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Objective To observe the long_term efficacy and adverse reactions of Rituximab( RTX)in the treatment of children with frequently relapsing nephrotic syndrome(PRNS),and to explore the feasible treatment plan of RTX in children with PRNS. Methods PRNS children with RTX[375 mg∕(m2·time),2_3 times]from Depart_ment of Dediatrics,Jinling Hospital,Nanjing Clinical School of Southern Medical University between Pebruary 2011 and December 2017 were retrospectively reviewed,and followed up for 12 _36 months. Age,gender,number of relapses, dose of steroids and immunosuppressants,adverse reactions and laboratory indicators(peripheral blood CD20 ﹢B lympho_cyte count,24_hour urine protein quantification,etc)were observed. Results Thirty_four patients(23 males and 11 females)with PRNS were included in the present study,and the median age for the first RTX treatment was 6 years (2_12 years). After the first treatment,there was complete remission in 34 patients(100%,34∕34 cases),and 12 pa_tients(35%,12∕34 cases)relapsed during follow_up. The number of relapse after treatment[(0. 27 ± 0. 45)times] significantly decreased compared with that before treatment[(2. 94 ± 1. 08)times;t﹦11. 9,P〈0. 05]. After the second treatment,3 children relapsed due to ＂infection＂ and no discomfort was found in the first 6 months;5 of 23 cases (21. 7%,5∕23 cases)relapsed once and 11 were unclear in the following 6 months. There was a difference between the 2 treatment intervals 〈12 months(12. 5%,2∕16 cases)and ≥12 months(55. 5%,10∕18 cases). After the third treatment,with an interval of 6 to 15 months,1 of 15 patients(6. 67%)relapsed and the rest were stable. In addition, there was a significant difference in the mean accumulated steroid dose of 20 patients between 6 months before treatment [(2. 50 ± 0. 87)g ]and 6 months after treatment[(1. 30 ± 0. 97)g;t﹦6. 05,P﹦0. 001]. Of the 15 patients after RTX treatment for 6_12 months Tacrolimus was reduced from[(1. 62 ± 0. 77)mg∕24 h ]to[(0. 62 ± 0. 96)mg∕24 h;t﹦6. 80,P﹦0. 000]. Two patients after RTX first infusion had chest tightness,palpitations,nausea,vomiting,dizzi_ness,and headache,3 cases had mild upper respiratory tract infection and 1 case had severe pulmonary infection. Conclusion Long_term follow_up of PRNS children treated with RTX turns out to be safe and effective.
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Objective To analyze the spectrum of children's kidney pathology by renal biopsy.Methods The clinical and pathological data of the cases in Jinling Hospital involving the patients younger than 18 years old who received renal biopsy from April 1st,2004 to December 31th,2017 were retrospectively collected,and compared with the renal pathological data of 1611 children aged 0-18 years from June 1982 to March 2004.Results This study included 9925 cases of kidney diseases proven by renal biopsy.The ratio of male to female was 1.79∶ 1.Primary glomerulonephritis (PGN) accounted for 66.14％,and secondary glomerulonephritis (SGN) accounted for 28.00％.Top five of the PGN were IgA nephropathy (IgAN,19.11％),mesangial proliferative glomerulonephritis (MsPGN,16.07％),minimal change disease (MCD,14.20％),focal segmental glomerulosclerosis (FSGS,6.19％)and membranous nephropathy (MN,4.70％) in whole children,IgAN (13.12％),MsPGN (11.20％),MCD (10.63％),FSGS (4.55％) and MN (2.54％) in males,and IgAN (5.99％),MsPGN (4.87％),MCD (3.57％),MN (2.16％) and FSGS (1.63％) in females.Top three of the SGN were Henoch-Schonlein purpura nephritis (HSPN,17.74％),lupus nephritis (LN,8.23％) and vasculitis nephropathy (1.82％).The male was in a dominant position in all kinds of pathologic types than female except LN.HSPN was the most frequent type in adolescents between 6-13 years old.LN was the commonest one in 14-18-year-old girls,while IgAN was the the most common in 14-18-year-old boys.Post infective nephritis was the most popular in 12-14-year-old teenagers.It was also found that MN ascended in female.When compared with the data before 2004,HSPN and LN accounted for a greater proportion in SGN,post infective nephritis displayed a smaller proportion.Conclusions PGN is the mainly kind of glomerular disease as before,and immune disorder related to glomerular diseases increase and post infective nephritis decreases in proportion.This study provides the reference and epidemic data for diagnosis,treatment and prevention of children's renal diseases.
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Objective To investigate the renoprotective effect of aspirin-triggered lipoxins(ATL)on kidney of mice with acute kidney injury(AKI).Methods Eighty-eight male specific pathogen-free(SPF)C57BL/6J mice were randomly divided into lipopolysaccharide(LPS)groups(including 2 h group,4 h group,8 h group,12 h group, 24 h group),ATL+LPS(including 2 h group,4 h group,8 h group,12 h group,24 h group)and normal control group according to random numble table,and each group had 8 mice.The mice in LPS groups were given LPS intraperitoneal injection to establish AKI animal models,while the mice in ATL+LPS groups were given ATL intraperitoneal injection 30 minutes before LPS intraperitoneal injection.The enzyme linked immunosorbent assay was used to test the serum creatinine(Scr),serum urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and urine neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),cysteine-rich protein-61 (Cyr61)and netrin-1 levels of mice.Results The kidney tissue injury scores of mice of ATL+LPS group[4 h:(22.32 ± 1.04)scores,8 h:(31.11 ± 1.86)scores,12 h:(18.22 ± 0.92)scores,24 h:(20.87 ± 3.18)scores] were lower than those of LPS group at the corresponding time points[4 h:(35.47 ± 2.27)scores,8 h:(52.28 ± 2.82) scores,12 h:(54.99 ± 4.56)scores,24 h:(53.41 ± 4.76)scores],and the differences were statistically significant(all P<0.01).The values of Scr,BUN,TNF-α and IL-1β in ATL+LPS group[Scr 8 h:(143.07 ± 5.02)μmol/L, BUN 12 h:(33.07 ± 3.52)mmol/L,TNF-α 4 h:(196.33 ± 14.181)ng/L and 8 h:(221.77 ± 10.11)ng/L,IL-1β 4 h:(50.25 ± 2.67 ng/L)]were lower than those in LPS group at the corresponding time points[Scr 8 h:(227.43 ± 11.17)μmol/L,BUN 12 h:(59.68 ± 3.84)mmol/L,TNF-α 4 h:(267.87 ± 26.48)ng/L and 8 h:(334.78 ± 21.08)ng/L,IL-1β 4 h:(89.45 ± 5.87)ng/L],and the differences were statistically significant(all P<0.01). The urine NGAL[4 h:(56.76 ± 4.01)μg/L,8 h:(65.44 ± 7.81)μg/L],KIM-1[8 h:(78.19 ± 9.48)μg/L] and netrin-1[8 h:(40.12 ± 2.01)ng/L,12 h:(36.87 ± 2.87)ng/L]of mice in ATL+LPS group were lower than those in LPS group at the corresponding time points[NGAL 4 h:(168.77 ± 10.77)μg/L,8 h:(155.33 ± 8.26) μg/L;KIM-1 8 h:(124.73 ± 13.47)μg/L;netrin-1 8 h:(89.17 ± 2.74)ng/L,12 h:(81.11 ± 3.88)ng/L],and the differences were statistically significant(all P<0.01).Conclusions ATL can treat LPS-induced AKI and play a renoprotective role in the kidney.
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Anti-neutrophil cytoplasm antibody-associated vasculitis (ANCA) is an autoimmune disease with multi organ involvement characterized by vascular wall inflammation and fibrinoid necrosis, including microscopic polyangitis (MPA), granuloma polyangitis (GPA), and eosinophilic granuloma polyangitis (EGPA). Because its clinical manifestations are complicated and non-speciifc, it is dififcult to make early diagnose. In recent years, some new progress has been made in diagnosis and treatment of this disease. The article will review the related information.
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Objective Alport syndrome is one of the diseases that may lead to the end-stage renal disease ( ESRD) in chil-dren, and the methods for its diagnosis and treatment remain quite limited.This study aimed to investigate the clinical and genetic di-agnosis of a Chinese family with hematuria companied by genetic nephritis. Methods We analyzed the renal pathology of 7 patients in a family, performed immunofluorescence staining of type-Ⅳcollagen in the nephridial and skin tissue, conducted gene sequencing i-dentification using the exon sequence method, and examined the blood and urine samples from the patients. Results Renal patholo-gy manifested mesenterium hyperplasia in the index patient, with IgM+under the light microscope, no thickening or thinning under the electromicroscope, and no absence of type-Ⅳcollagen on immunofluorescence analysis.Mutation of c.1365_1373del TCCAGGCCC (p.Pro456_Pro458del3) was observed in exon 21 of the COL4A5 gene.Only 1682 amino acids were found in the mutated protein as compared with 1685 in the wild type. Conclusion This is the first case of Alport syndrome induced by gene deletion mutation ever reported in China and abroad.There are many female patients in this family, all with a high risk of reproduction failure.Antepartal gene diagnosis or genetic diagnosis before embryo transfer may contribute to the prevention of the disease.
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Objective Gitelman Syndrome is a disease caused by the mutation of Na-Cl cotransporter gene(SLC12A3).The article studied the significance of diagnosis and identification by genetic mutation. Methods We collected the clinical data, then we sequenced the SLC12A3 gene by the first sequencing technology and MLPA. Results SLC12A3 complicated heterozygotic mutation was observed.One of them showed c.1964G>A, p.(Arg655His) and exon 8 deletion mutation, the other showed c.2543A>T, p.(Asp848Val) and c.976delG, p.(Val326fs) mutation of SLC12A3 gene in children. Conclusion The final diagnosis depended on gene diagnosis. Pediatrician must recognize the manifestations to advoid misdiagnosis.
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Objective Mizoribine ( MZR) is a new immunosuppressant , however , little domestic research has been done on MZR for treatment of nephrotic syndrome in children .This study was to investigate curative effect and adverse reaction of MZR in the treatment of children with frequently relapsing nephrotic syndrome , using prospective controlled trials . Methods A total of 59 pa-tients with frequency relapsing nephrotic syndrome were randomly divided into two groups .29 patients of treatment group were treated with MZR +glucocorticoid , while 30 patients of control group were given Tripterygium wilfordii ( TW)+glucocorticoid treatment , and the course of treatment lasted for 12 months.24-hour urine protein, urinary N-acetyl β-glucosidase (NAG), serum albumin, serum cholesterol, serum creatinine, recurrence frequency, and average prednisone dosage were observed . Results At the end of treat-ment, Serum albumin in treatment group was higher than that in control group [(40.95 ±6.12)g/L vs (30.25 ±9.02)g/L], and Se-rum cholesterol ([5.45 ±0.82]mmol/L vs [7.53 ±2.74]mmol/L), urinary protein ([0.89 ±0.52]g/24 h vs [1.63 ±2.02]g/24 h), urinary NAG enzyme ([21.43 ±14.16]U/g· Cr vs [41.67 ±12.35]U/g· Cr) levels were lower compared with control group . There was significant difference between the two groups .In terms of mean recurrence times , no significant difference was found at 6th months of follow-up between the two groups, however, treatment group had lower recurrence rate than control group at 3rd month, 9th month, 12th month of follow-up, which was of significant difference .The average amounts of hormone of treatment group were lower than those of control group ([0.56 ±0.16] mg/kg· d vs [0.72 ± 0.34]mg/kg· d)、([0.64 ±0.35]mg/kg· d vs [0.67 ±0.52]mg/kg· d)、([0.53 ±0.41] mg/kg· d vs [0.83 ±0.37] mg/kg· d)、([0.34 ±0.15] mg/kg· d vs [0.54 ±0.26] mg/kg· d) at 3rd month, 6th month, 9th month, 12th month of follow-up, which was of significant difference . Conclusion Compared to Tripterygium wil-fordii combined with hormone therapy , MZR combined with prednisone therapy in children with recurrent NS frequency can reduce the relapse rate and dosage of corticosteroid to improve the clinical remission rate .
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Objectives To explore the clinical manifestations, treatment and prognosis of a case of blindness caused by nephrotic syndrome with cerebral venous sinus thrombosis (CVST). Methods The clinical manifestations, diagnosis and treatment of a case of NS with CVST were analyzed. The latest domestic and foreign reseach progresses in treatment for CVST in children were reviewed. Results Epilepsy suddenly appeared with diplopia, binocular vision loss and blindness in anticoagulant therapy for the child with NS. Brain magnetic resonance venography (MRV) suggested CVST. MRV reexam-ined showed that the intracranial thrombosis was completely dissolved after urokinase thrombolysis for one month followed by ineffective heparin anticoagulation. At present, international standards of anticoagulant therapy have been adopted in the treatment for CVST patients. Coagulation function (e.g.APTT) and international standardization ratio were monitored in order to prevent bleeding. Conclusions It is better to perform neural imaging examination early in suspected CVST patients. Anti-coagulation and thrombolytic therapy should be given immediately once the risk of bleeding was excluded and used for 3-6 months.
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ObjectiveTo estimate the application of mycophenolate mofetil (MMF) and cyclophosphamide(CTX) intravenous pulse therapy on diffuse proliferative lupus nephritis (DPLN).MethodPubMed,Medline,EMBASE and CNKI were searched from the establishment of the database.Meta-analysis of 14 comparative studies on MMF and CTX in treatment of DPLN was performed,taking the remission,the relapse,the death of MMF and CTX for DPLN as primary efficacy variable,mean while taking the herpes zoster as safety evaluating indicator.ResultsMMF was better than CTX in remission rate ( P ＜ 0.05 ).There was no difference between in incidence rate of the relapse,the death and the herpes zoste MMF and CTX for DPLN ( P ＞ 0.05 ).ConclusionMMF was better than CTX on the efficacy and safety in DPLN.
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ObjectiveTo investigate the clinical application of tacrulimus (TAC, FK506) in children with primary nephrotic syndrome (NS). MethodsSixty-five primary NS children received routine or decreased-dosage glucocorticosteroid according to clinical NS types after hospitalization. At the same time, TAC was given orally with the dosage of 0.1 to 0.15 mg/kg, once every 12 hours, for 6 to 24 months. And the serum concentration of TAC was monitored during the course. ResultsAfter the treatment of TAC for 1 to 2 months, 65 patients were recovered with gradually reduced urinary protein, rapidly increased serum albumin, and improvement of cholesterol and triglycerides. Total remission rate was 83.1% and onset time was 7 to 54 days. Twelve cases experienced recurrence. Increased CD4, as well as 3/3 or 3/1 TAC genotype, indicated higher remission rate. Various pathological types had different remission rates or ratio, which were as follows: minimal change nephropathy (96.4%), mesangial proliferative glomendonephritis (90.0%), membranous nephropathy (2/3), membranous proliferative glomerulonephritis (3/5), focal segmental glomerulosclerosis (4/9). The patients would recover in the course of treatment under the conditions of TAC initial dose as 0.1 to 0.15 mg /kg per 12 hours and controlled serum concentration as 5 to 10 g/L. During the treatment, 12 cases appeared gastrointestinal symptoms, mainly as anorexia, nausea and vomiting, 1 abdominal pain, 2 headache, 1 tremor, 1 paresthesia, 3 insomnia, 4 transient increased Scr, 8 slightly increased NAG, 6 increased C3 and α-2 macroglobulin. The symptoms disappeared within one week or after stopping TAC. ConclusionsTAC is effective in primary NS children, even with abnormal liver function or tuberculosis infection. TAC can also be a substitute to cyclosporine A.
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Objective:To invesgate the correlation between Angiotensin converting enzyme(ACE) gene polymorphism and Henoch-Schonlein purpura nephritis(HSPN) in children. Methods:According to the clinical features,pathological changes,48 HSPN children have been devided into 4 clinical types,Uab,I-GH,R-GH and NS type,and Ⅱ-Ⅳ 3 histological degrees respectively.The correlations between serum ACE level,ACE gene polymorphism and clinical presentation,pathlogical changs,effect to therapy were analyzed.Results:In the 48 patients,35(72.9%),4(8.3%),4(8.3%) and 5(10.5%) patients belonged to Uab type,I-GH type,R-GH type and NS type respectively.20(41.7%),19((39.6%)) and 9(18.7%) patients belonged to Ⅱ,Ⅲ and Ⅳ histological degrees respectively.5 patients had DD genotype,25 patients had ID genotype and 18 patients had II genotype.The mean serum ACE level of DD genotype patients was(39.60?11.40)U/L,which was significant higher than that of ID genotype patients[(24.29?11.62)(U/L) and II genotype patients(4.49?11.41)U/L](P
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Objectives: The aim of the study was to evaluate the therapeutic effects of 6-mercaptopurine in the treatment of refractory childhood nephrotic syndrome (NS). Methods: According to the varieties of NS, 6-mercaptopurine (2 mg/kg body weight daily) combined with corticosteroid or 6-mercaptopurine (2 mg/kg body weight daily) alone after tapering of steroids were given to 28 consecutive children with primary NS in our hospital. Results: One month after the use of 6-mercaptopurine, proteinuria was decreased. The duration of improvement was 9～28 days, with mean duration of 17 days. Over-all effective rate was 85.7%. Among different varieties of NS, the best therapeutic effect was noted in steroid-dependent children; the better therapeutic effect in steroid-resistant children; and good therapeutic effect in frequently relapsing children. The effective rates were 100%, 84.6%, 81.8% respectively. All the pathological varieties of 28 children were confirmed by renal biopsy. The better therapeutic effects were noted in slight mesangial proliferative glomerulonephritis (MsPGN) and minimal change nephrotic syndrome (MCNS). The less therapeutic effect was noted in membranoproliferative glomerulonephritis (MPGN). Their therapeutic effective rates were 92.9%, 80%, 66.7% respectively. Unfortunately, drug-induced aplastic anemia was seen in 2 cases. Slight gastrointestinal reactions were present in 6 cases. There were no side reaction on the gonad. Conclusions: The great difference in the therapeutic effects is related to the different pathologic varieties of NS. With regard to the treatment of refractory NS in children, the pathological varieties should be confirmed by renal biopsy as soon as possible. Based on the renal biopsy, 6-mercaptopurine can be considered in the treatment of MsPGN and MCNS. As a result, relapses could be reduced; the duration of remission could be prolonged, and the side reactions from steroid treatment could be avoided. The use of 6-mercaptopurine for the treatment of refractory NS is one of the effective therapy.
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We have established adriamycin(ADR) nephropathy model, the expression of cyclophilin(CyP)mRNA was measured with RT PCR, and its relationship with the levels of total protein, albumin, cholesterol, 24 hour urine protein, BUN, and creatinine were determined.After four weeks,the levels of urine protein in ADR nephropathy animals were higher than 100mg/24h, whereas the levels in the control animals were lower than 6mg/24h. It was showed that the expression of CyP gene of kidney tissue in ADR nephropathy rats was significantly higher than that of the control animals. Meanwhile, it was found that there was negative correlation was found between the expression of Cyp gene and the levels of total protein and albumin,but positive correlation between the expression of CyP gene and the levels of 24 hour urine protein and cholesterol,and the expression of CyP gene had no correlation with the levels of BUN and creatinine. Our results suggested that the high levels of Cyp mRNA expression might contribute to renel tissue damage in ADR nephropathy,and it might reflect the degree of severity and prognosis in ADR nephropathy.
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To investigate the significance of liver biopsy in children with nephrotic syndrome,liver and renal biopsy samples were simultaneously examined with light microscopy,elctronic microscopy,and immunofluorescence in 10 patients. The results showed that all patients had abnormal liver histologic changes.Focal fatty degeneration in liver tissue was found under microscopic examination,and cytolysis and mild fatty degeneration were found in hepatocytes under electronic microscopic examination.The results suggested that disorder of lipid metabolism not only was toxic to glomeruli, but also deleterious to hepatocytes,then in turn enhanced abnormality in lipid metabolism. It is believed that hyperlipidemia is related to an increased anabolism of lipid and apolipoprotein, and reduction in catabolism of chylomicron and very low density lipoprotein .Therefore, with treatment of hyperlipidemia in these patients, it is possible to arrest progressive renal injury.