Observation On The Clinical Effects Of Cyclosporine A Combined With Glucocorticoids In Children With Primary Nephrotic Syndrome From A Single Center

BackgroundThe efficacy and safety of immunosuppression Cs A for primary nephrotic syndrome are still controversial.Primary nephrotic syndrome(PNS)is the common glomerular disease in childhood.Which are four clinical syndromes.Those clinical manifestations are mass albuminuria(24-hour urine protein> 50mg/kg)?hypoalbuminemia(serum albumin< 25g/L),edema and hyperlipidemia.About 90%etiology of children PNS is uncertain,most children are effective for glucocorticoids,although glucocorticoids have continued as the mainstay of therapy for nephrotic syndrome for more than 50 years,there are obesity,growth suppression,hypertension,diabetes,osteoporosis,cataracts and other common side effects with long-term or repeated using of glucocorticoids.According to PNS's responses to glucocorticoids therapy,PNS can be divided into steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS)and steroid-resistant nephrotic syndrome(SRNS),the frequency of relapse,steroid-dependent or steroid-resistant in children with nephrotic syndrome can cause slow progression for kidney disease,and even develop into chronic renal failure,bring heavy mental pressure and economic pressure to those children and their families.For the poor glucocorticoids' treatment of primary nephrotic syndrome often with immunosuppressive agents(Immunosuppressive agents,ISA)added for further comprehensive treatment.Currently,there are usually cyclophosphamide(Cyclophosphamide,CTX),cyclosporine(Cyclosporine A,CsA),mycophenolate mofetil(Mycophenolate mofetil,MMF)and tacrolimus(Tacrolimus,Tac),Rituximab(Rituximab,RTX)to be used.The treatment of traditional immunosuppressant on PNS has some effect,but these side effects are obvious,these short-term effects of CTXhas some side effects,such as gastrointestinal reaction,bone marrow suppression,liver function damage,and hemorrhagic cystitis and so on,the cumulative amount of CTX more than 200mg/kg,can also cause long-term side effects,such as gonadal damage,and the damage is difficult to accept for their family.The toxic side effects of MMF mainly are gastrointestinal reactions ? infection and bone marrow suppression for a small number of PNS children.RTX is a new drug,its efficacy and safety has not been established for widely use in children.CsA can cause damage to the renal tubulointerstitium,prone to kidney toxicity,need to monitor the plasma concentration during the treatment of Cs A,receiving CsA treatment more than two years in need of renal biopsy in order to early detection the basis of renal toxicity histological.The adverse drug reactions of Tac less than CsA,the immunosuppressive effects of Tac is about 10 to 100 times than CsA,which need a large number of randomized and controlled researches to confirm.Meantime,its price is more expensive,limiting its widely application.CsA,in 1979,first as an immunosuppressant for organ transplantation,in 1985,began to treat NS,in 1986,for the treatment of NS in children.Refering to research reports from home and abroad,most scholars' findings are different.But the majority of conclusions is that Cs A has a good effect for the children NS,plusing CsA can reduce the dosage of glucocorticoids for FRNS or SDNS in children,alleviating the side effects of glucocorticoids[1].For the treatment of SRNS,domestic guide had recommended cyclophosphamide as the drug of first choice.Recent studies more support the CsA as the drug of first choice in children with SRNS[2-3].Cyclosporine and tacrolimus are belong to calcineurin inhibitors,the later one that is more expensive.Those hospital admissions of children,mainly from rural areas in the northern of Henan province,the economic basis are relatively poor.The best choice of calcineurin inhibitors is CsA for them.In terms of sample datas,since evidence-based diagnosis and treatment of common childhood kidney disease treatment guidelines in 2009 released by the pediatric nephrology group of Chinese Medical Association.Our department adopted the new guidelines to treatment,recently,40 clinical cases data collected from January,2009 to January,2015 with cyclosporine A(cyclosporine A,CsA)combined glucocorticoid to treatment primary nephrotic syndrome,by longitudinal retrospective analysis,to observe their effect and safety,to provide evidences for these opinions of guides.ObjectiveTo observe the clinical effects and safe of cyclosporine A(CsA)in the treatment of primary nephrotic syndrome(NS)in children.MethodsA longitudinal retrospective analysis from the first month of 2009 to January,2015 for children PNS admitted in the department of Pediatric Nephrology,the First Affiliated Hospital of Xinxiang Medical University.There were 40 child patients with nephrotic syndrome(NS)treated with CsA [3~5mg/(kg*d)] combined with glucocorticoids,in which including steroid-resistant NS(SRNS)13 cases,steroid-dependent NS(SDNS)18 cases,frequent-relapses NS(FRNS)9 cases.Trough concentration of CsA was maintained 100 ~200?g/L.Total course of treatment was from one to two years,the dose was tapered gradually in 6~9 months after onset,the remission rate of child patients,24 h urine protein,plasma cholesterol,CD4+,CD8+,the ratio of CD4+/CD8+,and the occurrence of adverse drug reactions were observed closely.Results13(13/40,32.5%)cases were complete remission with CsA,18(18/ 40,45.0%)cases were partial remission,9(9/40,22.5%)cases wre ineffective in 3 months,the total efficiency is 77.50%.9cases(22.5%)were ineffective who were adjusted to other immunosuppressants to further treat after the 3 months follow-up,then the outcome of treatment is effective.15(15/40,37.5%)cases were complete remission,16(16/40,40.0%)cases wre partial remission,that total efficiency still was 77.5% when 6 months passed away with Cs A to treatment.22(22/40,55.0%)cases were complete remission,9(9/40,22.5%)cases were partial remission,the total effective rate was also 77.5% in 9months.24 cases(60%)were completely remission,7cases(17.5%)were partially remission,whose short-term complete remission rate is gradual increase along with the duration of treatment.After the 6,9,12 months follow up,the 31 cases' clinical biochemical parameters were significantly improved,serum albumin increased,24 h urine protein,serum cholesterol,CD4+ and the ratio of CD4+/CD8+ decreased,there was significant difference between after the treatment of CsA and before(P<0.01).The response to CsA was significant difference in between SRNS aand SDNS(P<0.05),however,it was to the contray in between SRNS and FRNS,between SDNS and FRNS(P>0.05).there was no significant difference in the efficacy of different pathological types.The main adverse effects of Cs A included hirsutism(75%),gingival hyperplasia(32.5%),gastrointestinal reactions 12.5%),mild hypertension(10%),elevating in serum creatinine(10%),liver function impairment(7.5%),meanwhile,one case(2.5%)of reversible encephalopathy syndrome in back of the brain,and all were acceptable.Conclusions1.In small samples of clinical study,the application of CsA combined glucocorticoids to treat children with NS were relatively safe and effective,a better efficacy for SDNS.2.There was no significant difference in the efficacy of different pathological types.3.CsA inhibit the activation and proliferation of CD4 T helper cell,restoring the balance of CD4+/CD8+,then inducing remission.