Application of rituximab in children with primary nephrotic syndrome / 医学研究生学报

Childhood primary nephrotic syndrome (PNS) is a challenging and persistent renal disorder. Corticosteroids is the first-line drug for the treatment of PNS. To reduce the side effects caused by the accumulation of corticosteroids dose and to maintain the remission state of the disease, immunosuppressants are applied to the treatment of PNS. However, many children with PNS still cannot get remission. Rituximab (RTX) is a novel immunosuppressive agent. In recent years, many studies have reported the treatment of PNS in children with RTX. This review analyzes the mechanism, course of treatment, dose, efficacy, and safety of RTX in the treatment of children with PNS.

Research progress of specific biomarkers in IgA nephropathy / 医学研究生学报

IgA nephropathy (IgAN) is the most common primary glomerular disease in the worldwide, and its immunopathological features are mainly the deposition of IgA in glomerular mesangial region and / or vascular loop. It has been found that the expression and changes of some factors involved in the pathological injury of IgAN can provide some evidence for the diagnosis, evaluation and prognosis of IgAN. This paper reviews the research progress of IgAN biomarkers in Multiple-Hits theory, miRNAs, complement system and cytokines.

A novel splicing mutation identified in a Chinese family with Alport syndrome and analysis of its pathogenicity / 医学研究生学报

Objective The purpose of this study was to identify a pathogenic variant in a Chinese family with Alport syndrome and analyze the pathogenicity of the variant. Methods Using targeted region capture and high-throughput sequencing technology, we identified the genetic variant of the proband with Alport syndrome, verified the variant in the family members by Sanger sequencing, and analyzed its influence on the pre-mRNA splicing process by in vitro minigene assay. Results A heterozygous variant c.2767G>T (p.Gly923Cys) was identified as a novel variant in exon 32 of the COL4A5 gene in the proband, which was confirmed by Sanger sequencing to be cosegregated with disease in the family. The minigene assay demonstrated that the c.2767G>T variant induced deletion of exon 32 of the COL4A5 gene. Conclusion A novel COL4A5 mutation was identified by targeted region capture and high-throughput sequencing, which has enriched the gene mutation spectrum of Alport syndrome. The exonic mutation c.2767G>T confirmed to be a splicing mutation by in vitro minigene assay, which may lead to a deeper insight into the molecular pathogenesis of Alport syndrome.

Analysis of efficacy of rituximab in treating primary focal segmental glomerulosclerosis in children / 医学研究生学报

Objective There are few studies on children with primary focal segmental glomerulosclerosis (FSGS) treated with rituximab (RTX).This study aimed to analyze the side effects and safety of the single dose of RTX in 10 children with primary FSGS, and further provide reference for the RTX treatment of FSGS . Methods We retrospectively analysed the clinical data of 10 FSGS children who hospitalized in the department of pediatrics in Nanjing General Hospital of Nanjing Military Area Command from April 2014 to August 2017.24 hours urinary protein, serum albumin, the count of circulating CD20+B cells and the RTX adverse reactions were analyzed after the treatment of RTX . Results From the 10 ca-ses, 6 cases were steroid-resistant nephrotic syndrome (SRNS), and 4 cases were frequently relapsing /steroid dependent nephrotic syn -drome (FRNS/SDNS).After single dose of RTX treatment , 5 cases achieved complete remission (CR), 2 partial remission (PR), and 3 non-remission (NR).Among the 6 cases of SRNS, 2, 1, 3 ca-ses achieved CR, PR, NR respectively; Among the 4 cases of FRNS/SDNS, CR was achieved in 3 patients, PR was achieved in 1 pa-tient.3 months after RTX treatment, urinary protein decreased from [2.41 (0.89-6.82) g/24 h] to [0.43 (0.05-1.1) g/24h], ser-um albumin increased from [31.60 (13.00-38.22) g/L] to [38.30 (27.18-53.20) g/L] .Adverse reactions occurred in 1 case in-cluding fever, chills, and chest tightness.These adverse reactions relieved after the decreased of RTX infusion speed .One developed severe pneumonia and proteinuria one month after RTX treatment .There was no increase in the number of infections in other children and no abnormalities in the respiratory tract , digestive tract, and nervous system during follow-up. Conclusion RTX treatment of primary FSGS has high security and has no serious adverse reactions .It is one of the effective treatments for children with FSGS .

The recognition of clinical application of glucocorticoids / 医学研究生学报

Because of the significant anti-inflammatory and immunosuppressive effects,glucocorticoids (GCs) have been widely used in clinic However,adverse reactions caused by long-term use of GCs and glucocorticoid resistance (GR) are always troublesome problems in clinical department.Therefore,it is the hot point to explore the ways to reduce adverse reactions of GCs and to improve sensitivity of GCs.In this article,we mainly discuss new strategies of reducing adverse reactions and improving sensitivity of GCs.

Effect and safety of Mizoribine on frequency recurrence nephrotic syndrome in children / 中华实用儿科临床杂志

Objective To observe urinary protein,serum albumin,cholesterol and recurrence of children with frequency recurrence nephrotic syndrome(NS) after using Mizorbine (MZR).Methods Eighteen cases of recurrent frequency NS were given enough hormone and MZR.Urinary protein,serum albumin,cholesterol,urinary N-acetyl-β-D-glucosaminidase(NAG) and recurrence were observed.The difference of recurrence between the children treated with steroid and the children treated with steroid and MZR more than 6 months were compared.Results In the combined treatment with both sufficient hormone and MZR,out of the 18 cases,there were one lost case and one invalid case.For the remaining 16 cases,edema subsided when they were reexamined in the first month,and the urine protein changed to negative within about 3 to 10 days (the average time was 6.33 days).There were 10 cases who were reexamined after 6 months,in which for 8 cases the serum albumin returned to normal in the first month (≥35 g/L),1case returned to normal in 3 month and 1 case in 6 month.The level of blood cholesterol returned to normal for 7 cases in the first month (＜ 5.7 mmol/L),3 cases returned to normal in 3 months.In the reexamining of urine protein in 24hours in the first month,7 cases returned to normal (＜0.4 g),2 cases reduced and there was no change in 1 case.Relapse occurred in 2 cases,in one of which the level of urine protein returned to normal if changing the MZR to alternate-day implosive therapy.After treatment,partial tubular functions restored and in the first month,the level of NAG returned to normal in 7 cases,decreased in 9 cases and increased in 1 case.In the experiment group,no child was observed vomiting,to have diarrhea and other gastrointestinal symptoms.The blood pressure,breathing and heart rate were within the normal range before and after the treatment.The increase of urea nitrogen and creatinine was observed only in 1 case.Conclusions MZR with enough hormone treating frequency recurrence NS can promote urine protein negative,and make serum albumin,cholesterol,urinary NAG decrease,and reduce the recurrence.When MZR made regular doses of the application can not effectively reduce the recurrence frequency,and the pulse treatment may be a kind of effective methods.

Nephrotic syndrome complicated with intracranial venous thrombosis treated with urokinase: report of 5 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the effect of urokinase and low molecular weight heparin in children with nephrotic syndrome complicated with intracranial venous thrombosis.</p><p><b>METHODS</b>Urokinase and low molecular weight heparin were administered to the 5 patients intravenously. The initial dose of urokinase was 2000 - 4000 U/(kg.d), the initial pulse dose was 20 000 - 40 000 U given within 15 - 30 minutes, and the left was infused by using a pump, from the second day 2000 U/(kg.d) urokinase was infused daily for 3 to 7 days. During the treatment thrombin time (TT), activated partial thromboplastin time (APTT) were tested 3 times every week, with particular attention to bleeding. Low molecular weight heparin 100 - 120 AXaIU/kg, 1 or 2 times per day was hypodermally injected for a course of two weeks. Anti-platelet drugs: long-term oral administration of dipyridamole 3 - 5 mg/(kg.d) was applied 2 - 3 times every day for 3 months.</p><p><b>RESULTS</b>The clinical symptoms disappeared after one month of the combined therapy of urokinase, low molecular weight heparin and dipyridamole in 5 cases of nephrotic syndrome complicated with intracranial venous thrombosis in children, the plasma viscosity returned to normal in 1 month, activated partial thromboplastin time, prothrombin time, fibrinogen degradation products returned to normal in 1 to 2 months, venous thrombosis disappeared after 1 to 3 months in head CT or MRI examination, showing the cerebral venous sinus thrombosis complete recanalization without relapse cases in follow-up.</p><p><b>CONCLUSION</b>The early application of urokinase and low molecular heparin and anti-platelet coagulation drugs was effective. The early diagnosis, treatment and prevention of intracranial vein thrombosis in patients with nephrotic syndrome is important.</p>

Clinical and pathological study of 47 cases with Alport syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical and pathological features of children with Alport syndrome (AS).</p><p><b>METHODS</b>A series of 47 patients with AS from unrelated families hospitalized from Jan. 1990 to Jan. 2007 were involved in this study. The clinical and histopathological data were collected and analyzed.</p><p><b>RESULTS</b>Of the 47 cases, 32 were male and 15 female, M/F: 2.1:1. The patient's age ranged from 15 months to 13 years, mean 9 years. Thirty-nine of the 47 cases had positive family history, X-linked dominant inheritance AS was diagnosed in 37 cases, autosomal recessive inheritance AS in 2 cases. Gross hematuria or microscopic hematuria were found in 59.3% of the cases as the first manifestations, while 29.8% showed edema or proteinuria. The major clinical manifestations were isolated hematuria (23.4%), hematuria and proteinuria (36.2%), nephrotic syndrome (29.8%), and renal failure (10.6%). Hematuria and proteinuria existed in all the cases, while only 7 to 13 years children had nephrotic syndrome and renal failure. Of the 47 patients, 33 (70.2%) showed mesangial proliferative glomerulonephritis (MsPGN) under the light microscope, 13 (27.6%) focal segmental glomerulosclerosis (FSGS), 1 (2.1%) membrane proliferative glomerulonephritis (MPGN). For immunofluorescence, there was IgM (40.4%) as the dominant deposition in 19 patients, IgA in 9 (19.1%), IgG in 9 (19.1%), and 10 (21.4%) were negative. Thirty-nine cases showed typical glomerular basement membrane (GBM) pathological changes under electron microscope, while thin basement membrane in 8 cases; 46 showed abnormal skin and/or renal alpha-chain distribution.</p><p><b>CONCLUSION</b>For Alport syndrome, number of male patients was higher than that of female patients. There was a significant difference among different age groups. Hematuria might be present throughout the course, while urine protein increases gradually. MsPGN was the dominant pathological change. The GBM pathological changes in younger children is not typical, so the immunofluorescence test of alpha-chain in collagen IV should be used as an important diagnostic method.</p>

Cyclosporin A treatment of 83 children with nephrotic syndrome of different pathological types / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of cyclosporin A (CyA) therapy in 83 children with nephrotic syndrome of different pathological types.</p><p><b>METHODS</b>Eighty-three children enrolled in this study were all hospitalized children with idiopathic nephrotic syndrome, aged 3 to 14 yrs (average 8.3 yrs) and included 52 males and 31 females. There were 35 cases with steroid-dependent, 17 with steroid resistant and 26 with frequent relapses. CyA was given to each patient with dosage of 5 mg/(kg.d) during the corticosteroid was diminished. The renwal biopsy was performed in all patients before the administration of CyA. The duration of CyA therapy lasted for about 3 to 6 months. The plasma concentration of CyA was monitored.</p><p><b>RESULTS</b>Eighty-three children with nephrotic syndrome of different pathological types were treated with CyA, including 42 cases of minimal change nephrotic syndrome (MCNS), 31 cases of mesangioproliferative glomerulonephritis (MsPGN), 5 cases of membranoproliferative glomerulonephritis (MPGN) and 4 cases of focal segmental glomerular sclerosis (FSGS). All the 83 patients tolerated well to the CyA treatment. Forty-five cases got complete remission, 23 partial remission, 15 cases no change after one month treatment with CyA in the hospital. The overall response rate was 82%. Patients with different renal pathological types showed different responses. Among them, MCNS and MsPGN exhibited the best response rates of 86% and 84%, respectively; MPGN cases showed a lower response rate and FSGS cases showed the lowest rate. The response time was 7 to 45 days. The blood concentration of CyA was monitored for 1 week and 2 weeks after the drug was given. The effective drug concentration was maintained at 100 to 200 microg/L, and the course lasted for 3 to 6 months. During the follow-up of 83 cases, in 17 of 68 cases the disease relapsed when therapy was tapered or discontinued. The relapse rate was 25%. The results indicated that CyA would be effective to the relapsed cases. The serum creatinine increased temporarily after administration of CyA in 5 cases, N-acetyl-beta-D-glucosaminidase (NAG) in 8 cases and eventually reached the normal range after the adjustment of dosage. The side effects included anorexia, nausea, vomiting and so on.</p><p><b>CONCLUSION</b>CyA is one of the effective substitutes for the treatment of nephrotic syndrome, especially for the cases with MCNS and MsPGN. And CyA could control refractory nephrotic syndrome effectively and rapidly. The clinical effect was related to the blood concentration of CyA and pathological types.</p>