Objective To summarize and analyze the clinicopathological characteristics of patients with DNAJ heat shock protein family member B9 (DNAJB9)-positive fibrillary glomerulonephritis (FGN). Methods The clinical and pathological data of 5 patients with DNAJB9-positive FGN diagnosed in Peking University First Hospital from January 2011 to January 2021 were retrospectively collected and analyzed. Results Among the 5 patients, the female to male ratio was 4∶1, and the median age was 29 years old (24-71 years old). The clinical manifestations included 2 cases with nephrotic syndrome and 3 cases with proteinuria. One patient had gross hematuria, and 4 cases had mild microscopic hematuria. None of the 5 patients had evidence of monoclonal gammopathy. The renal pathological pattern of FGN showed mesangial-proliferative glomerulonephritis, mesangial nodular sclerosis, membranoproliferative glomerulonephritis, and atypical membranous nephropathy. Crescents formation could be accompanied. Immunofluorescence staining showed smudgy and granular IgG and C3 deposition in the mesangial region and capillary wall, and the subtypes of IgG were mainly IgG1 and IgG4. Under electron microscopy, fibrillary deposits with a diameter of 8-30 nm were observed in the mesangial and subendothelial area, accompanied by deposition in basement membrane and occasionally subepithelial area. The renal prognosis of FGN patients was poor. One patient entered end-stage renal disease within one week, and another patient entered end-stage renal disease within one year despite immunosuppressant therapy in 2 cases with nephrotic syndrome at onset. One patient had worsening proteinuria despite renin-angiotensin system (RAS) blocker treatment. Two patients achieved complete renal remission and stable renal function after RAS blocker treatment. Conclusions Most FGN patients in China are young people. The main clinical manifestations are proteinuria or mild microscopic hematuria. The diagnosis depends on the discovery of fibrillary deposits in the mesangial area and subendothelial area with a diameter of about 10-30 nm under the electron microscope. DNAJB9 protein immunohistochemical staining can be used as an important marker for the diagnosis of FGN. The prognosis of FGN kidney is poor, and there is no effective targeted treatment option now.

Objective To analyze the clinicopathologic features and prognosis of children with Henoch-Sch?nlein purpura nephritis (HSPN). Methods The clinicopathological data of children with HSPN who were followed up for more than 5 years and underwent renal biopsy in Jinling Hospital affiliated to Medical School of Nanjing University from January 2001 to June 2015 were retrospectively analyzed. The follow-up endpoint event was defined as estimated glomerular filtration rate (eGFR)<90 ml·min^-1·(1.73 m²)^-1. Participants were divided into two groups according to whether the children had reached the primary endpoint event or not. Cox proportional hazards model was used to analyze the influencing factors of renal poor prognosis in children with HSPN. Kaplan-Meier survival curve method was used for survival analysis, and log-rank test was used to compare the difference of renal cumulative survival rate between segmental sclerosis/adhesion (S1) group and non-segmental sclerosis/adhesion (S0) group. Receiver operating characteristic curve (ROC curve) and area under the curve (AUC) were used to evaluate the diagnostic value. Results A total of 130 children with HSPN were enrolled in the study. The median onset age was 11.7(8.6, 13.3) years old, of whom 71 cases were males (54.6%). At a median follow-up time of 100.0(75.8, 119.0) months, 12 cases (9.23%) with HSPN reached the primary endpoint event. Compared with the non-endpoint event group, the endpoint event group had higher proportion of hypertension, higher levels of 24-hour urinary protein, serum cholesterol, serum uric acid, and serum creatinine, and lower levels of serum albumin (all P<0.05). There was no statistical difference in treatment between the two groups (all P>0.05). In terms of pathological features, compared with the non-endpoint event group, the endpoint event group had higher proportion of mesangial hyperplasia (M1), S1, tubular atrophy/interstitial fibrosis (T1/T2) and Glomerulus-Bowman's capsule adhesion (all P<0.05). Multivariate Cox regression model showed that S1 was significantly correlated with renal poor prognosis (HR=7.739, 95%CI 1.422-42.114, P=0.018). As was revealed in a Kaplan-Meier plot, renal cumulative survival rate in the S1 group was significantly lower than that in the S0 group (log-rank χ²=17.069, P<0.001). The ROC curve showed S1 accurately predicted the outcome (AUC=0.710, 95%CI 0.549-0.872) with specificity of 0.667(95%CI 0.349-0.901) and specificity of 0.754(95%CI 0.667-0.829). Conclusions S1 is an independent risk factor affecting renal poor prognosis and has a diagnostic value.

Objective To explore clinicopathological features and prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in children induced by antithyroid drugs. Methods The clinicopathological features, treatment and prognosis of 3 children with AAV induced by antithyroid drugs in the Department of Pediatric Nephrology and Rheumatology of the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively, and the literatures were reviewed. Results (1) Among the 3 cases, there were 2 females and 1 male, whose ages were 12.6, 13.9 and 13.1 years old, respectively. All patients had medication history of propylthiouracil (PTU) and/or methimazole (MMI) before onset. Initial manifestation was pallor and renal involvements with nephrotic proteinuria, hematuria and renal function abnormality, while 2 of them had hypertension. Extrarenal manifestations were also presented: case 1 presented with rash, arthralgia and cardiac insufficiency; case 2 had brain involvement with repeated convulsions; case 3 presented with arthralgia and lung involvement. They were all tested positive for p-ANCA and MPO-ANCA. Initial renal histopathology of the 3 cases were consistent with ANCA-associated glomerulonephritis, which were classified into sclerosis, crescentic and mixed class respectively. After 8 months of treatments, repeated renal biopsy of case 3 had demonstrated progression to sclerosis class. Antithyroid drugs (PTU or MMI) were discontinued in 3 cases, and the children were all treated with corticosteroid combined with intravenous pulse cyclophosphamide therapy. Plasma exchange was performed in case 2 and case 3 due to rapidly progressive glomerulonephritis and disease recurrence (suspected pulmonary hemorrhage), respectively. Case 3 was treated with rituximab combined with mycophenolate mofetil after recurrence. The extrarenal symptoms relieved quickly after treatments in all cases. P-ANCA and MPO-ANCA became negative in case 1 and case 2 after 6 months of treatments but they were persistently positive in case 3. Three cases were followed up for 24 months, 10 months and 12 months, respectively: case 1 develop chronic kidney disease (CKD) stage 2 with normal urinalysis; case 2 develop CKD stage 5 and had sudden death at home at 10-month follow-up; case 3 develop CKD stage 4 with nephrotic proteinuria and microscopic hematuria. (2) There were totally 30 pediatric cases with AAV induced by PTU and MMI, including 27 reported cases in the literature and 3 cases in this study. Symptoms of AAV appeared in children after an average administration of (37.5±4.0) months of PTU (range from one month to 96 months and 8 months of MMI alone). Kidney (28 cases, 93.3%) and lung (12 cases, 40.0%) were commonly involved, while brain (2 cases, 6.7%) was rarely involved. The pathological changes of kidney were crescent nephritis (5/23) and necrotizing pauci-immune complex nephritis (11/23). The total remission rate was 93.3%(28/30) after antithyroid drugs withdrawal and treatment with corticosteroids and immunosuppressive therapy, however, there were still severe cases with progression to CKD stage 5, and death. (3) Thirty cases were divided into complete response group (n=19) and incomplete response group (n=11) according to the treatment response. Compared with complete response group, the proportions of massive proteinuria (8/11 vs 5/19), fibrinoid necrosis (7/9 vs 4/14), deposition of immune complex in renal tissues (6/9 vs 2/14) and administration of immunosuppressants (10/11 vs 5/19), and degree of tubular atrophy (0/1/2/3 grade, 2/4/2/1 vs 9/5/0/0) in incomplete response group were higher (all P<0.05). Conclusions PTU and MMI can both induce AAV in children, and AAV may occur after short-term course of administration. Kidney and lung are commonly involved while brain involvement is rarely seen. Timely withdrawal of antithyroid drugs and proper treatments with corticosteroids and immunosuppressants can result in high remission rate, though there are still some severe cases. Nephrotic-range proteinuria, renal fibrinoid necrosis, immune-complex deposition and tubular atrophy may be the risk factors of AAV for poor prognosis.

Objective To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood. Methods 4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood. Results A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group (n=1 017), moderate-increasing BMI group (n=1 353), and high-increasing BMI group (n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively (P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6）, 96.2(86.4, 109.7), 95.3（87.5, 125.0) ml·min^-1·(1.73 m²)^-1, respectively (P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [β=3.16(95%CI 1.02-5.31), P_trend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [β=-2.30(95%CI -5.18-0.57), P_trend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle (OR=2.83, 95%CI 1.84-4.36, P_trend<0.001). Conclusions Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.

Objective To analyze the clinical and pathological characteristics, treatment and prognosis of renal changes in patients with Kimura disease and improve the clinicians′ understanding on renal manifestations of Kimura disease. Methods The clinical data of Kimura disease patients with definite diagnosis and detailed data in Peking Union Medical College Hospital from January 1980 to August 2020 were retrospectively analyzed. The patients were divided into renal impairment group and non-renal impairment group according to whether the kidney was involved or not and the related clinical data between the two groups were compared. The patients presenting with nephrotic syndrome were followed up. Results There were 60 patients with Kimura disease confirmed by pathological diagnosis with 48 males. The median age was 33(3, 62) years old, and the median duration was 36(12, 111) months. There were 18 cases complicated with renal injury in 49 patients with complete routine urine and renal function examination and the main manifestations of renal injury were proteinuria and/or microscopic hematuria. There was no significant difference at age, sex and absolute value of eosinophils between the two groups (all P>0.05). Compared with the renal inpairment group, patients in non-renal inpairment group had longer course of disease, higher levels of hypersensitive C-reactive protein and erythrocyte sedimentation rate, and lower median values of total eosinophils and total IgE, but there was no statistically significant difference (all P>0.05). Among the patients with renal involvement, 6 patients met the diagnostic criteria for nephrotic syndrome, and 5 of them completed renal biopsies. The renal pathological diagnosis was membranous nephropathy in 2 cases and minimal change disease in 3 cases, and no interstitial eosinophil infiltration was found in renal biopsy tissues. These patients had a good response to glucocorticoids and/or immunosuppressive therapy, and achieved complete remission of nephrotic syndrome; at the same time, lymphadenopathy caused by Kimura disease could be well controlled. Conclusions Kimura disease can combine with various renal lesions, and the pathology of nephrotic syndrome can be membranous nephropathy or minimal change nephropathy. After energetic treatment of glucocorticoids and/or immunosuppressive therapy, nephrotic syndrome can be completely relieved, and lymphadenopathy can be well controlled. The relationship between Kimura disease and renal disease needs further study.

Objective To explore the effects of different blood purification modes on short-term complications, quality of life and survival prognosis of patients with uremia. Methods The patients with uremia who received hemodialysis treatment at two blood purification centers in the First Affiliated Hospital of Dalian Medical University and Renal Care Hospital from January 1, 2017 to December 1, 2019 were enrolled in this study. According to the different blood purification modes, the patients were divided into high-flux hemodialysis (HFHD) group (HFHD group), HFHD+hemodiafiltration (HDF) per month group (HDF once a month group) and HFHD+HDF per week group (HDF once a week group). The three groups were matched with the ratio of 1∶1∶1 on the duration of hemodialysis based on the HDF once a week group. The differences of clinical indicators, medication and rehospitalization between baseline and end points were compared. The patients were followed up to 12 months after enrolled in the study or death. Patients in each group were divided into two subgroups, newly imported group and non-newly imported group based on whether or not they were newly enrolled in HD therapy from January 1, 2017 to December 1, 2019. Kaplan-Meier survival curve and Cox regression model were used to analyze the difference of survival prognosis in non-newly imported patients with different dialysis modes, and the EuroQol-5 Dimensions (EQ-5D-5L) was used to evaluate the difference of quality of life in newly imported patients after different dialysis modes treatment. Results A total of 139 patients were enrolled, including 43 cases in the HFHD group, 47 cases in the HDF once a month group, and 49 cases in the HDF once a week group. After treatment, the levels of serum creatinine, serum urea nitrogen and serum potassium in the HDF once a week group were significantly lower than those in the other two groups (both P<0.05). Compared with the other two groups, the consumptions of erythropoietin and intravenous iron, the hospitalization times and hospitalization days in the HDF once a week group were significantly decreased, and the level of albumin in the HDF once a week group were significantly increased (all P<0.05). Kaplan-Meier survival curve analysis of non-newly imported hemodialysis patients showed that the survival rate in the HDF once a week group was higher than that in the other two groups (Log-rank χ²=7.020, P=0.030). Multivariate Cox regression analysis showed that HDF was a protective factor for post-dialysis survival in uremia patients (HR=0.472, 95%CI 0.188-0.836, P=0.023). The total efficacy of EQ-5D-5L of the newly imported patients in the HDF once a week group was significantly higher than that in the other two groups (F=7.293, P=0.002). Conclusions The combination of HFHD with HDF per week therapy can significantly improve the short-term quality of life and nutritional status, and reduce the hospitalization frequency, length of hospital stay, the consumption of erythropoietin and intravenous iron and mortality risk in uremia patients.

Objective To explore the level of tibial growth plate chondrocyte mitophagy in young rats with chronic renal failure (CRF) and its effect on chondrocyte apoptosis. Methods Male 4-week-old Sprague-Dawley rats were randomly divided into two groups according to random number table method: normal control group (n=20, intragastric administration with distilled water) and CRF group (n=20, given adenine suspension 150 mg·kg^-1·d^-1). All the young rats were sacrificed after continuous gavage for 6 weeks. The length of tibia was measured on X ray film, the width of tibia growth plate was measured and compared on histological section, and the apoptosis rate of chondrocytes in growth plate was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The growth plate chondrocytes of two groups were isolated and cultured to the third generation in vitro, and the apoptosis rate of chondrocytes was detected by TUNEL assay. The co-localization of mitochondria and autophagy lysosomes in chondrocytes was observed by double fluorescence staining. Western blotting was used to detect the level of mitochondrial marker protein translocate of the outer mitochondrial membrane-20 (Tom-20) and autophagy marker light chain-3 protein (LC-3). The mitophagy of growth plate chondrocytes was observed by transmission electron microscope. Results Compared with the normal control group, the tibia length of CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], and the relative width of growth plate in histological section was narrower (0.56±0.19 vs 1.00±0.21, t=6.744, P<0.001). The apoptosis rate of chondrocytes in growth plate in CRF group was higher than that in the normal control group (17.2%±4.8% vs 5.1%±3.4%, t=6.505, P<0.001). The apoptosis rate of chondrocytes cultured in vitro in CRF group was higher than that in the normal control group (11.8%±6.2% vs 3.1%±1.2%, t=4.357, P<0.001). The result of double influorescence staining showed that there was co-localization between mitochondria and autophagy lysosomes in CRF group. Western blotting results showed that the levels of LC-3 protein (t=8.944, P<0.001) and Tom-20 protein (t=6.708, P<0.001) in CRF group were lower than those in the normal control group. Conclusion The level of tibial growth plate chondrocyte mitophagy in young rats with CRF increases, which will lead to a decrease in the number of mitochondria, an increase in the apoptosis and a decrease in the number of chondrocytes, and eventually lead to dysplasia of tibia.

Objective To investigate the effect of interleukin (IL)-7 receptor α (IL-7Rα) antibody on the immune inflammation and renal injury in MRL/lpr lupus mice. Methods Fifteen 3-4-week-old female MRL/lpr lupus mice (specific pathogen free) weighing 15-16 g were bred to 14-week-old and randomly divided into three groups: IL-7Rα antibody intervention group, isotype antibody (positive control) group and normal saline (negative control) group. The mice in the threc groups were intraperitoneally injected with IL-7Rα antibody, isotype antibody and normal saline respectively, with 100 μg three times a week for 4 weeks. At the age of 18-week old, the mice were sacrificed. Twenty-four-hour urinary protein was detected by Coomassie brilliant blue method, serum creatinine was detected by peroxidase method, and the expression of autoantibody (anti-double strand DNA antibody) and inflammatory factors such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-21 was detected by enzyme-linked immunosorbent assay method. Renal pathology was detected by PAS and Sirius red staining, and CD3 and F4/80 in renal tissues were detected by immunohistochemistry method. Regulatory T cells, follicullar helper T cells (Tfh) and follicular regulatory T cells (Tfr) were detected by flow cytometry. Results The 24-hour urinary protein, serum creatinine, serum anti-double strand DNA antibody and serum IFN-γ and IL-21 in the IL-7Rα antibody intervention group were significantly lower than those in the control groups (all P<0.01). However, there was no significant difference in serum TNF-α among the three groups (F=0.39, P>0.05). The positive infiltrating cells of CD3 and F4/F80, and the ratio of type Ⅰ/Ⅲ collagen fibers (F=41.11, P<0.01) of renal tissues in the IL-7Rα antibody intervention group were lower than those in the other two groups. Compared with the control groups, the ratio of regulatory T cells (CD4⁺CD25⁺Foxp3⁺)/effector T cells (CD4⁺CD25⁺) in blood of IL-7Rα antibody intervention group increased (F=21.64, P<0.01), while the ratio of Tfr (CD4⁺CXCR5⁺Foxp3⁺)/Tfh (CD4⁺CXCR5⁺) in peripheral blood and spleen increased (F=38.95, P<0.01; F=12.90, P<0.01). Conclusion IL-7Rα antibody can reduce the production of autoantibodies such as anti-double strand DNA antibody and inflammatory factors by increasing the ratio of regulatory T cells and Tfr/Tfh, thus alleviating immune inflammation and renal damage in MRL/lpr lupus mice.