Therapeutic effect of mycophenolate mofetil or cyclophosphamide in children with Henoch-Schönlein purpura nephritis of different age groups / 中国当代儿科杂志

OBJECTIVES@#To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups.@*METHODS@#A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions.@*RESULTS@#There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05).@*CONCLUSIONS@#The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Effect of Glucocorticoid Pulse Therapy on Short-term Prognosis of Anti-neutrophil Cytoplasmic Antibodies-associated Glomerulonephritis / 中国医学科学院学报

Objective To investigate the prognosis predictors of anti-neutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis treated with glucocorticoid(GC).Methods The clinicopathological data of patients with biopsy-confirmed ANCA-associated glomerulonephritis were retrospective analyzed by retrieving the medical database in Peking Union Medical College Hospital from January 2000 to May 2015. Pathological categories were re-classified. Renal remission rates,infection rates,and death events were compared between intravenous glucocorticoid(GC)pulse therapy group and non-pulse group. Logistic regression analysis was performed to analyze factors influencing the short-term prognosis.Results Among the 81 patients with ANCA-associated glomerulonephritis,49(60.5%)received GC pulse therapy and 32(39.5%)did not. The GC pulse group had significantly lower estimated glomerular filtration rate at baseline(eGFR0)than the non-pulse group(t=3.003,P=0.015)but significantly higher 24-hour urinary protein(24 hUP)(t=2.394,P=0.002)and Birmingham Systemic Vasculitis Activity Score(BVAS)(t=0.049,P=0.013). There was no significant difference in the cumulative amount of cyclophosphamide(CTX)(t=1.336,P=0.245)between these two groups. The overall renal remission rate of GC pulse group in the 6 month was significantly lower(48.7% vs. 79.3%;χ =6.591,P=0.024). Univariate analysis showed that baseline 24 hUP(t=6.222,P=0.017),eGFR0(t=3.727,P=0.046),and pathological category(χ =7.654,P=0.045)were associated with the overall renal remission rate in the 6 month. Multivariate analysis showed the crescent category was an independent factor(OR=20.63,95%CI:2.217-191.973,P=0.008;compared with sclerotic category)for overall renal remission rate in the 6 month,while GC pulse therapy was not an predictor(OR=0.271,95%CI:0.062-1.179,P=0.082). A total of 37 patients experienced infections within 6 months. The infection rate in GC pulse group(55.1%,27/49)was significantly higher than that of non-pulse group(31.3%,10/32)(P=0.042). Univariate regression analysis showed that eGFR0(t=1.912,P=0.049),baseline BVAS(t=-3.360,P=0.001)and GC pulse(χ =6.249,P=0.014)were associated with infection events within 6 months. Multivariate analysis showed that the baseline BVAS was the only predictor with 1.089 times for every 1 point increase in BVAS(OR=1.089,95%CI:1.006-1.179,P=0.034). Conclusions Crescentic category favors renal remission independently compared with sclerotic category. Patients with crescentic category may benefit more from intensive treatment. BVAS acts as an independent risk factor of infection.

Fibronectin Glomerulopathy Caused by the Y973C Mutation in Fibronectin: A Case Report and Literature Review / 中国医学科学杂志(英文版)

Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin. We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting nephrotic syndrome. Genetic analysis of fibronectin 1 gene showed heterozygosity for the Y973C mutation. However, this mutation was not found in her parents. She had stable renal function but persistent nephrotic proteinuria after one-year follow-up.

Clinicopathological Features of Idiopathic Membranous Nephropathy in 33 Adolescents / 中国医学科学院学报

Objective To investigate the clinicopathological features and prognosis of idiopathic membranous nephropathy(IMN)in adolescents. Methods This was a retrospective study on IMN patients hospitalized between June 2012 and December 2014,and a total of 33 IMN patients aged between 13 and 24 years old were enrolled in the study.Meanwhile,33 IMN patients aged more than 24 years old were selected randomly as control group during the same period.Diagnosis was confirmed by renal biopsy,and the secondary causes of membranous nephropathy were ruled out.Data collected from medical record and biopsy were analyzed. Results In the adolescent IMN group,the mean age at renal biopsy was(20±3)years old,and the male/female ratio was 22/11.Twenty-three cases presented as nephrotic syndrome.Systolic and diastolic pressures were(127±13)mmHg and(77±9)mmHg,respectively.The median 24-hour urine protein was 5.14(3.39,9.31)g/d,and the median serum creatinine was 62(52,73)μmol/L.The positive rate of serum anti-phospholipase A2 receptor in adolescent group was 54%.Compared with control group,the adolescent patients had lower incidence of hypertension and higher baseline estimated glomerular filtration rate level [15.2% vs.39.3%,χ=4.889,P=0.03;125 ml/(min·1.73m)vs.100 ml/(min·1.73m),U=137.5,P<0.001].According to IMN staging criteria in electron microscopy,adolescent patients were classified as one case in stage I,21 in stage Ⅱ,and 11 in stage Ⅲ or higher.The positive rates of IgG1,IgG2,IgG3 and IgG4 subclass staining in glomeruli were 46.9%,3.1%,56.3%,and 87.5%,respectively.Compared with control group,the adolescent patients had lower incidence of renal interstitial fibrosis and arteriolar lesions(6.1% vs.66.7%,χ=26.19,P<0.001;15.2% vs.66.7%,χ=18.11,P<0.001).Three patients lost to follow-up while others started steroid combined with cyclosporine A(n=20),cyclophosphamide(n=7),or mycophenolate(n=1)or solely(n=2).After a median follow-up of 18(12,24)months,the median proteinuria decreased to 0.20(0.10,0.42)g/d,whereas serum creatinine level remained stable [69(56.8,81.3)μmol/L].Seventeen patients(56.7%)achieved complete remission(CR),and the remaining 13 patients(43.4%)achieved partial remission(PR).The median time of CR and PR were three and six months,respectively.Only one patient relapsed during the follow-up.Also,21 cases received maintenance therapy including cyclosporine A(n=18),azathioprine(n=2)and mycophenolate(n=1).Conclusions The immunofluorescence IgG subclass in glomeruli and distribution of serum anti-phospholipase A2 receptor in adolescent IMN patients are similar to those in older IMN patients.IMN patients in adolescents responded well to immunosuppressive therapy.Cyclosporine A in low dose as maintenance therapy is effective after achieving remission,and will not increase risk of nephrotoxicity.

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy / 中国医学科学杂志(英文版)

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 m, 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/mm(AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m(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 mvs. -8.1±21.4 ml/min per 1.73 m, 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 mof body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Expression of calcineurin in podocytes in response to endoplasmic reticulum stress in diabetic nephropathy / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the regulation of calcineurin (CaN) by endoplasmic reticulum stress (ERS) in podocytes in vitro and in vivo at the stage microalbuminuria in diabetic nehropathy (DN).</p><p><b>METHODS</b>The urinary albumin excretions of C57BLKS/J (Lepr) db/db and db/m mice at the ages of 6, 9, and 12 weeks were measured. The expressions of CaN and synaptopodin of these mice were observed. In immortalized mouse podocytes, the expression of podocyte CaN incubated with different concentrations of paltimate was quantitatively determined by real-time PCR. The changes of CaN incubated with paltimate with or without ursodeoxy-cholic acid (UDCA) were analyzed by confocal microscopy and Western blotting.</p><p><b>RESULTS</b>As urine protein increased, the expression of CaN was enhanced and the expression of synaptopodin was reduced in early stage DN db/db mice potocytes. In immortalized mouse podocytes, as the concentrations of palmitate increased, CaN mRNA increased. By confocal microscopy, the fluorescence intensity of CaN increased in palmitate treatment group. After co-incubation with palmitate and UDCA, the fluorescence intensity decreased. The similar results were shown by Western blotting.</p><p><b>CONCLUSION</b>At the stage of microalbuminuria in DN, ERS in podocytes up-regulates the expression of CaN.</p>

Clinical features of 30 patients with cryoglobulinemia / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the clinical features of cryoglobulinemia.</p><p><b>METHOD</b>We retrospectively analyzed the clinical data of 30 patients admitted to Peking Union Medical College Hospital from January 2003 to March 2013 due to cryoglobulinemia.</p><p><b>RESULTS</b>The average age was(53.8±11.9)years in these 30 patients(12 men and 18 women),among whom 22 patient(73.3%)developed infectious diseases including hepatitis B(n=11)and hepatitis C(n=11);in addition,3 hepatitis B patients and 1 hepatitis C patient also had malignancies. Four patients(13.3%)were accompanied with malignant lymphocytic proliferation diseases,and three(10.0%)with connective tissue diseases. The cause of disease was unclear in 5 patients(16.7%). The clinical manifestations varied due to the primary diseases;notably,20 patients(66.7%)had an onset of purpura rash,22(73.3%)and 19(63.3%)were accompanied with hypertension and chronic renal insufficiency,respectively. The severity of renal involvement was relevant with the increase of C reactive protein,erythrocytes,sedimentation rate,and IgM and the decrease of complements. Treatment should be directed at the primary diseases. Glucocorticoid and immunosuppressants were good choices for relieving renal involvement. Elderly, type 1 cryoglobulinemia,and poor renal function were associated with the poor prognosis.</p><p><b>CONCLUSIONS</b>Cryoglobulinemia is mainly seen in middle and elderly patients. It can often affect multiple systems,in particular the kidney. Inflammatory markers,IgM,and complements is related with the disease severity. Age,primary disease,and renal function are related with prognosis.</p>

Clinical and pathological analyses of bevacizumab-induced renal impairment in four patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical and pathological characteristics of bevacizumab-induced renal impairment.</p><p><b>METHOD</b>The clinical and pathological data of 4 patients with bevacizumab-induced renal impairment in Peking Union Medical College Hospital was retrospectively analyzed.</p><p><b>RESULTS</b>There were 2 men and 2 women aged (56.5±11.5) years. Before bevacizumab treatment, three non-small cell lung cancer patients (75%) had normal renal function and only one pancreatic cancer patient (25%) had mild renal impairment. After 2-14 cycles of bevacizumab treatment, the most common clinical manifestation of bevacizumab-induced renal injury was proteinuria (>3.5 g/d) (n=4, 100%). Other clinical symptoms included microscopic hematuria (n=2, 50%), malignant hypertension (n=1, 25%), elevated serum creatinine level as accompanied with acute renal failure (n=1, 25%), and anuria (n=1, 25%). Thrombotic microangiopathy was the main pathological type (n=2, 50%), whereas other pathological types included membranoproliferative glomerulonephritis (n=1, 25%) and benign arteriolar nephrosclerosis (n=1, 25%). After the detection of renal impairment, bevacizumab therapy was stopped in all 4 cases (100%). Hemodialysis was performed in the patient with acute renal failure. The prognosis was relatively good. The renal function and proteinuria was completely recovered in one patient (25%), whereas the other three patients (75%) presented with persistent alleviated proteinuria but normal renal function.</p><p><b>CONCLUSIONS</b>Bevacizumab may cause renal injury via complex mechanisms. Therefore, urine protein excretion and renal function should be closely monitored during bevacizumab treatment to identify any renal injury. The prognosis is relatively good after discontinuation of bevacizumab.</p>

Endoplasmic reticulum stress is involved in podocyte apoptosis induced by saturated fatty acid palmitate / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Podocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) stress and consequent apoptosis, contributing to the onset of diabetes. We hypothesized that palmitate could induce podocyte apoptosis via ER stress, which initiates or aggravates proteinuria in diabetic nephropathy.</p><p><b>METHODS</b>Podocyte apoptosis was detected by 4',6-diamidio-2-phenylindole (DAPI) stained apoptotic cell count and Annexin V-PI stain. The expressions of ER molecule chaperone glucose-regulated protein 78 (GRP78), indicators of ER-associated apoptosis C/EBP homologous protein (CHOP), and Bcl-2 were assayed by Western blotting and real-time PCR. GRP78 and synaptopodin were co-localized by immunofluorescence stain.</p><p><b>RESULTS</b>Palmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L (10 hours, 13 hours, and 15 hours compared with 0 hour, P < 0.001) and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours (compared to control, P < 0.001). Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP, and decreased that of Bcl-2. Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to control (P < 0.001), with the maximum concentration being 0.75 mmol/L. Palmitate 0.5 mmol/L loading for 3 hours, 8 hours, and 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to 0 hour (P < 0.001), with the maximum effect at 3 hours. Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control.</p><p><b>CONCLUSION</b>Palmitate could induce podocyte apoptosis via ER stress, suggesting podocyte apoptosis and consequent proteinuria caused by lipotoxic free fatty acid could be ameliorated by relief of ER stress.</p>

Vocal fold bamboo nodes: diagnosis, treatment and pathology / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features, pathology and treatment of a rarely seen laryngeal lesion, the vocal fold bamboo nodes.</p><p><b>METHODS</b>Two patients with vocal fold bamboo nodes were retrospectively reviewed. The clinical features, pathology and treatment were presented.</p><p><b>RESULTS</b>Video laryngoscope examination showed bilaterally creamy yellow transverse band like deposits in the submucosa, which were the typical vocal fold bamboo nodes in patients with autoimmune disease. Immunofluorescence pathology showed IgA, C1q and IgM deposition in lamina propria. Both patients were initially treated with oral hormones and one patient subsequently underwent submucosal resection of the lesion. The results of pathological and immunofluorescence investigations were reported in this paper, together with a discussion of the relevant literature.</p><p><b>CONCLUSIONS</b>Vocal fold bamboo node is a special laryngeal lesion in patients with autoimmune disease. The pathological results showed immune complexes in the vocal fold lamina propria. A surgical intervention can be applied if steroid drugs are not effective or the dysraphism of the vocal folds exists due to the bamboo nodes.</p>

Correlations of podocyte injury with glucose regulated protein 78 expression and proteinuria in patients with diabetic nephropathy / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the podocyte injury in patients with diabetic nephropathy (DN) and analyze its relationship with glucose regulated protein 78 (GRP78) and proteinuria.</p><p><b>METHODS</b>The clinical data of 48 patients diagnosed as DN by renal biopsy were reviewed. All patients were divided into two groups according to proteinuria (>3.5 g/d, n=31 and 3.5 g/d, n=17). The density of podocytes was illustrated by immunohistochemistry staining of Wilms tumor-1 (WT-1), and the immunofluorescence double-staining results of synaptopodin and GRP78 in podocytes were detected.</p><p><b>RESULTS</b>The podocyte dentistry of urine protein > 3.5 g/d group was significantly lower than that of urine protein>3.5 g/d group urine protein<3.5 g/d group(P=0.003), and it was negatively correlated with proteinuria (P=0.005). The expressions of synaptopodin and GRP78 in podocytes were also negatively correlated with proteinuria (P=0.004 and P=0.001).</p><p><b>CONCLUSION</b>The podocyte injury is aggravated with increased proteinuria in DN patients, along with the decrease of the adaptive ability of endoplasmic reticulum to stress.</p>

Cyclosporine treatment in idiopathic membranous nephropathy nephrotic syndrome in adults: a retrospective study spanning 15 years / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cyclosporine is effective in treating nephrotic syndrome (NS) with idiopathic membranous nephropathy (IMN) in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is inconclusive. The aim of this study was to introduce the way how to titrate the cyclosporine to maintain complete remission without relapse.</p><p><b>METHODS</b>Patients with biopsy-proven IMN with NS treated with cyclosporine for at least 1 month from 1996 to 2011 at Peking Union Medical College Hospital were reviewed.</p><p><b>RESULTS</b>Mean age of the 51 eligible patients was 52 years, with 39 men. Mean proteinuria was (7.47 ± 3.14) g/d, serum albumin (24.50 ± 6.29) g/L, and serum creatinine (82.62 ± 21.18) mmol/L. Cyclosporine was commenced at a mean dose of (3.46 ± 0.63) mg×kg(-1)×d(-1). Oral prednisone (0.40 ± 0.29) mg×kg(-1)×d(-1) was given concomitantly in 38 patients. Cyclosporine was administered for a median of 16 months (range 1 - 93 months) and stopped in non-responders by month six. By month 3 (n = 47), the number in complete remission (CR) and partial remission (PR) was 3 and 24, which shifted to 12 and 17 by month 6 (n = 41). Male gender, heavy proteinuria, low serum albumin level, and high serum creatinine level were significant determinants in poor response by month six (P < 0.05 in all variables compared with responders). There was a significant reversible serum creatinine increase within 25% during month 3 to 12 (P < 0.05 in all variables compared with baseline value). Eleven patients maintained cyclosporine for more than 24 months with a cyclosporine dose of (1.04 ± 1.06) mg×kg(-1)×d(-1). Nine patients were in CR. Renal function, systolic and diastolic blood pressure remained stable. Renal impairment (> 30% rise of serum creatinine), secondary infection, hypertension, gingival hyperplasia and liver impairment occurred in 6, 4, 10, 4, and 1 patients, respectively.</p><p><b>CONCLUSIONS</b>The observation time for cyclosporine to effectively induce CR of NS in IMN adults should be at least six months. Long-term and low-dose of cyclosporine therapy is safe and effective to maintain CR in those responders.</p>

Clinical analysis of anti glomerular basement membrane disease with normal renal function / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical and pathologic characteristics of anti-glomerular basement membrane(GBM) disease with normal renal function.</p><p><b>METHODS</b>The clinical and pathologic data of 6 patients with anti-GBM disease and normal renal function in Peking Union Medical College Hospital were reviewed retrospectively. Furthermore, 29 patients with anti-GBM disease and impaired renal function in the same period in the same hospital were enrolled as the control group. Factors that may influence the prognosis were analyzed.</p><p><b>RESULTS</b>Six (17.1%) of all 35 patients maintained normal renal function for 12-133 months during follow-up. Five patients had microhematuria and proteinuria, one had pulmonary hemorrhage only, and three manifested as Goodpasture syndrome. Renal biopsies from 4 patients revealed linear deposition of IgG 2+-3+ along the glomerular capillary walls by immunofluorescence. As shown by normal light microscopy, mild mesangial proliferation and crescentic glomerulonephritis with a large amount of fibrinoid necrosis of glomerular capillary walls were observed in different patients; however, most pathological changes were mild. Five of these six patients were treated with immunosuppressive drugs and/or plasma exchange. Compared with the control group, the 6 patients with normal renal function had significantly higher hemoglobin[(77.97±20.62 vs.(99.67±19.80 g/L P=0.024], lower titers of anti-GBM antibody[(224.34 ± 145.79 vs.(80.23 ± 85.73 EU/ml P=0.027], and lower ratio of glomeruli with crescents[(0.58±0.29 vs.(0.17±0.27 ,P=0.005]. These 6 patients with normal renal function were followed up for 12-133 months, among whom 4 patients achieved complete remission and 2 had mild proteinuria and microhematuria.</p><p><b>CONCLUSION</b>Anti-GBM disease with normal renal function is not uncommon. Most patients have mild pathologic changes and good prognosis.</p>

Glomerular disease associated with Takayasu arteritis: 6 cases analysis and review of the literature / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the clinical features, renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis (TA).</p><p><b>METHODS</b>Patients with TA and renal biopsy-confirmed glomerular disease were investigated retrospectively. None of them had renal artery stenosis or occlusive changes.</p><p><b>RESULTS</b>Six patients with glomerulopathy, accounting for 3.75% of the 160 TA patients admitted to our hospital at the same period, were analyzed. All of them were females with a mean age of 35.5 +/- 10.0 years. Four cases presented with lower extremity edema. Laboratory tests showed that one was nephrotic syndrome, three were nephrotic range proteinuria, and two of them had mild renal dysfunction. The other two patients were asymptomatic microscopic hematuria and proteinuria. Renal pathology revealed mild immunoglobulin A nephropathy in two cases, mild mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, minimal change disease, and fibrillary GN in one case respectively. Five cases received glucocorticoids and cyclophosphamide therapy. Proteinuria and microscopic hematuria disappeared in 2 to 4 weeks after the initiation of therapy in three cases. The patient with membranoproliferative GN also reached complete remission of proteinuria and recovered renal function 6 months after the treatment.</p><p><b>CONCLUSIONS</b>TA may induce glomerular disease as a part of its histological spectrum. Apart from ischemic glomerular disease, glomerular disease should be suspected when TA patients have microscopic hematuria or proteinuria, that may be therapeutically responsive to glucocorticoids and immunosuppressive agent in relative early phase.</p>

Effects of very low-density lipoprotein on cellular lipid accumulation and the expression of monocyte chemoattractant protein-1 in human mesangial cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of very low-density lipoprotein (VLDL) on cellular lipid accumulation and the expression of monocyte chemoattractant protein-1 (MCP-1) in human mesangial cells.</p><p><b>METHODS</b>An established stable human mesangial cell line (HMCL) was used in all experiments. VLDL-induced cellular lipid deposition was visualized by Oil Red O staining and analyzed quantitatively by standard enzymatic procedures. MCP-1 mRNA and protein expression levels in treated HMCLs were determined by real-time quantitative RT-PCR and enzyme-linked immunosorbent assay, respectively. For adhesion study, HMCLs were treated with VLDL for 12 hours, followed by a one-hour incubation with THP-1 cells.</p><p><b>RESULTS</b>VLDL induced cellular lipid accumulation in HMCLs in a time- (0-24 h) and dose- (0-200 microg/ml) dependent manner, and the principal component of accumulated lipid is triglyceride. In HMCLs, MCP-1 mRNA expression was promoted by VLDL in a time- (0-6 h) and dose- (0-100 microg/ml) dependent manner, and VLDL also enhanced MCP-1 secretion in a dose-dependent manner. Such an effect was accompanied by increased adhesion of monocytes to HMCLs.</p><p><b>CONCLUSIONS</b>VLDL can induce cellular triglyceride accumulation and upregulate the expression of MCP-1 in human mesangial cells. Hence, VLDL may be involved in the pathogenesis of lipid-mediated renal injury.</p>

Lupus nephritis complicated with malignant hypertension: from renal vascular pathology to clinical relevance / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.</p><p><b>METHODS</b>We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.</p><p><b>RESULTS</b>Of 19 patients, 3 were men and 16 were women, with a mean age of 24.4 +/- 7.7 years old. All had positive antinuclear antibodies and low serum complement was found in 13 patients. All were anemic and 12 of them were thrombocytopenic. Impaired renal function was found in 17 patients with an average serum creatinine of 184.5 +/- 88.9 micromol/L. Severe intrarenal arteriolar lesion was found in all patients. Six patients had lupus vasculopathy, 11 patients had renal thrombotic microangiopathy lesion, 2 had severe arteriosclerosis. All patients received steroids and immunosuppressive drugs, 15 received angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) with resultant well-controlled blood pressure. Thrombocytopenia and hemolytic anemia resolved remarkably. The renal function improved or recovered in 14 of 17 patients, and 3 developed end-stage renal disease on maintenance dialysis.</p><p><b>CONCLUSIONS</b>Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension. Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type. On the basis of immunosuppressive drugs and steroids to control systemic lupus activity, timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.</p>

Effects of rosiglitazone on the expression connective tissue growth factor in tubulointerstitium in KKA(y) mice / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the expression of connective tissue growth factor (CTGF) in the tubulointerstitium in type 2 diabetic KKA(y) mice and the effect of rosiglitazone on it.</p><p><b>METHODS</b>KKA(y) and C57 BL/6 mice aged 16 weeks ( n = 5 in each group) were sacrificed as controls before treatment. Another 20 KKA(y) mice were treated with rosiglitazone (30 mg x kg (-1) d (-1), n = 10) or placebo (n = 10). The mice were sacrificed at 20 and 24-week-age (n = 5 at each time point). Protein expression of transforming growth factor-beta1 (TGF-beta1 ), CTGF, peroxisome proliferator-activated receptor-gamma (PPARgamma) , and fibronectin were assayed by Western blot, while protein CTGF, PPARgamma, and alpha-smooth muscle actin ( alpha-SMA) were assayed by immunohistochemistry in kidney tissue sections.</p><p><b>RESULTS</b>Proteinuria was significantly decreased in mice aged 24 weeks treated by rosiglitazone than same-aged mice treated with placebo [ (44. 53+/-1. 96) vs (63. 66 +/-5. 57) microg/24 h, P < 0. 05 ]. The expressions of TGF-beta1, CTGF, and fibronectin in mice aged 20 weeks treated with rosiglitazone decreased by 37% , 21% , and 52% than same-aged control (P <0. 01) , and those were decreased by 61% , 50% , and 51% in mice aged 24 weeks treated with rosiglitazone compared with same-aged control mice (P < 0. 01). CTGF in the tubulointerstitium were respectively downregulated by 25% and 44. 9% in treated mice aged 20 weeks and 24 weeks compared with the same-aged control mice ( P < 0. 01). The PPARgamma appeared in diabetic mice and increased by 18. 1% in mice aged 24 weeks and treated with rosiglitazone than the same-aged control mice (P <0. 05).</p><p><b>CONCLUSION</b>Heterogeneous rosiglitazone may upregulate the expression of PPARgamma in renal cortex, and remarkably inhibit the expressions of CTGF in the tubulointerstitium and renal cortex in diabetic KKA(y) mice.</p>

Clinical analysis of proteinuria and glomerular lesions in Henoch-Schönlein purpura nephritis of adults / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyze the characteristics of proteinuria and glomerular lesions in Henoch-Schönlein purpura nephritis (HSPN) of adults.</p><p><b>METHODS</b>The pathologic results and clinical data of 103 HSPN patients were analyzed.</p><p><b>RESULTS</b>Patients with mild or moderate proteinuria accounted for 40.8% and 37.9%, respectively. Patients with nephropathic proteinuria accounted for about 21.4%. Severer proteinuria resulted in higher blood pressure and increased cholesterol, and albumin decreased gradually (P < 0.01); meanwhile, total glomerular lesion, tubulointerstitial lesion, and vascular lesion also became severer (P < 0.01).</p><p><b>CONCLUSION</b>Proteinuria may indirectly reflect the severity of glomerular lesions in HSPN of adults.</p>

Altered expression of vascular endothelial growth factor and its receptors in transdifferentiated human proximal tubular epithelial cells induced by transforming growth factor beta1 / 中国医学科学院学报

<p><b>OBJECTIVE</b>To examine the expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1, VEGFR2) in transdifferentiated human proximal tubular epithelial (HK-2) cell induced by transforming growth factor beta1 (TGFbeta1).</p><p><b>METHODS</b>The transdifferentiation of HK-2 cells was detected by evaluation of expression of alpha-SMA by cytoimmunochemistry and RT-PCR. The VEGF mRNA was evaluated with RT-PCR. The secreted VEGF in the culture media was measured with ELISA. The cellular VEGF, VEGFR1, and VEGFR2 were measured with Western blot.</p><p><b>RESULTS</b>The immunostain of alpha-SMA were positive in HK-2 cell induced by TGFbeta1 at the concentration of 5 and 8 ng/ml for 72 h. The expression of alpha-SMA mRNA was induced by TGFbeta1 in concentration- and time-dependent manners. The expressions of mRNA and protein of VEGF were upregulated by TGFbeta1 at the concentration of 0.1 and 1 ng/ml for 72 h and at the concentration of 8 ng/ml for 12 h and 24 h when compared with the control. But expressions of mRNA and protein of VEGF were downregulated by TGFbeta1 at the concentration of 3, 5, and 8 ng/ml for 72 h and at the concentration of 8 ng/ml for 36, 48, and 72 h, respectively. Meanwhile, Protein levels of VEGFR1 and VEGFR2 were upregulated by TGFbeta1 in concentration- and time- dependent manners.</p><p><b>CONCLUSIONS</b>Increased expression of VEGFR1 and VEGFR2 and two-phase change in VEGF expression occurred in the process of tubular epithelial transdifferentiation induced by TGFbeta1. Reduced expression of VEGF may contribute to tubular epithelial transdifferentiation in a vicious circle.</p>