesiologists and pharmacists evaluated the patient′s adverse reactions and considered that there was a high possibility of type I Kounis syndrome caused by the combination of glucocorticoids, midazolam, and ondansetron.

With the spread of hemodialysis therapy and the continuous breakthrough of kidney transplantation technology, the survival period of patients with end-stage renal disease is prolonged, and malignant tumor has become one of the main causes for hospitalization and death of patients on hemodialysis and undergoing kidney transplantation. Due to the particularity of pharmacokinetics in patients on dialysis and the long-term maintenance immunosuppressive therapy in kidney transplant patients, many aspects need to be considered and balanced in these patients when they need anti-tumor drug treatments. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, and systematically answers many clinical questions about anticancer drug therapy in patients on hemodialysis and underwent kidney transplantation in the second chapter. This article interprets this part to provide references for the anti-tumor drug treatments of patients on dialysis and after kidney transplantation in China.

Circadian Clocks/genetics* ; Reactive Oxygen Species ; Methionine ; Gastrointestinal Microbiome ; Gastrointestinal Tract ; Racemethionine ; Gene Expression

Objective:To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts.Methods:Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMR Ⅰ subgroup and TCMR Ⅱ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection.Results:A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve ( AUC) of dd-cfDNA% was 0.76(95% CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95% CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups ( P=0.008) and TCMRⅡsubgroup ( P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups ( P=0.003). Conclusion:Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.