Rituximab treatment for refractory nephrotic syndrome in adults: a multicenter retrospective study

Figures & data

Figure 1. Study flow diagram.

Table 1. Baseline characteristics of study population before rituximab therapy.

Characteristic	Patients (n = 48)
Male sex, n (%)	33 (68.8)
Age, years	47.88 ± 16.93
Smoker, n (%)	8 (16.7)
Drinker, n (%)	6 (12.5)
BMI, kg/m^2	24.85 ± 3.52
Systolic BP, mmHg	135.08 ± 17.34
Diastolic BP, mmHg	82.75 ± 10.74
Serum creatinine, µmol/L	94.65 ± 44.58
eGFR, mL/min/1.73 m^2	84.65 ± 32.69
Proteinuria, g/24 h	6.77 ± 3.9
<4 g, n (%)	13 (27.0)
4–8 g, n (%)	19 (39.6)
>8 g, n (%)	26 (33.3)
Albumin, g/L	24.56 ± 6.55
Total cholesterol, mmol/L	6.09 (4.46,7.62)
Triglycerides, mmol/L	2.19 (1.50,3.54)
Receiving ACEI/ARB, n (%)	37 (77.1)
Receiving statin, n (%)	31 (64.6)
Disease duration, months	29.5 (12,60)
Reason of refractory
Steroid dependent, n (%)	4 (8.3)
Steroid resistant, n (%)	3 (6.3)
Frequently relapsing, n (%)	11 (22.9)
Steroid intolerant, n (%)	5 (10.4)
Resistant to immunosuppression, n (%)	25 (52.1)
Immunosuppressive therapy before RTX
Steroid only, n (%)	12 (25.0)
Cyclosporine or tacrolimus, n (%)	24 (50.0)
Cyclophosphamide, n (%)	10 (20.8)
Mycophenolate, n (%)	1 (2.1)
Others, n (%)	1 (2.1)
Prior immunosuppressive therapy
Steroid only, n (%)	12 (25.0)
One round of immunosuppression, n (%)	10 (20.8)
Two rounds of immunosuppression, n (%)	13 (27.1)
Three rounds of immunosuppression, n (%)	13 (27.1)
Renal histologic pathology
MCD, n (%)	15 (31.3)
FSGS, n (%)	5 (10.4)
MN, n (%)	26 (54.2)
MPGN, n (%)	2 (4.2)
Diabetes, n (%)	9 (16.7)
Hypertension, n (%)	22 (45.8)

ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor antagonist; eGFR: estimated glomerular filtration rate; FSGS: focal segmental glomerulosclerosis; MCD: minimal change disease; MN: membranous nephropathy; MPGN: membranoproliferative glomerulonephritis

Figure 2. The efficacy outcome in the 12-month follow-up. Histogram showed the percentage of patients who reached PR, CR, or NR. (A) outcome of all patients. (B) outcome of patients with podocytopathy (MCD and FSGS). (C) outcome of patients with MN. *p < 0.05 complete remission rates compared to baseline. PR: partial remission; CR: complete remission; NR: no response; MCD: minimal change disease; FSGS: focal and segmental glomerulosclerosis; MN: membranous nephropathy.

Figure 3. The independent Prognosis factors of complete remission in patients with MN receiving rituximab. The forest plot of Cox proportional hazard analysis showed the results of multivariate Cox proportional hazard analysis on the prognosis factors of complete remission in patients with MN receiving rituximab. BMI: body mass index; MAP: mean arterial pressure; eGFR: estimated glomerular filtration rate; Hb: hemoglobin. 95% CI: 95% confidence interval; HR: hazard ratio. p < 0.05 was considered to be statistically significant.

Figure 4. Kaplan–Meier curves for the complete remission after Rituximab in patients with MN and podocytopathy. Kaplan–Meier curves were shown for the proportion of cumulative complete remission during the follow-up period in patients receiving Rituximab with membranous nephropathy (MN) compared with the patients in podocytopathy group. 95% CI: 95% confidence interval; HR: hazard ratio. p < 0.05 was considered to be statistically significant.

Table 2. Prognosis factors of complete remission in patients with MN receiving rituximab based on the results of univariate Cox proportional hazard analysis.

	HR	HR (95% CI)	p Value
Gender	1.364	(0.434–4.289)	0.596
Age (per year)	1.011	(0.975–1.049)	0.547
Duration (per month)	0.994	(0.979–1.009)	0.415
BMI (per 1 kg/m^2)	1.192	(0.969–1.465)	0.096
Smoker	0.958	(0.271–3.444)	0.958
Drinker	1.391	(0.311–6.182)	0.664
MAP (per 1 mmHg)	1.059	(0.996–1.127)	0.067
Hypertension	2.307	(0.733–7.262)	0.153
Diabetes	0.288	(0.064–1.284)	0.103
eGFR (per 1 mL/min/1.73 m^2)	1.040	(1.001–1.041)	0.040*
URBC (per 1/µL)	1.005	(0.997–1.014)	0.176
Hb (per 1 g/L)	1.031	(0.995–1.069)	0.086
Alb (per 1 g/L)	1.021	(0.955–1.091)	0.542
ALT (per 1 IU/L)	1.026	(0.990–1.063)	0.153
TC (per 1 mmol/L)	0.953	(0.760–1.194)	0.675
TG (per 1 mmol/L)	0.915	(0.683–1.224)	0.549
Upro (per 1 grade)	0.873	(0.441–1.729)	0.697
CRP (per 1 mg/L)	0.938	(0.806–1.090)	0.403

BMI: body mass index; MAP: mean arterial pressure; eGFR: estimated glomerular filtration rate; URBC: urine red blood cell; Hb: hemoglobin; Alb: albumin; ALT: alanine transaminase; Upro: urine protein; TG: triglyceride; TC: total cholesterol; CRP: c-reactive protein; 95% CI: 95% confidence interval; HR: hazard ratio

Proteinuria was divided into three grades, less than 4 g is grade 1, 4–8 g is grade 2, and greater than 8 g is grade 3.

p < 0.05 was considered statistically significant.

Table 3. Adverse events of rituximab during follow-up.

Events	Patients (n = 48)
Hypertension	0
Gastrointestinal pain	0
Nausea or vomiting	1
Carbuncle	1
Abnormal ALT/AST	4
Urinary tract infection	2
Pneumonia	2
Rash or pruritis	5
Influenza-like symptoms	1
Headache or dizziness	0
Angioedema	0
Leucopenia or neutropenia	0

ALT: alanine aminotransferase; AST: aspartate aminotransferase