Study on predictors for treatment efficacy of rituximab in patients with PLA2R-negative primary membranous nephropathy

doi:10.16150/j.1671-2870.2025.03.006

Abstract

Abstract:

Objective To evaluate the clinical efficacy of rituximab (RTX) in patients with phospholipase A2 receptor (PLA2R)-negative primary membranous nephropathy (PMN) presenting as nephrotic syndrome, and to identify predictors for treatment efficacy. Methods This retrospective cohort study included 19 biopsy-proven PLA2R-negative PMN patients with nephrotic syndrome who received RTX at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between March 2020 and March 2024. Additionally, 38 PLA2R-positive PMN patients with nephrotic syndrome who received RTX were matched as controls. All patients were followed for at least 6 months (median = 12 months) to evaluate the clinical efficacy of RTX in both groups and to analyze potential predictors of treatment efficacy in PLA2R-negative MN patients. Results In PLA2R-negative PMN patients treated with RTX for 12 months, the 24-hour proteinuria significantly decreased from (9.8±4.3) g/d to (2.6±2.6) g/d and serum albumin increased from (20.3±4.3) g/L to (36.4±7.1) g/L (P<0.05). The overall change in estimated glomerular filtration rate showed no statistical significance [(90.7±30.0) mL·min^-1·1.73 m^-2 vs. (84.4±22.19) mL·min^-1·1.73 m^-2] (P>0.05). Overall remission rates in the PLA2R-negative group at 3 months (57.89%), 6 months (57.89%), 12 months (85.71%) were comparable to those in the PLA2R-positive group (P>0.05). However, the complete remission rate was significantly higher in the PLA2R-negative group at 3 months (21.5% vs. 0%, P=0.009 8) and 6 months (36.84% vs. 10.53%, P=0.030 5), indicating statistical significance. The univariate logistic regression analysis showed that factors influencing clinical remission at 12 months of RTX treatment in PLA2R-negative PMN patients were 3-month 24-hour proteinuria (OR=0.993, P=0.047 1) and 3-month serum albumin (OR=1.309, P=0.048 8). Conclusion RTX treatment is effective in treating PLA2R-negative PMN. Compared with the PLA2R-positive group, the overall remission rate at 12 months was comparable, with a slightly higher complete remission rate at 3 months. The 3-month 24-hour proteinuria and 3-month serum albumin levels may serve as potential predictors for clinical remission at 12 months in PLA2R-negative PMN patients.

Key words: Primary membranous nephropathy, Phospholipase A2 receptor, Rituximab, Remission rate, Predictor

CLC Number:

R692

XU Lili, HU Xiaofan, LI Hao, WANG Weiming. Study on predictors for treatment efficacy of rituximab in patients with PLA2R-negative primary membranous nephropathy[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(03): 279-285.

Figures/Tables 4

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References 19

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Items	PLA2R-Negative (N=19)	PLA2R-Positive(N=38)	P value
Age (years)	61(28-75)	61.5(23-76)	0.902 4
Male [n (%)]	8（42.11%）	18（47.37%）	0.782 4
Treatment-naïve [n (%)]	16(84.21%)	30（78.95%）	0.734 9
Follow-up(months)	15（9-19）	12(11-24）	0.280 3
Hypertension [n (%)]	9（47.37%）	19（50.0%）	>0.999 9
Diabetes mellitus [n (%)]	1(5.26%)	10(26.32%)	0.079 2
ARB/ACEI [n(%)]	12（63.16%）	28（71.79%）	0.554 3
Infection [n(%)]	4（21.05%）	7（18.42%）	>0.999 9
BMI(kg/m²)	24.54±2.58	24.55±3.07	0.986 2
Anti-PLA2R antibody(RU/mL)	1.76±0.12	96.50±110.80	0.000 7
Serum creatinine(μmol/L)	77.16±28.46	87.89±47.55	0.498 8
eGFR(mL·min^-1·1.73m^-²)	90.70±30.03	83.07±25.89	0.324 8
Triglycerides(mmol/L)	2.69±1.78	2.36±1.44	0.459 4
Cholesterol (mmol/L)	8.08±3.79	7.50±2.61	0.505 2
Hemoglobin (g/L)	122.10±17.77	118.50±16.33	0.455 3
Serum albumin (g/L)	20.26±4.37	20.87±4.43	0.627 2
Serum IgG(g/L)	6.06±2.02	5.14±2.28	0.142 8
Serum IgA(g/L)	2.67±0.81	2.03±0.85	0.009 5
Serum IgM(g/L)	1.08±0.45	0.93±0.58	0.349 0
24 h urine protein(mg/d)	9 772±4 269	8 946±3 990	0.474 6
24 h urine IgG(mg/d)	585.5±603.6	508.2±370.2	0.772 5
24 h urine albumin(mg/d)	6 808±3 194	5 938±2 869	0.314 1
24 h urine α1-microglobulin(mg/d)	49.45±21.07	59.52±45.23	0.953 6
24 h urine transferrin(mg/d)	570.0±217.9	515.4±273.8	0.462 6
NLR	2.184±1.230	2.083±1.172	0.765 6
Fibrinogen(g/L)	4.884±1.610	4.190±1.040	0.089 6
D-dimer(mg/L)	0.710 0±0.703 3	1.011 0±1.067 0	0.270 6
CD19 count(cells/μL)	235.2±77.2	255.2±150.7	0.885 4
CD3 count(cells/μL)	1 249.0±492.8	1 502.0±717.9	0.175 9
CD4 count(cells/μL)	824.9±293.3	944.3±430.6	0.284 9
CD8 count(cells/μL)	401.4±217.8	499.3±326.7	0.246 2

Items	PLA2R-Negative(N=19)	PLA2R-Positive(N=38)	P value
3-month
CR	4(21.5%)	0(0%)	0.0098
CR+PR	11(57.89%)	18(47.37%)	0.5765
6-month
CR	7(36.84%)	4(10.53%)	0.0305
CR+PR	11(57.89%)	23(60.53%)	>0.9999
12-month
CR	7/14(50%)	14/29(48.28%)	>0.9999
CR+PR	12/14(85.71%)	26/29 (89.66%)	>0.9999

Items	CR+PR
Items	OR	P
Age	1.030(0.951-1.119)	0.4482
Male [n(%)]	0.222(0.010-2.214)	0.2360
Follow-up time(months)	1.448(1.085-2.420)	0.0534
Treatment-naïve [n(%)]	2.167(0.084-31.87)	0.5759
Comorbid infection [n(%)]	0.154(0.011-1.851)	0.1361
BMI(kg/m²)	1.300(0.804-2.321)	0.3108
Serum creatinine(μmol/L)	0.991(0.957-1.031)	0.6292
eGFR(mL·min^-1·1.73m^-²)	0.999(0.962-1.038)	0.9544
Serum albumin(g/L)	0.989(0.757-1.286)	0.9298
Serum IgG(g/L)	0.580(0.278-1.027)	0.0854
24-hour urine protein(mg/day)	1.000(0.9998-1.000)	0.5131
24-hour urine IgG(mg/day)	1.000(0.9985-1.003)	0.7910
NLR	2.976(0.901-57.63)	0.2867
Fibrinogen(g/L)	1.660(0.774-4.516)	0.2416
CD19 count(cells/μL)	0.986(0.962-1.004)	0.1709
3-month 24-hour urine protein(mg/day)	0.993(0.998-0.999)	0.0471
3-month serum albumin(g/L)	1.309(1.043-1.945)	0.0488
3-month eGFR(mL·min^-1·1.73m^-²)	1.190(0.990-1.675)	0.1675
3-month CD19 count(cells/μL)	0	-