Clinical Study Of Rituximab In Combination With Calcineurin Inhibitors In The Treatment Of Lupus Podocytopathy

BackgroundLupus podocytopathy is a new type of glomerular nephritis caused by systemic lupus erythematosus(SLE),which clinically present nephrotic syndrome demonstrated minimal change disease(MCD),mesangial hypercellularity(MsP)or focal segmental glomerulosclerosis(FSGS);on electronic microscopy,diffuse effacement of the podocyte foot processes was the single morphologic feature in the absence of subepithelial or subendothelial electron dense deposits.Lupus podocytopathy are sensitive to glucocorticoid monotherapy.We found that nearly 90%of the patients relapsed with glucocorticoid monotherapy,Prolonged administration of prednisolone or frequnently relapsing is,however,associated with a high risk of the adverse effects of steroid.Moreover,Relapses had led to the histological transformation.Therefore,a new treatment that does not involve steroids or immunosuppressive agents is urgently needed.The published data suggest that RTX and CNI is effective to frequently relapsing and steroid-dependent nephrotic syndrome.In this study,Based on case report that a relapsing lupus lupus podocytopathy and successful prevention of relapse after rituximab treatment,we explore the effects of RTX in combination with calcineurin inhibitors in the treatment of lupus podocytopathy.PART1:Rituximab treatment for a frequently relapsed lupus podocytopathyObjective To observe the effect and safety of rituximab(RTX)treatment in a frenquent relapsed lupus podocytopathy.Methods a patient with steroid-dependent nephrotic syndrome or frequently relapsing nephrotic syndrome suffer from steroid toxicities.After her eighth relapse she received RTX and tacrolimus.prednisone are gradually reduced.the level of circulating B cell before angd after RTX therapy were examined,B cell depletion was defined CD20-positive cells<15/ul.Result After 24 months of follow-up,she maintained complete remisson even prednisone dosage was reduced to 5mg/d.B-cell counts continued to deplete after RTX treatment(2-11/ul).RTX was well tolerated and no adverse event occurred.Conclusion RTX can effectively prevent the recurrence of lupus podocytopathy,and its efficacy and safety still need to be further confirmed by increasing the sample.PART2:Clinical study of rituximab in combination with calcineurin inhibitors in the treatment of lupus podocytopathy.Objective This study aims to observe RTX in combination with CNI in the treatment of lupus podocytopathy.Methods From June 2015 to June 2016,11 cases of patients were diagnosed in our department.All of them,12 were females,with an average of 32.6 ± 10.0(range 19-47)years.duration of disease was 35.1±32.3(range 1-92)months.Afte remission,RTX was administered after remission of nephrotic syndrome induced by glucocorticoid monotherapy or glucocorticoid plus other immunosuppressive agents at a single dose of 375 mg/m2 every 6 months once or RTX 100mg every 3months four times.They also received CNI(Tacrolimus(FK506,3 mg/d)or cyclosporine(CsA,3 mg/Kg.d),The relapse rate and adverse reactions were observed.Result:Renal biopsies showed minimal change disease(MCD)in 2 patients,mesangical proliferation(MsP)in 6 patients,and FSGS in 3 patients.7 patients with complication relapsed 2-8(average 3.7±2.3)times,4 patient were primary lupus podocytopathy.The 4 patients received infusions of rituximab 375 mg/m2,and the 7 patients received infusions of rituximab 100mg,7 patients received tacrolimus and 4 patients received cyclosporine for the maintenance treatment.All patients achieved B cell depletion after 24h of RTX infusion.At 17.0 ± 7.1 months(12-30 months)after RTX treatment in 7 frequently relapsing patients,5 patients sustained remission and 2 patients(28.5%)relapsed.The per-patient average number of relapses decreased from 1.22±0.98 to 0.23±0.41(P=0.02)during 1 year of follow up.The maintenance prednisone dose decreased from 14.6 ± 7.6 mg/d to 7.1 ± 3.6 mg/d(p<0.001).Follow-up of 9 months after RTX treatment in 4 patients with primary lupus podocytopathy.3 patients sustained remission and 1 patient relapsed.The minimum maintenance dose of prednisone was 5.6±1.2 mg/d.One case of pruritus occurred during infusion,and the rest of the patients had a successful infusion without any adverse reactions.One patient suffered respiratory tract infection during follow-up.Conclusion:RTX in combination with calcineurin inhibitors in the treatment of lupus podocytopathy effectively and safely reduced relapse and the need for steroid dosage.Further controlled studies are warranted to better define the role of rituximab in lupus podocytopathy.Conclusion:1.RTX in combination with CNI in the treatment of lupus podocytopathy effectively reduced relapse and the maintenance steroid dose,Further controlled studies are needed to confirm.2.RTX in combination with CNI in the treatment of lupus podocytopathy treatment was safe.