Objective To explore the prevalence and independent associated factors of vascular calcification (VC) in non-dialysis chronic kidney disease (CKD) patients of stage 3-5. Methods It was a single-center cross-sectional observational study. Non-dialysis stage 3-5 CKD patients ≥18 years old who were admitted to the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from May 1, 2022 to December 31, 2022 with VC evaluation were enrolled. The patients' general information, laboratory examination and imaging data were collected. Coronary artery calcification (CAC), thoracic aorta calcification (TAC), abdominal aorta calcification (AAC), carotid artery calcification and aortic valve calcification (AVC) were evaluated by cardiac-gated electron-beam CT (EBCT) scans, lateral lumbar x-ray, cervical macrovascular ultrasound and echocardiography, respectively. The differences in clinical data and the prevalence of VC at different sites of patients with different CKD stages were compared, and the prevalence of VC at different sites of patients in different age groups [youth group (18-44 years old), middle-aged group (45-64 years old) and elderly group (≥65 years old)] and patients with or without diabetes were compared. Multivariate logistic regression analysis was used to analyse the independent associated factors of VC for different areas. Results A total of 206 patients aged (51±14) years were included, including 129 (62.6%) males. There were 44 patients with CKD stage 3 (21.4%), 51 patients with CKD stage 4 (24.8%), and 111 patients with CKD stage 5 (53.9%). CKD was caused by chronic glomerulonephritis [104 cases (50.5%)], diabetic kidney damage [35 cases (17.0%)], hypertensive kidney damage [29 cases (14.1%)] and others [38 cases (18.4%)]. Among 206 patients, 131 (63.6%) exhibited cardiovascular calcification, and the prevalence of CAC, TAC, AAC, carotid artery calcification, and AVC was 37.9%, 43.7%, 37.9%, 35.9% and 9.7%, respectively. The overall prevalence of VC in young, middle-aged and elderly patients was 24.6%, 73.6% and 97.4%, respectively. With the increase of age, the prevalence of VC in each site gradually increased, and the increasing trend was statistically significant (all P<0.001). The overall prevalence of VC in CKD patients with diabetes was 92.5% (62/67), and the prevalence of VC at each site in the patients with diabetes was significantly higher than that in the patients without diabetes (all P<0.001). Multivariate logistic regression analysis revealed that age (every 10 years increase, OR=2.51, 95%CI 1.77-3.56, P<0.001), hypertension (OR=5.88, 95%CI 1.57-22.10, P=0.009), and diabetes (OR=4.66, 95%CI 2.10-10.35, P<0.001) were independently correlated with CAC; Age (every 10 years increase, OR=6.43, 95%CI 3.64-11.36, P<0.001) and hypertension (OR=6.09, 95%CI 1.33-27.84, P=0.020) were independently correlated with TAC; Female (OR=0.23, 95%CI 0.07-0.72,P=0.011), age (every 10 years increase, OR=3.90, 95%CI 2.42-6.29, P<0.001), diabetes (OR=5.37, 95%CI 2.19-13.19, P<0.001) and serum magnesium (OR=0.01,95%CI 0-0.35, P=0.014) were independently correlated with AAC. Moreover, age and diabetes were independently correlated with carotid artery calcification, AVC and overall VC Conclusions The prevalence of VC in non-dialysis CKD patients of stage 3-5 is 63.59%, of which CAC reaches 37.9%, TAC is the most common one (43.7%), while AVC is the least one (9.7%). Age and diabetes are the independent associated factors for VC of all sites except TAC, while hypertension is an independent associated factor for both CAC and TAC.

Objective To investigate the value of soluble interleukin-6 (IL-6) receptor (sIL?6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients. Methods It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL?6R and its appearance rate (AR) was calculated. Patients were divided into high sIL?6R AR group and low sIL?6R AR group according to median value of sIL?6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL?6R AR. Kaplan?Meier method and log?rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL?6R AR group and low sIL?6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency. Results A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL?6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR （<2 094.7 pg/min） group, high sIL-6R AR （>2 094.7 pg/min） group had older age (t=-3.269, P=0.001), higher body mass index (t=-3.248, P=0.001), proportion of combined diabetes mellitus (χ²=8.890, P=0.003), 24 h glucose exposure (Z=-2.257, P=0.024), 24 h ultrafiltration capacity (Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio (t=-2.609, P=0.010), mass transfer area coefficient of creatinine (Z=-2.308, P=0.021), IL-6 AR (Z=-3.533, P<0.001) and solute glycoprotein 130 AR (Z=-8.670, P<0.001), and lower serum albumin (t=2.595, P=0.010) and residual renal function (t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index (β=0.194, P=0.005), serum albumin (β=-0.215, P=0.002) and dialysate lg[IL?6 AR] (β=0.197, P=0.011) were independently correlated with sIL?6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan?Meier analysis showed that high sIL?6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL?6R AR group (log-rank χ² =5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL?6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency (HR=2.286, 95% CI 1.254-4.165, P=0.007; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions Dialysate sIL?6R level was associated with body mass index, serum albumin and dialysate IL?6 level. Dialysate sIL?6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

Objective To analyze the mutation pathogenicity of the novel compound heterozygous mutation in the PKHD1 gene causing autosomal recessive polycystic kidney disease (ARPKD) family, expand the PKHD1 gene mutation database, and explore the genotype-phenotype correlations of PKHD1 gene mutation causing ARPKD. Methods Clinical data and peripheral blood of a patient with ARPKD caused by the novel compound heterozygous mutation in the PKHD1 gene and their family members were collected. High-throughput sequencing was used to detect pathogenic mutations in the proband, and PCR amplification and Sanger sequencing were used to verify the pathogenic mutations in the family. AlphaFold software was applied to predict changes in protein structure in the present or absent mutations, and the pathogenicity of mutations was analyzed. Results The patient was a young male who underwent splenectomy due to liver cirrhosis and hypersplenism at age 7. He developed end-stage renal disease at age 22, requiring maintenance peritoneal dialysis, and died of severe pneumonia and septic shock at age 24. Genetic testing revealed three compound heterozygous mutations in the PKHD1 gene inherited from his parents: a missense mutation (c.5935G>A) inherited from the father and a missense mutation (c.1187G>A) and a novel splice mutation (c.6332+1_6332+2insG) from the mother. The single missense mutation allele likely contributed to the prolonged survival. c. 6332+1_ 6332+2insG is a novel splicing mutation that has not been reported in the past, which can lead to early termination of protein translation. This discovery expands the PKHD1 gene mutation database. c. 1187G>A (p.S396N) and c.5935G>A (p.G1979R) occur in the PA14 and G8 domains of the protein, respectively, and are associated with early and severe liver phenotypes in patients. Conclusions The mutation types and amino acid localization of the PKHD1 gene are associated with the heterogeneity of clinical phenotypes in ARPKD patients. Analyzing structural changes in proteins before and after mutations can help understand the pathogenicity at a molecular level, establishing genotype-phenotype correlations and providing valuable insights for assessing prognosis and identifying high-risk ARPKD patients early.

Objective To summarize and analyze the clinical phenotype and genotype characteristics of atypical hemolytic uremic syndrome (aHUS) in Chinese children. Methods It was a retrospective study. The clinical data and genetic results of 6 children with aHUS admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2016 to October 2022 were analyzed, and literature on Chinese aHUS children with genetic screening data by searching databases such as Wanfang, CNKI, and PubMed were reviewed and summarized. Through literature search, the children with aHUS were divided into genetic variation group and non-genetic variation group according to the results of genetic testing, and the differences of clinical phenotype, laboratory examination, follow-up and outcomes were compared between the two groups. Logistic regression method was used to analyze the risk difference of disease recurrence, end-stage kidney disease and death between genetic variation group and non-genetic variation group. Results Among the 6 aHUS children in this center, there were 1 male and 5 females, with onset age of 7 months to 10 years old. Four patients had gene variations, including 1 patient of complement factor H (CFH) gene variation, 1 patient of C3 gene variation, and 2 patients of CFHR1 combined with CFHR3 gene variation. Six children had gross hematuria, proteinuria, hypertension and decreased complement C3. The mean values of serum creatinine in 4 genetic variation and 2 non-genetic variation children were 153.9 μmol/L and 214.3 μmol/L, respectively; the mean values of estimated glomerular filtration rate were 26.4 ml·min^-1·(1.73 m²)^-1 and 28.9 ml·min^-1·(1.73 m²)^-1, respectively; the mean values of hemoglobin were 81 g/L and 57 g/L; the mean values of platelet were 46×10⁹/L and 71×10⁹/L; the mean values of lactic dehydrogenase were 2 408 U/L and 2 106 U/L, respectively; there were 1 and 2 cases of positive CFH antibody, and 1 and 1 case of nervous system complication, respectively. Ninety-seven aHUS children were retrieved including the reported 6 cases in this center, with 60 males and 37 females, and median onset age of 5 years old. The positive detection rate of genetic variation was 58.8% (57/97). The main type of genetic variation was CFHR gene variation (43.9%, 25/57), followed by CFH gene variation (33.3%, 19/57).There was no significant difference in onset age, sex distribution, proportions of gross hematuria, massive proteinuria, hypertension, complement C3 decline, positive CFH antibody and treatment method, platelet, and lactic dehydrogenase between genetic variation group and non-genetic variation group (all P>0.05). Compared with the genetic variation group, non-genetic variation group had higher serum creatinine (Z=2.311, P=0.021) and lower hemoglobin (Z=-2.636, P=0.008). The median follow-up time in genetic variation group and non-genetic variation group was 1 year and 2 years, respectively. The proportions of non-remission and recurrence in the genetic variation group were significantly higher than those in non-genetic variation group (χ²=12.016,P=0.002; χ²=4.689,P=0.030). Logistic regression analysis showed that the recurrence risk of aHUS in children with genetic mutations was higher than that in children with non-genetic mutations (OR=2.807, 95% CI 1.014-7.772). Conclusions The main type of aHUS gene variation in Chinese children is CFHR gene variation, and the children with gene variation have poor prognosis and a higher risk of recurrence.

Objective To investigate the role of complement C3a receptor in the diabetic nephropathy pathogenesis of db/db mice, and to provide a new target for prevention and treatment of diabetic nephropathy. Methods Twelve 8-week-old male mice with type 2 diabetes mellitus (db/db mice) and 6 wild-type (db/m) mice were reared in the special pathogen free environment. The mice were grouped into db/m group, db/db group and C3a receptor antagonist group, with 6 mice in each group. db/db model mice were intraperitoneally injected with C3a receptor antagonist (SB290157, 10 mg/kg) once every two days for 8 weeks in C3a receptor antagonist group. Blood and urine samples were collected, and body weight of mice, fasting blood glucose, serum creatinine, blood urea nitrogen, urinary microalbumin/urinary creatinine and urinary N-acetyl-β-D-glucosaminidase (NAG) were detected. Renal tissues were collected, and HE, PAS and Masson stainings were used to observe the pathological changes. Immunohistochemistry, immunofluorescence and Western blotting were used to detect the protein expression levels of C3 and C3a receptor. Western blotting was used to analyze the protein expression levels of kidney injury molecule-1 (Kim?1), α-smooth muscle actin (α?SMA), zonula occluden-1 (ZO?1), vimentin and E?cadherin in renal tissues. Immunofluorescence was used to analyze the protein expression levels and distribution of α?SMA, ZO?1 and Kim?1, and immunohistochemistry was used to analyze the protein expression levels of interleukin-1 (IL?1) and tumor necrosis factor-α (TNF?α). TUNEL assay was used to detect apoptotic cells in renal tissues. Results Compared with db/m group, body weight, fasting blood glucose, urinary microalbumin/urinary creatinine and urinary NAG in db/db group were significantly higher, while these indicators in C3a receptor antagonist group were slightly lower than those in db/db group (all P<0.01). There were no significant differences in serum creatinine and blood urea nitrogen among the three groups (all P>0.01). Compared with db/m group, db/db group had glomerular hypertrophy, necrosis and exfoliation of renal tubular epithelial cells, and dilation of renal tubules, and C3 and C3a receptor protein expression levels were higher (both P<0.01). Compared with db/db group, C3a receptor antagonist group had less glomerular lesions, mild necrosis of renal tubular epithelial cells and less tubular dilation. Compared with db/m group, the protein expression levels of Kim?1, IL?1 and TNF?α in kidney tissues of db/db group were significantly higher, while Kim?1, IL?1 and TNF?α in C3a receptor antagonist group were significantly lower than those in db/db group (all P<0.01). Compared with db/m group, the protein expression levels of α?SMA and vimentin of renal tubular epithelial cells in db/db group were significantly higher, while the protein expression levels of ZO?1 and E?cadherin were significantly lower (all P<0.01). Compared with db/db group, the protein expression levels of α?SMA and vimentin of renal tubular epithelial cells in C3a receptor antagonist group were significantly lower, and the protein expression levels of ZO?1 and E?cadherin were significantly higher (all P<0.01). Compared with db/m group, the number of apoptotic cells of kidney tissues in db/db group was increased, while the number of apoptotic cells in C3a receptor antagonist group was reduced compared with db/db group. Conclusions The expression levels of C3 and C3a receptor of kidney tissues in db/db mice are significantly increased. Antagonistic C3a receptor can reduce the body weight, blood glucose, urinary microalbumin/urinary creatinine and urinary NAG, alleviate renal pathological injury, inhibit renal tissue inflammation, apoptosis and renal tubule epithelial?mesenchymal transition in db/db mice.

It was a single-center cross-sectional study to investigate the association of serum C3 level with blood pressure and estimated glomerular filtration rate (eGFR) in patients with idiopathic membranous nephropathy (IMN). The clinical and pathological data of 98 patients with IMN diagnosed by renal biopsy in the Department of Nephrology of East Hospital Affiliated to Tongji University from August 1, 2018 to October 31, 2023 were retrospectively analyzed. The demographic characteristics, serum complement C3 and other clinical data were compared between the non-hypertension group (n=37) and hypertension group (n=61). Pearson or Spearman correlation analysis method was used to analyze the correlation between serum C3 and eGFR in IMN patients and IMN patients with hypertension. Multiple linear regression analysis was used to analyze the related factors of eGFR in IMN patients with chronic kidney disease stage 1-3 in hypertension group. The results showed that compared with the non-hypertension group, the patients in hypertension group were older, and had higher levels of serum creatinine, cystatin C, urinary microalbumin to creatinine ratio, serum C3 and C4, and lower eGFR (all P<0.05). The correlation analysis showed that there was no correlation between serum C3 level and eGFR in IMN patients (r=0.118, P=0.247). However, serum C3 level was positively correlated with eGFR in IMN patients with hypertension (r=0.325, P=0.011). Multiple linear regression analysis showed that eGFR was negatively correlated with age (β=-0.328, P=0.013), and positively correlated with serum C3 level (β=0.228, P=0.048). The study shows that serum C3 level in hypertension group is higher than that in non-hypertension group in IMN patients. Moreover, serum C3 is positively correlated with eGFR.

Glycogen storage disease (GSD) is a rare autosomal recessive inherited disease in clinic. The paper reported a case of GSD Ⅰ a diagnosed by genetic testing, who had been experiencing numerous joint pains for 4 years, and had increased serum creatinine and severe high lactic acid metabolic acidosis. The serum creatinine declined and acidosis recovered after active fluid therapy and acidosis correction. The paper summarized the characteristics of this GSD patient with renal insufficiency and the relevant literature contents, to improve the understanding of clinicians on the disease and treatment effect.

A 65-year-old male was admitted because of anorexia, gross hematuria, skin purpura and acute renal insufficiency. Cardiovascular interventional examination was performed in other hospital 3 months before admission. During hospitalization, multiple blood cultures suggested positive Streptococcus gordonii, decreased blood complement and increased rheumatoid factor. Echocardiography revealed mitral valve vegetations (4 mm), and renal biopsy revealed endocapillary proliferative glomerulonephritis, diagnosed as infective endocarditis-associated glomerulonephritis. The combination of effective antibiotics and plasma exchange therapy significantly improved clinical symptoms and acute renal failure. The case suggests that plasma exchange is effective and safe in the treatment of immune complex-mediated glomerulonephritis caused by infective endocarditis, providing a new option for the treatment of such diseases.

This paper reports a case of recurrent peritoneal dialysis-associated peritonitis caused by Salmonella, as identified through metagenomic next-generation sequencing. This patient was treated regularly with peritoneal dialysis due to stage 5 chronic kidney disease. One month ago, she was hospitalized for peritoneal dialysis-associated peritonitis. The result of bacterial culture of the dialysate was Salmonella, and she was discharged after anti-infective treatment for 3 weeks. However, on the 12th day after discharge, the patient was readmitted to the hospital due to peritonitis.Both metagenomic next-generation sequencing and bacterial culture of the fluid confirmed the presence of Salmonella. After 3 weeks of intraperitoneal and intravenous anti-infection treatment, the patient underwent metagenomic next-generation sequencing to assess pathogen eradication before discharge.

Diabetic nephropathy (DN) is a microvascular complication caused by diabetes mellitus, which often leads to structural and functional damages of several kidney cell types, and has become an important cause of chronic kidney disease and end-stage renal disease. Connexins are involved in maintaining cell function and tissue homeostasis in various organs by forming semi-channels and mediating gap-junctional intercellular communication. Connexin 43 (Cx43) is the most abundant and widely studied connexin in kidney. Accumulating evidences have shown that Cx43 is involved in the pathological process associated with glomerular mesangial cells, podocytes and renal tubular epithelial cells during the development of DN. However, the molecular mechanism of Cx43 in regulating kidney cell homeostasis of DN is still unclear. The paper systematically reviews the relationship between Cx43 and pathogenesis of DN from the perspective of signaling pathway regulation, and explores the therapeutic potential of targeting Cx43 in the intervention of DN.

IgA nephropathy (IgAN) is the most common primary glomerular disease and main reason of progression to end?stage renal disease in patients with kidney diseases. Various clinical, pathological, demographic and new factors discovered by researchers in recent years play important roles in the prognosis assessment of IgAN. Furthermore, developing prognostic evaluation models based on several different factors to identify patients at high risk of progression in the early disease stage is clinically significant. This article reviews the researches progress of influencing factors and relevant evaluation models for prognosis of IgAN.

Medical accessibility reflects the actual ability of patients to use healthcare services, and is an important indicator for evaluating the quality of healthcare services from both the supply and demand perspectives. Inadequate medical accessibility is prevalent in dialysis patients and adversely affects clinical prognosis. In recent years, the number of peritoneal dialysis patients in China has increased remarkably, and the inequality of medical accessibility is particularly serious. However, the relationship between medical accessibility and clinical prognosis of peritoneal dialysis is still uncertain, and requires further study to provide evidence for formulating relevant health policies. This article reviews the concept and research indicators of medical accessibility, and the influence of medical accessibility on the clinical prognosis, to raise the awareness of medical accessibility inequality and help to improve care quality and survival rate in dialysis patients.