Association of Anti-Phospholipase A2 Receptor Antibody with the Efficacy of Traditional Chinese Medicine (Shenqi Particle) for Patients with Idiopathic Membranous Nephropathy: A Prospective, Cohort Clinical Study
Membranous nephropathy (MN) is an autoimmune disease and represents the most common cause of nephrotic syndrome in adults. In China, the incidence of MN is estimated at approximately 12 cases per million per year, with a mean age of onset between 50 and 60 years and a male predominance of 2:1. A 10-year renal biopsy analysis revealed that MN accounted for 29.1% of all pathological kidney diseases, making it the most prevalent condition in this category. The Kidney Diseases: Improving Global Outcomes (KDIGO) guidelines, updated in 2019, recognized anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies as a valuable molecular risk factor for the progression of kidney dysfunction. Monitoring these antibodies is recommended for diagnosing and assessing immune activity in MN. Circulating anti-PLA2R autoantibodies can aid in monitoring disease activity and guiding personalized therapy for patients with primary MN.
Traditional Chinese medicine (TCM) has been widely used in China to treat idiopathic MN, with Shenqi particle being one of the prominent formulations. A prospective, multicenter, randomized, controlled clinical trial conducted between 2008 and 2011 confirmed the efficacy and safety of Shenqi particles in adult patients with primary membranous nephropathy (PMN). However, the relationship between anti-PLA2R antibody levels and the efficacy of TCM (Shenqi particle) in treating idiopathic MN remained unexplored. This study aimed to investigate this association and provide insights into the potential role of anti-PLA2R antibodies in predicting treatment outcomes.
This prospective cohort study was conducted at Longhua Hospital, affiliated with Shanghai University of Traditional Chinese Medicine. The study protocol was approved by the institutional review board for human studies (Approval No: 2016LCSY022) and registered on the Chinese Clinical Trial Registry (Registration No: ChiCTR-OOC-16009632). Informed consent was obtained from all participants. Patients aged between 18 and 75 years with biopsy-proven MN (stages 1–4), 24-hour urinary protein excretion greater than 1 g/day after a minimum observation interval of 6 months, and an estimated glomerular filtration rate (eGFR) above 30 mL/min/1.73 m² were included. Additionally, patients were required to exhibit TCM syndrome differentiation of spleen deficiency, damp heat, and blood stasis, as per the guiding principles for clinical research of new TCM. Exclusion criteria included other types of MN, such as rapidly progressive MN or secondary MN, diabetes or hemoglobin A1c levels above 6.2 mmol/L, recent treatment with steroids or immunosuppressive medications, active infections, uncontrolled hypertension, or TCM syndrome differentiation not matching the specified criteria.
Of the 327 patients screened, 215 were excluded based on the exclusion criteria, leaving 112 patients eligible for the study. These patients had a mean age of 49.79 ± 14.64 years and a median disease duration of 20 months (range: 6–156 months). Most patients had MN at histological stages I or II, and their blood pressure was well controlled. The cohort consisted of 76 men and 36 women, with an average proteinuria level of 4.10 ± 2.60 g/24 h and an average serum albumin level of 28.23 ± 7.04 g/L. Patients were divided into two groups based on baseline anti-PLA2R antibody levels: 49 patients with levels exceeding 20 RU/mL were classified as the “positive group,” while the remaining 63 patients with levels below 20 RU/mL formed the “negative group.” Baseline clinical and laboratory characteristics were comparable between the two groups, except for sex proportion and triglyceride levels.
All patients were treated with Shenqi particle for 48 weeks. Shenqi particle is composed of 13 different Chinese herbs, prepared by boiling in water and spray drying. Patients received 9.6 g of Shenqi particle three times daily. Additionally, Bai’ao Lumbrokinase capsule (600,000 U/time, three times/day) or Huoxue Tongmai capsule (4 capsules/time, three times/day) was administered. For hypertensive patients, the target blood pressure was set below 130/80 mmHg, with angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers prescribed as needed. Clinical data, including age, sex, serum creatinine, serum albumin, 24-hour urinary protein excretion, serum cholesterol, triglycerides, and anti-PLA2R antibody levels, were collected. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Patients were followed up monthly, with clinical and laboratory parameters evaluated every three months and anti-PLA2R antibody levels assessed every six months. PLA2R antibody testing was performed using enzyme-linked immunosorbent assay (EUROIMMUN AG, Lubeck, Germany).
The primary outcomes included complete remission (CR) and partial remission (PR). CR was defined as proteinuria below 300 mg/day with normal serum albumin and serum creatinine, while PR was defined as proteinuria above 300 mg/day or a reduction of less than 50% from baseline with normal or increased serum albumin and stable serum creatinine. Non-remission was defined as failure to meet these criteria. Of the 49 patients in the positive group, 19 achieved remission at 48 weeks, including three with CR. In the negative group, 52 out of 63 patients achieved remission, including 13 with CR. The negative group demonstrated a significantly higher remission rate (82.53%) compared to the positive group (38.77%).
After 48 weeks of treatment, 24-hour proteinuria improved significantly in both groups, with the negative group showing greater improvement than the positive group. Serum albumin levels increased significantly in both groups, with no significant difference between the groups. Serum cholesterol and triglyceride levels decreased significantly in both groups, but no intergroup differences were observed. Kidney function, as measured by eGFR, remained stable in both groups, with no significant changes in serum creatinine or eGFR. Adverse events were minimal, with only one case of mild liver injury reported in the negative group, which resolved spontaneously by the 24th week. No severe adverse events were reported in either group.
In conclusion, serial evaluation of circulating anti-PLA2R antibodies may help predict the response to TCM in MN. Patients with negative anti-PLA2R antibodies exhibited better outcomes compared to those with positive antibodies. Shenqi particle demonstrated efficacy in improving proteinuria, serum albumin, and lipid profiles in patients with idiopathic MN, particularly in the negative group. This study highlights the potential of Shenqi particle as a promising alternative therapy for adults with PMN, especially for those who have not responded to conventional treatments such as glucocorticoids or immunosuppressants. However, the absence of a control group limits the generalizability of the findings, and further research is warranted to validate these results.
doi.org/10.1097/CM9.0000000000001565
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