1. TSHD7A becomes another novel biomarker for idiopathic membranous nephropathy In 2009, phospholipase A2 receptor 1 (PLA2R1), discovered by LH. Beck et al. at Boston University School of Medicine, was identified as the major autoantigen in the pathogenesis of adult idiopathic membranous nephropathy (IMN), and a series of studies subsequently found that nearly 30% of IMN patients do not have circulating autoantibodies against PLA2R1. The presence of autoantibodies against PLA2R1 in this group of patients is not clear. In November 2014, the New England Journal of Medicine (NEJM) again published a study by LH. Beck and his team that made a surprising new finding. The team identified a glomerular protein with a molecular weight of 250 kD in the sera of 15 IMN patients (six from Europe and nine from the United States) who were negative for anti-PLA2R1 antibodies, while sera from 74 IMN patients positive for anti-PLAR21 antibodies, 76 with other types of glomerular disease, and 44 healthy controls did not recognize this antigen. Mass spectrometry analysis identified this antigen as the type 1 platelet-reactive protein 7A domain (THSD7A). Immunohistochemical analysis of kidney puncture samples from 15 patients with IMN who were negative for anti-PLA2R1 antibodies revealed that THSD7A was located in podocytes and that IgG isolated from these kidney puncture samples specifically recognized THSD7A. It was further found that, similar to serum anti-PLA2R1 antibodies, titers of serum anti-THSD7A antibodies also correlated with the activity of IMN. The finding of THSD7A in IMN patients negative for anti-PLA2R1 antibodies suggests that THSD7A may be another autoantigen in the pathogenic mechanism of IMN. 2. plasma suPAR cannot be used as a diagnostic biomarker for FSGS In 2011, C. Wei and his research team from the University of Miami Miller School of Medicine found for the first time that plasma soluble urokinase-type fibrinogen activator receptor (suPAR) levels were significantly elevated in adult patients with idiopathic FSGS, and suggested that suPAR may be associated with disease progression in idiopathic FSGS This finding was subsequently published in the United States and Europe. Subsequently, this finding was further confirmed in adult and pediatric patients with idiopathic FSGS from the United States and Europe. suPAR is gradually being recognized as a possible autoantigen in the pathogenesis of idiopathic FSGS and is used as its biomarker, offering hope for the diagnosis and treatment of idiopathic FSGS. However three clinical studies from Belgium, Japan and India, published in Kidney International in April 2014, questioned suPAR as a diagnostic biomarker for idiopathic FSGS. Meijers and his research team from Belgium included 54 patients with biopsy-proven FSGS and 476 patients with non-FSGS CKD. It was found that plasma suPAR levels in patients were negatively correlated with their eGFR levels regardless of the type of renal disease, and that plasma suPAR levels did not differ significantly between patients with idiopathic FSGS and non-FSGS patients within the same eGFR range, so that plasma suPAR levels, taking into account differences in patient renal function, could not discriminate between cases of idiopathic FSGS and non- FSGS cases. The study from Japan, which included 69 patients with biopsy-proven glomerular disease (38 with FSGS, 11 with MCD, 11 with IgA, and 9 with membranous nephropathy), also observed a negative correlation between plasma suPAR levels and patients’ eGFR levels in patients with different pathological types of glomerular disease. In patients with normal eGFR, plasma suPAR levels did not differ significantly between patients with FSGS and all other pathological types and healthy controls. This study suggests that plasma suPAR levels do not distinguish FSGS from other glomerular pathology types within the normal range of eGFR. Another study from India, which included 469 children with different types of nephrotic syndrome and 83 healthy children, found that more than half (49.7%-68.1%) of children with each type of nephrotic syndrome had elevated plasma suPAR levels (>3000 pg/ml), and this percentage did not differ significantly between pathological types. It was further found that the elevated plasma suPAR levels did not decrease in children during the remission phase of induction therapy. Together, the three studies suggest that plasma suPAR levels are not effective in differentiating FSGS from other pathological types of glomerular disease and therefore cannot be used as a diagnostic biomarker for FSGS. 3. rituximab and tacrolimus in nephrotic syndrome Patients with recurrent or hormone-dependent nephrotic syndrome have long plagued clinicians and patients as a group of refractory glomerular diseases. Previously, patients had to face serious side effects from long-term hormone application and traditional immunosuppressants, so a new and more effective and safe treatment method is urgently needed. Rituximab has been highly anticipated since its inclusion in the KDIGO guidelines in 2012, yet there have been very few relevant multicenter randomized double-blind controlled trials. In April 2014, the Journal of the American Society of Nephrology (JASN) published a cohort study from Italy (Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis Study, NEMO) [8], which included 30 patients with recurrent or hormone-dependent nephrotic syndrome (2 adults; 22 MCD/MesGN and 8 FSGS), all of whom were treated with rituximab (375 mg/m2) in combination with hormones or immunosuppressive agents (28 patients on 1 mg/m2). All patients were treated with rituximab (375 mg/m2) in combination with hormones or immunosuppressive agents (28 patients with 1 dose of rituximab and 2 patients with 2 doses of rituximab), using their own before-and-after control. After 1 year of follow-up, all patients were in remission, with a significantly lower annual per capita number of relapses (2.5 vs. 0.5, P<0.001), a significantly lower per capita hormone maintenance dose (0.27 mg/kg vs. 0 mg/kg, P<0.001), and a significantly lower cumulative dose of hormone required for a single induction of remission compared with that before the application of rituximab (Figure 4) ( The NEMO study suggests that rituximab may be effective and safe in preventing relapse and reducing the dosage of immunosuppressants in adult or pediatric patients with recurrent or hormone-dependent nephrotic syndrome. In October 2014, Katsumoto Lijima and his team from Japan published in the Lancet a multicenter, double-blind, randomized controlled trial of rituximab for Childhood-onset Refractory Nephrotic Syndrome (RCRNS). Syndrome Study (RCRNS Study). A total of 52 children with recurrent or hormone-dependent nephrotic syndrome were enrolled in the study, and the primary outcome measure was a relapse-free period in which the trial group was given rituximab (375 mg/m2) once weekly for four weeks in combination with a standard hormonal regimen, and the control group was given placebo once weekly for four weeks in combination with a standard hormonal regimen. At one-year follow-up, the median relapse-free period was significantly longer in the rituximab-treated group than in the placebo-treated group (267 days, 95% CI 223C374 vs. 101 days, 95% CI 70C155; P<0.0001) (Figure 5), and there was no significant difference in the incidence of serious adverse events between the two groups (P=0.36). an effective and safe drug for the treatment of recurrent or hormone-dependent nephrotic syndrome in children. In the KDIGO guidelines published in 2012, both tacrolimus and cyclosporine are listed as second-line agents for idiopathic membranous nephropathy. However, there is a lack of larger clinical trials on the efficacy of tacrolimus alone in idiopathic membranous nephropathy, and in the only RCT of tacrolimus alone in idiopathic membranous nephropathy (2007), the number of patients included in the trial was small (only 48), although the remission rate was significantly higher in the tacrolimus alone versus the supportive care group. in October 2014, another study from Spain on a multicenter cohort study of tacrolimus alone for idiopathic membranous nephropathy (GLOSEN study) yielded encouraging results. The study included 122 patients with biopsy-proven idiopathic membranous nephropathy and stable renal function who were treated with tacrolimus alone. After a mean follow-up of 30 months, 84% of patients achieved remission (total remission rates at month 6, month 12, and month 18 in that order: 60%, 78%, and 84%) (Figure 6), with 8% of patients treated with tacrolimus in combination with hormone therapy having a comparable remission rate (80% total remission rate at month 18), and the lower the patient's baseline urine protein volume, the greater the likelihood of remission. The study also found that 4% of patients who achieved induction remission relapsed, and that relapsed patients had significantly higher urine protein quantification at the start of tacrolimus reduction therapy than non-relapsed patients. The GLOSEN study suggests that tacrolimus alone is an effective option for patients with idiopathic membranous nephropathy with stable renal function, and that prolonging the duration of tapered therapy may prevent relapse to some extent.