Efficacy of Rituximab Combined with Glucocorticoid for Nephrotic Syndrome and the Impact on Renal Function, Coagulation Function, and Inflammatory Response

By Si Shi¹, Jie Zeng², Yang Liu¹, Bingquan Li²

Affiliations

1. Department of Nephrology, Jingmen Central Hospital, Jingmen, China
2. Department of Nephrology, Xianyang Central Hospital, Xianyang, China

doi: 10.29271/jcpsp.2025.07.871

ABSTRACT
Objective: To explore the efficacy of rituximab combined with glucocorticoid for nephrotic syndrome and the impact on renal function, coagulation function, and inflammatory response.
Study Design: Observational study.
Place and Duration of the Study: Department of Nephrology, Xianyang Central Hospital, Xianyang, China, from February 2021 to 2023.
Methodology: Sixty patients with nephrotic syndrome were divided into the control group and the observation group, which received glucocorticoid prednisone and rituximab combined with prednisone for treatment for six months, respectively.
Results: At the end of the treatment, the total effective rate and the serum albumin level remarkably increased, while the serum creatinine, 24-hour urine protein levels and the serum fibrinogen, D-dimer, C-reactive protein, interleukin, and tumour necrosis factor α levels were remarkably decreased (p <0.05) in the observation group as compared to the control group.
Conclusion: Rituximab combined with glucocorticoid effectively enhances the patient's renal and coagulation functions, while decreasing the inflammatory response in nephrotic syndrome.

Key Words: Rituximab, Glucocorticoid, Nephrotic syndrome, Coagulation, Inflammatory response.

INTRODUCTION

Nephrotic syndrome, which is one of the common kidney diseases, caused by increased glomerular basement membrane permeability due to various reasons.^1,2 In clinic, symptomatic treatments such as diuresis and antihypertensive therapy are often given for nephrotic syndrome, and glucocorticoids are added as adjunctive treatment medicines.^3,4 However, some patients do not see any improvement in their condition after the long-term use of glucocorticoids, and hormone dependence or resistance may also develop with poor prognosis.^5,6

Rituximab is a therapeutic agent which can specifically bind to the human B cell surface antigen CD20. It has obvious cytotoxic effects.^7,8 The present study explored the treatment efficacy of rituximab combined with glucocorticoid for nephrotic syndrome and the impact on renal function, coagulation function, and inflammatory response of patients.
 

METHODOLOGY

This study retrospectively reviewed sixty patients with neph-rotic syndrome in Xianyang Central Hospital, Xianyang, China, between February 2021 and 2023. According to the treatment method, the patients were divided into the control group (30 cases) and the observation group (30 cases). Inclusion criteria were primary nephrotic syndrome, aged >18 years, not using immunosuppressive agents in the past three months, and no contraindication to the studied medicines. Exclusion criteria were severe organic disorders, concomitant infectious diseases, secondary nephrotic syndrome, consciousness disorders, mental illness, or malignant tumours, and pregnant and lactating women.

All patients were given symptomatic treatments such as diuresis, electrolyte balance regulation, blood pressure reducing and others. In addition, glucocorticoid prednisone (1 mg/kg) was used in the control group, once per day, for six months. In the observation group, the patients used prednisone (the same dose as given in the control group) with addition to rituximab therapy. In the first week of admission, the rituximab was intravenously injected at a dosage of 500 mg per time, two times. After two weeks of withdrawal, the intravenous injection was performed again, and the dosage was the same as the first week. The treatment was performed for six months, and the total dosage of rituximab was 6g. There was no serious adverse reaction in each group.

After six months, the total efficacy of the treatment was evaluated. Before and after treatment, the blood and urine samples of patients were taken. The renal function indicators, coagulation indicators, and inflammatory factors were detected.

SPSS statistics software was adopted for statistical analysis. The qualitative data (frequencies or percentages) were compared using the Chi-square test. The measurement data conformed to normal distribution by Kolmogorov-Smirnov test. They were expressed as mean ± standard deviation, with a comparison between two groups using an independent samples t-test and comparison between before and after treatment using the paired sample t-test. When the p-value was less than 0.05, the difference was statistically significant.

RESULTS

The control group contained 24 males and 6 females. The age ranged from 23-77 years (45.23 ± 6.12 years). The disease course was 1-7 years (5.03 ± 1.03 years). The observation group contained 20 males and 10 females. The age ranged from 22-74 years (47.27 ± 7.15 years). The disease course was 2-8 years (5.45 ± 1.14 years). The basic data had no significant difference between these two groups (p >0.05). After treatment, the total effective rate in the observation group was 96.66%, which was obviously higher than 80.00% in the control group (p <0.05; Table I).

After treatment in both groups, the serum creatinine and 24-hour urine protein significantly decreased, and the serum albumin level was significantly increased (all p <0.05), and each index had a significant difference between the groups (all p <0.05, Table II). After treatment, the coagulation indicators including fibrinogen and D-dimer in both groups were remarkably decreased compared to before treatment, and those in the observation group were further decreased compared to the control group (p <0.05, Table II). After treatment, each inflammatory factor was obviously decreased in both groups, and each index in the observation group was significantly lower than the control group (p <0.05, Table II).

Table I: Total treatment efficacy.
 

Groups	n	Remarkably effective (n)	Effective (n)	Ineffective (n)	Overall effective rate (%)
Control	30	7	17	6	80.00
Observation	30	10	19	1	96.66
χ2					4.043
p					0.044
The p-values were determined by the Chi-square test.

Table II: Renal function, coagulation, and inflammatory factors.

Parameters	Group	n	Before treatment	After treatment	tb	pb
Serum creatinine (μmol/L)	Control	30	121.04 ± 23.15	88.06 ± 21.32	7.232	<0.001
	Observation	30	118.09 ± 20.72	66.87 ± 18.20	9.894	<0.001
	ta		0.520	4.140
	pa		0.605	<0.001
Serum albumin (g/L)	Control	30	18.75 ± 3.73	26.41 ± 5.28	7.046	<0.001
	Observation	30	20.06 ± 4.48	34.95 ± 8.70	7.731	<0.001
	ta		1.240	4.594
	pa		0.220	<0.001
24-hour urine protein (g)	Control	30	6.55 ± 1.39	3.57 ± 0.72	11.760	<0.001
	Observation	30	6.13 ± 1.49	2.12 ± 0.41	14.124	<0.001
	ta		1.132	9.727
	pa		0.262	<0.001
Fibrinogen (g/L)	Control	30	5.27 ± 1.03	3.63 ± 0.48	7.350	<0.001
	Observation	30	6.03 ± 2.10	2.05 ± 0.30	10.126	<0.001
	ta		1.774	15.424
	pa		0.081	<0.001
D-dimer (mg/L)	Control	30	2.52 ± 0.25	2.01 ± 0.32	7.984	<0.001
	Observation	30	2.63 ± 0.42	1.19 ± 0.17	16.769	<0.001
	ta		1.225	12.175
	pa		0.225	<0.001
C-reactive protein (mg/L)	Control	30	27.55 ± 4.83	19.34 ± 1.28	8.858	<0.001
	Observation	30	28.32 ± 3.71	12.06 ± 2.32	18.399	<0.001
	ta		0.685	15.034
	pa		0.496	<0.001
Interleukin 6 (ng/L)	Control	30	193.78 ± 27.30	168.36 ± 31.01	3.342	0.002
	Observation	30	201.25 ± 32.77	120.82 ± 23.55	9.907	<0.001
	ta		0.959	6.687
	pa		0.341	<0.001
Tumour necrosis factor α (pg/L)	Control	30	125.72 ± 17.43	95.97 ± 15.63	7.138	<0.001
	Observation	30	130.10 ± 18.29	64.37 ± 11.24	15.241	<0.001
	ta		0.952	8.987
	pa		0.345	<0.001
aThe p-values were determined by independent sample t-test; bThe t and p-values were determined by paired sample t-test.

DISCUSSION

The present study explored the efficacy of rituximab combined with glucocorticoid prednisone for nephrotic syndrome. Results showed that the total effective rate was significantly increased, the serum creatinine and 24-hour UP levels were significantly decreased, and the serum albumin level was significantly increased in the observation group as compared to the control group. In addition, there was no serious adverse reaction in two groups. This indicates that compared with glucocorticoid, rituximab combined with glucocorticoid can further enhance the treatment efficacy of patients with nephrotic syndrome, but does not increase the adverse reactions.

The blood of patients with nephrotic syndrome is often in a hypercoagulable state. In this disease, hypoalbuminaemia can cause the synthesis and loss of fibrinogen, accelerate the formation of blood coagulation factors, and reduce the plasma colloid osmotic pressure. This causes insufficient effective blood volume, leading to blood concentration and thrombosis.^9,10 It was found that after the onset of nephrotic syndrome, the concentration of coagulation factors XI and IX in the body will significantly decrease, while the concen-tration of fibrinogen and β-thromboglobulin will increase. The antithrombin activity decreases, and the blood viscosity increases.^11,12 In this study, the fibrinogen and D-dimer levels after treatment were obviously decreased in the observation group compared to the control group. This suggests that rituximab combined with glucocorticoid can optimise the coagulation function of nephrotic syndrome patients, thus enhancing the treatment efficacy.

Research has shown that patients with nephrotic syndrome have a certain level of micro-inflammation in their bodies.^13,14 CRP, IL-6, and TNF-α are commonly used clinical indicators for measuring the inflammatory response, which can accu-rately represent the physical condition and improvement after treatment of patients with nephrotic syndrome.^15,16 CRP is a non-specific biomarker of inflammation and tissue damage, which rapidly increases after the body is exposed to inflammatory stimuli such as infection and tissue damage.^17,18 IL-6 is a chemotactic factor that can react with inflammatory factors in the body during immune regulation. When the body experiences an inflammatory response, the level of IL-6 will significantly increase and be distributed around the kidney tissue, exacerbating renal function damage.¹⁹ As an important inflammatory mediator, TNF-α is closely related to the occurrence of kidney diseases and can enhance the inflammatory response.²⁰ In the present study, the serum CRP, IL-6, and TNF-α levels after treatment were obviously decreased in the observation group compared to the control group. This indicates that, compared to glucocorticoid, rituximab combined with glucocorticoid can further reduce the inflammatory response in nephrotic syndrome patients, which may be related to its enhanced treatment efficacy.

This study has some limitations. Firstly, the sample size of this study was relatively small, which may affect the results. Secondly, the patients were followed for only six months. In the future research, a bigger sample-size trial involving a prolonged follow-up is required to obtain better results.

CONCLUSION

Rituximab combined with glucocorticoid has good efficacy for nephrotic syndrome. It effectively enhances the patient's renal function and coagulation function and decreases the inflammatory response. This treatment strategy is safe and is worth further clinical application.

ETHICAL  APPROVAL:
The study has been approved by the Ethics Committee of Xianyang Central Hospital.

PATIENTS’ CONSENT:
Written consent was obtained from all the patients.

COMPETING INTEREST:
The authors declared no conflict of interest.

AUTHORS’ CONTRIBUTION:
SS: Designed the study, completed the experiment, and wrote the article.
JZ: Revised the article and optimised the language.
YL, BL: Directed the conception of the work and did the analysis.
All authors approved the final version of the manuscript to be published.

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