Correlation Between Serum Anti-phospholipase A2 Receptor Antibody And Immunotherapy Of Idiopathic Membranous Nephropathy

Background and objectiveIdiopathic membranous nephropathy(IMN)is one of the most common pathological types of adult primary nephrotic syndrome(NS).The pathological manifestations are mainly glomerular basement membrane epithelial cell immune complex deposition and diffuse thickening of basement membrane.The clinical manifestations of IMN are different,about 80% of patients present with nephrotic syndrome,and about 20% of patients present with non-nephrotic proteinuria.At the same time,the prognosis of IMN is quite different,about 30% of patients with clinical manifestations of NS can spontaneously relieve,but about 30% of patients progress to end-stage renal disease(ESRD).For patients with IMN who have a clinical manifestation of NS and have a high risk of progressing to ESRD,immunosuppressive therapy should be given as soon as possible.IMN alone is poorly treated with glucocorticoids and often requires a combination of immunosuppressive agents.The Kidney Disease Improving Global Outcomes(KDIGO)guidelines in 2012 recommend that the initial immunotherapy of IMN use glucocorticoids combined with alkylating agents or calcineurin inhibitor(CNI),tacrolimus(TAC)is a commonly used CNI,which is widely used in clinical practice because of its high clinical remission rate and small side effects in combination with glucocorticoid.The pathogenesis of IMN is complex and is currently considered to be an organ-specific autoimmune disease.In 2009,Beck et al.found that the phospholipase A2 receptor(PLA2R)on the glomerular podocyte membrane is the pathogenic antigen of IMN and found anti-PLA2 R antibody in 70% of IMN patients' serum,which is a major breakthrough in the history of IMN pathogenesis.Recent studies have shown that serum anti-PLA2 R antibodies can be used as specific indicators for the diagnosis of IMN,but there are relatively few studies on the correlation between serum anti-PLA2 R antibody and immunotherapy of IMN.This study compares and analyzes various indexes before and after prednisone plus tacrolimus treatment in IMN patients with different anti-PLA2 R antibody levels,and explores the correlation between serum anti-PLA2 R antibody and immunotherapy of IMN patients.Provide clinical reference for the treatment of IMN in the future.MethodsA total of 65 patients who were diagnosed as IMN and positive for anti-PLA2 R antibody from June 2016 to June 2017 in the Department of Nephrology in First Affiliated Hospital of Zhengzhou University,were included in this study.According to the level of anti-PLA2 R antibody before treatment,the patients were divided into low-level antibody group and high-level antibody group.Both groups were treated with prednisone and tacrolimus.The starting dose of prednisone was 0.5 mg/kg/d,and gradually decreased after 6-8 weeks of oral administration,3-4 weeks decrement 2.5mg,reduced to 5mg / d for 8 weeks.The starting dose of tacrolimus was 0.05 mg / kg / d,divided into 2 times a day,orally once every 12 hours,detecting the concentration of tacrolimus in 5-7 days,then testing once every 1-2 months,and the tacrolimus blood concentration was maintained at 4-10 ng/ml.During the treatment,two groups of patients were given angiotensin II receptor antagonist(valsartan)treatment under the condition of blood pressure.At the same time,two groups of patients were given to prevent osteoporosis and anticoagulation therapy.Patients with elevated blood lipids were given rosuvastatin calcium tablets for lipid-lowering therapy.The 24-hour urine protein quantitation,serum albumin,serum anti-PLA2 R antibody,serum creatinine,eGFR and other indexes were observed before and after 3,6 and 12 months of treatment,These indexes were statistically analyzed.Results1.Among 65 patients with IMN,there were 32 patients in the low-level antibody group and 33 patients in the high-level antibody group.There was significant difference in serum anti-PLA2 R antibody between the two groups(P<0.05),but there was no significant difference in other general data between the two groups(P>0.05).2.After 3,6 and 12 months of treatment,the 24-hour urine protein quantitation in the low-level antibody group and the high-level antibody group decreased significantly(P<0.05),and the serum albumin increased significantly in both groups(P<0.05).At the same time,the recovery of 24-hour urine protein quantitation and serum albumin in the low-level antibody group were significantly better than those in the high-level antibody group(P<0.05).3.After 3,6 and 12 months of treatment,the serum anti-PLA2 R antibody in the low-level antibody group and the high-level antibody group were significantly lower than that before treatment(P<0.05).4.After 12 months treatment,there was no significant difference in serum creatinine and eGFR between the low-level antibody group and the high-level antibody group(P>0.05),and there was no significant difference between the two groups(P>0.05).5.After 3,6 and 12 months treatment,the total remission rate in the low-level antibody group was significantly higher than that in the high-level antibody group(P<0.05).After 12 months treatment,the complete remission rate of the low-level antibody group was significantly higher than that in the high-level antibody group(P<0.05).ConclusionPrednisone combined with tacrolimus in the treatment of IMN,patients with low serum anti-PLA2 R antibody levels before treatment have better therapeutic effects than patients with high antibody levels.Serum anti-PLA2 R antibody has certain reference value for predicting the clinical remission time of IMN patients.