Real-World Effects of Chinese Herbal Medicine for Idiopathic Membranous Nephropathy (REACH-MN): Protocol of a Registry-Based Cohort Study

Introduction: Some encouraging findings of Chinese herbal medicine (CHM) in management of idiopathic membranous nephropathy (IMN) obtained in the setting of clinical trials are hard to validate in the daily clinical practice due to a complicated treatment scenario of CHM in practice. The primary objective of this registry is to provide a description of treatment patterns used in management of IMN and assess clinical remission in daily practice in a Chinese population sample with IMN.Methods and analysis: This is a prospective, multicenter cohort which will comprise 2000 adults with IMN regardless of urinary protein levels that will be recruited from 11 nephrology centers across China. The participants will be followed for up to at least 2 years. Primary outcome is composite remission (either complete remission or partial remission) 24 months after enrolment. The secondary outcomes are complete remission, partial remission, time to remission, no response, relapse, proteinuria, annual change of glomerular filtration rate, antibodies against PLA2R, and composite endpoint of 40% reduction of glomerular filtration rate, doubling of serum creatinine, end-stage renal disease, and death. Propensity score analysis will be used for matching and adjustment.Ethics and dissemination: This study has been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (BF2020-094-01). Results of the study will be published in both national and international peer-reviewed journals, and presented at scientific conferences. Investigators will inform the participants as well as other IMN patients of the findings via health education.Study registration: ChiCTR2000033680 (prospectively registered).

Diagnostic Utility of Serum and Urine Biomarkers in Idiopathic Membranous Nephropathy: a Systematic Review and Meta-analysis

Background Membranous nephropathy is an autoimmune nephropathy that is one of the most common pathological types of nephrotic syndrome. It is important to find and apply specific biomarkers for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, there are limited data about their diagnostic value. Therefore, an overall meta-analysis helps to identify effective biomarkers for the clinical diagnosis of IMN. Methods A systematic literature search was carried out in PubMed, Embase, Cochrane and Web of Science from inception until December 31, 2020. Two researchers searched for studies that met the inclusion criteria. The results of the joint study were expressed in terms of sensitivity and specificity. Results The meta-analysis included 24 studies with biomarkers for the clinical diagnosis of IMN, including phospholipase A2 receptor (PLA2R), thrombospondin type I domain-containing 7A (THSD7A), lysosome membrane protein-2 (LIMP-2) and circular RNAs. The diagnostic efficiency of PLA2R for IMN had a combined sensitivity of 60% and a combined specificity of 100%. The diagnostic efficiency of THSD7A for IMN had a combined sensitivity of 3% and a combined specificity of 99%. The diagnostic efficiency of urinary LIMP-2 for IMN was 100%, and the specificity was 100%. The diagnostic efficiency of exosomal circRNAs for IMN was 100%, and the specificity was 100%. Conclusions This meta-analysis shows that PLA2R and THSD7A are of important diagnostic value for IMN. More studies are needed in the future to reveal the diagnostic value of LIMP-2 and circRNAs for IMN. At the same time, other new diagnostic biomarkers in IMN need to be found in the future.

Clinical Study of THSD7A, SOD2 and AR Antigens in Idiopathic Membranous Nephropathy

Background To explore the expression of THSD7A, SOD2 and AR podocyte antigens in the renal tissue of patients with idiopathic membranous nephropathy (IMN) and its clinical diagnostic value in IMN. Method This study retrospectively collected 150 renal tissue specimens and clinical data of patients undergoing renal biopsy in the Department of Nephrology, Shandong Provincial Hospital, including 130 IMN and 20 non-IMN patients. We use immunohistochemical staining to detect the expression of THSD7A, SOD2, AR antigens in the kidney tissue of patients. We focus on analyzing the clinical and pathological characteristics of IMN patients with positive THSD7A antigen expression, and analyze the prognosis of THSD7A-IMN patients and tumor occurrence. Meanwhile, the sensitivity and specificity of those antigens for the diagnosis of IMN were discussed. Results There were only 6 patients with THSD7A positive expression among 150 patients with glomerular disease, of which 5 patients were all IMN patients, and the patients' serum anti-PLA2R antibodies(anti-PLA2R-ab) were all negative. The positive rate of THSD7A in IMN was 3.85%, and the positive rate in IMN patients with anti-PLA2R-ab negative was 5.50%. Meanwhile, the sensitivity and specificity of renal tissue THSD7A in diagnosing IMN is 4.0% and 95%. In addition, the IgG subtype of THSD7A-IMN was mainly IgG4; Among them, 2 patients with IMN had both THSD7A and PLA2R antigen staining. This study also suggests that there is no significant difference in clinical and pathological characteristics between THSD7A positive and negative group. The follow-up of THSD7A-IMN patients found no tumors. This study also showed that there were 11 cases of anti-PLA2R-ab negative IMN patients with SOD2 antigen expression (8.56%), 10 cases of anti-PLA2R-ab negative and 4 cases of anti-PLA2R-ab positive IMN patients with AR antigen expression (10.77%), but no obvious SOD2 and AR antigen expression in SMN and other glomerular diseases. Conclusions Glomerular THSD7A antigen has a certain expression rate and high specificity in IMN, but its expression rate is low, and it can be used as a specific diagnostic index for IMN supplement. Kidney tissue SOD2, AR podocyte target antigens have a low positive rate in IMN, and further research is needed to evaluate the condition of IMN.

Membranous nephropathy associated with IgG4-related disease successfully treated with obinutuzumab

IgG4-releated disease is typically associated with interstitial nephritis, but rare cases of idiopathic membranous nephropathy as renal manifestation have been described. Obinutuzumab was successfully used in refractory membranous nephropathy, but evidence for the treatment of IgG4-related disease with obinutuzumab is lacking so far. We report one patient's case with membranous nephropathy associated with IgG4-related disease, who was treated with obinutuzumab following anaphylactic reaction to rituximab. Obinutuzumab treatment resulted in a sustained complete remission of membranous nephropathy and decrease of IgG4 to the normal range. This case demonstrates that membranous nephropathy associated with IgG4-related disease can successfully be treated with obinutuzumab.