Urinary Extracellular Vesicle: A Potential Source of Early Diagnostic and Therapeutic Biomarker in Diabetic Kidney Disease / 中华医学杂志(英文版)

<p><b>Objective</b>Diabetic kidney disease (DKD) has become one of the major causes of end-stage renal disease. Urinary extracellular vesicles (uEVs) contain rich biological information which could be the ideal source for noninvasive biomarkers of DKD. This review discussed the potential early diagnostic and therapeutic values of proteins and microRNAs in uEVs in DKD.</p><p><b>Data Sources</b>This review was based articles published in PubMed, Embase, Cochrane, and Google Scholar databases up to November 20, 2017, with the following keywords: "Diabetic kidney disease", "Extracellular vesicle", and "Urine".</p><p><b>Study Selection</b>Relevant articles were carefully reviewed, with no exclusions applied to the study design and publication type.</p><p><b>Results</b>There is no "gold standard" technology to separate and/or purify uEVs. The uEVs contain a variety of proteins and RNAs and participate in the physiological and pathological processes of the kidney. UEVs, especially urinary exosomes, may be useful biomarkers for early diagnosis and treatment to DKD. Furthermore, the uEVs has been used as a therapeutic target for DKD.</p><p><b>Conclusion</b>Proteins and nucleic acids in uEVs represent promising biomarker for the diagnosis and treatment of DKD.</p>

Clinical and pathological features in IgA nephropathy with IgG deposition in the glomerular mesangial area / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between the clinical and pathological findings in IgA nephropathy with or without IgG deposition in the glomerular mesangial area.</p><p><b>METHODS</b>The data were collected from 122 patients with a diagnosis of IgA nephropathy by renal biopsy in the Third Affiliated Hospital of Southern Medical University between November, 2009 and February, 2016. All the samples were examined by light microscopy, immunofluorescence and electron microscopy. According to the results of immunofluorescence assay, the patients were divided into IgA group (n=63) and IgA-IgG group (n=59). The pathological classification of IgA nephropathy was analyzed according to Oxford classification and Lee's classification. The clinical and pathological findings were compared between the two groups.</p><p><b>RESULTS</b>Compared with the patients with IgA nephropathy but without IgG deposition, patients with IgA nephropathy with IgG deposition had higher serum creatinine, higher 24-h urine protein, higher blood uric acid, higher triglyceride levels (P<0.05) and lower eGFR (P<0.05); more of these patients were in Lee's grade IV-V, had renal tubular atrophy and/or interstitial fibrosis, and had MEST scores more than 3 (P<0.05).</p><p><b>CONCLUSION</b>Patients with IgA nephropathy with IgG deposition in the glomerular mesangial have severer clinical symptoms and more serious pathological changes. Measures should be taken to control IgG deposition in patients with IgA nephropathy to delay the progress of the disease.</p>

Association between hypertriglyceridemic waist?to?height ratio phenotype and chronic kidney disease in a community population in South China: a cross-sectional study / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between hypertriglyceridemic waist to height ratio phenotype (HWHtR) and chronic kidney disease (CKD) in a community population in South China.</p><p><b>METHODS</b>A cross sectional study was conducted among 2142 residents in Zhuhai (Guangdong Province, China) from June to October of 2012. The HWHtR phenotype was defined as a waist to height ratio(WHtR) ≥0.55 and triglyceride level ≥2.0 mmol/L, based on which the participants were divided into HWHtR group and nonHWHtR group. CKD was defined as an eGFR<60 mL/min per 1.73 m2 or an ACR ≥30 mg/g. A logistic regression model was established to investigate the relationship between chronic kidney disease and HWHtR phenotype.</p><p><b>RESULTS</b>Compared with the nonHWHtR group, the HWHtR group had a higher prevalence of chronic kidney disease (11.1% vs 33%, P<0.001). Analysis using the logistic regression model showed that HWHtR was significantly associated with CKD in the unadjusted analyses (OR=3.23, 95% CI: 2.32-4.48, P<0.001). After adjustment for age, sex, history of hypertension, history of diabetes, systolic blood pressure, diastolic blood pressure, drinking, physical exercise, education and current smoking, HWHtR was significantly associated with CKD (OR=2.36, 95% CI: 1.52-3.67, P<0.001); the association of HWHtR and CKD was still significant after further adjustment for BMI (OR=2.12, 95%CI: 1.34-3.35, P<0.001).</p><p><b>CONCLUSION</b>Our finding suggests that HWHtR is associated with CKD in this community population.</p>

Association of waist-to-hip ratio with insulin resistance in non-diabetic normal-weight individuals: a cross-sectional study / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relationship between waist-to-hip ratio (WHR) and insulin resistance(IR) in non-diabetic normal-weight individuals and investigate how this association differs between male and femalesubjects.</p><p><b>METHODS</b>From June to October, 2012, we performed a cross-sectional survey among 2142 community-based non-diabetic Chinese participants, who were divided into 4 groups according to the gender-specific quartiles of WHR. Homeostatic model assessment of insulin resistance (HOMA-IR), calculated as the product of fasting plasma glucose (mmol/L) and fasting insulin (mU/L) divided by 22.5, was used as the indicator of insulin resistance. Logistic regression models were used to explore the association of WHR with IR in these subjects.</p><p><b>RESULTS</b>In the unadjusted model, WHR was significantly associated with IR in women (OR=6.60, 95%CI: 2.86-15.26, P<0.001); the association was still significant (OR=3.28, 95%CI: 1.34-8.04, P=0.009) after adjustment for the potential confounders including the history of hypertension, coronary heartdisease, current smoker, physical inactivity, and body mass index.</p><p><b>CONCLUSION</b>WHR is independently associated with IR in non-diabetic Chinese women with normal body weight.</p>

Association of waist-to-hip ratio with chronic kidney disease in non-diabetic subjects / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relationship between waist-to-hip ratio (WHR) and chronic kidney disease (CKD) in non-diabetic subjects and compare the difference between male and female subjects.</p><p><b>METHODS</b>We performed a cross-sectional survey among 2142 community-based southern Chinese participants without diabetes from June to October 2012. We divided all the participants into 4 groups according to the gender-specific quartiles of WHR. Logistic regression models were used to explore the associations of WHR with CKD in these subjects.</p><p><b>RESULTS</b>In the unadjusted model, WHR was significantly associated with CKD in women (OR=7.29, 95% CI: 3.56-16.32, P<0.001), and the association was still significant (OR=6.13, 95% CI: 2.56-15.20, P=0.003 ) after adjustment for the potential confounders (including age, history of hypertension, coronary heart disease, current smoker, physical inactivity, education level, systolic blood pressure, diastolic blood pressure, serum triglyceride, serum high density lipoprotein, blood glucose, and BMI). The odds ratio (OR) for having CKD in the highest versus lowest quartile of WHR levels was 2.44 (95% CI: 0.98-4.97, P=0.103) in men in the unadjusted model.</p><p><b>CONCLUSION</b>WHR levels are associated with CKD in non-diabetic women but not in non-diabetic male subjects.</p>

Detection of PLA2R1 in renal biopsy specimens of patients with idiopathic membranous nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the prevalence of PLA2R1 in renal biopsy specimens of patients with idiopathic membranous nephropathy (IMN) and explore the relationship between PLA2R1 and IMN.</p><p><b>METHODS</b>A total of 108 adult patients with biopsy-proved glomerular diseases were enrolled in this study, including 41 with IMN, 2 with hepatitis B-associated membranous nephropathy, 8 with V lupus nephritis, 27 with IgA nephropathy, 19 with minimal change nephropathy, 5 with mild mesangial proliferative glomerulonephritis, and 6 with focal segmental glomeruloselerosis (FSGS). Indirect immunofluorescence assay was used to detect PLA2R1 in the biopsy specimens and the clinical variables of the IMN patients were analyzed.</p><p><b>RESULTS</b>In 35 of the 41 (85.37%) patients with IMN, PLA2R1 was detected with a fine granular pattern in the subepithelial deposits along the glomerular capillary loops. PLA2R1 antigen was not detected in patients with other glomerulopathies. No significant differences were found in age, serum creatinine, serum albumin, or 24-h urinary protein level between PLA2R1-positive and negative patients with IMN (P>0.05).</p><p><b>CONCLUSION</b>According to our results, 85.37% of adult patients with biopsy-proven IMN are positive for PLA2R1 antigen, which, however, does not contribute to variations of the patients' clinical manifestations.</p>

Prevalence of chronic kidney disease and prediabetes and associated risk factors: a community-based screening in Zhuhai, Southern China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prevalence of chronic kidney disease (CKD) and prediabetes has increased in China, and at different rates in different locations. Therefore a community-based screening research was conducted in order to determine the prevalence of CKD and prediabetes, and to analyze associated risk factors of CKD and prediabetes in a city of Southern China.</p><p><b>METHODS</b>A total of 7801 community residents aged 18 year and older from 6 communities were screened by a stratified random cluster sampling method. An estimated glomerular filtration rate (eGFR), albuminuria, fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Age-standardized prevalence was calculated by the direct method with the use of data on the population distribution in China in 2006. Multivariate logistic analysis was used to analyze the risk factors of CKD and prediabetes, and association of insulin resistance (IR) with CKD and prediabetes was analyzed.</p><p><b>RESULTS</b>The age-standardized prevalence of CKD was 12.5%, eGFR < 60 ml×min(-1)×1.73 m(-2) was 2.7% and ACR (albumin to creatinine ratio) > 30 mg/g was 10.3%. The age-standardized prevalence of prediabetes was 12.1%. Logistic regression suggests that IR was a common independent risk factor of CKD and prediabetes. Further analysis show that HOMA-IR was increased with the aggravation of kidney injury and FPG.</p><p><b>CONCLUSION</b>CKD and prediabetes have become a major public health problem in Zhuhai, Southern China; insulin resistance may be an important risk factor.</p>

Prevalence and distribution of metabolic syndrome in a southern Chinese population Relation to exercise, smoking, and educational level

To investigate the prevalence and distribution of metabolic syndrome [MetS] and the impact of exercise, smoking, and educational level on the risk of MetS in a southern Chinese population. A cross-sectional study was conducted in Zhuhai City, China from June to August 2012. Data on exercise, smoking, and educational level, anthropometric parameters, blood pressure, lipid, and glucose levels were collected. The prevalence of MetS [as defined by the International Diabetes Federation] was determined. Data necessary to evaluate MetS, the socio-economic characteristics, and lifestyle were obtained for 4645 subjects aged 18-75 years old. A total of 19.8% of the participants had MetS. The adjusted odds of having MetS were lower among males [adjusted odds: 0.75; 95% confidence interval [CI]: 0.57-1.01] compared with females. Those participants who currently smoked had a higher risk of developing MetS compared with non-smokers [adjusted odds: 1.61; 95% CI: 1.13-2.50]. Those who had no physical exercise had a higher risk of developing MetS compared with those who physically exercised more than 60 minutes/day [adjusted odds: 1.51; 95% CI: 1.12-2.23;]. Compared with those with no education, every category of attained educational level had a lower risk of developing MetS [P<0.001]. The findings in this study revealed that current smokers had a greater risk of developing MetS compared with non-smokers. Increased physical activity and higher levels of education attained served as protective factors for the population

Expression of MMP-2 and TIMP-1 in renal tissues of patients with chronic active antibody-mediated renal graft rejection / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of matrix metalloprotein-2 (MMP-2) and tissue inhibitor of metallopeptidase inhibitor-1 (TIMP-1) in the renal allografts of patients with chronic active antibody-mediated rejection (ABMR), and explore their role in the pathogenesis of ABMR.</p><p><b>METHODS</b>Immunohistochemistry and computer-assisted image analysis were used to detect the expression of MMP-2 and TIMP-1 in the renal allografts of 46 patients with interstitial fibrosis and tubular atrophy (IF/TA), with 15 normal renal tissue specimens as the control. The association of MMP-2 and TIMP-1 with the pathological grade of IF/TA in ABMR was analyzed.</p><p><b>RESULTS</b>The expressions of MMP-2 and TIMP-1 significantly increased in the renal tissues of the patients as compared with the normal renal tissues (P<0.05). MMP-2 expression tended to decrease, while TIMP-1 and serum creatinine increased with the pathological grades of IF/TA (P<0.05). In IF/TA group, the expression of TIMP-1 was positively correlated to serum creatinine level (r=0.718, P=0.00<0.05).</p><p><b>CONCLUSION</b>Abnormal expressions of MMP-2 and TIMP-1 can promote the development of renal fibrosis in chronic ABMR.</p>

Effect of low-dose FK778 on the progression of chronic renal ailograft rejection in a rat model / 中华器官移植杂志

Objective To study the effect of low-dose FK778 in preventing chronic renal al- lograft rejection in rats.Methods The rat model of chronic renal allograft rejection was established by using micro-surgery technique.The recipients were divided into two groups.The recipients in the study group were treated with FK778 at a dose of 5mg?kg~(-1)?d~(-1)dissolved in carboxymethylcellulose by means of gavage and the controls were treated with carboxymethylcellulose.Urinary protein con- centrations were measured every 4 weeks for 24 weeks.On 24th week after operation,the rats were killed and the kidney grafts were taken out for histological and immunohistological examinations as well as quantitative real-time RT-PCR analysis.Results After 24 weeks of treatment,proteinuria, the severity of chronic rejection,glomeruIosclerosicytes and monocytes/macrophages in the study group were significantly milder than in control group.And the expression of TGF-?mRNA and PDGF-B mRNA was significantly reduced in the study group as compared with that in the control group.Conclusion Low-dose of FK778 might prevent the rats from chronic renal allograft rejection.

Astragali and acanthopanax root for idiopathic nephrotic syndrome hypoadrenocorticism in children:the protection and clinical significance / 实用儿科临床杂志

Objective To search for a way of treating chi1dren's idtopathic nephrotic syndrome (INS) hypoadrenocorticismand its significance. Meethods Thirty-nine patients (31 males and 8 females) with INS were randomly divided into twogroups: 21 patients in tera-peutic group (treated by prednisone, astragali and acanthopanax root) and 18patients in control group (Simply treated by prednisone). 1ml blood was respectively drawn from all thepatients at 8 o'clock (one time before treatment and one time after treatment), the serum cortisol wasdetermined by radioimmunoassay (RIA). Results In control group, the levels of serum cortisol still remained lower than the normal value aftertreatment and the levels after large dosages prednisone treatment were markedly lower than that beforetrea-tment. The values of serum cortisol returned to be normal after treatment in therapeutic group. Conclusion Astragali and acanthopanax root can restore the hypoadrenocorticism in children with INS.