Efficiency and safety of Tripterygium Wilfordii Hook F for IgA nephropathy: an update systematic review and meta-analysis

Background:Immunoglobulin A Nephropathy(IgAN)currently stands as the most prevalent primary chronic glomerular disease worldwide.The latest guidelines recommend the application of renin-angiotensin system inhibitors(RASi)in conjunction with corticosteroids for the treatment of IgAN patients exhibiting persistent proteinuria of≥1 g/d.However,numerous randomized controlled trials(RCTs)have revealed a heightened risk of adverse events associated with corticosteroid treatment.Multi-glycoside of Tripterygium wilfordii Hook.f.(GTW),a traditional Chinese medicine(TCM),has been employed in the treatment of Chronic Kidney Disease(CKD)for an extensive period.Recent years have witnessed an increasing number of RCTs providing evidence supporting the effectiveness of GTW therapy in IgAN.Despite this,there remains a paucity of systematic reviews on the application of GTW therapy for IgAN.Consequently,this study undertakes a systematic review to assess the clinical efficacy and safety of GTW therapy,aiming to elucidate the role of GTW therapy in the treatment of IgAN.Methods:To collect relative information of randomized controlled trials(RCTs)of GTW in the treatment of IgAN,we searched for theses and dissertations publicized before April 10,2023,in PubMed,Embase,the Cochrane Library,China National Knowledge Infrastructure(CNKI),Wanfang Data knowledge service platform(Wanfang Data),Chinese Scientific Journal Database(VIP),and Clinical Trial.The language limitation is English and Chinese.Independently,two reviewers performed literature screening,data extraction,and quality evaluation,and the meta-analysis was carried out with RevMan 5.4 and StataSE 15.0 software.Results:21 RCTs involving 1,405 Chinese patients were included.Compared to ACEI/ARB alone or in combination,GTW with RASi or alone reduced 24 h-Upro,ALB,Scr,GFR,BUN,CD4+,VEGF,ET-1,and improved clinical efficacy.However,no associations were found for TC,Ccr,and adverse events due to limited literature.Conclusion:This study highlights that Multi-glycoside of Tripterygium wilfordii Hook.f.(GTW)exhibits potential in safeguarding renal function and preserving the integrity of the basement membrane in patients with Immunoglobulin A Nephropathy(IgAN).Consequently,GTW emerges as a promising therapeutic option for individuals with IgAN.Nevertheless,it is crucial to acknowledge the limitations stemming from insufficient methodology and a small sample size,which currently obscure the relationships between certain clinical variables,such as total cholesterol(TC)and creatinine clearance(Ccr).Therefore,the substantiation of our findings necessitates more rigorous and expansive trials to enhance the robustness and generalizability of the results.

Efficacy of activating blood and resolving stasis therapy for IgA nephropathy:a systematic review and meta-analysis

Background:To systematically evaluate the efficacy and safety of activating blood and resolving stasis in patients with IgA nephropathy.Methods:From inception to May 2022,databases including PubMed,Embase,the Cochrane Library,Web of Science,WanFang database,Chinese Biomedical Database,VIP,and China National Knowledge Infrastructure were searched for randomized controlled trials about enhancing blood circulation and removing stasis for IgA nephropathy.For the articles that satisfied the requirements,quality assessment and meta-analysis were done.Results:Seventeen randomized controlled trials with a total of 1653 patients were included.Meta-analysis showed that activating blood and resolving stasis could increase therapeutic effectiveness(risk ratio(RR)=-0.47,95%confidence interval(CI)(-0.37,-0.2),P=0.0006)and decrease levels of serum creatinine(RR=-0.47,95%CI(-0.37,-0.2),P=0.0006),urea nitrogen(RR=0.85,95%CI(1.44,0.26),P=0.005),24-hour urinary protein quantification(RR=1.6,95%CI(2.44,0.95).P=0.00001),and urine red blood cell count(RR=1.7,95%CI(2.57,0.82),P=0.0001).There was no significant difference between the two groups in terms of security(RR=0.6,95%CI(0.36,1.01),P=0.05).Conclusion:Western medicine combined activating blood and resolving stasis is more efficient than Western medicine therapy alone in treating IgA nephropathy,but it still needs to be supported by additional large-scale,multi-center randomized controlled clinical trials due to the poor quality of the included trials.

IgA nephropathy associated with Crohn's disease

The relationship between IgA nephropathy(IgAN)and Crohn’s disease was reported.IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure,and up to 50%of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis.However,specific and effective therapeutic strategies are still lacking.In this review,we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies.Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved,the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.

Analysis of the Effect of Hormone Therapy Combined with Hydroxychloroquine in the Treatment of IgA Nephropathy

Objective:To explore and analyze the effect of hormone therapy combined with hydroxychloroquine in the treatment of IgA nephropathy.Methods:30 patients with IgA nephropathy who were admitted to the Urology Department of Jiuquan hospital from August 2021 to May 2023 were selected as the research subjects,and they divided into an observation group and control group by drawing lots,with 15 cases in each group.The observation group underwent hydroxychloroquine treatment in addition of hormone therapy,and the control group underwent conventional treatment and hormone therapy.The rate of effectiveness of treatment,serum index,and renal function of both groups were compared.Results:The incidence of adverse reactions in the observation group was significantly lower than that in the control group(P<0.05).There was no significant difference in serum creatinine and serum albumin(P>0.05)between the groups before treatment;after treatment,the serum creatinine and serum albumin in the steroid group were significantly better than those in the reference group(P<0.05).Besides,there was no significant difference in urine protein quantification and glomerular filtration rate between the groups before treatment(P>0.05);after treatment,the hormone group’s urine protein quantification and glomerular filtration rate were significantly better than those in the reference group(P<0.05).The rate of effectiveness of the hormone group was significantly higher than that of the reference group(P<0.05).Conclusion:Hormone therapy combined with hydroxychloroquine in the treatment of IgA nephropathy is more effective than hormone therapy alone,thus this treatment plan is worthy of promotion and application.

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy

Objective To investigate whether glomerular density （GD） could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate （eGFR） of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria 〈 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a 〉 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 （AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%） determined by ROC curve. The low GD group （GD 〈 1.99 per mm2） experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 （six patients in lower GD group, while one patient in the other group）. For patients with time-average proteinuria 〈 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline （4.5±16.7 ml/min per 1.73 m2 vs. –8.1±21.4 ml/min per 1.73 m2, P = 0.038）; two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Baseline proteinuria, urinary osmotic pressure, and renal function as positive predictors of corticosteroids plus cyclophosphamide treatment efficacy in IgA nephropathy

Background Very limited data are available on factors predictive of corticosteroids plus cyclophosphamide treatment efficacy on IgA nephropathy （IgAN）.The aim of the study was to research the clinical factors predictive of treatment efficacy in IgAN.Methods One hundred and fifty-nine patients with IgAN （proteinuria ≥2 g/d and estimated glomerular filtration rate 30-89 ml·min-1·1.73 m-2） were treated with corticosteroids/cyclophosphamide followed by a 12-month follow-up.According to their response,these patients were divided into remission group （proteinuria ＜0.5 g/d） and non-remission group （proteinuria ≥0.5 g/d）,and their clinical data collected.Results In the present study,72.96％ of the individuals underwent a complete remission,and their response was related to baseline proteinuria,urinary osmotic pressure,and renal function （P ＜0.05）.Patients with baseline proteinuria more than 3 g/d,urinary osmotic pressure greater than 600 mOsm/L,and eGFR 60-89 ml·min-1·1.73 m-2 responded well to the combination of corticosteroids and cyclophosphamide （86.90％ vs.57.33％,P=0.000; 81.48％ vs.64.10％,P=0.014; 83.17％ vs.55.17％,P=0.000）.Conclusion The response to the combination of corticosteroids and cyclophosphamide might be well associated with baseline proteinuria,urinary osmotic pressure,and renal function in patients with IgAN.

Existence and significance of hepatitis B virus DNA in kidneys of IgA nephropathy

AIM: To investigate the existence and significance of hepatitis B virus (HBV) DNA in the pathogenesis of IgA nephropathy(IgAN).METHODS: Fifty cases of IgAN with HBV antigenaemia and/or hepatitis B virus antigens (HBAg, or HBsAg, HBcAg)detected by immunohistochemistry in renal tissues were enrolled in our study. The distribution and localization of HBV DNA were observed using in situ hybridization.Southern blot analysis was performed to reveal the state of renal HBV DNA.RESULTS: Among the 50 patients with IgAN, HBs antigenemia was detected in 17 patients (34%). HBAg in renal tissues was detected in 48 patients (96%), the positive rate of HBAg, HBsAg, and HBcAg was 82% (41/50), 58% (29/50),and 42% (21/50) in glomeruli, respectively; and was 94%(47/50), 56% (28/50) and 78% (39/50) in tubular epithelia,respectively. Positive HBV DNA was detected in 72% (36/50)and 82% (41/50) cases in tubular epithelia and glomeruli respectively by in Situ hybridization, and the positive signals were localized in the nuclei of tubular epithelial cells and glomerular mesangial cells as well as infiltrated interstitial lymphocytes. Moreover, 68% (34/50) cases were proved to be HBV DNA positive by Southern blot analysis, and all were the integrated form.CONCLUSION: HBV infection might play an important role in occurrence and progress of IgAN. In addition to humoral immune damages mediated by HBAg-HBAb immune complex,renal tissues of some IgAN are directly infected with HBV and express HBAg in situ, and the cellular mechanism mediated by HBV originating from renal cells in situ may also be involved in the pathogenesis of IgAN.

Childhood Henoch-Schnlein Purpura Nephritis and IgA Nephropathy: One Disease Entity?——A Clinico-pathologically Comparative Study

Summary： In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Schoenlein purpura nephritis （HSPN）, 31 children with IgA nephrop- athy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and followup study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8 % children with IgA nephropathy, but only 10 % in HSPN （P〈0.05）. The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59 % had gastrointestinal symptoms and 47 % suffered from arthralgia, compared with only abdominal pain in 3.2 % children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5 % of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9 % of IgA nephropathy and 6.3 % of HSPN, but endothelial proliferation in 65.6 % of HSPN and 29 % of IgA nephropathy （all P〈0.01）. Thin basement membrane nephropathy was only found in 6. 5 % children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, lodse and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2% of HSPN, and overwhelming IgG deposits in 12.5 % of HSPN with relatively weak IgA deposits, moreover 6.3 % of HSPN showed linear IgG deposits in glomerular capillary. Totally 71. 9 G of HSPN had IgG deposits in glomeruli and only 19.4% of IgA nephropathy showed glomerular IgG deposits （P〈0. 01）. No IgG deposit was observed in 81. 6 % of IgA nephropathy, among them most showed IgA and IgM and/or C3 deposits, moreover overwhelming IgG deposits and linear IgG deposits couldn＇t be found in IgA nephropathy. Mean 20 months follow-up showed complete remission in 72.5% of HSPN, but only 19.4% in IgA nephropathy after 34 months follow-up. Moreover, 64.5 % of IgA nephropathy had consistent hematuria and proteinuria and 16. 1% had active nephritides （P〈0.05）. It was concluded that significant clinico-pathological difference was found between HSPN and IgA nephropathy, which didn＇t support the one disease entity hypothesis. HSPN and IgA nephropathy are probably two diseases with similar immune abnormalities.

Association of liver cirrhosis related IgA nephropathy with portal hypertension

A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.

IgA nephropathy treatment with traditional Chinese medicine:A case report

BACKGROUND IgA nephropathy(IgAN)is a common primary glomerular disease that leads to end-stage renal disease with poor therapy efficacy.Traditional Chinese medicine(TCM)is effective in the treatment of IgAN and has the potential to become an alternative treatment for IgAN.Professor Yan-Qin Zou is a nephropathy expert,a National Chinese Medicine Master,and an heir to the Menghe School of Medicine.CASE SUMMARY A 28-year-old man had positive urinary protein and elevated serum creatinine(Scr)results and was diagnosed with IgAN 2-3 years prior to the outpatient department visit at our hospital in 2017.Professor Zou used the following methods to treat the patient:Invigorating the spleen and tonifying the kidney,removing dampness and clearing turbidity,quickening the blood and transforming stasis,and freeing vessels and regulating collaterals.She adjusted the prescription in accordance with the patient’s symptoms.After 6 mo of treatment,the symptoms had resolved and serological indexes were also decreased[Scr from 288.5 to 188.6μmol/L,blood urea nitrogen(BUN)from 10.9 to 9.5 mmol/L,serum uric acid(UA)from 612 to 503μmol/L].During follow-up,BUN,Scr,and UA levels remained stable.CONCLUSION Professor Zou’s therapeutic strategy to treat IgAN using TCM was efficacious and a good reference for application.

Effects of yiqi yangyin huoxue therapy on IgA nephropathy: a systematic review and meta-analysis of randomized controlled trials

Objective To assess the efficacy and safety of Yiqi Yangyin Huoxue therapy (YYHT) for the treatment of IgA nephropathy. Methods Databases articles about YYHT in treating IgAN patients were searched through February 2018. Comparisons were YYHT alone or YYHT in combination with western medicine as experimental intervention, and western medicine as the control. Randomized controlled trials (RCTs) were selected. Cochrane collaboration tool was used for assessing risk of bias to evaluate methodologies. RevMan 5.3 software was applied to analyze the data of included trials. Results A total of 21 studies involving 1473 patients were included. Meta-analysis results demonstrated that YYHT alone or YYHT in combination with western medicine were more efficacious than only western medicine in decreasing proteinuria [MD =-0.41, 95% CI (-0.53,-0.29), P < 0.00001] and the urine red blood cells [MD =-7.46, 95% CI (-9.28,-5.64), P < 0.00001]. There also showed improvement in the clinical total effective rate [OR = 2.78, 95% CI (2.14, 3.61), P < 0.00001] between the two groups. Some of the included trials did not report the adverse events. Conclusions Current evidence shows that YYHT can reduce proteinuria and urine red blood cells and improve the total efficacy rate. Since poor quality and publication bias of some included trials, more evidence-based medicine studies needed to define the role of YYHT in the treatment of IgAN.

Anti-glomerular basement membrane disease with IgA nephropathy: A case report

BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare autoimmune disease manifesting as acute progressive nephritis syndrome with or without varying degrees of pulmonary hemorrhage.Anti-GBM disease coexisting with Immunoglobulin A(IgA)nephropathy is rarer and has different clinical manifestations and prognoses than simple anti-GBM disease.We describe a case of coexistence of these two diseases.CASE SUMMARY A 49-year-old man with hematuria and proteinuria accompanied by a slight elevation of serum creatinine was admitted to our hospital.The pathological results of renal biopsy and the elevated serum anti-GBM antibody titer supported a diagnosis of anti-GBM disease combined with IgA nephropathy.After treatment with corticosteroids and cyclophosphamide,the patient's serum creatinine was relatively stable,and the hematuria and proteinuria moderately improved in the subsequent six months.CONCLUSION Anti-GBM disease coexisting with IgA nephropathy is rare.The clinical manifestations and prognosis are better than those of simple anti-GBM disease.In this case,the patient's condition was improved and his renal function remained relatively stable with corticosteroid and cyclophosphamide treatment.New detection methods to identify whether the crescents in this case were derived from anti-GBM disease or IgA nephropathy are worthy of further exploration.

Protective effects of Yishen Sanjie Huayu compound on the renal artery disease in rats with IgA nephropathy through ERK/NF-κB pathway

Objective:To observe the effect of Yishen Sanjie Huayu compound prescription on ERK/NF-κB signaling pathway in IgA nephropathy(IgAN)rats,and explore its effect on preventing and treating IgA nephropathy intrarenal arteriole disease.Methods:Fifty-five male SD rats were randomly divided into blank group,model group,ShenfukangⅡcapsule group and Losartan potassium tablet group.Bovine serum albumin(BSA)was used for intragastric administration and carbon tetrachloride(CCl4).IgAN rat model was established by subcutaneous injection and lipopolysaccharide(LPS)tail vein injection.ShenfukangⅡcapsule group and Losartan potassium tablet group were given each drug suspension 2ml/head/d one week after modeling Gavage was started.The blank group and the model group were given an equal volume of normal saline.The 24h urine protein(UTP)of the rats was measured at 4,8,and 12 weeks after the administration,and the blood creatinine(SCr)was measured after 12 weeks.,urea nitrogen(BUN),aldosterone(ADS),angiotensinⅡ(AngⅡ),immunohistochemical Envi-sion System two-step method to detect vascular endothelial growth factor(VEGF)and human matrix in the whole rat kidney and small artery area The expression of metalloproteinase-9(MMP-9),proliferating cell nuclear antigen(PCNA),extracellular regulatory protein kinase(ERK)1/2,nuclear transcription factor-κB(NF-κB),and the small arteries of rat kidney tissue The intima,media,vessel wall/vascular outer diameter value.Results:Compared with the model group,the expressions of VEGF,MMP-9,PCNA,ERK1/2 and NF-κB in kidney tissues of the ShenfukangⅡcapsule group and the Losartan potassium tablet group decreased(P<0.05),24hUTP and SCr,BUN level decreased(P<0.05),kidney tissue damage was alleviated;intima and vessel wall/vascular outer diameter values were significantly reduced(P<0.01),there was no significant difference in ADS between the groups.The AngⅡof the Tanpotassium tablets group was lower than that of the model group(P<0.05).Conclusion:Yishen Sanjie Huayu compound can inhibit the ERK/NF-κB signaling pathway in rats with IgA nephropathy,reduce the levels of VEGF,MMP-9,PCNA,ERK1/2,NF-κB,and inhibit intrarenal arteriole vascular endothelial cells Proliferate and reduce kidney damage.

翟文生教授治疗免疫球蛋白A沉积性肾病(IgA nephropathy)的经验

目的:总结翟文生教授治疗原发性免疫球蛋白A沉积性肾病(IgA nephropathy)临床经验。方法:探讨该病的病因病机,提出热、瘀、虚是IgA肾病病机、辨证论治的关键;重视清热解毒利咽、活血化瘀、扶正补虚在治疗中的作用。结果与结论:翟文生教授治疗IgA肾病的经验对临床有重要的指导意义。

Effect of Adhesion Molecule P-selectin and Dendritic Cells on Tubulointerstitial Lesions in IgA Nephropathy

To observe the expression of P-selectin and the localization of dendritic cells (DCs) in human kidney with IgA nephropathy, and to evaluate their function in human renal tubulointerstitial lesions and renal dysfunction, 45 biopsy specimens of patients with IgA nephropathy were divided into 3 groups according to the degree of renal tubulointerstitial lesions: i. e. mild group ( n =29), moderate group ( n =10), severe group ( n =6). Ten normal renal tissues severed as control. The expression of P-selectin was analysed by immunohistochemistry. CD1a +CD80 +DCs were investigated by double immunostaining method and the images were analyzed with Axioplan 2 microscopy. The experimental results showed that (1) P-selectin was not expressed in normal controls, but presented mainly in renal tubular epithelial cells, which was greater in severe group than mild and moderate groups. The expression of P-selectin was associated with the degree of renal tubulointerstitial lesions. (2) CD1a +CD80 +DCs were hardly observed in nomal renal tissues, but in renal tissues of patients with IgA nephropathy, CD1a +CD80 +DCs were mostly found in renal tubulointerstitium. Also the distribution area, number and density of CD1a +CD80 +DCs in severe group was much more than other groups, which was associated with the degree of renal tubulointerstitial lesions and the lever of serum creatine. The distribution of CD1a +CD80 +DCs was associated with the expression of P-selectin in patient′s renal tubulointerstitium. The present study demonstrated that P-selectin and DCs might play an important role in renal tubulointerstitial lesions of IgA nephropathy, and DCs recruited into the renal tissues with IgA nephropathy might be mediated by P-selectin.

Effects of rhein on intestinal epithelial tight junction in IgA nephropathy

AIM: To investigate the effects of rhein on intestinal epithelial tight junction proteins in rats with IgA nephropathy (IgAN). METHODS: Twenty-eight female Sprague-Dawley rats were randomly divided into four groups (7 per group): Control, IgAN, Rhein-treated, and Rheinprevented. Bovine serum albumin, lipopolysaccharide and CCl4 were used to establish the rat model of IgA nephropathy. The Rhein-treated group was given rhein from week 7 until the rats were sacrificed. The Rheinprevented group was given rhein from week 1. Animals were sacrificed at the end of week 10. We observed the changes in the intestinal epithelial tight junctions using transmission electron microscopy, and expression of intestinal epithelial tight junction proteins zona occludens protein (ZO)-1 and occludin by immunofluorescence using laser confocal microscopy. Changes in mRNA and protein expression of ZO-1 and occludin were measured by reverse transcriptase polymerase chain reaction and Western blotting. The ratio of urinary lactulose/mannitol was measured by high performance liquid chromatography (HPLC) for assessing the intestinal permeability. RESULTS: In the control group, the tight junctions lied between epithelial cells on the top of the outer side of the cell membrane, and appeared in dense dotted crystal structures, the neighboring cells were binded tightly with no significant gap, and the tight junction protein ZO-1 and occludin were evenly distributed in the intestinal epithelial cells at the top of the junction. Compared with the control group, in the IgAN group, the structure of the tight junction became obscured and the dotted crystal structures had disappeared; the fluorescence of ZO-1 and occludin was uneven and weaker (5.37 ± 1.27 vs 10.03 ± 1.96, P < 0.01; 4.23 ± 0.85 vs 12.35 ± 4.17, P < 0.01); the mRNA expression of ZO-1 and occludin decreased (0.42 ± 0.19 vs 0.92 ± 0.24, P < 0.01; 0.40 ± 0.15 vs 0.97 ± 0.25, P < 0.01); protein expression of ZO-1 and occludin was decreased (0.85 ± 0.12 vs 1.98 ± 0.43, P < 0.01; 0.72 ± 0.15 vs 1.38 ± 0.31, P < 0.01); and the ratio of urinary lactulose/mannitol increased (3.55 ± 0.68 vs 2.72 ± 0.21, P < 0.01). In the Rheinprevented and Rhein-treated groups, compared with the IgAN group, the intestinal epithelial tight junctions were repaired; fluorescence of ZO-1 and occludin was stronger (11.16 ± 3.52 and 8.81 ± 2.30 vs 5.37 ± 1.27, P < 0.01; 10.97 ± 3.40 and 9.46 ± 2.40 vs 4.23 ± 0.85, P < 0.01); mRNA of ZO-1 and occludin increased (0.81 ± 0.17 and 0.64 ± 0.16 vs 0.42 ± 0.19, P < 0.01; 0.82± 0.22 and 0.76 ± 0.31 vs 0.40 ± 0.15, P < 0.01); protein expression of ZO-1 and occludin was increased (2.07 ± 0.41 and 1.57 ± 0.23 vs 0.85 ± 0.12, P < 0.01; 1.34 ± 0.21 and 1.15 ± 0.17 vs 0.72 ± 0.15, P < 0.01); and the ratio of urinary lactulose/mannitol decreased (2.83 ± 0.43 and 2.87 ± 0.18 vs 3.55 ± 0.68, P < 0.01). CONCLUSION: Rhein can enhance the expression of ZO-1 and occludin, repair damaged tight junctions, and protect the intestinal barrier.

Correlation between podocyte excretion and proteinuria in diabetic nephropathy patients

Objective： To observe the podocyte injury in diabetic nephropathy （DN） patients by identifying the urinary podocytes and the situation of detached podocytes in glomeruli and to demonstrate the correlation between podocyte excretion and proteinuria, blood glucose, serum creatinine in different phases in DN patients. Methods： Urinary podocytes and the podocalyxin （PCX） expression state of podocytes in glomeruli were identified and observed by indirect immunofluorescent method. The DN patients were divided into three groups according to the volume of proteinuria, namely small, medium and large volume proteinuria groups. The podocytes in the urine of every group were calculated. The DN patients were divided into five groups according to the chronic kidney disease （CKD） phases, then the positive podocytes in urine were calculated. Meanwhile, the 24-hour protein in urine, fasting blood glucose （FBG） and the serum creatinine of DN patients were tested. The correlations among the proteinuria, serum creatinine, FBG and the number of positive podocytes in the urine of DN patients were statistically analyzed. Results： Urinary positive podocytes were found in 88% of the patients with DN, whereas podocytes were found in 0% of patients with minimal changed disease （MCD） and healthy cases. The expression of PCX was absent in DN patients. In contrast, PCX was expressed integrally in MCD patients. The positive podocytes was 1.49±0.95/ml in small-volume proteinuria group, 2.15±0.70/ml in the medium-volume proteinuria group, and 3.48±1.27/ml in the large-volume proteinuria group. There was no significant difference between the small- and medium- volume proteinuria groups, and there were significant differences between other groups （P〈0.05）. The positive podocyte number tended to increase as proteinuria was increased. By Pearson analysis, the correlation between podocyte number and proteinuria was podocytes in urine from different groups of DN patients, CKD pc I sitive statistically. The difference of the number of positive -V group was significant statistically. The correlation between serum creatinine of CKD Ⅰ -Ⅲ group and positive podocytes in urine was positive statistically. The correlation between serumcreatinine of CKD Ⅳ- Ⅴ group and positive podocytes in urine was not significant statistically. The correlation between FBG and positive podocytes in urine was not significant either. Conclusion： The mechanism of the podocyte injury in DN patients is present. The podocyte injury in DN may positively correlate to proteinuria and serum creatinine of CKD Ⅰ -ⅢDN patients, but not to the FBG and serum creatinine of CKD Ⅳ-Ⅴ patients.