Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients' clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the "dominant" phenotype in idiopathic double-positive AAV.

Application potential of extracellular vesicles derived from mesenchymal stem cells in renal diseases.

The high prevalence and complex etiology of renal diseases already impose a heavy disease burden on patients and society. In certain kidney diseases such as acute kidney injury (AKI) and chronic kidney disease (CKD), current treatments are limited to slowing rather than stabilizing or reversing disease progression. Therefore, it is crucial to study the pathological mechanisms of kidney disease and discover new therapeutic targets and effective therapeutic drugs. As cell-free therapeutic strategies are continually being developed, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have emerged as a hot topic for research in the field of renal diseases. Studies have demonstrated that MSC-EVs not only reproduce the therapeutic effects of MSCs but also localize to damaged kidney tissue. Compared to MSCs, MSC-EVs have several advantages, including ease of preservation, low immunogenicity, an inability to directly form tumors and ease of artificial modification. Exploring the detailed mechanisms of MSC-EVs by developing standardized culture, isolation, purification and drug delivery strategies will help facilitate their clinical application in kidney diseases. Here, we provide a comprehensive overview of studies about MSC-EVs in kidney diseases and discuss their limitations at the human nephrology level.

Sex disparities in clinicopathological features and outcomes of patients with myeloperoxidase-ANCA-associated vasculitis: a retrospective study of 366 cases in a single Chinese center.

There are a few studies that reported sex disparities in clinical features, pathological features and outcomes among ANCA-associated vasculitis (AAV) patients, but studies focusing on sex-specific differences of myeloperoxidase (MPO)-AAV patients are scarce. Therefore, the purpose of this study was to analyze sex differences in clinicopathological features and outcomes of MPO-AAV. Patients diagnosed with MPO-AAV in Xiangya Hospital from January 2010 to June 2021 were included in the study and separated into female and male groups. The differences in clinical manifestations, laboratory parameters, pathological features and prognosis between the two groups were retrospectively analyzed. Three hundred and sixty-six patients were included and divided into female group (n = 176) and male group (n = 190). The age of the male group was 62.41 ± 10.49 years, significantly higher than that of the female group (58.69 ± 16.39, p = 0.011). Compared with the female group, the male group had a shorter duration of disease, higher levels of hemoglobin, eosinophil count, proteinuria, serum C4, and lower levels of serum globulin, serum IgG and serum IgM (p < 0.05). No significant differences in kidney pathological features were observed between the two groups. During a median follow-up of 37.6 months, there was no significant difference in renal survival and patient survival between the two groups, but male patients had a worse composite outcome of renal and patient survival compared with the female patients (p = 0.044). This study found that male patients with MPO-AAV had a higher age of onset, shorter duration of disease, higher levels of hemoglobin, eosinophil count, proteinuria, serum C4, and lower levels of serum globulin, serum IgG and serum IgM. Male patients fared worse than female patients in terms of the composite outcome of renal and patient survival.

Neferine mitigates cisplatin-induced acute kidney injury in mice by regulating autophagy and apoptosis.

PURPOSE: The nephrotoxicity caused by cisplatin severely limits the application and affects related platinum-based therapeutics. Neferine is a dibenzylisoquinoline alkaloid extracted from a Chinese medicinal herb (Nelumbo nucifera Gaertn), which can decrease cisplatin-induced apoptosis of NRK-52E cells by activating autophagy in vitro in our previous study. In this article, we aimed to further investigate the protective effect of neferine, against to the cispltain-induced kidney damage in mice. METHODS: Six groups were designed in our study. Renal index, mice serum creatinine and blood urea nitrogen levels were detected after the mice were killed. HE staining was used to observe the pathological changes of each group. The apoptosis of mouse kidney tissue was detected by TUNEL. Immunofluorescence and Western blot were used to detect the expression of cleaved-caspase3 and LC3. The transmission electron microscope was used to reveal the changes of apoptosis and autophagy of renal tubular epithelial cells in different groups. RESULTS: In our findings, the pathological changes of acute kidney injury were easily observed in cisplatin-treated mice while those in the neferine-pretreated groups were significantly alleviated. The apoptosis induced by cisplatin in mice increased evidently compared with the control group, which was decreased in the mice with neferine pretreatment. What' more, we found that autophagy increased obviously in mice pretreated by neferine contrast to the cisplatin-treated mice. CONCLUSION: In our study, neferine can effectively alleviate cisplatin-induced renal injury in mice, as well act as an autophagy-regulator in kidney protection.

Clinical features and prognosis of MPO-ANCA and anti-GBM double-seropositive patients.

Background: Several lines of evidence implicate that there are distinct differences between patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody double-seropositive patients (DPPs) and single-positive patients. Hence, we conducted a retrospective study from a single center in China to analyze the clinical and pathological features, and prognosis of DPPs. Methods: 109 patients with MPO-ANCA-associated vasculitis (MPO-AAV), 20 DPPs and 23 patients diagnosed with anti-GBM disease from a large center in China were included in this study. The ratio of patients with renal biopsy in three groups were 100%, 50% and 100%, respectively. Their clinical and pathological characteristics, and outcomes were analyzed. The intensity of immune deposits in the kidney at diagnosis was detected by immunofluorescence (IF). Furthermore, multivariate Cox hazard model analysis was used to assess the clinical and histological predictors of end-stage renal disease (ESRD) and death for DPPs. Results: In our study, we found that patients in the DPPs group were older than the other two groups (p = 0.007, MPO-AAV vs. DPPs; p < 0.001, DPPs vs. anti-GBM). The DPPs group had a higher value of serum creatinine (p = 0.041) and lower estimated glomerular filtration rate (eGFR) (p = 0.032) compared with MPO-AAV patients. On the contrary, the DPPs group had a lower serum creatinine (p = 0.003) compared with patients with anti-GBM group. The proportion of patients with cardiac system involvement in the DPPs group was higher than anti-GBM patients (p = 0.014). Cellular crescents could be generally observed in renal biopsy of DPPs and patients with anti-GBM glomerulonephritis. In addition, Bowman's capsule rupture was more common in DPPs than MPO-AAV patients (p = 0.001). MPO-AAV had a better renal and overall survival outcome than DPPs (p < 0.001). There was no significant difference of renal and overall survival outcome between DPPs and patients with anti-GBM disease. The incidence of ESRD in DPPs was negatively associated with lymphocyte count (HR 0.153, 95% CI 0.027 to 0.872, p = 0.034) and eGFR (HR 0.847, 95% CI 0.726 to 0.989, p = 0.036). Elevated serum creatinine was confirmed as a risk factor of both renal (HR 1.003, 95% CI 1.000 to 1.005, p = 0.019) and patient survival in DPPs (HR1.461, 95% CI 1.050 to 2.033, p = 0.024). Conclusion: In summary, compared with anti-GBM disease, DPPs tended to involve multi-organ damage rather than limited to the kidney. It is highlighted that serologic DPPs have a worse renal and patient prognosis than MPO-AAV. Moreover, we found that the risk factors of renal survival of DPPs include low lymphocyte count, elevated serum creatinine and reduced eGFR, and serum creatinine can predict patient survival.