Objective To evaluate the efficacy and safety of rituximab (RTX) in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). Methods This was a single-center, retrospective and single-arm study. The clinical data of AAGN patients who received RTX induction therapy at the First Affiliated Hospital of Zhejiang University School of Medicine from April 2016 to July 2021 and had a follow-up period of more than 6 months were collected. The follow-up was up to June 2022. The Birmingham Vasculitis Activity Score (BVAS) from 2003 was used to assess vasculitis activity. The treatment regimen for RTX was once every 1 to 2 weeks, with 375 mg/m² each time. For some patients, the dose was adjusted according to the immune status before medication. The clinical outcomes, renal remission, recurrence and safety was analyzed. Kaplan-Meier method was used to analyze the cumulative renal remission rate. Results A total of 43 AAGN patients were included in the study, with age of (57.6±16.6) years, 19 males (44.2%) and 34 (79.1%) newly treated patients. There were 34 patients (79.1%) with positive myeloperoxidase-ANCA and 8 patients (18.6%) with positive proteinase 3-ANCA. The dosage of RTX used at the 12-month follow-up was 600 (500, 1 200) mg. At 6 months of follow-up, 32 patients (74.4%) achieved renal remission, and renal remission time was 5.0 (3.3, 5.8) months. Three patients (7.0%) progressed to end-stage renal disease, and two patients (4.7%) died. Compared with patients without renal remission, patients with renal remission had lower baseline serum creatinine (Z=-2.853, P=0.004), serum uric acid (t=-2.861, P=0.007), urine protein/urine creatinine ratio (Z=-2.130, P=0.033) and proportion of methylprednisolone pulse therapy (χ² =5.002, P=0.025), and higher estimated glomerular filtration rate (Z=-2.728, P=0.006). At 12 months of follow-up, 33 patients (76.7%) achieved renal remission, and the cumulative renal remission rate was 82.4%. Two patients (4.7%) had renal recurrence, 5 patients (11.6%) progressed to end-stage renal disease, and 3 patients (7.0%) died. Infection (4 patients, including 2 severe infections) was the main adverse event, all of which occurred within 6 months of RTX treatment. Conclusions The clinical remission rate and safety of RTX in the treatment of AAGN are both relatively high.

Objective To summarize the clinicopathologic characteristics of malignant hypertension (MHT) patients with acute kidney injury (AKI) and application of renin?angiotensin?aldosterone system inhibitor (RAASi). Methods It was a retrospective cohort study. The adult patients with MHT and AKI admitted to Peking University First Hospital from January 1, 2012 to July 14, 2022. The patients were categorized into RAASi group and non-RAASi group based on RAASi administration from AKI onset to discharge. The clinicopathological data between the two groups were compared, and application of RAASi was analyzed. Results A total of 179 patients were enrolled with age of 31 (26, 37) years and 148 males (82.7%). Ninety-five patients (53.1%) received dialysis treatment. The common causes of MHT were essential hypertension (125 patients, 69.8%), renal hypertension (39 patients, 21.8%) and endocrine hypertension (7 patients, 3.9%). AKI severity distribution showed 41 patients (22.9%) in stage 1, 1 patient (0.5%) in stage 2 and 137 patients (76.5%) in stage 3. Among MHT patients, 94 patients (52.5%) had been treated with RAASi before AKI, and 13 patients (7.3%) discontinued RAASi after AKI. Among 85 patients (47.5%) without receiving RAASi treatment before AKI, 68 new patients (38.0%) received RAASi treatment after AKI, and 40 patients (22.3%) were treated with the support of dialysis. Compared with non-RAASI group (n=30), proportions of chronic kidney disease (χ²=6.324, P=0.012) and post-AKI hyperkalemia (χ²=4.048, P=0.044) in RAASi group (n=149) were lower, and the proportion of dialysis treatment (χ²=5.638, P=0.018), admission diastolic blood pressure (Z=-3.609, P<0.001) and maximum diastolic blood pressure during hospitalization (Z=-1.978, P=0.048) were higher. There were no statistically significant differences in the rates of target blood pressure control and renal function recovery between the two groups during hospitalization (all P>0.05). During hospitalization, 64 patients received renal biopsies, of which 50 patients (78.1%) had typical MHT vascular lesions such as "onion skin" in renal arterioles. Twenty-seven patients (42.2%) were complicated with glomerular diseases, and IgA nephropathy was the most common type (85.2%, 23/27). The proportions of glomerular ischemia and sclerosis, endothelial cell proliferation and acute renal tubular injury in RAASi group (n=54) were lower than those in non-RAASi group (n=10), and proportions of thrombosis and "onion skin" change were higher than those in RAASi group (n=10), but the differences were not statistically significant (all P>0.05). Renal function recovery occurred in 47 patients (26.3%) by discharge. Among 95 dialysis patients, 26 patients (27.4%) achieved dialysis independence at discharge. Conclusions MHT patients with AKI exhibit severe renal pathology and short-term poor prognosis. RAASi is primarily prescribed to those with relatively better kidney function or those receiving dialysis support.

Objective To explore the influencing factors for skin pruritus and to construct a nomogram prediction model in peritoneal dialysis (PD) patients. Methods It was a retrospective cross-sectional investigation study. The PD patients who were regularly followed up between July, 2023 and April, 2024 in PD center of the First Affiliated Hospital of Sun Yat-sen University were enrolled in this study. The pruritus status was evaluated by the 14-Item UP-Dial Scale. The general demographic data and clinical data were collected. The patients were divided into pruritus group and non-pruritus group according to the presence or absence of skin itching. The differences of clinical data and laboratory results were compared between the two groups. Logistic regression was used to analyze the associated factors for pruritus in PD patients. The nomogram model was constructed by R software. The receiver operating characteristic (ROC) curve analysis and the Hosmer?Lemeshow goodness-of-fit test were used to evaluate the performance of the model, and its clinical effectiveness was evaluated using the calibration curve. Results A total of 315 PD patients were enrolled in this study, with age of (48.0±12.9) years, including 134 females (42.5%). Among them, 161 patients (51.1%) experienced skin pruritus. Of whom, 111 patients (68.9%) had mild pruritus, 34 patients (21.1%) had moderate pruritus, 16 patients (9.9%) had severe pruritus. The age (t=-2.266, P=0.024), proportion of diabetes mellitus (χ2=3.910, P=0.048), Charson comorbidity index (Z=-2.458, P=0.014), blood eosinophil percentage (Z=-2.385, P=0.017), C-reactive protein (Z=-2.590, P=0.010), serum phosphorus (Z=-3.233, P=0.001) and β2 microglobulin (Z=-2.756, P=0.006) level in the pruritus group were higher than those in the non-pruritus group, and the measured glomerular filtration rate (mGFR) level (Z=-3.708, P<0.001) of patients in the pruritus group was lower than that in the non-pruritus group. There were 262 patients in the training set and 53 patients in the validation set. The multivariate logistic regression analysis in the training set revealed that advanced age (OR=1.032, 95% CI 1.010-1.054, P=0.004), lower mGFR (OR=0.758, 95% CI 0.648-0.886, P<0.001), higher serum phosphorus (OR=2.761, 95% CI 1.282-6.024, P=0.010), and elevated blood eosinophil percentage (OR=1.098, 95% CI 1.012-1.191, P=0.025) were independent factors associated with pruritus in PD patients. The nomogram model constructed based on these indicators demonstrated good discrimination and calibration. In the training set, the area under the ROC curve (AUC) was 0.757 (95% CI 0.699-0.816), with Hosmer-Lemeshow test χ2=4.979, P=0.760. In the validation set, the AUC was 0.779 (95% CI 0.651-0.907), and Hosmer-Lemeshow test χ2=12.938, P=0.114. Conclusions The prevalence of skin pruritus is 51.1% in PD patient. Advanced age, lower mGFR, higher serum phosphorus and higher blood eosinophil percentage are the independent influencing factors for pruritus in PD patients. The nomogram model constructed based on these indicators shows excellent predictive performance for skin pruritus in PD patients.

Objective To investigate the role of RNA helicase DDX5 in renal interstitial fibrosis and its potential mechanism, and provide possible molecular target for the diagnosis and treatment of renal interstitial fibrosis. Methods The animal and cell models of unilateral ureteral obstruction (UUO) and DDX5-pharmacological and genetic blocking were established. Twenty-four male mice aged 6-8 weeks and weighting about 18-22 g were divided into sham operation group, UUO group, sham operation+RX5902 group and UUO+RX5902 group by random number table method, with 6 mice in each group. Supinoxin (RX5902, a phosphorylated DDX5 inhibitor, 75 mg/kg) was administered by gavage in mice in the sham operation+RX5902 group and UUO+RX5902 group on day 0 and day 3 after the operation, respectively. The mice were sacrificed to collect kidney specimens one week after the surgery. The human renal tubular epithelial cell line (HK?2 cells) was routinely cultured and divided into control group, scramble siRNA group, DDX5 siRNA group, TGF?β1 group, scramble siRNA+TGF?β1 group and DDX5 siRNA +TGF?β1 group. The dosage of RX5902 was 20 nmol/L, and the dosage of transforming growth factor?β1 (TGF?β1) was 10 ng/ml. HE staining and Masson staining were used to evaluate renal tubule injury and collagen fiber deposition. Western blotting, immunofluorescence and immunohistochemistry were used to detect the protein expression levels of DDX5 and fibrosis-related indexes such as fibronectin and α-smooth muscle actin (α-SMA). The flow cytometry was used to detect the cell cycle. Results In comparison to sham operation group, UUO group exhibited significantly elevated protein expression levels of fibronectin, α-SMA and DDX5 in kidney tissues (all P<0.05), accompanied by notable nuclear translocation of DDX5. TGF-β1 stimulation facilitated the upregulation of fibronectin, α-SMA, and DDX5 expression, as well as DDX5 nuclear translocation in HK-2 cells (all P<0.05). Pharmacological and genetic inhibition of DDX5 attenuated UUO or TGF-β1-induced elevated protein levels of fibronectin and α-SMA. Compared with scramble siRNA+TGF-β1 group, DDX5 siRNA+TGF-β1 group exhibited reduced protein expression levels of fibronectin, α-SMA and DDX5 in HK-2 cells (all P<0.05). Compared with UUO group, UUO+RX5902 group showed alleviation of renal epithelial cell exfoliation, renal tubule atrophy or lumen dilation and decreased scores of both tubular injury and interstitial collagen deposition, along with reduced protein expression levels of fibronectin, α-SMA and DDX5 (all P<0.05). Similarly, RX5902 inhibited TGF-β1-induced fibrotic responses in HK-2 cells (all P<0.05). Flow cytometry analysis results revealed that TGF-β1 stimulation resulted in a significant increase in the proportion of HK-2 cells in the G2/M phase. Conversely, silencing of DDX5 led to a significant reduction in the proportion of HK-2 cells in the G2/M phase (all P<0.05). Conclusions DDX5 is significantly elevated in the renal tissues of UUO mice and TGF-β1-induced HK-2 cells. The pharmacological and genetic blockade of DDX5 can delay renal fibrosis by reducing cell cycle arrest and alleviating cell damage.

To investigate the potential protective effect of thalidomide (THD) on diabetic nephropathy (DN) and its underlying mechanisms. Twenty-four C57BL/6J mice were randomly divided into control, DN and DN+THD200 groups by random number table method. The DN mouse model was established via intraperitoneal injection of streptozotocin. The DN+THD200 group received THD treatment (200 mg·kg^-1·d^-1) for 8 weeks. Blood and urine biochemical parameters, as well as renal histopathological changes, were compared among the three groups. For in vitro experiments, a high glucose (HG)-induced injury model was established in mouse glomerular podocytes (MPC5). Cells were divided into control (NG), HG, HG+DMSO, HG+THD100 (100 μg/ml), and HG+THD200 (200 μg/ml) groups. THD-treated cells were exposed to THD for 24 h. Western blotting and real-time quantitative PCR were performed to respectively detect protein and mRNA expression levels of ferroptosis-related molecules, including nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO?1), and glutathione peroxidase 4 (GPX4). Immunofluorescence was used to evaluate the expression of solute carrier family 7 member 11 (SLC7A11) and 4-hydroxynonenal (4-HNE). The results showed that, compared with control group, DN group exhibited significantly lower blood urea nitrogen, serum creatinine and 24 h urinary albumin levels (all P<0.05). Compared with DN group, DN+THD200 group exhibited significantly lower blood urea nitrogen, serum creatinine and 24 h urinary albumin levels (all P<0.05). Histopathological examination revealed glomerular expansion, mesangial widening, and basement membrane thickening in DN group compared to control group, which were markedly ameliorated by THD treatment. In vitro, HG group showed significantly decreased protein and mRNA expression levels of GPX4, NRF2 and HO?1 compared to NG group. Both HG+THD100 and HG+THD200 groups exhibited upregulated expression levels of these proteins and corresponding mRNA compared to HG group (all P<0.05). Immunofluorescence demonstrated HG group had enhanced 4-HNE fluorescence intensity and reduced SLC7A11 fluorescence intensity, which were reversed by THD treatment. THD alleviates renal injury in DN mice and mitigates HG-induced ferroptosis in MPC5 cells, potentially via activation of NRF2?HO?1?GPX4 signaling pathway.

Downhill esophageal varices (DEV) is a rare cause of upper gastrointestinal bleeding. It is different from ascending esophageal varices caused by portal hypertension, and caused by obstruction of the superior vena cava. It can be secondary to an indwelling central venous catheter. It is very dangerous when DEV is complicated with upper gastrointestinal bleeding,and there is no unified treatment strategy at present. We report a case of hemodialysis patient with left upper limb swelling for 6 months and intermittent hematemesis for 3 months. Combined with gastroscopy and CT venography, the patient was considered to have DEV rupture and hemorrhage. The patient was discharged after comprehensive treatment including closure of internal arteriovenous fistula, ligation of bleeding points of esophageal varices, recanalization of superior vena cava, and "culprit" vein embolization. There was no recurrence after half a year of follow-up. This case is helpful for clinicians to improve the recognition on this disease and explore the experience of diagnosis and treatment.

The research advancements of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney disease (CKD) were a central theme at the 2024 American Society of Nephrology (ASN) Kidney Week. Clinical studies reaffirmed the cardio-renal benefits of SGLT2i in CKD patients, including those with advanced-stage disease and elderly populations. Notably, these benefits persisted for up to 12 months after treatment discontinuation. Furthermore, CKD management has evolved from a traditional "three-pillar" approach to a "four-pillar" strategy, with combination therapies demonstrating significant synergistic potential for cardio-renal protection. Mechanistic studies revealed novel pathways through which SGLT2i exert renoprotective effects, including promoting renal regeneration, modulating epigenetic modifications, regulating immune cell activity, and restoring proximal tubule metabolic homeostasis. Further research is warranted to optimize therapeutic outcomes and maximize clinical benefits for patients.

Acute kidney injury (AKI) is a common clinical acute and critical condition. There is a lack of clinical interventions or therapeutic drugs that can significantly improve AKI outcomes. Lipids, including fatty acids, triglycerides, sphingolipids, phospholipids and cholesterol play crucial roles in energy metabolism, cell membrane composition, cell signaling, and cell homeostasis and survival. Recent lipidomics studies have revealed significant alterations in the content and composition of renal lipids during AKI, highlighting their important roles in the onset, progression, and outcomes of the disease. A common feature of AKI across multiple etiologies is altered lipid metabolism, characterized by insufficient energy generation due to mitochondrial damage and deposition of excess lipids in the kidney. The article summarizes the characteristics of renal lipid metabolism in physiological state, alterations of renal lipid metabolism in AKI and molecular mechanisms related to lipid metabolism disorders that aggravate AKI through mitochondrial damage, oxidative stress, autophagy dysfunction, activation of inflammatory and immune responses and regulated cell death, to provide new ideas and therapeutic targets for the clinical treatment of AKI.

Patients with chronic kidney disease (CKD), whether undergoing dialysis treatment or not, are at a high risk of hyperkalemia. Recurrent episodes of hyperkalemia can, significantly increase the risks of cardiovascular events and mortality, hospitalization, and renal replacement therapy in CKD patients, and severely affect the long-term survival benefits of CKD patients. Potassium ion binders play an important role in controlling hyperkalemia in CKD patients, reducing complications, and avoiding the reduction or discontinuation of renin-angiotensin- aldosterone system inhibitors. To guide the normative use of potassium ion binders, the Nephrology Branch of Chinese Research Hospital Association has organized a group of expert renal disease specialists. They have formulated this consensus based on the latest domestic and international management guidelines/consensus and research findings, combined with domestic clinical practice, to improve the long-term prognosis of hyperkalemia in Chinese CKD patients.

Immune checkpoint inhibitors (ICI) are a recently emerged class of antitumor therapeutic agents which have shown good respond in the treatment of various tumors. The accompanying immune-related adverse events (irAE) are a new class of adverse drug reactions that are closely related to ICI therapy and can affect multiple organs. Although the incidence of renal irAEs is approximately 1.4%-5.8%, the number of patients is increasing significantly as the base population using the ICI drug continues rapidly expanding. If severe renal irAE are not recognized and treated in time, they may rapidly progress to renal failure, which will bring adverse consequences to the treatment of kidney and tumor. In view of this, the Chinese Society of Nephrology organized an expert group to prepare this consensus basing on relevant domestic and international consensus, guidelines, and research. The propose of this consensus is to introduce the diagnosis, treatment, and management of renal irAE, and provide guidance and suggestions to clinical practitioners on standardization of diagnosis and treatment of renal irAE.