What is new in the pathogenesis and treatment of IgA glomerulonephritis

Recently,new findings have been clarified concerning both pathogenesis and treatment of IgA nephritis.The four hits theory has been confirmed but several genetic wide association studies have allowed finding several genes connected with the pathogenesis of the disease.All these new genes apply to each of the four hits.Additionally,new discoveries concerning the microbiota and its connection with immune system and IgA generation have allowed finding out the role of the mucosa in IgA nephropathy pathogenesis.The IgA treatment is also changed included the future possibilities.The treatment of the chronic kidney disease,associated with the nephropathy,is mandatory,since the beginning of the disease.The classical immunosuppressive agents have poor effect.The corticosteroids remain an important cornerstone in any phase of the disease.More effect is related to the treatment of B cells and plasma cells.In particular,in very recent studies have been documented the efficacy of anti B cell-activating factor and anti A proliferation-inducing ligand agents.Most of these studies are to date in phase II/III.Finally,new agents targeting complement are arising.These agents also are still in randomized trials and act principally in hit 4 where the immunocomplexes in the mesangium activate the different pathways of the complement cascade.

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.

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.

Clinicopathologic analysis of IgA nephropathy patients with anemia

Objective:To explore the clinicopathological characteristics of IgA nephropathy(IgAN)patients with anemia.Methods:The clinical and pathological data of patients diagnosed with primary IgAN at the Renmin Hospital of Wuhan University from January 2017 to December 2019 were colleted.The patients were divided into anemia group and without anemia group based on the pressure value when performing the Kidney kidney biopsy.Compare the data of the two groups of patients.Results:A total of 314 subjects were enrolled,including 181 females(57.64%),and the female-male ratio was 1.36∶1.Their age was(37±13)years.There were 113 patients(35.99%)in anemia group,201 cases(64.01%)in non-anemic group.Univariate analysis showed that compared with non-anemia group,anemia group had higher serum creatinine and 24h urine protein levels,higher proportion of females and eGFR<60 ml·min^(-1)·(1.73m^(2))^(-1),lower serum albumin,higher proportion of tubular atrophy/interstitial fibrosis(T1/2),endothelial cell proliferation(E1)and crescent formation(C1/2),which were statistically significant(all P<0.05).Anemia group had a higher proportion of Ⅳ~Ⅴlevel in Lee's classification.There was a difference in Lee's grading composition between the two groups,and the difference was statistically significant(P<0.01).Spearson correlation analysis showed that the glomerular and tubulointerstitial lesions were negatively correlated with serum hemoglobin、albumin and eGFR,but positively corelated with proteinuria(P<0.05).Multivariate Logistic regression analysis found that decreased serum albumin level,increased serum creatinine and hypertension were independent risk factors for anemia in IgAN patients.Conclusions:Anemia can aggravate the pathological damage and clinical manifestations in patients with IgA nephropathy.The anemia must be corrected in time during treatment and follow-up.At the same time.it should be paid more attention to the changes of serum albumin level,blood pressure monitoring and the protection of renal function.

A Case Report of Posterior Reversible Encephalopathy Syndrome with Rapidly Progressive Glomerulonephritis Combined with Membranous Nephropathy

Rapidly progressive glomerulonephritis is a group of clinical syndromes,in which renal function of patient progressively deteriorates with pathological manifestation of extensive glomerular crescent formation.Among which,anti-glomerular basement membrane antibody glomerulonephritis is the rarest but the most aggressive subtype.This paper discusses a case of rapidly progressive glomerulonephritis combined with membranous nephropathy.There were posterior reversible encephalopathy syndromes during diagnosis and treatment.Diagnosis was confirmed in time by laboratory examination and renal pathology.Condition of the patient was alleviated through close work between all departments.This allowed us to further understand the case characteristics of rapidly progressive glomerulonephritis combined with membranous nephropathy,importance of effective prevention,and significance of various complications during treatment,so as to alleviate pain and improve prognosis in patient.

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.

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.

Systemic Sarcoidosis Associated to IgA Nephropathy

The sarcoidosis was rarely associated to IgA nephropathy. We report a 38-year-old man presented decreased visual acuity and xerostomia. He had two axillary lymphadenopathies and pitting edema of legs in physical examination. The ophthalmological examination revealed a right posterior uveitis. Biological investigations showed a mild renal insufficiency and elevated serum level of angiotensin-converting enzyme, β2 microglobulin and IgA. He had a proteinuria and a microscopic hematuria. The kidney echography was without abnormalities. Histological study of the renal biopsy found results in favor to IgA nephropathy. Biopsies performed in accessory salivary gland and lymph nodes revealed non-necrotising epitheloid and gigantocellular granulomatous inflammation suggesting a sarcoidosis. The diagnosis of a sarcoidosis associated to IgA nephropathy was posed. The treatment was based on oral prednisolone with gradual tapering doses. He regained normal vision. The renal function had not worsened. No relapse of sarcoidosis was noted during our follow up.

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.

Underlying IgM heavy chain amyloidosis in treatment-refractory IgA nephropathy: A case report

BACKGROUND Monoclonal immunoglobulin can cause renal damage,with a wide spectrum of pathological changes and clinical manifestations without hematological evidence of malignancy.These disorders can be missed,especially when combined with other kidney diseases.CASE SUMMARY A 61-year-old woman presented with moderate proteinuria with normal renal function.She was diagnosed with IgA nephropathy combined with monoclonal gammopathy of undetermined significance after the first renal biopsy.Although having received immunosuppressive treatment for 3 years,the patient developed nephrotic syndrome.Repeated renal biopsy and laser microdissection/mass spectrometry analysis confirmed heavy chain amyloidosis.After nine cycles of bortezomib,cyclophosphamide and dexamethasone,she achieved very good partial hematological and kidney responses.CONCLUSION Renal injury should be monitored closely in monoclonal gammopathy patients without obvious hematological malignancy,especially in patients with other preexisting renal diseases.

Influence of the period between onset of IgA nephropathy and medical intervention on renal prognosis

Background. The clinical course of IgA nephropathy (IgAN) is highly variable. In order to verify the necessity of early medical intervention in IgAN patients, the present study investigated the clinical impact of the duration between disease onset and first medical intervention on renal prognosis. Methods. We enrolled 57 patients diagnosed with IgAN on the basis of biopsy performed at our hospital. The medical records of these patients were traceable to the last 10 years, during which they had not undergone dialysis or treatment at any other hospital. On the basis of histological assessment of prognosis, these patients were classified according to the Japanese guidelines into the following groups: groups I, good prognosis;group II, relatively good prognosis;group III, relatively poor prognosis;and group IV, poor prognosis. We investigated the correlation between the duration of disease onset and the first consultation with a nephrologist and the rate of increase in serum creatinine over a 10 year period. In addition to the abovementioned patients, 6 patients with IgAN who underwent dialysis within the 10 years were separately evaluated. These patients came under the poor prognosis category;i.e., they belonged to group IV. Results. The duration between disease onset and medical consultation was significantly longer in younger patients or in those with asymptomatic proteinuria at onset when compared to that in older patients or in those with other urinary abnormalities. There was a significant correla tion between this duration and renal prognosis, particularly in group III patients. Although the duration between onset and consultation was not correlated to the serum creatinine level at the time of first medical intervention, urinary protein level among group IV patients at the time of first consultation was significantly higher in patients with dialysis than that in those without dialysis. Conclusions. Early medical intervention may lead to a better renal prognosis, particularly in group III patients, who form a major portion of the IgAN population. It therefore appears that early diagnostic screening and subsequent intervention are important for a good prognosis in IgAN patients.

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.

Effect of Tripterine on Notch Signaling Pathway in IgA Nephropathy Rats

The objective of the study was to investigate the effect of tripterine on the Notch signaling pathway in renal tissue of IgA nephropathy rats.SD male rats were divided into the control group,IgA nephropathy model group,benazepril group,1 mg/kg/day tripterine intervention group,and 10 mg/kg/day tripterine intervention group according to the random number table method,with 10 rats in each group.The urinary sediment and 24-h urinary protein quantity were detected by conventional methods.The expressions of Notch1,Jagged1,Hes1,and Hey1 in renal tissue of rats were detected by real-time fluorescent quantitative polymerase chain reaction.IgA nephropathy model was successfully established.The hematuria and proteinuria in model group were higher than those of control group(P<0.05).The expressions of Notch1,Jagged1,Hes1,and hey1 in kidney tissue of IgA nephropathy rats were significantly increased(P<0.05).Compared with the model group,hematuria and proteinuria in the tripterine intervention group were alleviated.The expressions of Notch1,Jagged1,Hes1,and Hey1 in rat renal tissue were decreased(P<0.05).Moreover,the expressions of Notch1,Jagged1,Hes1,and Hey1 in renal tissue of rats in 10 mg/kg/day tripterine intervention group were decreased(P<0.05).Tripterine can decrease the levels of hematuria and proteinuria in IgA nephropathy rats.The expression of the Notch signaling pathway in IgA nephropathy rats is increased by the down-regulation of tripterine,suggesting that tripterine has a certain therapeutic effect on IgA nephropathy rat.Moreover,its role may be realized through this signal pathway so as to provide a new mentality for the diagnosis and treatment of IgA nephropathy.

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.

Identification of susceptibility loci and relevant cell type for IgA nephropathy in Han Chinese by integrative genome-wide analysis

Although many susceptibility loci for IgA nephropathy(IgAN)have been identified,they only account for 11.0%of the overall IgAN variance.We performed a large genome-wide meta-analysis of IgAN in Han Chinese with 3616 cases and 10417 controls to identify additional genetic loci of IgAN.Considering that inflammatory bowel disease(IBD)and asthma might share an etiology of dysregulated mucosal immunity with IgAN,we performed cross-trait integrative analysis by leveraging functional annotations of relevant cell type and the pleiotropic information from IBD and asthma.Among 8669456 imputed variants,we identified a novel locus at 4p14 containing the long noncoding RNA LOC101060498.Cell type enrichment analysis based on annotations suggested that PMA-I-stimulated CD4+CD25–IL17+Th17 cell was the most relevant cell type for IgAN,which highlights the essential role of Th17 pathway in the pathogenesis of IgAN.Furthermore,we identified six more novel loci associated with IgAN,which included three loci showing pleiotropic effects with IBD or asthma(2q35/PNKD,6q25.2/SCAF8,and 22q11.21/UBE2L3)and three loci specific to IgAN(14q32.32/TRAF3,16q22.2/TXNL4B,and 21q21.3/LINC00113)in the pleiotropic analysis.Our findings support the involvement of mucosal immunity,especially T cell immune response and IL-17 signal pathway,in the development of IgAN and shed light on further investigation of IgAN.