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 association of metabolic syndrome(MS) with cardiovascular disease(CVD) mortality and all-cause mortality in peritoneal dialysis patients.Methods:A retrospective analysis was performed on patients who underwent peritoneal dialysis from January 1, 2013 to July 31, 2021 in the Shaoxing People′s Hospital. Patients were divided into MS group and non-MS group. The differences in baseline biochemical variables, comorbidities, and clinical outcomes between the two groups were compared. Kaplan-Meier method was used to obtain survival curves, the Cox regression model was used to evaluate the influence of MS for survival rates, and the inverse probability of treatment weighting(IPTW) was used to eliminate influence of the confounders in the groups.Results:A total of 494 peritoneal dialysis patients were enrolled in this study, which were divided into MS group( n=266) and non-MS group( n=228). The total median follow-up time was(31±22) months. At baseline, the standard mean difference( SMD) in smoking history, drinking history, CVD history, prevalence of chronic glomerulonephritis, left ventricular ejection fraction, B-type natriuretic peptides, hemoglobin, blood calcium, hypersensitive C-reactive-protein, intact parathyroid hormone, ultrafiltration and 4 h dialysate/plasma creatinine in the two groups were greater than 0.1. Their SMD decreased to under 0.1 after IPTW, showing a good balance between the two groups. The analysis of the survival curve of Kaplan Meier showed that the cumulative survival rate and cumulative CVD survival rate in MS group were significantly lower than those in non-MS group before and after IPTW( P<0.05). After IPTW was used to eliminate the effect of confounders, multivariate Cox regression analysis still displayed that MS was an independent risk factor for all-cause mortality( HR=1.824, 95% CI 1.121-2.968, P=0.015) and CVD mortality( HR=2.470, 95% CI 1.324-4.609, P=0.004)in peritoneal dialysis patients. Conclusion:The prevalence of metabolic syndrome is high in peritoneal dialysis patients. MS is an independent risk factor for all-cause mortality and CVD mortality in peritoneal dialysis patients.

Sarcopenia is a systemic syndrome characterized by decreased muscle mass and muscle strength and decline of motor function.Sarcopenia affects quality of life and disease prognosis of patients seriously, because of the low awareness rate, low treatment rate and high cardiovascular risk. Patients with uremia undergoing peritoneal dialysis are likely to suffer from sarcopenia due to dietary restriction, loss of protein and high catabolism. This article summarizes the diagnostic methods, risk factors, predictive markers and intervention measures for sarcopenia in peritoneal dialysis patients.

Objective:To investigate the association of serum magnesium with cardiovascular disease (CVD) and all-cause mortality in peritoneal dialysis patients.Methods:A retrospective study was performed in patients who initiated peritoneal dialysis from January 1, 2013 to July 31, 2019 in the Shaoxing People's Hospital. According to the standard of serum magnesium, the patients were divided into control group (Mg≥0.7 mmol/L) and low-magnesium group (Mg<0.7 mmol/L). The differences in baseline biochemical variables, comorbidities, medications, and clinical outcomes between the two groups were compared. Logistic regression was used to analyze the related factors of hypomagnesemia. Kaplan-Meier survival analysis and Fine-Gray model were used to compare the difference in cumulative survival rate between the two groups. Cox regression model and competitive risk model were used to analyze the risk factors of all-cause mortality and CVD mortality.Results:A total of 381 peritoneal dialysis patients were enrolled in this study. Among them, 321 patients were in control group and 60 patients in low-magnesium group. The total median follow-up time was 27(15, 43) months. There were significant differences in serum albumin, magnesium, phosphorus, intact parathyroid hormone, low-density lipoprotein chloesterol, high sensitivity C-reactive protein and 4-hour dialysate-to-plasma creatinine (4 h D/Pcr) between the two groups. CVD was the main cause of death in patients on peritoneal dialysis. Multivariate logistic regression analysis showed that hypoalbuminemia ( OR=0.901, 95% CI 0.831-0.976, P=0.011), hypophosphatemia ( OR=0.217, 95% CI 0.080-0.591, P=0.003), higher hsCRP ( OR=1.276, 95% CI 1.066-1.528, P=0.008), and higher 4 h D/Pcr ( OR=1.395, 95% CI 1.014-1.919, P=0.041) were independent risk factors for patients with hypomagnesemia. Kaplan-Meier survival curve analysis showed the cumulative survival rate of patients in low-magnesium group was significantly lower than that of control group (Log-rank χ2=5.388, P=0.020). Fine-Gray model analysis showed the cumulative CVD survival rate of low-magnesium group was significantly lower than that of control group ( Gray=6.915, P=0.009). Multivariate-corrected Cox regression model and competitive risk model analysis showed that higher serum magnesium level was a protective factor for all-cause mortality and CVD mortality when serum magnesium was used as a continuous variable ( HR=0.137, 95% CI 0.020-0.946, P=0.044; SHR=0.037, 95% CI 0.002-0.636, P=0.023, respectively). Hypomagnesemia was an independent risk factor for all-cause mortality and CVD mortality when serum magnesium was used as categorical variable ( HR=1.864, 95% CI 1.044-3.328, P=0.035; SHR=2.117, 95% CI 1.147-3.679, P=0.029, respectively). Conclusions:Hypomagnesemia is susceptible to peritoneal dialysis patients with hypoalbuminemia, hypophosphatemia, higher hsCRP and higher peritoneal transport characteristics. Hypomagnesemia is an independent risk factor for CVD mortality and all-cause mortality in peritoneal dialysis patients.

Objective To investigate the relationship between (serum neutrophil gelatinase-associated lipocalin,sNGAL) and cardiovascular events in patients with chronic kidney disease(CKD).Methods 300 patients with CKD were divided into two groups according to the level of sNGAL:high sNGAL group (n=158) and low sNGAL group (n=142).The incidence of cardiovascular events and cumulative survival rate were analyzed by ROC curve,and the correlation between sNGAL and cardiovascular risk factors,cardiovascular events in patients with chronic renal disease was analyzed.Influencing factors of cardiovascular events in CKD patients was analyzed.Results There were significant differences in the data about BMI,diabetes proportion,CKD staging,eGFR,hsCRP,24h proteinuria,HDL,iPTH,phosphate and blood calcium between the two groups (P＜0.05).The 3-year cumulative survival rate of high sNGAL group(77.2％) was significantly lower than that of low sNGAL group(96.5％),and the 3-year incidence of cardiovascular events (37.9％) was significantly higher than that of low sNGAL group (9.8％) (P＜ 0.05).AUC in diagnosing cardiovascular events in high sNGAL group (0.746) was significantly higher than that in eGFR(0.636),age (0.504),serum calcium (0.545),HDL(0.594) and LDL (0.508,all P＜0.05).There was a significant correlation between sNGAL and eGFR,HDL,BMI,hs-CRP,iPTH and phosphate (P＜ 0.05).Both univariate and multivariate fact ors COX showed that sNGAL was a risk factor of cardiovascular events in patients with CKD (P＜0.05),((HR=1.976 and 1.588,95％ CI=1.443-2.724 and 1.144-2.143,respectively,P=0.O00 and 0.000)).Conclusions The incidence of cardiovascular events in patients with CKD with high sNGAL is significantly increased.sNGAL is an independent factor of cardiovascular events in patients with chronic renal disease.

Objective:To investigate the value of serum anti-PLA2 R as a diagnostic marker of idiopathic membranous nephropathy( IMN).Methods:All available articles about serum anti-PLA2 R as a marker of IMN which were published at home and abroad from 2009.1 to 2013.12 were pooled from the databases of PubMed,Elsevier,Springer,CNKI,VIP and Wanfang database et al. The quality of the papers were evaluated by the quality assessment for studies of diagnostic accuracy studies( QUADAS).And then a meta-analysis was conducted by the statistical softwares of Meta-Disc and Stata.The diagnostic value of serum anti-PLA2 R in IMN was evaluated by the statistical indicators of pooled sensitivity, pooled specificity, pooled likelihood ratio and summary receiver operating characteristic curve( ROC curve).Sensitivity analysis was performed by reducing a paper in order,and publication bias was tested by Egger funnel plot.Results: Seven articles were selected to the meta-analysis according to the inclusion criteria and 967 cases were included in the study ( 454 IMN patients and 513 controls ).Heterogeneity test showed no heterogeneity threshold effect ( Spearman correlation coefficient was 0.107,P=0.819),but there was heterogeneity caused by non threshold effects(Cochrane-Q was 16.89,P=0.009 7).So random model was used to pool the effect size.The overall combined effect sizes:sensitivity was 69%,95%CI:0.65-0.73;specificity:98%,95%CI:0.96-0.99;pooled positive likelihood ratio 16.37,95%CI:4.06-65.95;pooled negative likelihood ratio 0.32,95%CI:0.24-0.43;AUC of SROC:0.854 0,Q*=0.785 0.Sensitivity analysis showed that this research was stable and reliable and Egger funnel plot showed little publication bias.Conclusion: Serum anti-PLA2 R is an useful biomarker to the diagnosis of IMN.