A Preliminary Study On The Diagnosis And Treatment Of Membranous Nephropathy

Objects1. To evaluate the prevalence of serum anti-PL A2R(Phosphalipase A2receptor) antibodies in IMN(Idiopathic membranous nephropathy) and SMN(Secondary membranous nephropathy) patients; to check the concordance between IFA(Immunofluorescence assay) and ELISA(Enzyme-linked immunosorbent assay) tests.2. To evaluate the relationship between serum anti-PLA2R antibodies and glomerular IgG4subclass in IMN and MLN(Membranous lupus nephritis) patients; to estimate the value of these two markers in the differential diagnosis of IMN and MLN and discuss their application in the diagnosis of SMN and AMN(Atypical membranous nephropathy).3. To evaluate the effects of level of serum albumin before immunosuppressive treatment on remission rate, time to achieve remission, drug dosage and adverse reactions among IMN patients.MethodsSera of patients who underwent renal biopsy at Peking Union Medical College Hospital from October2011to April2014and were diagnosed with IMN, SMN(mainly MLN) and AMN were detected for anti-PLA2R antibodies. Results of glomerular immunofluorescence staining of IgG subclasses of these patients were reviewed and the intensities of each subclass were recorded. Prevalence of the antibody and each IgG subclass were calculated and fourfold tables were made according to the lab results. Sensitivity, specificity, positive and negative predictive values and agreement rates of different markers were calculated, which were than applied to differential diagnosis of AMN patients whose etiologies were not clear. Part of the serum samples were detected by two methodologies and concordance of the two tests were checked. Patients diagnosed as IMN who underwent renal biopsy at Peking Union Medical College Hospital from January2010to December2012and who were followed up regularly for at least1year after discharge with intact medical records were included. All enrolled patients were divided into two groups by their serum albumin concentration before treatment. Baseline feature, follow-up records, drug dosages and adverse events were reviewed and analyzed respectively between the two groups.Results59IMN patients and21MLN patients were included. Anti-PLA2R antibodies were detected in41patients in IMN group and the prevalence was69.5%; only1patient in MLN group showed positive result of serum anti-PLA2R antibody and the prevalence was only4.8%. IgG4tended to be dominantly expressed in the glomerulus in IMN group while IgG3and IgG1were highly expressed in MLN group. The intensity and prevalence of IgG4in IMN group were significantly higher than MLN group(P<0.001). Within the IMN group,35patients showed positive results of both serum anti-PLA2R antibodies and glomerular IgG4;6patients were positive for serum anti-PLA2R antibodies but negative for glomerular IgG4;17patients were positive for glomerular IgG4but negative for serum anti-PLA2R antibodies;1patient were negative for both tests. The sensitivity of serum anti-PLA2R antibody was69.5%and the specificity was95.2%; the sensitivity of glomerular IgG4was78.0%and the specificity was71.4%. Their agreement rates were both76.2%. The sensitivity of combined marker consisting of serum anti-PLA2R antibody and glomerular IgG4was91.5%and the specificity was66.7%. The agreement rate was85.0%.26patients were included in AMN group. The prevalence of anti-PLA2R antibody of patients secondary to HBV infection and Sjogren syndrome were66.7%(4/6) and33.3%(1/3) repectively.24serum samples were detected both by IFA and by ELISA. Both tests showed17positive results and7negative ones while the antibody concentration were linearly correlated with the immunofluorescence intensity(R2=0.506).60patients were included in H-ALB group(SAlb>25g/L) among which53patients were treated with immunosuppressive therapy while52patients were included in L-ALB group(SAlb≤25g/L) and all were treated with immunosuppressive therapy. The mean follow-up time was25.1±8.0months and24.7±9.3months respectively.98%patients in L-ALB group presented nephrotic syndrome while only35%patients in H-ALB group presented the same.54.7%patients in H-ALB group were treated with1immunosuppressive agent, which was of no significant difference from L-ALB group(48.1%, P=0.435).90.6%patients in H-ALB group were treated with corticosteroids, which was of no significant difference from L-ALB group(96.2%, P=0.449). Remission rates of the two groups are86.8%and88.5%respectively, of no significant difference(P=0.795). The mean time to achieve PR(partial remission) of H-ALB group is significantly shorter than that of L-ALB group(3.6±2.9months vs6.0±5.2months, P=0.006), but the mean time to achieve CR(complete remission) of H-ALB group is of no significant difference from L-ALB group(9.8±3.7months vs11.8±5.0months, P=0.062). At the time of PR and CR, the mean exposure period of corticosteroids and CsA and the accumulative dosage of CTX of H-ALB group were shorter or less than L-ALB group but no significant difference were found(P=0.072,0.112and0.380). Adverse events were recorded in45.3%patients in H- ALB group and in59.6%patients in L-ALB group. No significant difference were noticed(P=0.141).Conclusions1. Serum anti-PL A2R antibodies are of high specificity for IMN, but can be detected in some SMN patients as well.2. Glomerular immunofluorscence staining of IgG subclasses showed different characteristics. IgG4is predominant in IMN while IgG3and IgG1are highly expressed in MLN.3. The sensitivity and agreement rate can be improved if serum anti-PLA2R antibody and glomerular IgG4are united to diagnose IMN. The combined marker can also be used in the diagnosis of SMN patients and AMN patients of unkown reasons.4. Results of ELISA are highly concordant with results of IFA.5. Concentration of serum albumin before treatment has no significant effects on what or how many types of immunosuppressive agents are applied.6. Patients with a higher serum albumin level achieve partial remission sooner and are exposed less to corticosteroids than patients with a lower serum albumin level when they achieve partial remission. Patients with a higher serum albumin level have a tendency to achieve complete remission sooner and a tendency to be exposed less to immunosuppressive agents when they achieve complete remission.7. Concentration of serum albumin before treatment has no significant effects on adverse events.