Objective:To discuss the effect of angiotensin(1-7)[Ang(1-7)]on high-turnover bone disease in the uremic rats,and to clarify its possible mechanism.Methods:Thirty SD rats were randomly divided into sham operation group(n=6)and experimental group(n=24).The rats in experimental group underwent 5/6 nephrectomy(Platt method)+high-phosphorus(P)diet[1.2％P,1.0％calcium(Ca)]to establish the model of uremic high-turnover bone disease.The successfully modeled rats were then randomly divided into model group,Ang(1-7)group,angiotensin-converting enzyme 2(ACE2)activator dimethylacetamide amidoxime(DIZE)group,and Mas receptor antagonist group(A779 group),with 6 rats in each group.The levels of Ca,P,blood creatinine(Scr),blood urea nitrogen(BUN),and 24 h urinary protein(UP)in serum of the rats in various groups were detected by automatic biochemical analyzer at 12 and 18 weeks after operation;immunofluorescence staining was used to detect the levels of intact parathyroid hormone(iPTH)in the rats in various groups;ELISA method was used to detect the levels of osteocalcin(OC),type Ⅰ collagen N-terminal peptide(NTX),and tartrate-resistant acid phosphatase(TRAP)-5b in serum of the rats in various groups;high-resolution micro-CT scan was used to detect the bone density(BMD),tissue mineral density(TMD),trabecular thickness(Tb.Th),and trabecular separation(Tb.Sp)in femur tissue of the rats in various groups;Von Kossa staining and Giemsa staining were used to observe the pathomorphology of cortical bone and trabecular bone of the rats in various groups,and the trabecular bone volume(TBV)was calculated;fluorescence microscope was used to detect the mineral apposition rates(MAR)of the rats in vanious groups,and the osteoblast index(OBI)and osteoclast index(OCI)of the rats in various groups were calculated.Results:At 12 and 18 weeks after operation,compared with sham operation group,the weights of the rats in model group,Ang(1-7)group,DIZE group,and A779 group were decreased(P＜0.05).At 12 and 18 weeks after operation,compared with sham operation group,the levels of 24 h UP,Scr,and BUN in serum of the rats in model group,Ang(1-7)group,DIZE group,and A779 group were increased(P＜0.05);at 18 weeks after operation,compared with model group,the levels of 24 h UP and Scr in serum of the rats in Ang(1-7)group and DIZZ group were decreased(P＜0.05),and the levels of 24 h UP,Scr and BUN in serum of the rats in A779 group were increased(P＜0.05).The successful establishment of the uremic high-turnover bone disease model was confirmed.At 12 and 18 weeks after operation,compared with sham operation group,the serum iPTH,P,OC,NTX,and TRAP-5b levels ofthe rats in model group,Ang(1-7)group,DIZE group,and A779 group were all significantly increased(P＜0.05);at 18 weeks after operation,compared with model group,the serum NTX and TRAP-5b levels of the rats in Ang(1-7)group and DIZE group were decreased(P＜0.05),while the serum iPTH,P,NTX and TRAP-5b levels in A779 group were increased(P＜0.05).The high-resolution micro-CT scan results showed that compared with sham operation group,the values of femur BMD and TMD of the rats in model group,Ang(1-7)group,DIZE group,and A779 group were all significantly decreased(P＜0.05);compared with model group,the values of femur BMD and TMD of the rats in Ang(1-7)group and DIZE group were increased(P＜0.05),while the values of BMD and TMD of the rats in A779 group were decreased(P＜0.05).Compared with sham operation group,the femur Tb.Th of the rats in model group was decreased(P＜0.05),and the Tb.Sp was increased(P＜0.05);the femur Tb.Th of the rats in Ang(1-7)group and DIZE group were increased(P＜0.05),and the Tb.Sp was decreased(P＜0.05).Compared with model group,the femur Tb.Th of the rats in A779 group was decreased(P＜0.05),and the Tb.Sp was increased(P＜0.05).The bone pathological examination results showed that compared with sham operation group,the femur TBV of the rats in model group,Ang(1-7)group,DIZZ group and A779 group were decreased(P＜0.05),and MAR,OBI and OCI were increased(P＜0.05);compared with model group,the OBI and OCI of the rats in Ang(1-7)group and DIZE group were decreased(P＜0.05),and TBV was increased(P＜0.05),while the OBI and OCI of the rats in A779 group were increased(P＜0.05),and TBV was decreased(P＜0.05).Conclusion:The ACE2/Ang(1-7)/Mas axis improves high-turnover bone disease in the uremic rats.

Objective: To examine the causal relationship between body mass index (BMI) and 25 types of autoimmune diseases (ADs) using Mendelian randomization (MR) study method. Methods: The genome-wide association study (GWAS) data for BMI and 25 types of ADs were obtained from IEU OPEN GWAS database. Single nucleotide polymorphisms (SNPs) related to BMI were used as instrumental variables, 25 types of ADs were used as study outcomes, and MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy was tested using MR-Egger regression and MR-PRESSO, and results robustness was verified with leave-one-out method. Results: Cochran's Q test showed heterogeneity of MR analysis results (P<0.05), and a random effect model was employed. The results of MR analysis showed that elevated BMI increased the incidence risks of type 1 diabetes mellitus (OR=1.519, 95%CI: 1.281-1.801), IgA nephropathy (OR=1.227, 95%CI: 1.134-1.327), adult Still disease (OR=1.002, 95%CI: 1.001-1.003), multiple sclerosis (OR=1.303, 95%CI: 1.115-1.523), narcolepsy (OR=1.029, 95%CI: 1.017-1.040), Hashimoto thyroiditis (OR=1.561, 95%CI: 1.391-1.751), autoimmune hepatitis (OR=1.481, 95%CI: 1.076-2.038), rheumatoid arthritis (OR=1.209, 95%CI: 1.054-1.386), psoriasis vulgaris (OR=1.719, 95%CI: 1.427-2.070) and pernicious anemia (OR=1.001, 95%CI: 1.000-1.002). No causal relationship was found with other ADs (all P>0.05). MR-Egger regression identified no horizontal pleiotropy of instrumental variables (all P>0.05), while MR-PRESSO test identified partial horizontal pleiotropy (all P<0.05), which remained consistent with the original results after adjustment (P>0.05). Leave-one-out analysis showed results robustness. Conclusion There are causal relationship among BMI and type 1 diabetes mellitus, IgA nephropathy, adult Still disease, multiple sclerosis, narcolepsy, Hashimoto thyroiditis, autoimmune hepatitis, rheumatoid arthritis, psoriasis vulgaris and pernicious anemia.

Objective To investigate the effect of body mass index(BMI)on the clinicopathological characteristics of patients with idiopathic membranous nephropathy(IMN).Methods A total of 261 patients with IMN were divided into the normal group(66 cases),the overweight group(105 cases)and the obese group(90 cases)according to BMI.Clinical and renal pathological data of patients were compared between the three groups.The correlation between BMI and clinicopathological indexes was analyzed by Pearson or Spearman's correlation.The influencing factors of estimated glomerular filtration rate(eGFR)were analyzed by multiple linear regression,and the influencing factors of interstitial fibrosis(IF),tubular atrophy(TA),glomerulosclerosis(GS)and mesangial cell proliferation(MCP)were analyzed by binary Logistic regression.Results Compared with the normal group,the prevalence of diabetes mellitus,triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were elevated in the overweight group.The prevalence of hypertension,hemoglobin(HGB),uric acid(UA),LDL-C,TG,24-h urinary protein(UTP)and serum complement 3(C3)were elevated,and high-density lipoprotein cholesterol(HDL-C)was decreased in the obese group(P＜0.05).The prevalence of hypertension,UA,TG and serum C3 were elevated in the obese group compared to the overweight group(P＜0.05).The glomerular basement membrane(GBM)thickness was higher in the obese group and the overweight group than that in the normal group,and the proportion of GS and IF was higher in the obese group than that in the normal group(P＜0.05).BMI was positively correlated with hypertension,TG,LDL-C,serum C3,UTP,GS,IF,MCP and deposition in the mesangial region of C3,and negatively correlated with HDL-C(P＜0.05).Multiple linear regression analysis showed that age,blood urea nitrogen(BUN),anti-phospholipase A2 receptor antibody(anti-PLA2R),UTP and TA were independent risk factors of eGFR.Binary Logistic regression analysis showed that elevated BMI,age,UTP and serum creatinine(Scr)were independent risk factors for IF.Age,Scr and elevated UA were independent risk factors for TA.Elevated BMI and decreased eGFR were independent risk factors for GS.Elevated BMI was an independent risk factor for MCP.There was no significant difference in the treatment protocol of IMN patients between the three groups.Conclusion Obesity can exacerbate multiple clinical and pathological outcomes in IMN patients.

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.

The paper reports a rare case of alkaptonuria (AKU) with IgA nephropathy, and analyzes its clinical manifestations, imaging findings, pathological features, gene diagnosis and treatment process, so as to provide reference for the diagnosis and treatment of the disease. The clinical symptoms of the patient were mainly black urine, microscopic hematuria and proteinuria. Renal pathology showed mild mesangial hyperplasia IgA nephropathy, and renal tubular epithelial cytochrome deposition. Genetic analysis indicated that a pathogenic mutation was detected on the AKU-related homogentisate 1, 2-dioxygenase gene possibly associated with the phenotype of the patient. Genetic testing and renal pathology were effective methods to make a definite diagnosis for the case.

Objective To investigate the relationship between the incipient serum C-reactive protein (CRP) and clinicopathologic features in anti-neutrophil cytoplasmic antibody associated vasculitis (AAV).Methods Data of 138 consecutive AAV patients were collected.According to their serum CRP levels,patients were divided into group 1 with normal CRP,group 2 with slightly increased CRP and group 3 with severely increased CRP.Clinical features of AAV and histopathologic features of the kidney injury were compared among groups.Results CRP levels increased in 77.53％ AAV patients on admission.Patients in the group of severely increased CRP had the highest levels of BVAS,serum C3,serum ANCA titer,leukocyte counts and the lowest levels of hemoglobin and albumin among the 3 groups (all P ＜ 0.05).The mortality during the stage of therapy was highest in patients with severely increased CRP (P ＜ 0.05).The focal kidney damage was more obvious in patients with severely increased CRP.There was no significant difference in renal prognosis among patients with different CRP levels.Conclusion The levels of incipient serum C-reactive protein of AAV vary in different patients and are positively correlated with patients' inflammation status as well as the disease activity,but are not correlated with the severity of kidney injury.

In recent years, microRNAs (miRNAs) have been found to be one of the key factors of post transcriptional gene regulation, which are involved in occurrence and development of many diseases. Peritoneal dialysis (PD) has become an effective alternative treatment approaches for patients with end stage renal disease (ESRD). Peritoneal fibrosis is one of the most important factors leading patients to withdraw from long-term PD, hence restricts the application and development of PD. MicroRNAs are closely related to the development of peritoneal fibrosis. This article reviews the role of miRNAs in the pathogenesis and treatment of peritoneal fibrosis.

Objective To observe the expressions of oxidized low density lipoprotein ( OxLDL ) receptor CD36 in kidney tissue of diabetic rats and in tubular cells incubated with OxLDL, and to explore the association of CD36 with the tubular injury and renal fibrosis in the process of diabetic nephropathy. Methods Diabetic rat model with hyperlipidemia was established by feeding with high sugar and fat diet and injection of low dose streptozotocin intraperitoneally. The expression of CD36 in kidney tissues was analyzed immunohistochemically. Meanwhile, the tubular sclerosis and fibrosis injury index were estimated and calculated. NRK-52E cells were stimulated with 50 mg/L OxLDL for 5, 10, 24, and 48 h, or 100 and 150 mg/L OxLDLs for 2 and 3 days. The protein expression of CD36 was detected by Western blot. Results The expression of CD36 in the renal tubulointerstitium of diabetic rats was increased comparing to that in control rats, and was localized mainly at tubular region. The renal tubular damage index(STI)ofdiabetesgroupwashigherthanthatincontrolgroup(5.54±1.5vs0.65±0.15,P<0.05). OxLDL stimulated CD36 expression in NRK-52E cells in a dose-and time-dependent manner. Conclusion The expression of CD36 was increased in renal tubular of diabetic rats, in consistent with STI. OxLDL increased CD36 expression in NRK-52E cells. These results suggest that the expression of CD36 is associated with renal tubular damages in experimental rat diabetes.

Objective To investigate the association of radial arterial calcification damage with bone mineral density (BMD) and bone metabolism biomarkers in uremia patients.Methods Sixty-seven incident hemodialysis patients were recruited into uremic group.Serum creatinine,calcium,phosphorus,lumbar spine and femoral neck BMD were measured.Parathyroid hormone (iPTH),25OHD,1,25(OH)2D,fibroblast growth factor (FGF) 23,bone specific alkaline phosphates (BAP) and osteocalcin (BGP),type Ⅰ collagen pyridine crosslinked C-telopcptidc (ICTP) were detected.Radial artery calcification was analyzed by von Kossa staining and transmission electron microscopy.Arterial type Ⅰ collagen (Col Ⅰ) expression was examined.Twenty-three healthy cases received serum and BMD examination only as control.Results Uremic patients presented higher serum phosphate,iPTH,FGF23,lower serum calcium,25OHD,1,25 (OH)2D (all P ＜ 0.05),and lower lumbar spine and femoral neck BMD (all P ＜ 0.01) compared to controls.Significant calcium deposit was observed in radial arteries in 24 uremic cases (35.8％),including 10 cases of diabetes.Immunohistochemistric assay confirmed that Col Ⅰ expression increased around calcification site and electron microscope revealed that more calcium and phosphorus plaque attached among collagen fibers.No correlation was showed between iPTH and radial artery calcification (r =-0.08,P =0.306),but after stratified by iPTH levels,correlation of iPTH and calcification was found in low iPTH (＜ 150 ng/L) group and high iPTH group (＞ 300 ng/L) (r =-0.41,0.31,P=0.044,0.023).Diabetes,lumbar spine and femoral neck BMD,ICTP,FGF23 were correlated with arterial calcification (r =0.62,-0.25,-0.43,0.34,0.86,P =0.000,0.001,0.012,0.018,0.000).Multiple regression analysis showed femoral neck BMD,ICTP,FGF23 levels were independently associated with radial arterial calcification (β =-0.221,0.181,0.260,P =0.021,0.024,0.036).Conclusion In uremic patients,reduced BMD,abnormal bone turnover rate,especially accelerated bone reabsorption,and increased serum FGF23 level are independently associated with radial artery calcification.