Objective To investigate the association between serum complement C5a level and clinicopathological characteristics, remission status, and renal function progression in patients with primary membranous nephropathy (PMN), and to evaluate its potential as a prognostic biomarker. Methods It was designed as a single-center prospective cohort study. PMN patients who were hospitalized and underwent renal biopsy at the Department of Nephrology, Affiliated Hospital of Qingdao University, between June 1, 2022 and June 1, 2024 were enrolled. The clinical, pathological and follow-up data of patients were collected. Serum complement C5a level and anti-phospholipase A2 receptor (PLA2R) antibody titer were measured at the time of renal biopsy. Patients were categorized into three groups according to complement C5a tertiles, and clinical characteristics were compared among the groups. The primary outcome was achievement of clinical remission, while the secondary outcome was renal function progression. Spearman rank correlation analysis was performed to evaluate the correlations of complement C5a level with clinical parameters. Cox regression analysis was used to identify independent predictors of clinical remission in PMN patients. Kaplan-Meier survival analysis was performed to compare clinical remission rates and renal survival rates among patients with different complement C5a levels, and log-rank test was used to assess the differences among those groups. The receiver-operating characteristic curve (ROC curve) was used to evaluate the predictive value of serum complement C5a for the clinical remission of PMN patients. Results A total of 125 patients were included in the study, with age of (56.79 ± 11.12) years. Among them, 85 patients (68.00%) were males, and 93 patients (74.40%) had positive anti-PLA2R antibodies. Compared with the low complement C5a group, the moderate complement C5a group exhibited higher body mass index, anti-PLA2R antibody titer and proportion of positive anti-PLA2R antibody, and had lower IgG level (all P<0.05). Compared with the low complement C5a group, the high complement C5a group exhibited higher 24-hour urinary protein excretion, anti-PLA2R antibody titer, proportion of positive anti-PLA2R antibody, triglyceride, total cholesterol and complement C4, and had lower serum albumin and IgG levels (all P<0.05). Compared with the moderate complement C5a group, the high complement C5a group showed elevated 24-hour urinary protein excretion and anti-PLA2R antibody titer, and reduced serum albumin level (all P<0.05). Spearman rank correlation analysis results showed that serum complement C5a level was positively correlated with anti-PLA2R antibody titer (r=0.571, P<0.001) and 24-hour urinary protein excretion (r=0.456, P<0.001), but was negatively correlated with serum albumin level (r=-0.490, P<0.001). The follow-up duration was 21.60 (16.80, 28.80) months. Multivariate Cox regression analysis showed that serum C5a level [hazard ratio (HR)=0.975, 95% confidence interval (CI) 0.966-0.984, P<0.001] and 24-hour urinary protein excretion (HR=0.860, 95% CI 0.779-0.949, P=0.003) were independent predictors of clinical remission. Kaplan-Meier survival analysis revealed a statistically significant difference in cumulative clinical remission rate and renal survival rate among the three groups (Log-rank test, χ²=42.897, P<0.001; χ²=7.210, P=0.027). ROC curve analysis showed that the area under the curve for serum complement C5a level in diagnosing clinical remission in PMN patients was 0.953 (95% CI 0.906-1.000, P<0.001), indicating its excellent predictive efficacy. Conclusions The serum C5a level is closely related to the disease activity and clinical remission of PMN. The elevated complement C5a level is an independent risk factor for failure to achieve clinical remission, and the complement C5a level has a good predictive effect on clinical remission. The serum complement C5a may become a sensitive biomarker for disease assessment and prognosis judgment in PMN patients.

Objective To investigate the renal pathological characteristics in patients with advanced schistosomiasis and kidney diseases, and compare the clinical prognosis between membranous nephropathy (MN) patients with advanced schistosomiasis and primary MN patients without advanced schistosomiasis. Methods This was a single-center retrospective cohort study. The patients diagnosed with advanced schistosomiasis who underwent renal biopsy at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2003 and December 2024 were enrolled. Clinical, pathological and follow-up data of patients were collected. The primary endpoint event was defined as a decrease in estimated glomerular filtration rate (eGFR) to <15 ml·min?1·(1.73 m2)?1 or a reduction of >50% from baseline. Kaplan-Meier survival analysis was used to examine the differences in primary endpoint event among patients grouped by gender, age, and baseline renal function. MN patients complicated with advanced schistosomiasis were assigned to the combined group. The age, gender, serum albumin, eGFR, 24-hour urinary protein, and treatment regimens was used as covariates, 21 patients with primary MN without advanced schistosomiasis were selected from 865 concurrent primary MN patients as control group by propensity score matching (1∶1 nearest neighbor matching, caliper 0.2). The 24-hour urinary protein, serum albumin and eGFR at 6, 12, 18 and 24 months of follow-up were compared between the two groups. Results There were 37 patients with kidney diseases complicated with advanced schistosomiasis enrolled in the study. The patients had age of 70.0 (65.5, 73.0) years and 25 males (67.5%). The duration from disease onset to confirmed diagnosis was 7.0 (1.5, 14.5) months. Nephrotic syndrome was present in 21 patients (56.8%) and chronic nephritic syndrome was present in 15 patients (40.5%). The 24-hour urinary protein was 3.71 (1.42, 6.92), and eGFR was 56.0 (35.1, 75.8) ml·min?1·(1.73 m2)?1. Renal pathological types included MN in 21 patients (56.8%), IgA nephropathy in 8 patients (21.6%), tubulointerstitial lesions in 3 patients (8.1%), focal segmental glomerulosclerosis in 3 patients (8.1%), and others in 2 patients (5.4%). Among the 37 patients, 31 patients (83.8%) completed at least one follow-up. The follow-up duration was 16 (5, 37) months, and 7 patients (22.6%) reached the primary endpoint event. Kaplan-Meier analysis showed no significant differences in primary endpoint event among patients with different genders, ages or baseline renal function (Monte Carlo permutation test, P=0.871; P=0.429; P=0.849). At 6 months of follow-up, compared with baseline, both groups showed significant decreases in 24-hour urinary protein (combined group: Z=-3.110, P=0.002; control group: Z=-3.114, P=0.002) and significant increases in serum albumin (combined group: Z=2.623, P=0.009; control group: Z=3.562, P<0.001). At 12 months, the control group still had significantly reduced 24-hour urinary protein (Z=-3.154, P=0.002) and elevated serum albumin (Z=3.336, P<0.001). At 18 months, the 24-hour urinary protein level in the combined group was markedly higher than that in the control group (Z=2.028, P=0.043). At 24 months, eGFR in the combined group decreased significantly compared with baseline (t=-2.533, P=0.044) and was obviously lower than that in the control group (t=-2.928, P=0.010); 24-hour urinary protein in the combined group was higher than that in the control group (Z=2.221, P=0.026); No significant change in eGFR and decreased 24-hour urinary protein were observed in the control group compared with baseline (t=-0.482, P=0.640; Z=-2.934, P=0.003). Conclusions MN is the predominant renal pathological subtype in advanced schistosomiasis patients with kidney diseases. At the 2-year follow-up, primary MN patients without advanced schistosomiasis shows sustained resolution of proteinuria and stable renal function, while those with advanced schistosomiasis experience recurrent proteinuria and a higher proportion of renal function decline, suggesting a relatively poor prognosis.

Objective To compare the long-term patency status between upper arm autogenous arteriovenous fistula (UAF) and arteriovenous graft (AVG) in patients with poor forearm vessels. Methods It was a retrospective study. The chronic kidney disease patients with poor forearm vessels who underwent UAF or AVG creation at the First Affiliated Hospital of Zhengzhou University between January 2019 and December 2022 were enrolled. Patients were followed until access abandonment, method change in renal replacement therapy, death, loss to follow-up, or June 30, 2024. Clinical data of patients were collected, clinical outcomes and intervention data of complications were compared between the two groups. After potential confounders were controlled by propensity score matching, a competing risk model was used to analyze primary and cumulative patency rates. Results A total of 223 patients were included in UAF or AVG group. There were no statistically significant differences in age, gender distribution, dialysis duration, proportion of ≥ 3 years of dialysis duration, and proportion of diabetes between the two groups (all P>0.05). Regarding the anastomotic vein, the perforating vein was most commonly used in the UAF group [82.51% (184/223)], whereas the basilic vein was most commonly used in the AVG group [58.30% (130/223)]. The primary failure rate in the UAF group was significantly higher than that in the AVG group [11.66% (26/223) vs. 1.35% (3/223), χ2=19.510, P<0.001]. The access intervention rate in the UAF group was significantly lower than that in the AVG group [46.64% (104/223) vs. 71.30% (159/223), χ2=28.032, P<0.001]. Furthermore, the incidence of cephalic arch lesions in the UAF group was significantly higher than that in the AVG group [8.97% (20/223) vs. 2.69% (6/223), χ2=8.005, P=0.005]. The primary patency rate in the UAF group was significantly higher than that in the AVG group (Gray test, χ2=27.56, P<0.001), whereas the cumulative patency rate was significantly lower than that in the AVG group (Gray test, χ2=15.23, P<0.001). After excluding cases of primary failure, the cumulative patency rate in the UAF group remained significantly lower than that in the AVG group (Gray test, χ2=3.89, P=0.048). Conclusions The primary patency rate and primary failure rate in the UAF group are higher than those in the AVG group, while total intervention rate and the cumulative patency rate are lower than those in the AVG group. Selection of UAF requires balancing its high risk of early failure against the long-term benefit of a low intervention rate once successful access is established.

Objective To evaluate the complications and catheter survival in children with different break-in periods after urgent-start peritoneal dialysis catheter insertion, and to provide evidence for optimizing dialysis treatment strategies in pediatric patients. Methods A retrospective cohort study was conducted. The pediatric patients who underwent peritoneal dialysis catheter insertion and urgent-start peritoneal dialysis initiation at the Department of Nephrology, Capital Children's Medical Center, Capital Medical University, from January 1, 2012 to December 31, 2024 were enrolled. All clinical data of the subjects were collected. Patients were divided into two groups according to the duration of break-in period: short break-in group (break-in period <7 days) and long break-in group (break-in period 7-14 days). Baseline clinical characteristics, 90-day complications, and 30-day and 90-day catheter survival rates after catheter insertion were compared between the two groups. Results Thirty-four children were included in the study, including 17 males, with the age of 109.5 (55.0, 147.3) months. There were no statistically significant differences between short break-in group (24 patients) and long break-in group (10 patients) in gender, age, body mass index, indications for initial renal replacement therapy, catheter implantation methods, complications, primary diseases, serum creatinine, blood urea nitrogen, and estimated glomerular filtration rate (all P>0.05). In terms of mechanical complications, there were no statistically significant differences in the incidences of catheter leakage, catheter obstruction and catheter dysfunction between short break-in group and long break-in group (3/24 vs. 1/10, P=1.000; 1/24 vs. 1/10, P=0.508; 3/24 vs. 0/10, P=0.539). For infectious complications, there were no statistically significant differences in the incidences of peritonitis and exit-site infection between short break-in group and long break-in group (11/24 vs. 1/10, P=0.061; 1/24 vs. 1/10, P=0.508). The proportion of 30-day catheter survival after catheter insertion was 20/24 in the short break-in group and 10/10 in the long break-in group (P=0.296). The proportion of 90-day catheter survival after catheter insertion was 13/24 in the short break-in group and 8/10 in the long break-in group (P=0.251). Conclusions For children requiring emergency peritoneal dialysis, break-in periods of less than 7 days and 7 to 14 days after catheter insertion yield similar proportions of complications and catheter survival outcomes. Shortening the break-in period after catheter placement may be a potentially safe and effective treatment strategy.

Objective To observe the effect of SET and MYND domain containing 3 (SMYD3)-mediated histone H3 lysine 4 trimethylation (H3K4me3) on oxidative stress and inflammatory response in hypertensive renal disease (HRD), and to explore its underlying molecular mechanism. Methods (1) Animal experiments: The HRD mouse model was established in 24 male C57BL/6 mice (8 weeks old, weighing 25-30 g) via subcutaneous implantation of osmotic minipumps pre-filled with angiotensinⅡ(AngⅡ). The mice were randomly assigned using a random number table method to the control group, HRD group, BCI-121 (selective inhibitor of SMYD3) group, and HRD+BCI-121 group, with 6 mice in each group. Serum creatinine (Scr), blood urea nitrogen (BUN), and the urine albumin to creatinine ratio were measured. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reduced glutathione (GSH) in renal homogenates were detected. HE and PAS staining were performed to observe renal pathological changes. Immunofluorescence was performed to assess the localization of SMYD3 and quantify F4/80 fluorescence intensity. Western blotting was used to evaluate the protein expression levels of SMYD3 and H3K4me3. Immunohistochemistry was used to detect the protein expression level of thioredoxin-interacting protein (TXNIP). (2) Cell experiments: Human renal proximal tubular epithelial cells (human kidney-2, HK-2) were cultured in vitro. Cells were transfected with negative control small interfering RNA (si?NC) or SMYD3 small interfering RNA (si?SMYD3) and divided into the si?NC group, si?SMYD3 group, si?NC+AngⅡ group and si?SMYD3+AngⅡ group. Western blotting was used to detect the protein expression levels of SMYD3, H3K4me3, heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), TXNIP and NOD?like receptor family pyrin domain?containing protein 3 (NLRP3). Quantitative real-time PCR was performed to measure the mRNA expression levels of inflammatory factors interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α). Fluorescent probe assay was used to detect intracellular reactive oxygen species production. Co-immunoprecipitation was used to verify the interaction between SMYD3 and H3K4me3. Chromatin immunoprecipitation was applied to examine the enrichment of SMYD3 and H3K4me3 in the TXNIP promoter region. Results Animal experiments showed that, compared with the control group, the protein expression levels of SMYD3 and H3K4me3 were significantly higher, BUN, Scr, and urinary albumin-to-creatinine ratio were higher, GSH and SOD levels were lower, and MDA level was higher in the HRD group (all P<0.05). Compared with the control group, renal tubular and interstitial injury was significant, mesangial matrix proliferation was observed, the infiltration of F4/80? macrophages in renal tissue was significantly increased, and the positive expression of TXNIP protein was enhanced in the HRD group. Compared with the HRD group, the protein expression levels of SMYD3 and H3K4me3 were significantly lower in the HRD+BCI-121 group (both P<0.05). Meanwhile, the levels of BUN, Scr and urinary albumin-to-creatinine ratio were significantly decreased (all P<0.05); renal pathological damage was alleviated; the levels of GSH and SOD were significantly increased; the level of MDA was significantly decreased (all P<0.05); the infiltration of F4/80? macrophages in the kidney was reduced in the HRD+BCI-121 group; and the positive expression of TXNIP protein was weakened. Cell experiments showed that, compared with the si-NC group, the si-NC+AngⅡgroup showed lower protein expression levels of HO-1 and NQO1, increased intracellular reactive oxygen species production, and higher mRNA expression levels of IL-6, IL-1β, and TNF-α (all P<0.05). Compared with the si-NC+AngⅡ group, the protein expression levels of HO-1 and NQO1 were significantly increased, intracellular reactive oxygen species production was significantly decreased, and the mRNA expression levels of IL-6, IL-1β, and TNF-α were significantly lower in the si-SMYD3+AngⅡ group (all P<0.05). Co-immunoprecipitation assays confirmed that SMYD3 interacted with H3K4me3 in HK-2 cells. Chromatin immunoprecipitation assays showed that, compared with the si-NC group, the enrichment levels of SMYD3 and H3K4me3 in the TXNIP promoter region and the protein expression levels of TXNIP and NLRP3 were significantly increased in the si-NC+AngⅡ group (all P<0.05). Compared with the si-NC+AngⅡ group, the enrichment levels of SMYD3 and H3K4me3 in the TXNIP promoter region and the protein expression levels of TXNIP and NLRP3 were significantly decreased in the si-SMYD3+AngⅡ group (all P<0.05). Conclusions SMYD3-mediated H3K4me3 modification regulates the TXNIP/NLRP3 signaling pathway, thereby contributing to oxidative stress and inflammatory responses in HRD. These findings suggest that SMYD3 may represent a potential therapeutic target for HRD.

Q fever is a zoonotic disease caused by infection with Coxiella burnetii. There have been few reports of related cases in China. This case report describes a 53-year-old woman with chronic Q fever-induced proteinase 3 (PR3)?anti?neutrophil cytoplasmic antibody (ANCA)- associated vasculitis with renal involvement. The patient had a history of feeding pigeons and undergoing heart valve replacement surgery, placing her in a high-risk group for Q fever infection. The early clinical manifestations of this case lacked specificity, and later were manifested as infective endocarditis with negative blood culture, combined with PR3?ANCA?associated vasculitis and renal damage. Metagenomic next-generation sequencing was used to detect the pathogen in blood and kidney tissue, ultimately confirming the diagnosis of Coxiella burnetii infection. Following treatment with doxycycline, hydroxychloroquine and prednisone, the patient's valvular heart disease improved significantly, and the PR3 antibody nearly turned negative. This case suggests that when PR3?ANCA-related renal impairment is complicated by infective endocarditis, it is necessary to be alert to infections caused by specific pathogens.

Dense deposit disease (DDD), a major subtype of C3 glomerulopathy, is an exceptionally rare pediatric renal disease characterized by persistent hypocomplementemia secondary to dysregulated activation of the alternative complement pathway and the deposition of electron-dense material within the lamina densa of the glomerular basement membrane. The paper reports the diagnostic and therapeutic course of a 10-year-old girl with DDD presenting with persistent hypocomplementemia, and discusses the clinical characteristics and management strategies of pediatric DDD. The patient was admitted with a 7-month history of recurrent proteinuria and edema. A renal biopsy performed prior to admission confirmed DDD. However, the disease proved resistant to glucocorticoid therapy. Her serum complement C3 levels were persistently depressed, yet there were no significant abnormalities in the detection of C3 nephritic factor, complement factor H and complement factor I, or main complement-related genes. Sequential conventional therapies——including intravenous methylprednisolone pulse therapy, glucocorticoids combined with cyclophosphamide or tacrolimus, and plasma exchange yielded unsatisfactory clinical responses. Eculizumab was subsequently introduced as targeted therapy, and the disease did not achieve remission. Thereafter, the therapeutic strategy was modified to a combination of glucocorticoids and mycophenolate mofetil. During the 24-month follow-up, urine protein decreased significantly, renal function remained stable, and no severe adverse events occurred. Currently, clinical evidence supporting the efficacy of eculizumab in pediatric DDD remains limited. This case provides practical insights into the management of refractory childhood DDD.

This article reports a familial case of 17q12 microdeletion syndrome with renal involvement as the initial manifestation. The proband was a 19-year-old male diagnosed with hydronephrosis and renal cysts at a local hospital at age 17, who developed diabetes mellitus requiring insulin therapy at age 18. Due to persistent poor glycemic control, he was referred to our hospital. Given the initial presentation of renal involvement accompanied by early-onset diabetes, maturity-onset diabetes of the young type 5 was strongly suspected. Initial whole-exome sequencing failed to identify pathogenic variants correlating with the clinical phenotype. Subsequent multiplex ligation-dependent probe amplification (MLPA) analysis revealed a large heterozygous deletion spanning exons 1-9 of the hepatocyte nuclear factor 1Bgene. Further copy number variation sequencing revealed that both the father and the son carried a pathogenic heterozygous deletion of 1.42 Mb in the 17q12 region of chromosome 17. Familial validation demonstrated that this deletion was inherited from the father (who presented with gout and early-onset diabetes), while the mother's genetic testing results were normal, leading to a definitive diagnosis of 17q12 microdeletion syndrome. The patient was discharged with a regimen of insulin aspart 6 U before meals, insulin detemir 10 U at bedtime, and acarbose 50 mg three times daily. At 3-month follow-up, fasting blood glucose was 6-8 mmol/L and 2-hour postprandial blood glucose was 9-11 mmol/L. This case suggests that 17q12 microdeletion syndrome should be considered in patients with early-onset diabetes and renal structural abnormalities, and that copy number variation analysis (e.g., MLPA) is warranted when whole-exome sequencing yields negative results.