Haemoperfusion Combined With Xuebijing Injection Improves Inflammatory Status And Prognosis In Patients With End-Stage Renal Disease

Summary

This study investigated the efficacy of haemoperfusion combined with Xuebijing in ESRD patients by analyzing inflammatory, immune, renal indices, and prognostic factors. This work further enriches clinical evidence for combination blood purification therapy and provides practical reference for optimizing comprehensive intervention in ESRD management.

Abstract

End-stage renal disease (ESRD) is an irreversible, chronic, progressive disease that seriously affects patients' quality of life, and clinical treatment currently faces certain challenges. A total of 100 ESRD patients from the Affiliated Hospital of North China University of Science and Technology were enrolled in this retrospective study and divided into HT and HI groups based on treatment modality. Both groups were treated with haemoperfusion, and the HI group was additionally treated with Xuebijing injection. The main assessments of the two groups were inflammatory factor indexes, immune indexes, renal function indexes, and clinical efficacy. Secondary outcomes included quality of life [Health Questionnaire (SF-36) score], complication and adverse reaction rates. Patient survival rates were calculated to analyze the correlation between microinflammatory status and prognosis. Logistic regression and receiver operating characteristic (ROC) analyses were conducted to further explore prognostic factors and predict complication risk. After treatment, the indicators in both groups differed significantly compared with the pre-treatment values (P < 0.05). Inflammatory indexes, renal function indexes, complication rates, and adverse reaction rates in the HI group were lower than those in the HT group, whereas immune indexes, clinical efficacy, SF-36 score, and survival rate were higher than those in the HT group (P < 0.05). Logistic regression analysis and ROC results showed that inflammatory indexes, immune indexes, and renal function indexes were closely associated with prognosis (P < 0.05). Combined therapy of haemoperfusion and Xuebijing shows favorable clinical efficacy in ESRD patients, improving renal function, alleviating the inflammatory response, regulating immune function, and contributing to favorable prognostic outcomes, and warrants further clinical exploration and validation.

Introduction

End-stage renal disease (ESRD), as the terminal stage of deterioration and progression of various chronic kidney diseases, is a serious threat to human health. The normal structure and function of the patient's kidneys are severely damaged, and they are unable to effectively perform key physiological functions such as excretion of metabolic wastes, regulation of water-electrolyte and acid-base balance¹. Pathological mechanisms involve multiple factors that drive disease progression. In ESRD caused by diabetic nephropathy, for example, a long-term hyperglycaemic environment leads to impaired renal microcirculation, thickening of the glomerular basement membrane, proliferation of resident cells, and production of large amounts of extracellular matrix, resulting in glomerulosclerosis, which in turn leads to the progressive loss of renal units. During the process of ESRD, the immune system is also abnormally activated, releasing a large number of inflammatory factors, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which persistently attack the renal intrinsic cells, accelerating renal fibrosis². Clinically, patients often suffer from a series of symptoms such as nausea, vomiting, loss of appetite, itchy skin, edema, anemia, etc., which seriously affect the quality of life, and are prone to fatal complications such as heart failure, respiratory failure, gastrointestinal bleeding, etc., which significantly increase the disability and mortality rate of the patients³.

Currently, the main treatments for ESRD include renal replacement therapy (dialysis therapy and renal transplantation) and drug therapy⁴. Dialysis treatment is divided into hemodialysis and peritoneal dialysis. Hemodialysis removes metabolic wastes and excess water from the blood through extracorporeal circulatory devices using the principle of a semipermeable membrane, corrects electrolyte and acid-base imbalances, and partially replaces renal excretory function, which can significantly alleviate uremic symptoms and prolong the patient's survival. However, long-term hemodialysis can cause many problems, such as hemodynamic instability during dialysis, which can easily lead to acute complications such as hypotension and arrhythmia. Peritoneal dialysis, on the other hand, uses the body's own peritoneum as a semi-permeable membrane and achieves the exchange of substances between blood and dialysis fluid by instilling dialysis fluid into the peritoneal cavity, which is relatively easy to operate, has little impact on hemodynamics, and can better protect residual renal function. However, peritoneal dialysis is prone to infectious complications such as peritonitis, and long-term peritoneal dialysis can also lead to peritoneal dysfunction, which affects the effectiveness of dialysis⁵. Kidney transplantation is an ideal treatment for ESRD, and successfully transplanted kidneys can maximize the restoration of renal physiological function and significantly improve patients' quality of life. However, renal transplantation faces a huge problem of donor shortage, and there is a serious imbalance between organ supply and demand, with many patients deteriorating or even dying while waiting for a suitable donor; at the same time, after renal transplantation, patients need to take immunosuppressant drugs over a long period of time in order to prevent the rejection of transplanted kidneys, which will increase the risk of infections, tumors, and other diseases⁶. Pharmacological treatments are mainly used to control the complications of ESRD patients, such as the use of erythropoietin to correct anemia, active vitamin D and its analogs to regulate calcium and phosphorus metabolism disorders, and antihypertensive drugs to control hypertension. However, these pharmacological treatments can only relieve some of the symptoms and slow down the progression of the disease, but cannot fundamentally reverse the failure of renal function⁷.

Haemoperfusion (HP) is a therapeutic technique to remove endogenous and exogenous poisons, drugs, and medium and large molecule toxins from the blood by adsorption through extracorporeal circulation, by introducing the patient's blood into a perfusion device equipped with solid adsorbents⁸. Its commonly used adsorbents are activated carbon and resin. Activated carbon has a strong adsorption capacity, which is effective in the adsorption of medium- and large-molecule toxins, such as creatinine, uric acid, parathyroid hormone, etc.; while resin adsorbent has selective adsorption characteristics, which can adsorb inflammatory mediators, cytokines, and other substances specifically⁹. In ESRD treatment, HP can effectively remove medium and large molecule toxins that are difficult to remove by conventional hemodialysis, reduce the damage of toxins to the various systems of the body, improve the clinical symptoms of patients, and reduce the risk of complications such as renal bone disease and peripheral neuropathy¹⁰.​

Xuebijing injection is a Chinese medicinal preparation extracted and refined from safflower, red peony, chuanxiong, danshen, angelica, and other blood-activating and stasis-removing Chinese medicines with multi-target pharmacological effects. Modern pharmacological studies have shown that Xuebijing can effectively antagonize endotoxin, inhibit the excessive release of inflammatory mediators, regulate the body's immune function, and attenuate the damage to tissues and organs caused by inflammatory reactions¹¹. In ESRD patients, a chronic microinflammatory state exists in the body. Xuebijing can reduce the damage of inflammation to the kidney and other organs by inhibiting the production and release of inflammatory factors, and also improve microcirculation and increase renal blood perfusion, which has a positive effect on the protection of residual renal function¹².​

In recent years, more and more studies have attempted to combine HP and Xuebijing in the treatment of ESRD. Clinical studies have shown that the combination of HP and Xuebijing can more comprehensively remove inflammatory mediators from the patient's body than a single treatment method. It is also more effective in relieving clinical symptoms, effectively reducing nausea, vomiting, skin itching, and other symptoms, and improving the quality of life of patients¹³. However, there are few reports on the effects of inflammatory indexes, immune indexes, and renal function indexes on the prognosis of patients after the combination of the two treatments. Therefore, the present study further analyzes the prognostic effects of the combination of HP and Xuebijing in the treatment of ESRD by comparing the related indices, with a view to providing a scientific basis for clinical improvement of patients' prognosis.

Protocol

This study strictly followed the ethical principles of the Declaration of Helsinki and received ethical approval from the Ethics Committee of the Affiliated Hospital of North China University of Science and Technology (Approval No.: SQ2024018). As a retrospective clinical investigation based on fully anonymized medical records, this trial was exempted from written informed consent by the authorized ethics committee.

This single-center retrospective study compared the clinical efficacy of haemoperfusion monotherapy versus combined Haemoperfusion (HP) and Xuebijing injection for ESRD. It also explored the relationships between inflammatory, immune, and renal function indicators and clinical prognosis. A total of 100 patients diagnosed with ESRD were enrolled from the Affiliated Hospital of North China University of Science and Technology between February 2018 and February 2019. Patients were divided into the HT and HI groups, with 50 cases in each group, according to the clinical treatment regimen formulated by attending physicians. All enrolled patients received HP treatment, while an additional Xuebijing injection intervention was administered to patients in the HI group. A total of 110 patient records were initially collected. After strict exclusion screening, 103 qualified cases were included. Three cases were lost to follow-up during the research period, and 100 cases were ultimately included in the final statistical analysis. Therapeutic differences between the two regimens were compared and analyzed to provide clinical evidence for optimizing treatment strategies and improving the long-term prognosis of ESRD patients. This study was a retrospective single-center investigation with a limited sample size. For this reason, multivariable regression and propensity adjustment were not performed, and baseline characteristic comparison was used to control potential confounding factors. The overall research workflow of the present study is presented in Figure 1. Detailed information on experimental materials and reagents was summarized in Table of materials. The raw experimental data are provided in Supplementary Table 1.

Inclusion and exclusion criteria

Inclusion criteria: (1) Conforming to the clinical diagnostic criteria for ESRD¹⁴(2) Age 30–75 years; (3) First-time admission for treatment; (4) Good treatment compliance and willingness to adhere to the study protocol; (5) Sufficient mental capacity to accurately report symptoms and respond to clinical inquiries; (6) Tolerance to the medications administered in this study.

Exclusion criteria: (1) Complicated with severe hypertension, hypotension, arrhythmia, anemia, or other concurrent disorders; (2) Continuous use of hormones, immunosuppressants, or other similar agents within the prior 3 months; (3) Presence of malignant tumors at any site; (4) Complicated with hemorrhagic disorders, severe cardiovascular diseases, or other life-threatening conditions; (5) Complicated with chronic infectious diseases; (6) Complicated with abnormal brain, cardiac, or hepatic function; (7) Previous or concurrent participation in other clinical trials or research studies; (8) Discontinuation of treatment or voluntary withdrawal from the study for personal reasons; (9) Other conditions deemed unsuitable for inclusion by the investigating clinicians; (10) Other factors that may interfere with the assessment of follow-up outcomes.

Interventions

All patients in both groups received routine HP intervention. The HA130 disposable perfusion device was adopted for HP treatment. The blood flow rate was set at 180–200 mL/min, and each haemoperfusion treatment lasted for 2 h. The intervention was performed twice a month for a continuous treatment course of 3 months. Additional Xuebijing injection was administered to patients in the HI group. A total of 100 mL of Xuebijing injection was mixed with 100 mL of normal saline, and intravenous infusion was performed twice daily for 7 consecutive days. This 7-day infusion cycle was repeated each month throughout the 3-month treatment period, corresponding to three treatment cycles in total.​

Conventional treatment was provided to patients in both groups throughout the treatment period. All patients received standard hemodialysis as routine renal replacement therapy at a frequency of three sessions per week, with each session lasting four hours. Haemoperfusion was combined with hemodialysis by conducting haemoperfusion immediately prior to hemodialysis on the same treatment day. This arrangement achieved coordinated implementation of the two therapeutic modalities. Additional routine supportive care included standardized administration guidance for iron preparations and erythropoietin. All patients were educated on a low-salt, low-phosphorus, and low-sugar dietary regimen. They were also recommended to ingest adequate high-quality protein. Routine management of blood pressure blood glucose and electrolyte homeostasis was also performed to sustain stable clinical conditions throughout the study.

Observation indicators

Outcome indicators were selected based on clinical relevance, with unified and standardized reporting throughout the research. Multiple laboratory and clinical indicators were detected and recorded comprehensively before and after treatment for comparative analysis.

Main indicators

Inflammation indicators

Fasting peripheral venous blood samples (3 mL) were collected from all patients before and after intervention. Collected samples were centrifuged and stored under refrigeration for unified laboratory testing. Enzyme-linked immunosorbent assay was used to detect and calculate serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) in patients¹⁵.

Immunological indicators

Serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM were detected using a fully automated biochemistry analyser¹⁶. These three immunoglobulins were selected as core immune markers, as classic and clinically accessible indicators for evaluating humoral immune status in ESRD populations. Dynamic changes of the above indices reflected systemic immune activation and immune fluctuation caused by clinical intervention.

Renal function indicators

Serum creatinine, urea nitrogen, and β2-microglobulin levels were measured with a fully automated biochemical analyzer to evaluate the improvement of renal function after treatment¹⁷.

Clinical efficacy

Overall clinical efficacy was evaluated independently by combining clinical symptom relief, complication control, and quality-of-life changes to avoid circular reasoning with laboratory index results. The evaluation criteria were defined as follows. The obvious effect meant that clinical symptoms, including dialysis-related pruritus, fatigue, and nausea, were significantly relieved or completely disappeared, no treatment-related complications occurred during the treatment period, and the patient’s quality of life was significantly improved. Effective meant that clinical symptoms were moderately relieved, no severe treatment-related complications occurred, and the patient’s quality of life was slightly improved. Ineffective meant that clinical symptoms showed no obvious relief or even aggravated, treatment-related complications occurred that required additional intervention, and the patient’s quality of life did not improve or deteriorated.

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Secondary indicators

Quality of life

The Health Status Questionnaire (36-item Short Form Health Survey, SF-36) was adopted to assess the overall quality of life of patients in both groups. Multiple dimensions were covered, including physiological function, physical activity, somatic pain, general health status, social interaction, emotional regulation, and mental health. The total score of the scale was 100 points, and higher scores represented a better quality of life¹⁸.

Complications

The incidence of clinical complications in the two groups was recorded and summarized during the treatment period. Main observation contents included shock, hypocalcemia, acidosis, venous thrombosis, abnormal liver function, coagulation of perfusion lines, heart failure, pulmonary infection, phlebitis, and so on.

Adverse reaction incidence

All adverse reactions related to treatment were recorded and counted in the two groups. Common monitoring contents included rash, fever, nausea, vomiting, local pain, hypotension, dizziness, palpitation, and so on.

Follow-up visits

A long-term follow-up plan was formulated to observe the sustained effect of treatment and potential long-term adverse events. The overall follow-up duration was 84 months. Three cases were lost to follow-up in the cohort, with an overall follow-up rate of 97.56%. Core prognostic endpoints were uniformly observed during follow-up, including overall survival (OS) and progression-free survival (PFS). The OS was defined as the time from the initiation of intervention to all-cause death of patients. The PFS was defined as the time from the initiation of intervention to the occurrence of renal function deterioration, persistent dialysis dependence, renal disease-related death, or all-cause death. The primary prognostic endpoint in this study was a composite of major adverse renal events, defined as the occurrence of all-cause death, unplanned hospital readmission, disease progression (renal function progression or worsening renal function), or initiation of long-term dialysis during follow-up. Patients who experienced any event were coded as 1, and those without events were coded as 0.

Sample size calculation

Power analysis was performed via G*Power 3.1.9.7 software to estimate the required sample size. Considering the inherent limitations of retrospective observational research, the sample size calculation was only used for auxiliary reference based on the primary clinical efficacy outcome. The test α value was set at 0.05, and the statistical test power was set at 85%. No independent sample size estimation was conducted for multiple secondary endpoints. The final enrolled sample size of 50 patients in each group was determined according to the actual available clinical data within the study period.

Statistical methods

All statistical methods were applied in strict accordance with the retrospective study design. All raw data in the present study were analyzed using SPSS 28.0 statistical software, and the research flow chart was drawn with Lucidchart. The normal distribution test was completed for all quantitative data. Baseline demographic and clinical data were summarized with enumeration data and measurement data, and continuous variables were expressed as mean ± SD. Inflammatory indexes, immune indexes, renal function indexes, and quality of life scores were presented as mean ± SD. An independent sample t-test was applied for inter-group comparison of continuous indicators. The constituent ratios of clinical efficacy, complications, and adverse reactions were expressed as percentages. Kaplan-Meier survival curves were plotted, and the Log-Rank test was used for survival difference comparison. Logistic regression analysis was used to explore the correlation between laboratory indicators and long-term prognosis. ROC curves and AUC values were constructed to evaluate the predictive value of index changes after treatment. The methodological details of logistic regression and ROC curve analysis were fully clarified in the present study. The chi-square test was used for inter-group comparison of counting data. All statistical tests were two-sided. Effect sizes, including Cohen’s d and Cohen’s V, together with 95% confidence intervals, were reported for all comparative analyses. A P-value less than 0.05 was regarded as statistically significant.

Results

This study enrolled 100 patients with end-stage renal disease (ESRD) treated between February 2018 and February 2019. All participants were assigned to either the HT group or the HI group according to different treatment strategies, so as to compare and evaluate the clinical effects of the two interventions. Baseline demographic and clinical characteristics of the two groups are summarized in Table 1. Statistical analyses were performed using an independent samples t-test for continuous variables and a c...

Discussion

ESRD is a serious threat to human health as the end stage of various chronic kidney diseases that are prolonged and progressively deteriorating¹⁹. As renal disease progresses to ESRD, the glomerular filtration rate drops markedly, severely impairing key renal functions, including waste excretion, fluid, electrolyte, and acid-base balance. This leads to substantial toxin accumulation, triggering severe complications and symptoms that significantly reduce quality of life and threaten patient surviva...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Blood Glucose Meter	Johnson & Johnson	OneTouch Verio	Monitoring blood glucose levels during treatment
Blood Pressure Monitor	Omron Healthcare	Model HEM-7301IT	Monitoring vital signs during treatment
Fully automated biochemistry analyser	Beckman Coulter K.K.	AU5800	For automatic detection of renal function, inflammatory and immune parameters
Haemoperfusion	Jianfan Biotechnology Group Co. Ltd	HA130	Therapeutic apheresis for toxin and inflammatory factor clearance
Human TNF-α ELISA kit	Shanghai Enzyme-linked Biotechnology Co., Ltd.	ml077385	For enzyme-linked immunosorbent assay of human serum TNF-α concentration
Human IL-6 ELISA kit	Shanghai Enzyme-linked Biotechnology Co., Ltd.	ml027379	For enzyme-linked immunosorbent assay of human serum IL-6 levels
Human hs-CRP ELISA kit	Shanghai Enzyme-linked Biotechnology Co., Ltd.	ml106583	For enzyme-linked immunosorbent assay of human serum hs-CRP levels
SPSS Software	IBM Corporation	Version 28.0	RRID: SCR_002865 / Data statistical analysis
xuebijing injection	Tianjin Hongri Pharmaceutical Co., Ltd.	Z20040033	Traditional Chinese medicine injection for anti-inflammation