Abstract
Rationale & Objective
Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. Although rituximab has improved outcomes, resistance or intolerance occurs in a subset of patients. Zuberitamab, a chimeric anti-CD20 immunoglobulin G1 monoclonal antibody, may offer an alternative therapeutic option. This study aimed to evaluate the effectiveness and safety of zuberitamab in patients with phospholipase A2 receptor (PLA2R)–associated IMN.
Study Design
Single-center, retrospective observational cohort study.
Setting & Participants
Sixty patients with biopsy-proven or serologically diagnosed PLA2R-associated IMN were treated with zuberitamab at Henan Provincial People’s Hospital between July 2023 and June 2024. Thirty-five received zuberitamab as first-line therapy; 25 received it as second-line therapy following prior immunosuppressive treatment.
Intervention(s)
Zuberitamab infusions administered in 2-3 doses over several months, guided by B-cell kinetics.
Outcomes
The primary outcome was complete or partial remission of proteinuria at 3 and 6 months. Secondary outcomes included changes in serum albumin, serum creatinine, estimated glomerular filtration rate, CD19+ B cells, and anti-PLA2R antibody titers.
Results
At month 3, 80% (48/60) of patients achieved remission (5 complete and 43 partial). By month 6, 13 patients achieved complete remission (11 first line and 2 second line; P = 0.03), and 35 achieved partial remission. Serum albumin levels improved, whereas proteinuria and creatinine levels declined in both groups. At 6 months, PLA2R antibody < 2 RU/mL was seen in 90.9% (30/33) of first-line and 81.0% (17/21) of second-line patients (P = 0.29). No serious adverse events were observed.
Limitations
Single-center, retrospective design; short follow-up; no direct comparator group; incomplete biomarker data owing to testing limitations.
Conclusions
Zuberitamab was associated with favorable clinical and immunologic responses in patients with IMN, including those previously treated with rituximab. These findings support its potential role as a therapeutic option, warranting further validation in prospective studies.
Index Words: diopathic membranous nephropathy, zuberitamab, phospholipase A2 receptor antibodies, CD20-targeted therapy, nephrotic-range proteinuria, B-cell depletion, glomerular disease
Plain-language Summary
Membranous nephropathy is a kidney disease that often causes severe protein loss in the urine. While current treatments like rituximab can be effective, not all patients respond, and some relapse. We studied a newer treatment option called zuberitamab, a type of antibody therapy that also targets immune cells involved in this disease. We looked at 60 patients who received this treatment and tracked how they responded over time. Most patients improved, with many experiencing reduced protein levels and better kidney function. Side effects were mild. Our findings suggest that zuberitamab may be a useful option for patients who cannot take or no longer respond to other treatments. Larger and longer term studies are needed to confirm these results.
Membranous nephropathy (MN) is a leading cause of adult nephrotic syndrome, with 30%-50% of high-risk patients progressing to kidney failure within 5-10 years.1,2 Idiopathic MN (IMN) is primarily characterized by the formation of autoantibodies and the deposition of immune complexes along the glomerular capillary loops. The M-type phospholipase A2 receptor (PLA2R), identified by Beck et al3 in 2009, is recognized as a key pathogenic antigen in IMN. Circulating anti-PLA2R autoantibodies are detectable in approximately 70%-80% of patients with MN.3,4 Active treatment with glucocorticoids and immunosuppressants is recommended when spontaneous remission is unlikely. However, calcineurin inhibitors are associated with high relapse rates and nephrotoxicity. Because immunoglobulins produced by autoreactive B cells contribute to glomerular barrier damage and proteinuria, therapies aimed at B-cell depletion and suppression of antibody production are central to IMN management.
Rituximab has demonstrated efficacy and a favorable safety profile, particularly in patients who are intolerant of, or resistant to, conventional therapies. It is currently recommended as a first-line alternative regimen for MN by the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines.5 Antibody-dependent cellular cytotoxicity is recognized as one of the primary mechanisms underlying the therapeutic action of rituximab.6,7 Several novel anti-CD20 monoclonal antibodies have been developed to enhance direct cytotoxicity and improve antibody-dependent cellular cytotoxicity. Zuberitamab, a chimeric anti-CD20 immunoglobulin G1 monoclonal antibody, binds to a region of the CD20 antigen (positions 167-183), similar to rituximab (Fig 1). Preclinical studies suggest zuberitamab may have stronger antibody-dependent cellular cytotoxicity activity compared with rituximab.8 In clinical trials for diffuse large B-cell lymphoma, zuberitamab demonstrated comparable efficacy and safety with rituximab.8 It has since been included in China’s national basic medical insurance for use in combination therapy for diffuse large B-cell lymphoma. Structurally, zuberitamab comprises 2 heavy chains (451 amino acids each) and 2 light chains (213 amino acids each). Compared with rituximab, 26 amino acids differ (16 in the variable region, 1 in the constant region of the heavy chain, and 9 in the variable region of the light chain), whereas the constant regions are otherwise identical (Fig 2). In vitro studies have shown that zuberitamab exhibits higher B-cell binding affinity and enhanced antibody-dependent cellular cytotoxicity relative to rituximab.8 It has also demonstrated greater efficacy than rituximab in patients with primary immune thrombocytopenia.8 In clinical scenarios in which rituximab’s high cost limits accessibility, zuberitamab offers a critical alternative with optimized efficacy and affordability. The objective of this study was to evaluate the effectiveness and safety of zuberitamab in patients with IMN, followed prospectively over a median follow-up period of 6 months after treatment.
Figure 1.
Comparison of the binding epitopes of zuberitamab with the anti-CD20 monoclonal antibody rituximab. The red box highlights the binding epitope.
Figure 2.
Illustration of the 26 distinct epitopes in zuberitamab compared with the anti-CD20 monoclonal antibody rituximab. The orange box indicates variable regions, whereas the blue box denotes constant regions.
Methods
Study Design and Patients
This was a real-world observational study. Eligible patients were aged 18 years or older and had either a biopsy-confirmed diagnosis of PLA2R-associated IMN or a positive anti-PLA2R antibody (PLA2R-Ab) result based on enzyme-linked immunosorbent assay (≥14 RU/mL).5 In accordance with the 2021 KDIGO guidelines, a kidney biopsy is not required to diagnose MN in patients who present with nephrotic syndrome, a stable estimated glomerular filtration rate (eGFR), and a positive anti-PLA2R-Ab test.9 Persistent proteinuria was confirmed through repeated measurements.
Patients were excluded for glomerulonephritis, kidney transplant biopsy, secondary MN owing to autoimmune diseases, malignancies, infections, medications, or other etiologies; comorbid conditions requiring immunosuppressants/corticosteroids; life-threatening infections/malignancies/psychiatric disorders; pregnancy/breastfeeding; or postinitiation use of other immunosuppressants with zuberitamab.
The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Henan Province People’s Hospital (approval number: 2025-08). Written informed consent was obtained from all participants.
Treatment
Treatment decisions were individualized and consensus based between physicians and patients. Supportive care included sodium restriction (<3 g/d), moderate protein intake (0.8 g/kg/d), and full-dose renin-angiotensin system inhibitors. Blood pressure and proteinuria were managed with β-blockers or calcium channel blockers as needed; diuretics relieved edema, and statins controlled hypercholesterolemia. Patients with nephrotic syndrome and severe hypoalbuminemia (serum albumin < 25 g/L) received prophylactic anticoagulation to mitigate thromboembolic risk.
Zuberitamab infusions were administered after premedication with dexamethasone, diphenhydramine, and hydration. Infusion rates started at 50 mL/h for 30 minutes, escalating incrementally to a maximum of 150 mL/h. The first and second doses were spaced 2-4 weeks apart; subsequent intervals exceeded 4 months and were guided by CD19+ B-cell recovery.
Outcomes
Serum albumin, serum creatinine, and proteinuria levels were assessed at baseline, 2 weeks, 3 months, and 6 months. eGFR, CD19+ B-cell counts, and PLA2R-Ab titers were also evaluated at each time point. The primary outcome was the proportion of patients achieving complete (CR) or partial remission (PR) at 3 and 6 months. CR was defined as 24-hour proteinuria < 0.3 g/d with a stable eGFR. PR was defined as 24-hour proteinuria between 0.3 and 3.5 g/d, with a reduction of ≥50% from baseline and a stable eGFR. Patients not meeting these criteria during the follow-up were classified as nonresponders. Patients whose eGFR declined to <30 mL/min/1.73 m2 and failed to recover within 3 months were considered to have discontinued zuberitamab and were excluded from further follow-up. Secondary outcomes included changes in serum albumin, proteinuria, serum creatinine, renal function, CD19+ B-cell counts, and PLA2R-Ab titers over time. Treatment safety was also evaluated, focusing on the incidence of serious and nonserious adverse events (AEs).
Statistical Analyses
All patients with at least 3 months of follow-up data were included in the analysis. Patients achieving PR or CR at 3 months were included in outcome comparisons. Continuous variables were reported as mean ± standard deviation or median (interquartile range [IQR]), as appropriate. Group comparisons were performed using paired or independent sample t tests. For nonnormally distributed variables, the Wilcoxon signed-rank test or the Mann-Whitney U test was applied. Categorical variables were compared using the χ2 test or Fisher exact test, as appropriate. A P value of <0.05 was considered statistically significant. In cases in which PLA2R-Ab titers decreased below the assay detection limit of 2 RU/mL, values were recorded as 0.
Results
Baseline Characteristics of Patients
Between July 2023 and June 2024, 84 patients with IMN received zuberitamab at Henan Province People’s Hospital. Exclusions (n = 24) included 13 with other glomerular diseases (eg, minimal change disease and systemic lupus erythematosus), 9 with incomplete follow-up, and 2 with eGFR < 30 mL/min/1.73 m2. The final cohort (n = 60) (Table 1) comprised 31 patients with biopsy-confirmed IMN and 29 with anti-PLA2R-Ab--positive IMN (≥14 RU/mL), all diagnosed as PLA2R-associated IMN. Thirty-five patients received zuberitamab as first-line therapy. The remaining 25 patients received zuberitamab as second-line therapy owing to relapse or insufficient response to prior immunosuppressive treatments. Relapse was defined as proteinuria > 3.5 g/24 h following previous CR or PR (Fig 3).
Table 1.
Baseline Characteristics of Patients
| Characteristic | Overall (n = 60) |
First-Line Therapy (n = 35) | Second-Line Therapy (n = 25) | P Value |
|---|---|---|---|---|
| Age, y | 53.5 ± 13.97 | 51.69 ± 14.34 | 56.04 ± 10.99 | 0.08 |
| Male/Female | 39/23 | 19/18 | 20/5 | 0.04 |
| Duration of persistent proteinuria, mo | 4.5 (1.0, 27.0) | 2 (0.54, 3.00) | 36 (21, 60) | 0.001 |
| SBP, mm Hg | 130.27 ± 19.38 | 128.11 ± 18.74 | 133.42 ± 20.26 | 0.31 |
| DBP, mm Hg | 78.34 ± 9.24 | 77.20 ± 9.58 | 80.00 ± 8.65 | 0.28 |
| Hematuria, n (%) | 38 (63.3) | 20 (57.1) | 18 (72.0) | 0.24 |
| RBC/HP | 4.37 (2.02, 13.18) | 5.55 (2.3, 23.1) | 3.13 (1.52, 11.90) | 0.76 |
| Serum albumin, g/L | 25.97 ± 6.47 | 25.56 ± 6.12 | 26.58 ± 7.04 | 0.57 |
| Proteinuria, g/24 h | 6.24 ± 3.54 | 5.43 (3.30, 6.96) | 5.69 (4.20, 7.95) | 0.42 |
| Serum creatinine, μmol/L | 85.02 ± 39.50 | 75.99 ± 35.30 | 99.40 ± 42.33 | 0.03 |
| eGFR, mL/min/1.73 m2 | 88.18 ± 29.40 | 94.80 ± 27.64 | 77.64 ± 29.11 | 0.03 |
| eGFR < 60 mL/min/1.73 m2, n (%) | 11 (18.3) | 3 (8.5) | 8 (32.0) | 0.04a |
| Total cholesterol, mmol/L | 6.81 ± 1.87 | 6.84 ± 1.89 | 6.76 ± 1.83 | 0.88 |
| Triglycerides, mmol/L | 2.35 ± 1.27 | 2.41 ± 1.47 | 2.25 ± 0.98 | 0.71 |
| LDL-C, mmol/L | 3.93 ± 1.46 | 3.86 ± 1.48 | 4.03 ± 1.47 | 0.71 |
| HDL-C, mmol/L | 1.33 ± 0.43 | 1.40 ± 0.47 | 1.24 ± 0.36 | 0.19 |
| CKD stages, n (%) | ||||
| CKD1 | 33 (55.0) | 22 (65.7) | 11 (41.7) | 0.19 |
| CKD2 | 17 (28.3) | 10 (25.7) | 7 (29.2) | 0.55 |
| CKD3 | 10 (16.7) | 3 (8.6) | 7 (29.2) | 0.08a |
| Titer of PLA2R-Ab, RU/mL | 28.05 (4.26, 159.60) | 25.16 (0, 153.16) | 44.33 (0, 288.61) | 0.62 |
| B cell (counts/μL) | 201.5 (139.25, 286.0) | 213.5 (163.5, 383) | 185.0 (78.25, 251.5) | 0.71 |
| Zuberitamab 2 g | 54 (90.0) | 33 (94.3) | 21 (84.0) | 0.29a |
| Zuberitamab 3 g | 5 (8.3) | 2 (5.7) | 3 (12.0) | 0.39a |
| Zuberitamab 3.6 g | 1 (1.7) | 0 (0) | 1 (4.0) | 0.42a |
| HBP, n (%) | 16 (25.8) | 10 (27.0) | 6 (24.0) | 0.96 |
| DM, n (%) | 9 (14.5) | 7 (18.9) | 2 (8.0) | 0.28a |
Abbreviations: CKD, chronic kidney disease; DBP, diastolic blood pressure; DM, diabetes mellitus (fasting glucose concentration ≥ 7 mmol/L and/or 2 h ≥ 11.1 mmol/L or taking hypoglycemic drugs for more than 3 mo); eGFR, estimated glomerular filtration rate; HBP, high blood pressure (SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg or taking blood pressure medication for more than 3 mo); HDL-C, high-density lipoprotein cholesterol; HP, high power microscope; LDL-C, low-density lipoprotein cholesterol; PLA2R-Ab, phospholipase A2 receptor antibody; RBC, red blood cell; RU, relative units; SBP, systolic blood pressure.
Estimated using the Fisher exact test.
Figure 3.
Patient flowchart. Abbreviations: MCD, minimal change disase; SLE, systemic lupus erythematosus.
Among the 25 patients with prior immunosuppressive therapy, regimens included glucocorticoids (n = 1 alone), calcineurin inhibitors (n = 7, 2 combined with glucocorticoids), Tripterygium wilfordii (n = 2, 1 with glucocorticoids), and rituximab-based regimens (n = 9). Among the 9 receiving rituximab, 1 used monotherapy, whereas others combined it with glucocorticoids (n = 2), tacrolimus (n = 4), or triple therapies (eg, rituximab + glucocorticoids + cyclophosphamide/mycophenolate). Nine patients had prior exposure to ≥3 immunosuppressant classes. Despite temporary PR in 9 patients, none achieved CR or sustained response after prior therapies.
Sixty PLA2R-associated IMN patients were followed for a median follow-up period of 6 months (IQR, 5-9 months). Patients were divided into first-line (n = 35) or second-line (n = 25) groups based on prior treatment history. Baseline differences included a lower male-to-female ratio (54.3% vs 83.3%; P = 0.04), a shorter proteinuria duration (median 2 vs 36 months; P = 0.001), a lower serum creatinine level (76 vs 99 μmol/L; P = 0.03), and a higher eGFR (95 vs 78 mL/min/1.73 m2; P = 0.03) in first-line patients, whereas second-line patients had a higher proportion with eGFR < 60 mL/min/1.73 m2 (32% vs 8.5%). Overall, 90% (54/60) received 2 g of cumulative zuberitamab, with 8.3% (5/60) at 3 g and 1.7% (1/60) at 3.6 g.
Effectiveness
At the 3-month follow-up, 48 (80.0%) patients had achieved either CR or PR. CR was observed in 5 patients (all from the first-line group), with none in the second-line group (P = 0.07). PR was achieved in 43 patients (24 in the first-line group and 19 in the second-line group; P = 0.53). By the 6-month follow-up, a total of 48 (80.0%) patients remained in remission. Of these, 13 achieved CR (11 in the first-line group and 2 in the second-line group; P = 0.03), and 35 achieved PR (18 in the first-line group and 17 in the second-line group; P = 0.20) (Figs 4 and 5). The median time to PR was 3 months (IQR, 2-4 months) (Fig 5A), whereas the median time to CR was 6 months (IQR, 4-6 months) (Fig 6B). The likelihood of achieving CR was significantly higher in the first-line group compared with that in the second-line group (unadjusted hazard ratio, 5.5; 95% confidence interval, 4.4-6.6; P = 0.03) (Fig 5B).
Figure 4.
Patient outcomes at 3 and 6 months.
Figure 5.
Remission of proteinuria after zuberitamab therapy. (A) Kaplan-Meier curves for the probability of reaching the remission of proteinuria (complete remission or partial remission) after zuberitamab administration in the study group considered in patients who received zuberitamab as first-line therapy (blue line) and patients who received it as second-line therapy (green line). (B) Kaplan-Meier curves for the probability of reaching the remission of proteinuria (complete remission) after zuberitamab administration in the study group considered in patients who received zuberitamab as first-line therapy (blue line) and patients who received it as second-line therapy (green line).
Figure 6.
Median serum albumin, proteinuria and the proportion of patients with positive PLA2R-Ab titers at various time points. (A) Median % changed serum albumin, (B) Patients (%) with positive PLA2R-Ab titers, (C) Median % changed Proteinuria and (D) Patients (%) with PLA2R-Ab depeleted. Abbreviation: PLA2R-Ab, phospholipase A2 receptor antibody.
Nine patients showed no improvement in proteinuria but maintained stable renal function at both the 3-month and 6-month follow-up assessments. In the second-line group, 1 patient had a persistent decline in eGFR to <30 mL/min/1.73 m2 that did not recover within 6 months, and another experienced a decrease in eGFR to <30 mL/min/1.73 m2 at month 6. In the first-line group, 1 patient also experienced a decline in eGFR to <30 mL/min/1.73 m2 at month 6. These 3 patients (cases 2, 8, and 9) were considered treatment failures.
We closely monitored changes in serum albumin, proteinuria, serum creatinine, eGFR (calculated using the CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equation), PLA2R-Ab levels, and circulating CD19+ B-cell counts following treatment with zuberitamab (Table 2 and Fig 6). Serum albumin levels increased in both groups at the 2-week, 3-month, and 6-month follow-up assessments (Table 2 and Fig 6A). Proteinuria levels decreased in both groups over time (Fig 6C). Serum creatinine decreased at both 3 and 6 months, whereas eGFR improved at these same time points (Fig 7A and B). There was no significant difference in serum albumin levels between the 2 groups at either 3 or 6 months. However, proteinuria decreased significantly more in the first-line group compared with the second-line group at month 6 (P = 0.05). Similarly, serum creatinine decreased significantly in the first-line group at month 3 (P = 0.001) (Fig 7A), and eGFR improved significantly in the first-line group at the same time point (P = 0.001). Compared with the second-line group, the first-line group showed greater reductions in serum creatinine (P < 0.001) and greater improvements in eGFR (P < 0.001) as early as 2 weeks after the first 1-g dose of zuberitamab (Fig 7B).
Table 2.
Effectiveness Outcomes
| Variable | First-Line Therapy (n = 35) | Second-Line Therapy (n = 25) | P Value |
|---|---|---|---|
| 3-mo outcomes | |||
| Complete remission (%) | 5 (14.3) | 0 (0) | 0.07a |
| Partial remission (%) | 24 (68.6) | 19 (76.0) | 0.53 |
| No response (%) | 6 (17.1) | 6 (24.0) | 0.53a |
| 6-mo outcomes | |||
| Complete remission (%) | 11 (31.4) | 2 (8.0) | 0.03 |
| Partial remission (%) | 18 (51.4) | 17 (68.0) | 0.20 |
| No response (%) | 6 (17.1) | 6 (24.0) | 0.51a |
| Serum albumin (g/L) | |||
| Baseline | 25.56 ± 6.12 | 26.58 ± 7.04 | 0.57 |
| 2 wk | 29.00 ± 6.77 | 27.71 ± 6.41 | 0.50 |
| Increased % from baseline | 13.4 | 4.3 | |
| 3 mo | 33.83 ± 5.73 | 33.98 ± 6.01 | 0.93 |
| Increased % from baseline | 32.4 | 27.80 | |
| 6 mo | 34.79 ± 8.71 | 33.39 ± 8.31 | 0.59 |
| Increased % from baseline | 36.81 | 25.60 | |
| 24-h proteinuria (g) | |||
| Baseline | 5.43 (3.39, 7.48) | 5.76 (4.43, 7.95) | 0.42 |
| 2 wk | 3.93 (2.94, 5.87) | 4.75 (3.77, 8.05) | 0.19 |
| Decreased % from baseline | 27.6 | 17.5 | |
| 3 mo | 1.90 (1.16, 2.91) | 2.40 (1.75, 3.51) | 0.70 |
| Decreased % from baseline | 65.0 | 58.3 | |
| 6 mo | 0.76 (0.30, 2.59) | 2.95 (145, 4.84) | 0.05 |
| Decreased % from baseline | 86.0 | 48.8 | |
| Serum creatinine (μmol/L) | |||
| Baseline | 75.99 ± 32.30 | 99.40 ± 42.33 | 0.03 |
| 2 wk | 71.69 ± 26.11 | 108.29 ± 47.03 | <0.001 |
| 3 mo | 64.46 ± 17.26 | 94.82 ± 35.47 | 0.001 |
| 6 mo | 75.27 ± 36.05 | 98.54 ± 57.08 | 0.12 |
| eGFR (mL/min/1.73 m2) | |||
| Baseline | 94.80 ± 28.00 | 77.64 ± 29.11 | 0.03 |
| 2 wk | 96.21 ± 29.08 | 72.66 ± 31.49 | <0.001 |
| 3 mo | 103.57 ± 22.64 | 78.16 ± 22.56 | 0.001 |
| 6 mo | 95.29 ± 27.47 | 82.02 ± 32.98 | 0.19 |
| Titer of PLA2R-Ab (RU/mL) | |||
| Baseline | 25.16 (0.00, 153.15) | 44.33 (0, 196.94) | 0.56 |
| 2 wk | 7.02 (0, 56.6) | 20.07 (0, 46.63) | 0.16 |
| 3 mo | 0 (0, 0) | 0 (0, 0) | 0.63 |
| 6 mo | 0 (0, 0) | 0 (0, 0) | 0.09 |
| Patients (%) with PLA2R-Ab ≥ 14 RU/mL based on ELISA, n (%) | |||
| Baseline (%) | 10 (27.0) | 17 (68.0) | 0.39 |
| 3 mo (%) | 2 (5.4) | 5 (20.0) | 0.39a |
| 6 mo (%) | 1 (2.7) | 4 (16.0) | 0.29a |
| Patients (%) with PLA2R-Ab 2-14 RU/mL based on ELISA, n (%) | |||
| Baseline (%) | 5 (14.3) | 5 (20) | 1.00a |
| 3 mo (%) | 5 (16.7) | 3 (13.6) | 1.00a |
| 6 mo (%) | 1 (3.0) | 0 (0) | 1.00a |
| Patients (%) with PLA2R-Ab < 2 RU/mL based on ELISA, n (%) | |||
| Baseline | 9 (25.7) | 2 (12.0) | <0.001 |
| 3 mo | 24 (80.0)b | 13 (59.1)c | 0.10 |
| 6 mo | 30 (90.9)d | 17 (81.0)e | 0.29 |
| CD19+ B lymphocytes (count/μL) | |||
| Baseline | 177 (170, 365) | 60.50 (51.00, 28.50) | 0.71 |
| 2 wk | 2.00 (0.21, 3.00) | 1.00 (0.59, 2.00) | 0.41 |
| 3 mo | 3.00 (1.26, 3.30) | 1.65 (0.32, 4) | 0.96 |
| 6 mo | 5 (1.23, 10.00) | 4 (2, 15.5) | 0.25 |
Abbreviations: eGFR, estimated glomerular filtration rate; ELISA, enzyme-linked immunosorbent assay; PLA2R-Ab, phospholipase A2 receptor antibody; RU, relative units.
Estimated using the Fisher exact test.
n = 30.
n = 22.
n = 33.
n = 21.
Figure 7.
Changes of serum creatinine, eGFR, CD19+ B-cell counts and PLA2R-Ab titers at various time points. (A) Serum creatinine, (B) eGFR (calculated using the CKD-EPI formula), (C) CD19+ B-cell counts, and (D) PLA2R-Ab titers. Abbreviations: CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; PLA2R-Ab, phospholipase A2 receptor antibody.
Circulating CD19+ B-cell counts at baseline and at 2 weeks, 3 months, and 6 months were 201.5 (IQR, 139.25-282) cells/μL, 1.38 (0.34-2.0) cells/μL, 1.68 (0.88-4.0) cells/μL, and 5.0 (1.93-19.0) cells/μL, respectively (Fig 7C). CD19+ B-cell counts decreased to <5 cells/μL in all patients within 2 weeks of zuberitamab infusion. Reconstitution of CD19+ B cells (defined as counts >5 cells/μL) occurred in 6 of 28 available measurements within 3 (21.4%) months, in 15 of 32 measurements within 6 (46.9%) months, and in 12 of 13 measurements within 9 (92.3%) months. Fifteen patients received a third infusion of zuberitamab at a median interval of 9 (IQR, 6.5-10) months after the second infusion (Fig 7C).
The median serum PLA2R-Ab titers at baseline, 2 weeks, 3 months, and 6 months after zuberitamab treatment were 28.05 (IQR, 4.26-159.60) RU/mL, 8.38 (IQR, 0-54.79) RU/mL, 0 (IQR, 0-3.44) RU/mL, and 0 (IQR, 0-0) RU/mL, respectively (Fig 7D). All posttreatment values were significantly lower than those at baseline (P < 0.001). No significant differences in PLA2R-Ab titers were observed between the first-line and second-line groups at any follow-up point (Table 2 and Fig 7D). Among the 27 patients with baseline PLA2R-Ab titers ≥ 14 RU/mL (10 in the first-line group and 17 in the second-line group), 20 (8 in the first-line group and 12 in the second-line group) patients exhibited a reduction to undetectable levels (ranging from 2.09-11.32 RU/mL; median, 4.3 RU/mL) by 3 months. At 6 months, 22 of these 27 (9 in the first-line group and 13 in the second-line group) patients had undetectable PLA2R-Ab (<2 RU/mL) levels. In the full cohort, 37 patients had undetectable PLA2R-Ab levels at 3 months, and 47 patients at 6 months (Fig 7D).
Among the 9 patients with rituximab-refractory (cases 1, 3, 4, 6, 7, 8, and 9) or relapsed (cases 2 and 5) disease, 8 out of 9 (88.9%) achieved CR or PR following zuberitamab treatment. One patient (case 8) did not achieve PR by month 10 and continued to have detectable PLA2R-Ab titers despite stable renal function. One additional patient (case 9) experienced a decline in eGFR to <30 mL/min/1.73 m2 at month 6 and was considered a treatment failure with zuberitamab (Table 3).
Table 3.
Summary of the Patients Who Had a History of Rituximab
| Patients | Age (y) | Sex | Duration of Nephrosis | Previous IS | Follow-up Times (mo) |
Zuberitamab Dose (g) | Titer of PLA2R-Ab Before |
Titer of PLA2R-Ab After |
Urinary Protein (g/d) Before |
Urinary Protein (g/d) After |
S ALB Before |
S ALB After |
Response |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 50 | M | 5 | RTX 2 g/GC | 9 | 2 | 26.85 | <2 | 4.2 | 0.16 | 27.7 | 37.29 | CR |
| 2 | 73 | M | 96 | RTX 2 g/TAC | 3 | 2 | 67.23 | 11.23 | 9.16 | 1.86 | 21.77 | 38 | PR |
| 3 | 58 | M | 36 | RTX 3 g/CYC/GC | 9 | 3 | <2 | <2 | 3.63 | 1.61 | 36.67 | 39.76 | PR |
| 4 | 69 | M | 252 | RTX 2 g/GC/CYC/MMF/TW | 6 | 2 | 10.14 | <2 | 4.62 | 1.67 | 30.56 | 35.24 | PR |
| 5 | 55 | M | 60 | RTX 2 g/TAC | 14 | 3 | 49.86 | <2 | 12.1 | 0.83 | 17.17 | 38.77 | PR |
| 6 | 71 | M | 28 | RTX 3 g/GC | 14 | 3.6 | 293.45 | 2.98 | 6.81 | 2.76 | 30.12 | 33.49 | PR |
| 7 | 46 | M | 216 | RTX 2 g/GC | 6 | 2 | <2 | <2 | 4.43 | 1.07 | 32.60 | 39.02 | PR |
| 8 | 54 | F | 12 | RTX 3 g/TAC | 10 | 3 | 19.19 | 3.1 | 5.08 | 3.75 | 31.47 | 36.22 | NR |
| 9 | 51 | M | 12 | RTX 2 g | 6 | 2 | 99.83 | <2 | 5.76 | 16.33 | 10.4 | 14.16 | NR |
Abbreviations: CR, complete remission; CYC, cyclophosphamide; F, female; GC, glucocorticoid; IS, immunologic suppression; M, male; MMF, mycophenolate mofetil; PLA2R, phospholipase A2 receptor; PR, partial remission; RTX, rituximab; S ALB, serum albumin; TAC, tacrolimus; TW, Tripterygium wilfordii.
At month 6, 12 patients had not achieved clinical remission; their characteristics are summarized in Table 4. Of these, 6 had a history of treatment with at least 1 immunosuppressant, including 3 who had received rituximab. Four patients were PLA2R-Ab negative (PLA2R-Ab < 14 RU/mL) at baseline. Among the remaining 8 PLA2R-Ab–positive patients, 2 exhibited immunologic response (PLA2R-Ab depletion [< 2 RU/mL]), but none had achieved clinical remission by the last follow-up. Three patients (cases 2, 8, and 9) experienced sustained declines in eGFR to <30 mL/min/1.73 m2 that did not recover within 3 months; these cases were considered treatment failures. One patient (case 12) achieved delayed PR by month 9, with proteinuria decreasing to 1.6 g/d.
Table 4.
Summary of the Patients Who Did Not Achieve Proteinuria Remission Following Zuberitamab Infusions
| Case No. |
Age (y) | Gender | Duration of Nephrosis | Kidney Biopsy |
Follow-up Time | Zuberitumab Dose (g) | Titer of PLA2R Before | Titer of PLA2R-Ab After |
Urinary Protein (g/d) Before |
Urinary Protein (g/d) After |
S ALB Before |
S ALB After |
Creatitine Before |
Creatinine After | Treatments Before Zuberitamab | Immunologic Remission |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 74 | F | 12 | Yes | 9 | 2 | <2 | <2 | 5.72 | 4.34 | 18.98 | 22.6 | 78.3 | 88.3 | None | - |
| 2 | 70 | M | 12 | Yes | 6 | 2 | >1,500 | 589.77 | 3.26 | 8.25 | 13.26 | 17.86 | 131.4 | 200.3 | None | No |
| 3 | 52 | F | 1 | No | 6 | 2 | 41.55 | <2 | 2.52 | 3.68 | 27.4 | 35.68 | 43.8 | 44.7 | None | Yes |
| 4 | 58 | M | 0.5 | Yes | 7 | 2 | 1,284.66 | 27.27 | 9.6 | 5.85 | 22.1 | 16.46 | 79 | 124.6 | None | No |
| 5 | 38 | M | 3 | No | 10 | 2 | 10.6 | <2 | 10.7 | 4.77 | 16.34 | 21.04 | 114.6 | 72 | None | Yes |
| 6 | 50 | M | 1 | Yes | 7 | 2 | <2 | <2 | 18.25 | 12.32 | 20.49 | 29.46 | 106.5 | 74.2 | None | - |
| 7 | 61 | M | 24 | No | 6 | 3 | 617.41 | 14.16 | 8.52 | 7.06 | 18.52 | 28.25 | 140 | 139.3 | TAC | No |
| 8 | 51 | M | 12 | No | 6 | 2 | 99.83 | <2 | 5.76 | 16.33 | 10.4 | 14.16 | 208.5 | 280.8 | RTX 2 g | Yes |
| 9 | 61 | F | 24 | Yes | 8 | 2 | 412.15 | 614.36 | 5.69 | 8.48 | 17.93 | 17.31 | 99.4 | 193.7 | TAC | No |
| 10 | 61 | M | 12 | No | 6 | 2 | 422.78 | 120.67 | 6.67 | 3.28 | 22.38 | 19 | 84.9 | 71 | TAC | No |
| 11 | 54 | F | 12 | Yes | 10 | 3 | 19.19 | 3.1 | 5.08 | 3.75 | 31.47 | 36.22 | 52.3 | 75 | RTX 3 g/TAC | Yes |
| 12 | 58 | M | 36 | Yes | 9 | 3 | <2 | <2 | 3.63 | 1.6 | 36.67 | 40.59 | 181.6 | 184.7 | RTX 2 g/CYC/GC | - |
Abbreviations: CYC, cyclophosphamide; F, female; GC, glucocorticoid; M, male; MMF, mycophenolate mofetil; PLA2R, phospholipase A2 receptor; PLA2R-Ab, phospholipase A2 receptor antibody; RTX, rituximab; S ALB, serum albumin; TAC, tacrolimus.
Safety
Nine AEs were reported in 13 patients (Table 5). The incidence of serious AEs was comparable between the first-line and second-line groups. Most AEs were infusion related and nonserious in nature. A total of 7 patients experienced 4 types of infusion-related reactions. During the first zuberitamab infusion, 3 patients developed skin rash, 1 experienced generalized chills, 2 reported a dry throat, and 1 reported a headache. These symptoms resolved within minutes following either temporary interruption or a reduction in the infusion rate. Infusions were subsequently resumed at half the original rate. All events were classified as mild, as they were not accompanied by signs of anaphylaxis such as hypotension or respiratory distress. Importantly, none of these AEs recurred during subsequent zuberitamab infusions.
Table 5.
Adverse Drug Events According to Treatment in Patients With Different Outcomes
| Adverse Event | Overall (n = 60) |
First-Line Therapy (n = 35) |
Second-Line Therapy (n = 25) |
|---|---|---|---|
| Infusion-related reaction | |||
| Skin rash | 4 | 2 | 2 |
| Generalized chills | 1 | 1 | 0 |
| Headache | 1 | 0 | 1 |
| Dry throat | 2 | 1 | 1 |
| Events according to treatment | |||
| Bronchitis | 1 | 0 | 1 |
| Abnormal liver function | 1 | 1 | 0 |
| Urinary tract infections | 1 | 1 | 0 |
| Transient creatinine elevation | 1 | 0 | 1 |
| eGFR < 30 mL/min/1.73 m2 | 3 | 1 | 2 |
Abbreviation: eGFR, estimated glomerular filtration rate.
One patient experienced a viral upper respiratory tract infection and bronchitis, and another developed a urinary tract infection; both recovered fully with outpatient anti-infective therapy. No infection required hospitalization. One patient developed transient liver function abnormalities 1 month after receiving a 2-g dose of zuberitamab; these resolved within 7 days following liver-protective treatment. Another patient experienced a transient elevation in the serum creatinine level at month 3, which resolved by month 6. Three patients (1 in the first-line group and 2 in the second-line group) experienced deterioration in kidney function, defined as a sustained decrease in eGFR to <30 mL/min/1.73 m2 at the last follow-up. No cases of malignancy or death occurred during the study period (Table 5).
Discussion
Zuberitamab has demonstrated comparable efficacy and safety with rituximab in the treatment of diffuse large B-cell lymphoma. In addition, a recent randomized, double-blind, placebo-controlled phase 2 trial conducted in China further validated its safety and efficacy for primary immune thrombocytopenia at 100-mg dose.8 In this study, zuberitamab was associated with B-cell depletion and clinical/immunologic remission, regardless of first-line or second-line use. Over a median 6-month follow-up period, 80.0% (48/60) of patients achieved CR or PR of proteinuria, with 82.9% (29/35) in the first-line group and 76.0% (19/25) in the second-line group. These findings suggest zuberitamab as a promising first-line immunosuppressive therapy option for MN, with superior response rates when used initially compared with second-line settings.
Currently, anti-CD20 therapies are not covered by medical insurance for MN in Henan Province, China, making treatment cost an important consideration. In our cohort, zuberitamab was administered at a cost of ¥7,040 per 1-g dose, compared with ¥7,400 per 1-g dose for rituximab. In prior nonrandomized studies, the remission rate for rituximab-treated MN patients has ranged from 57%-89%.10, 11, 12, 13 In the Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy trial, 51% (19 of 37) of patients achieved remission at 6 months following a 2-g rituximab dose.14 Similarly, Seitz-Polski et al15 reported a 64% remission rate (18 of 28) at 6 months after a 2-g dose.9 These data underscore the need for head-to-head trials to directly compare zuberitamab with rituximab in MN.
Anti-PLA2R-Ab titers are closely correlated with disease activity in MN, typically rising during periods of disease activity and declining before remission. As such, reduction or depletion of anti-PLA2R-Abs is considered a key therapeutic goal. Prior studies have shown that depletion of anti-PLA2R-Abs at 6 months is strongly predictive of clinical remission, and a 50% reduction in antibody titers has been reported to precede a comparable reduction in proteinuria by approximately 10 months.16 In our study, immunologic remission (defined as a serum PLA2R-Ab titer of <2 RU/mL) was achieved in 87.0% (47 of 54) of patients, including 90.9% (30 of 33) in the first-line group and 81.0% (17 of 21) in the second-line group.
Renal dysfunction is increasingly recognized in MN, particularly among patients with a history of failed prior therapy. Sustained reductions in proteinuria are well established as being associated with improved long-term outcomes in chronic kidney disease. In our cohort, 11 patients had an eGFR of <60 mL/min/1.73 m2 at baseline, including 3 in the first-line group and 8 in the second-line group. After 6 months of treatment, renal function improved in 6 of these patients (1 in the first-line group and 5 in the second-line group), whereas 2 patients (1 from each group) maintained stable kidney function. In both groups, mean eGFR increased from baseline levels by the end of follow-up. Serious AEs were rare. Only 3 patients experienced a decline in eGFR to <30 mL/min/1.73 m2 accompanied by persistent proteinuria. These findings support the overall safety profile of zuberitamab in this cohort.
Notably, 12 patients (cases 1-12; Table 4) did not respond to zuberitamab treatment. Among them, 5 patients failed to achieve immunologic remission, which may have been related to initially high anti-PLA2R-Ab titers. Previous studies have shown that a high PLA2R titer at diagnosis is associated with an increased risk of long-term renal impairment.17,18 Among the remaining 7 patients, 5 exhibited varying degrees of serum albumin elevation despite not meeting the criteria for PR of proteinuria. We hypothesize that the relatively short follow-up duration in some cases may have contributed to these outcomes. Similar to rituximab, the therapeutic effect of zuberitamab may become more apparent with a longer follow-up period.19 One patient (case 8) declined kidney biopsy. Although anti-PLA2R-Abs were positive and immunologic remission was achieved by month 6, an alternative cause of proteinuria could not be fully excluded.
The emergence of resistance to rituximab remains a significant clinical challenge. This may result from mutations or downregulation of the CD20 antigen, impairing B-cell depletion, or from the persistence of long-lived, antibody-producing plasma cells that lack CD20 expression. Consequently, rituximab may fail to induce remission in approximately 20%-40% of patients, resulting in treatment resistance or relapse.12,13,19, 20, 21 These limitations underscore the need for additional therapeutic options in MN. In our cohort, 9 patients had a prior history of rituximab treatment, 7 of whom subsequently achieved CR or PR with zuberitamab at 6 months of follow-up. These preliminary findings suggest that zuberitamab may offer therapeutic benefit in patients with a prior history of rituximab.
Overall, our study suggests that zuberitamab safely and persistently reduced proteinuria when used as either first-line or second-line therapy in patients with MN. The treatment was well tolerated, with evidence of sustained immunologic suppression throughout the follow-up period. Comparable remission rates were observed in both treatment groups, supporting the potential role of zuberitamab as an alternative CD20-targeted therapeutic option in this population.
This study has several limitations. First, the retrospective, single-center design introduces potential selection bias, as the patient cohort may not fully represent the broader IMN population, limiting the generalizability of the findings. The homogeneity of the sample from a single center reduces external validity, especially for different regions or health care settings. Second, the relatively short follow-up period (median, 6 months) may not capture the long-term durability of treatment responses, potential relapses, or AEs, possibly underestimating these outcomes. A longer follow-up period is necessary for more comprehensive assessment. In addition, the absence of a parallel control group prevents direct comparisons between zuberitamab and other treatments, such as rituximab, limiting the strength of conclusions on its relative efficacy and safety. Last, owing to issues with insurance and test costs, the lack of immunoglobulin monitoring and incomplete B-cell and PLA2R-Ab testing during follow-up may have affected the understanding of the full immunologic response to treatment.
In conclusion, zuberitamab was associated with reduced proteinuria and stabilization of kidney function in patients with MN, with a favorable safety profile. These findings suggest that zuberitamab may represent a valuable therapeutic option for patients with MN in China, both as an initial treatment option and as a second-line option for those who do not respond to conventional therapies. Although our study provides preliminary observational evidence, the safety and efficacy of zuberitamab should be further validated in prospective, randomized controlled trials.
Article Information
Authors’ Full Names and Academic Degrees
Linna Wang, MD, Miaomiao Yang, MM, Lei Yan, MD, and Fengmin Shao, MD.
Authors’ Contributions
Research area and study design: LW and FS; data acquisition: MY; data analysis and interpretation: LW; statistical analysis: LW; supervision or mentorship: LW, MY, LY, and FS. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Support
This study was supported by China Postdoctoral Science Foundation Project 2015M582858.
Financial Disclosure
The authors declare that they have no relevant financial interests.
Data Sharing
The data sets generated and/or analyzed during this study are provided within the article. For further requests, please contact the corresponding author.
Peer Review
Received January 9, 2025. Evaluated by 2 external peer reviewers, with direct editorial input from an Associate Editor and the Editor-in-Chief. Accepted in revised form April 21, 2025.
Footnotes
Complete author and article information provided before references.
References
- 1.Alsharhan L., Beck L.H., Jr. Membranous nephropathy: core curriculum 2021. Am J Kidney Dis. 2021;77:440–453. doi: 10.1053/j.ajkd.2020.10.009. [DOI] [PubMed] [Google Scholar]
- 2.Ronco P., Beck L., Debiec H., et al. Membranous nephropathy. Nat Rev Dis Primers. 2021;7:69. doi: 10.1038/s41572-021-00303-z. [DOI] [PubMed] [Google Scholar]
- 3.Beck L.H., Jr., Bonegio R.G., Lambeau G., et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361:11–21. doi: 10.1056/NEJMoa0810457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Sethi S. New "antigens" in membranous nephropathy. J Am Soc Nephrol. 2021;32:268–278. doi: 10.1681/asn.2020071082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100:S1–S276. doi: 10.1016/j.kint.2021.05.021. [DOI] [PubMed] [Google Scholar]
- 6.Iannello A., Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev. 2005;24:487–499. doi: 10.1007/s10555-005-6192-2. [DOI] [PubMed] [Google Scholar]
- 7.Decaup E., Rossi C., Gravelle P., et al. A tridimensional model for NK cell-mediated ADCC of follicular lymphoma. Front Immunol. 2019;10:1943. doi: 10.3389/fimmu.2019.01943. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Xu M., Shu J., Qian S., et al. Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study. Lancet Reg Health West Pac. 2024;47 doi: 10.1016/j.lanwpc.2024.101096. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Bobart S.A., De Vriese A.S., Pawar A.S., et al. Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies. Kidney Int. 2019;95:429–438. doi: 10.1016/j.kint.2018.10.021. [DOI] [PubMed] [Google Scholar]
- 10.Remuzzi G., Chiurchiu C., Abbate M., et al. Rituximab for idiopathic membranous nephropathy. Lancet. 2002;360:923–924. doi: 10.1016/s0140-6736(02)11042-7. [DOI] [PubMed] [Google Scholar]
- 11.Fervenza F.C., Cosio F.G., Erickson S.B., et al. Rituximab treatment of idiopathic membranous nephropathy. Kidney Int. 2008;73:117–125. doi: 10.1038/sj.ki.5002628. [DOI] [PubMed] [Google Scholar]
- 12.Fervenza F.C., Abraham R.S., Erickson S.B., et al. Rituximab therapy in idiopathic membranous nephropathy: a 2-year study. Clin J Am Soc Nephrol. 2010;5:2188–2198. doi: 10.2215/cjn.05080610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Ruggenenti P., Cravedi P., Chianca A., et al. Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol. 2012;23:1416–1425. doi: 10.1681/asn.2012020181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Scolari F., Delbarba E., Santoro D., et al. Rituximab or cyclophosphamide in the treatment of membranous nephropathy: the RI-CYCLO randomized trial. J Am Soc Nephrol. 2021;32:972–982. doi: 10.1681/asn.2020071091. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Seitz-Polski B., Dahan K., Debiec H., et al. High-dose rituximab and early remission in PLA2R1-related membranous nephropathy. Clin J Am Soc Nephrol. 2019;14:1173–1182. doi: 10.2215/cjn.11791018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Ruggenenti P., Debiec H., Ruggiero B., et al. Anti-phospholipase a2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy. J Am Soc Nephrol. 2015;26:2545–2558. doi: 10.1681/asn.2014070640. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Kanigicherla D., Gummadova J., McKenzie E.A., et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int. 2013;83:940–948. doi: 10.1038/ki.2012.486. [DOI] [PubMed] [Google Scholar]
- 18.Hoxha E., Harendza S., Pinnschmidt H., Panzer U., Stahl R.A. M-type phospholipase A2 receptor autoantibodies and renal function in patients with primary membranous nephropathy. Clin J Am Soc Nephrol. 2014;9:1883–1890. doi: 10.2215/cjn.03850414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Dahan K., Debiec H., Plaisier E., et al. Rituximab for severe membranous nephropathy: a 6-month trial with extended follow-up. J Am Soc Nephrol. 2017;28:348–358. doi: 10.1681/asn.2016040449. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Fervenza F.C., Appel G.B., Barbour S.J., et al. Rituximab or cyclosporine in the treatment of membranous nephropathy. N Engl J Med. 2019;381:36–46. doi: 10.1056/NEJMoa1814427. [DOI] [PubMed] [Google Scholar]
- 21.Teisseyre M., Cremoni M., Boyer-Suavet S., et al. Advances in the management of primary membranous nephropathy and rituximab-refractory membranous nephropathy. Front Immunol. 2022;13 doi: 10.3389/fimmu.2022.859419. [DOI] [PMC free article] [PubMed] [Google Scholar]