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Background: The currently recommended dose of rituximab for primary membranous nephropathy is as high as that for lymphoma. However, the clinical manifestations of membranous nephropathy vary widely. Therefore, achieving individualized treatment is a topic that needs to be explored. This study assessed the efficacy of monthly mini-dose rituximab monotherapy in patients with primary membranous nephropathy. Methods: This retrospective study included 32 patients with primary membranous nephropathy treated at Peking University Third Hospital between March 2019 and January 2023. All patients were anti-phospholipase A2 receptor (PLA2R) antibody-positive and received rituximab 100 mg intravenously monthly for at least 3 months without other immunosuppressive therapy. Rituximab infusions were sustained until either remission of the nephrotic syndrome or a minimum serum anti-PLA2R titer ˂ 2 RU/mL was achieved. Results: The baseline parameters included: proteinuria, 8.5 ± 3.6 g/day; serum albumin, 24.8 ± 3.4 g/L; and anti-PLA2R antibody, 160 (20–2659) RU/mL. B-cell depletion was achieved in 87.5% patients after the first dose of rituximab 100 mg and in 100% after the second equivalent dose. The median follow-up was 24 months (range 18–38). Twenty-seven (84%) patients achieved remission, with 11 (34%) patients achieving complete remission by last follow-up. The relapse-free survival from the last infusion was 13.5 months (range 3–27). Patients were stratified into the low-titer (< 150 RU/mL, n = 17) and high-titer groups (≥ 150 RU/mL, n = 15) based on the anti-PLA2R titer. Sex, age, urinary proteins, serum albumin, and estimated glomerular filtration rate at baseline did not differ significantly between the two groups. At 18 months, compared to the low-titer group, the rituximab dose (960 ± 387 vs 694 ± 270 mg, p = 0.030) was higher, while serum albumin (37.0 ± 5.4 vs 41.3 ± 5.4 g/L, p = 0.033) and the complete remission rate (13% vs 53%, p = 0.000) were both lower in the high-titer group. Conclusions: Monthly rituximab 100 mg appeared as a potential effective regimen for treating anti-PLA2R-associated primary membranous nephropathy with a low anti-PLA2R titer. The lower the anti-PLA2R titer, the lower the rituximab dose required to achieve remission. Trial registration: A retrospective study, registered at ChiCTR (ChiCTR2200057381) on March 10, 2022. [ABSTRACT FROM AUTHOR]

Introduction: Vascular calcification (VC), which is a pathological process of abnormal calcium and phosphorus deposition in blood vessels, valves, heart and other tissues, is highly prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that intermedin (IMD), a kind of small molecule active peptide, may play roles in VC in hemodialysis (HD) patients. This study aims to evaluate serum IMD levels and establish their relation to VC and other parameters in HD patients. Methods: A total of 116 patients on maintenance HD treatment and 52 age- and sex-matched healthy controls were enrolled in this study. Serum IMD levels were measured by radioimmunoassay (RIA). VC was evaluated by abdominal aortic calcification scores. Results: Serum IMD levels were significantly lower in HD patients than in controls [24.89 (13.55, 50.24) pg/ml vs. 137.79 (93.21, 201.64) pg/ml, P < 0.0001]. In addition, IMD was negatively correlated with the serum phosphate level (P = 0.036) in HD patients. However, compared with the group whose IMD levels were above the median, patients with IMD levels less than the median had a lower incidence of VC (P = 0.031). Multivariate logistic regression analyses revealed that serum IMD levels more than 24.89 pg/ml (P = 0.014, OR = 0.285), higher serum iPTH levels (P < 0.0001, OR = 1.093) and older age (P = 0.009, OR = 1.003) were significant independent determinant factors for VC in HD patients. Conclusion: The serum IMD levels were significantly lower in HD patients than that in healthy group. In addition to higher PTH levels and older age, compensatory elevated IMD levels may be an independently determinant factor for VC in HD patients. This was the first study about IMD and VC in dialysis patients. [ABSTRACT FROM AUTHOR]

Background: Idiopathic multicentric Castleman disease (iMCD) is an uncommon lymphoproliferative disorder and lacks treatment consensus. Herein, we report a case of iMCD complicated with Sjögren's syndrome (SS) and secondary membranous nephropathy (SMN).Case Presentation: A 45-year-old female with dry mouth for 3 months and anasarca and proteinuria for 2 months was admitted. She also experienced chest tightness, wheezing, fever, weight loss, moderate proteinuria and hypoalbuminemia. A computed tomography (CT) scan revealed a tissue mass in the thymus area and enlarged multiple lymph nodes. Her symptoms did not improve after resection of the thymus mass. The pathological findings were "reactive hyperplasia of the mediastinal lymph nodes and thymic hyperplasia". Lymph node biopsy findings confirmed iMCD with human herpes virus-8 (HHV-8) negativity. Based on anti-nuclear antibody (ANA) 1:320, anti-SSA and anti-SSB antibody positivity, salivary flow less than 0.1 ml/min and lip biopsy with focal lymphocytic sialadenitis, SS was diagnosed. Kidney biopsy showed secondary membranous nephropathy with endocapillary cell proliferation and infiltration of plasma cells and lymphocytes in the tubulointerstitium. Serum interleukin-6 (IL-6) levels were significantly increased, and therapy with tocilizumab (anti-IL-6 receptor antibody) worked well. The combination of cyclophosphamide (CyS) with methylprednisolone (MP) maintained satisfactory remission.Conclusions: Our case of iMCD with SS and SMN is rare. There is a need for increased awareness of the disease to avoid unnecessary procedures and misdiagnoses. IL-6 was extremely high, and there was a rapid response to anti-IL-6 receptor agents. The combination of CyS with MP maintained complete remission. [ABSTRACT FROM AUTHOR]

Purposes: The main purposes of this article are to describe an unprecedented phenomenon in which significant amount of a shoulder peak impurity was observed during normal non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis of a recombinant fusion protein X, and to evaluate the root cause for this phenomenon. Methods: A series of experiments were conducted to study the nature of this degradation. Effects of iodoacetamide (IAM), heating temperature, duration, and SDS on the formation of this specific impurity were evaluated using a variety of characterization techniques. Results: The formation of the impurity as observed in CE-SDS was actually due to alkylation of lysine and serine residues with IAM, as confirmed by peptide mapping and LC-MS/MS, which increased the molecular weight and therefore decreased the electrophoretic mobility. The amount of impurity was also strongly dependent on sample preparation conditions including the presence or absence of SDS. Conclusions: Our study clearly suggested that even though IAM has been used extensively as an alkylation reagent in the traditional non-reducing CE-SDS analysis of monoclonal antibodies and other proteins, alkylation with IAM could potentially lead to additional impurity peak, and therefore complicating analysis. Therefore, before performing CE-SDS and other analyses, the effects of sample preparation procedures on analytical results must be evaluated. For protein X, IAM should be excluded for CE-SDS analysis. [ABSTRACT FROM AUTHOR]

Background/Aims: Possible predictive value of aortic-brachial arterial stiffness mismatch assessed by pulse wave velocity PWV ratio in peritoneal dialysis patients' outcomes need to be further elucidated. The aim of this study is to investigate the predictor value of PWV ratio on peritoneal dialysis (PD) patients' outcomes in China. Methods: In this longitudinal cohort study, patients who started PD during September 20, 2005, to February 05, 2008, were included. All the patients were followed until January 31, 2018. Aortic-brachial arterial stiffness mismatch was assessed using carotid-femoral pulse wave velocity divided by carotid-radial pulse wave velocity (PWV ratio). Results: A total of 181 incident PD patients were included. The median survival of patients in PWV ratio above median group (4.03 years, 95% CI 4.64-7.99 years) was shorter than that of PWV ratio below median group (10.43 years, 95% CI 9.74-11.12 years, p< 0.001). The cardiovascular mortality rate in PWV ratio above median group were significantly higher than that of PWV below median group (log rank test, p< 0.001). Univariate Cox regression analysis showed that both PWV ratio (HR 2.42, 95% CI 1.80-3.25, p< 0.001) and CF-PWV (HR 1.27, 95% CI 1.16-1.38, p< 0.001) were associated with high patients' all-cause mortality. Multivariable Cox regression analysis showed that the PWV ratio was a strong and significantly predictor of cardiovascular mortality (HR 2.08 95% CI 1.16-3.71, p=0.014) after adjusting for coronary heart disease history (HR 2.39, 95% CI 1.20-4.76, p=0.013), diabetes mellitus history (HR 2.84, 95% CI 1.51-5.33, p=0.001). However, the CF-PWV was failed to be included as a significant predictor for both all-cause and CVD mortality in the multivariable Cox regression model. Conclusion: Aortic-brachial arterial stiffness mismatch as assessed by PWV ratio, a new arteries stiffness risk parameter, is a significant prognostic indicator of CVD mortality in PD patients. We demonstrated that the discriminative power of the PWV ratio for both all-cause and CVD mortality was better than that CF-PWV. [ABSTRACT FROM AUTHOR]