Abstract
Objective: To evaluate the effects of combined hemodialysis (HD) and hemoperfusion (HP) on serum parathyroid hormone (PTH), phosphorus (P), and calcium (Ca) levels in patients with chronic glomerulonephritis (CGN). Methods: A retrospective analysis was conducted on 118 CGN patients treated between May 2022 and May 2024. Based on therapeutic regimen, participants were divided into the HP group (n=52) and HD+HP group (n=66). Clinical efficacy, bone metabolism indices (PTH, P, Ca), renal function parameters (24 h urinary protein (24 h Upro), blood urea nitrogen [BUN], serum creatinine [SCr], estimated glomerular filtration rate [eGFR]), inflammatory markers (IL-17, TNF-α, hs-CRP), hemorheology, coagulation/fibrinolysis indices (tissue-type plasminogen activator [t-PA]), serum uremic toxins, adverse events, and 36-Item Short Form Health Survey (SF-36) quality-of-life scores were compared. Logistic regression was applied to identify factors associated with poor therapeutic response. Results: The HD+HP group showed a higher total effective rate than the HP group (89.39% vs. 73.08%, P=0.021). Compared with HP alone, HD+HP significantly reduced PTH, P, 24 h Upro, BUN, SCr, inflammatory markers, and uremic toxins, while increasing Ca, eGFR, t-PA, and SF-36 scores (all P<0.05). The incidence of adverse events was comparable between groups (30.30% vs. 26.92%, P=0.687). Multivariate analysis identified disease duration >5 years (OR=4.930, 95% CI: 1.339-18.147, P=0.016) and HP monotherapy (OR=3.069, 95% CI: 1.103-8.539, P=0.032) as independent predictors of poor efficacy. Conclusion: Combined HD and HP therapy yields superior therapeutic and biochemical outcomes compared with HP alone in CGN patients.
Keywords: Chronic glomerulonephritis, hemodialysis, hemoperfusion, parathyroid hormone, phosphorus, calcium
Introduction
Chronic glomerulonephritis (CGN) is a glomerular disease primarily characterized by proteinuria, hematuria, hypertension, and edema, often progressing to end-stage renal disease (ESRD) [1]. It represents a major cause of chronic kidney disease (CKD), with nearly seven million global cases and a 10.81% increase in prevalence reported in 2021 [2]. CGN progresses insidiously, presenting with hematuria, proteinuria, hypertension, edema, nocturia, fatigue, and anemia; in advanced stages, oliguria, nausea, muscle cramps, and metabolic acidosis may develop, severely compromising patients’ health and quality of life [3,4]. Pathological subtypes include membranous nephropathy, mesangial proliferative glomerulonephritis, and IgA nephropathy, arising from the interaction of immune, genetic, and environmental factors [5].
Chronic inflammation is central to CGN pathogenesis, with elevated interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) playing key roles [6-8]. Progressive renal impairment leads to mineral metabolism disorders such as hyperphosphatemia and hypocalcemia, accompanied by decreased 24-hour urinary protein (24 h Upro), blood urea nitrogen (BUN), serum creatinine (SCr), and estimated glomerular filtration rate (eGFR) [9]. Parathyroid hormone (PTH) contributes to mineral dysregulation and bone abnormalities by promoting calcium release and phosphate excretion [10,11]. CGN also involves increased blood viscosity and coagulation-fibrinolytic imbalance, reflected by elevated plasminogen activator inhibitor-1 (PAI-1) and reduced tissue-type plasminogen activator (t-PA) [12,13].
A range of therapeutic modalities is available for CGN, including symptomatic treatment, immunosuppression, and renal replacement therapy such as hemodialysis (HD) and hemoperfusion (HP) [14-17]. However, these treatments are often limited by steroid resistance, significant drug toxicities (e.g., hypotension, circuit clotting, thrombocytopenia), low bioavailability, and inadequate targeting precision [14]. Notably, few studies have explored the impact of treatment regimens on patients’ serum parathyroid hormone (PTH), phosphorus (P), and calcium (Ca) levels [15]. Specifically, HD eliminates toxins, solutes, and excess fluid via a synthetic filter to restore homeostasis, while HP achieves blood purification through adsorption by binding target molecules to adsorbent materials [16,17]. To address these research gaps, this study focuses on investigating how the HD-HP combination therapy influences serum PTH, P, and Ca concentrations in CGN patients, aiming to provide data-driven insights for optimizing clinical management of the disease.
Materials and methods
Patient selection
Ethical approval for this retrospective study was obtained from the Ethics Committee of Shanxi Provincial People’s Hospital. All patient data were anonymized before analysis. A total of 118 CGN patients admitted between May 2022 and May 2024 were enrolled. Based on treatment modality, patients were divided into the HP group (n=52) and the HD+HP group (n=66). Baseline demographic and clinical characteristics did not differ significantly between groups (P>0.05), confirming comparability (Figure 1).
Figure 1.
Flowchart of patient selection. HD, hemodialysis; HP, hemoperfusion.
Inclusion criteria: (1) Confirmed CGN diagnosis [18]; (2) Age 18-80 years; (3) No prior treatment; (4) Absence of contraindications; (5) Hemodynamic stability and intact neurological function; (6) Complete medical records.
Exclusion criteria: (1) Hyperthyroidism or advanced renal dysfunction; (2) Malignancy; (3) Hematologic or autoimmune disease; (4) Pregnancy or lactation; (5) Secondary nephropathies; (6) Severe cardiopulmonary or renal impairment; (7) Active severe infection; (8) Multiple myeloma.
Therapeutic protocols
All patients received a standardized pharmacotherapy regimen including oral Vitamin D2 Calcium Hydrogen Phosphate Tablets (0.15 g, twice daily; Renqi Pharmaceutical, Jiangxi, China, H36022014) and Lanthanum Carbonate Chewable Tablets (0.5 g, once daily; Mingrui Pharmaceutical, Hunan, China, H20203039).
Sample size was calculated for comparison of two independent proportions, assuming 60% and 85% response rates for the HP and HD+HP groups, respectively (α=0.05, 1-β=0.8, δ=25%), yielding 49 cases per group. The final cohort (52 HP, 66 HD+HP) satisfied this criterion.
The HP group underwent 2-hour HP sessions using bicarbonate dialysate at 500 mL/min. The HD+HP group additionally received HD with sodium bicarbonate dialysate (Na+ 140 mmol/L, Cl- 140 mmol/L, K+ 2.0 mmol/L, Ca2+ 1.5 mmol/L), with dialysate and blood flow rates of 500 mL/min and 200-250 mL/min, respectively. Each 4-hour session was conducted 1-2 times weekly for six 14-day cycles.
Treatment allocation was not randomized but based on each patient’s clinical condition, financial status, and personal preference after full discussion with the patient and family. Written informed consent was obtained from all participants.
Data extraction
Data were retrieved from hospital electronic records. Baseline variables included sex, age, disease duration, diagnostic type, and family history. Clinical outcomes, biochemical parameters, inflammatory markers, hemorheology, coagulation/fibrinolysis indicators, adverse events, and quality-of-life scores were analyzed.
Outcome measures
Therapeutic effectiveness [19]: Outcomes were classified after 3 months as clinical control, marked effectiveness, effectiveness, or ineffectiveness. Total efficacy combined the first three categories.
Bone metabolism: Serum PTH, P, and Ca were measured pre- and post-treatment (3 months) using an automated biochemical analyzer (Tianlong, Xi’an, China, ZY-400).
Renal function: 24 h Upro, BUN, SCr, and eGFR (Cockcroft-Gault) were assessed before and 3 months after treatment.
Inflammatory biomarkers: IL-17, TNF-α, and hs-CRP were quantified via ELISA (Abbkine, Wuhan, KTE6022, KTE6032; Yipu, Wuhan, CSB-E08617h).
Hemorheology: Whole blood viscosity (WBV) under high- and low-shear conditions was measured (Jumu, Shanghai, b3513).
Coagulation/fibrinolysis: Serum PAI-1 and t-PA were determined via ELISA (Baiyixin, Wuhan, TD711259, TD711260).
Uremic toxins: Serum β2-microglobulin (β2-MG), homocysteine (Hcy), and advanced glycation end-products (AGEs) were analyzed by ELISA (Yipu, Wuhan, E-EL-H2188, CSB-E08895h, CSB-E09412h).
Adverse events: Hypotension, circuit clotting, thrombocytopenia, puncture-site oozing, and pruritus were recorded.
Quality of life: 36-Item Short Form Health Survey (SF-36) [20] (Physical Functioning, Bodily Pain, Social Functioning, Role-Emotional, Mental Health) were assessed pre- and post-treatment (0-100 scale).
Primary endpoints included treatment efficacy, bone metabolism, renal function, and adverse events; secondary endpoints encompassed inflammatory, hemorheological, and coagulation markers, uremic toxins, and quality-of-life outcomes.
Statistical analysis
Statistical analysis was performed using SPSS v20.0. Categorical data were expressed as n (%) and compared using χ2 tests. Continuous data were expressed as mean ± standard error of the mean (SEM) and were analyzed using independent-samples and paired t-tests where appropriate. Variables significant at P<0.05 in univariate analysis were entered into stepwise multivariate logistic regression to identify independent predictors of treatment response. Statistical significance was set at P<0.05.
Results
Baseline patient demographics
Baseline characteristics of enrolled participants are summarized in Table 1. Age, sex, disease duration, diagnostic subtype, and family history were comparable between the two groups (P>0.05), confirming baseline homogeneity.
Table 1.
Comparison of baseline characteristics
| Indicators | HP group (n=52) | HD+HP group (n=66) | χ2/t | P |
|---|---|---|---|---|
| Sex | 0.008 | 0.930 | ||
| Male | 28 (53.85) | 35 (53.03) | ||
| Female | 24 (46.15) | 31 (46.97) | ||
| Age (years) | 45.63±7.01 | 44.39±6.82 | 0.969 | 0.335 |
| Illness duration (years) | 5.60±2.35 | 5.32±2.11 | 0.681 | 0.498 |
| Diagnostic category | 0.833 | 0.659 | ||
| Membranous nephropathy | 28 (53.85) | 30 (45.45) | ||
| Mesangial proliferative glomerulonephritis | 17 (32.69) | 26 (36.39) | ||
| Immunoglobulin A nephropathy | 7 (13.46) | 10 (15.15) | ||
| Family medical history | 0.324 | 0.569 | ||
| No | 46 (88.46) | 56 (84.85) | ||
| Yes | 6 (11.54) | 10 (15.15) |
Therapeutic effectiveness
As shown in Table 2, the overall treatment effectiveness was significantly higher in the HD+HP group compared with the HP group (P<0.05).
Table 2.
Therapeutic effectiveness assessment
| Indicators | HP group (n=52) | HD+HP group (n=66) | χ2 | P |
|---|---|---|---|---|
| Clinical control | 8 (15.38) | 17 (25.76) | ||
| Marked effectiveness | 20 (38.46) | 29 (43.94) | ||
| Effectiveness | 10 (19.23) | 13 (19.70) | ||
| Ineffectiveness | 14 (26.92) | 7 (10.61) | ||
| Overall effectiveness | 38 (73.08) | 59 (89.39) | 5.293 | 0.021 |
Bone metabolic parameters
Changes in bone metabolism markers (PTH, P, and Ca) are illustrated in Figure 2. Baseline values were comparable between groups (all P>0.05). After treatment, both groups demonstrated significant reductions in PTH and P, alongside an increase in Ca (all P<0.05). The HD+HP regimen achieved greater PTH and P reductions and more pronounced Ca elevation than HP alone (all P<0.05).
Figure 2.
Bone metabolism marker profiles. A. Pre- and post-treatment assessment of parathyroid hormone (PTH). B. Phosphorus (P) levels pre- and post-treatment. C. Calcium (Ca) concentrations measured at baseline and study conclusion. Note: *P<0.05, **P<0.01 denote intragroup differences from pre-treatment; #P<0.05 indicates a significant difference compared to the HP group at the identical time point.
Renal function assessment
Renal function indices, including 24 h Upro, BUN, SCr, and eGFR, are shown in Figure 3. Baseline parameters did not differ significantly (all P>0.05). Following therapy, both groups exhibited significant improvements in all indices (all P<0.05), with the HD+HP group showing superior improvement compared to HP monotherapy (all P<0.05).
Figure 3.
Renal function indicators. A. 24-hour urinary protein (24 h Upro) pre- and post-treatment. B. Blood urea nitrogen (BUN) variations before and after intervention. C. Serum creatinine (SCr) measurements prior to and following treatment. D. Estimated glomerular filtration rate (eGFR) values across both groups. Note: *P<0.05, **P<0.01 for within-group comparisons to pre-treatment; #P<0.05 for between-group comparisons to the HP group at the identical time point.
Inflammatory biomarker levels
As presented in Table 3, pretreatment serum levels of IL-17, TNF-α, and hs-CRP were similar between groups (all P>0.05). Post-treatment, all markers decreased significantly (all P<0.05), with the HD+HP group demonstrating greater reductions than the HP group (all P<0.05).
Table 3.
Inflammatory biomarker concentrations
| Indicators | HP group (n=52) | HD+HP group (n=66) | t | P |
|---|---|---|---|---|
| IL-17 (ng/L) | ||||
| Before | 12.60±3.69 | 12.83±4.12 | 0.315 | 0.753 |
| After | 8.23±2.60* | 5.14±1.84** | 7.552 | <0.001 |
| TNF-α (ng/L) | ||||
| Before | 38.19±9.13 | 38.67±6.98 | 0.324 | 0.747 |
| After | 25.31±6.06* | 20.08±3.70** | 4.279 | <0.001 |
| hs-CRP (mg/L) | ||||
| Before | 5.15±1.69 | 5.83±2.15 | 1.870 | 0.064 |
| After | 3.98±1.26* | 2.42±1.13** | 7.076 | <0.001 |
Note: IL-17, interleukin-17; TNF-α, tumor necrosis factor-alpha; hs-CRP, high-sensitivity C-reactive protein.
P<0.05 for within-group comparisons to pre-treatment;
P<0.01 for within-group comparisons to pre-treatment.
Hemorheological parameters
WBV values at high and low shear rates are presented in Table 4. No baseline difference was noted (P>0.05). After treatment, viscosity reduced significantly in both groups, with the HD+HP therapy yielding markedly lower post-treatment WBV compared to HP alone (P<0.05).
Table 4.
Hemorheological parameters
| Indicators | HP group (n=52) | HD+HP group (n=66) | t | P |
|---|---|---|---|---|
| Whole blood viscosity at high shear rate (mPa·s) | ||||
| Before | 4.99±1.44 | 5.10±1.06 | 0.478 | 0.634 |
| After | 4.18±1.38* | 3.73±1.07** | 1.996 | 0.048 |
| Whole blood viscosity at low shear rate (mPa·s) | ||||
| Before | 9.86±2.36 | 9.75±2.53 | 0.241 | 0.810 |
| After | 7.96±1.62* | 6.29±1.41** | 5.981 | <0.001 |
P<0.05 denote intragroup differences from pre-treatment;
P<0.01 denote intragroup differences from pre-treatment.
Coagulation/fibrinolysis markers
As shown in Table 5, baseline levels of PAI-1 and t-PA did not differ significantly (both P>0.05). Post-treatment, PAI-1 levels decreased while t-PA increased in both groups (both P<0.05), with more favorable changes observed in the HD+HP group (both P<0.05).
Table 5.
Coagulation/fibrinolytic system indicators
| Indicators | HP group (n=52) | HD+HP group (n=66) | t | P |
|---|---|---|---|---|
| PAI-1 (μmol/L) | ||||
| Before | 39.75±3.87 | 39.97±4.44 | 0.283 | 0.778 |
| After | 35.33±4.36* | 24.47±3.77** | 14.497 | <0.001 |
| t-PA (μmol/L) | ||||
| Before | 3.02±1.04 | 3.15±1.00 | 0.689 | 0.492 |
| After | 4.67±2.00* | 5.99±1.52** | 4.074 | <0.001 |
Note: PAI-1, Plasminogen Activator Inhibitor-1; t-PA, tissue Plasminogen Activator.
P<0.05 denote intragroup differences from pre-treatment;
P<0.01 denote intragroup differences from pre-treatment.
Serum uremic toxins
Table 6 details β2-MG, Hcy, and AGEs. Baseline levels were comparable (all P>0.05). After therapy, all markers decreased significantly in both groups (all P<0.05), with HD+HP treatment achieving more pronounced reductions than HP alone (all P<0.05).
Table 6.
Assessment of serum uremic toxin parameters
| Indices | HP group (n=52) | HD+HP group (n=66) | χ2/t | P |
|---|---|---|---|---|
| β2-MG (mg/L) | ||||
| Before | 44.67±8.30 | 43.85±11.15 | 0.442 | 0.659 |
| After | 34.56±8.41 | 23.97±7.08 | 7.424 | <0.001 |
| Hcy (μmol/L) | ||||
| Before | 21.40±6.09 | 22.00±6.71 | 0.502 | 0.617 |
| After | 12.38±3.57 | 9.55±2.51 | 5.050 | <0.001 |
| AGEs (U/mL) | ||||
| Before | 3.82±1.13 | 3.97±0.87 | 0.815 | 0.417 |
| After | 3.25±1.29 | 2.84±0.88 | 2.048 | 0.043 |
Note: β2-MG, β2-microglobulin; Hcy, homocysteine; AGEs, advanced glycation end-products.
Adverse events
Adverse reactions - including hypotension, circuit clotting, thrombocytopenia, puncture-site oozing, and pruritus - are summarized in Table 7. The total incidence of adverse events was similar between groups (P>0.05), indicating comparable safety profiles.
Table 7.
Recorded adverse reactions
| Indicators | HP group (n=52) | HD+HP group (n=66) | χ2 | P |
|---|---|---|---|---|
| Hypotension | 4 (7.69) | 8 (12.12) | ||
| Perfuser/circuit clotting | 5 (9.62) | 8 (12.12) | ||
| Thrombocytopenia | 6 (11.54) | 10 (15.15) | ||
| Puncture site oozing | 3 (5.77) | 5 (7.58) | ||
| Pruritus | 3 (5.77) | 4 (6.06) | ||
| Total | 14 (26.92) | 20 (30.30) | 0.162 | 0.687 |
Quality of life evaluation
Quality of life, assessed via the SF-36 questionnaire, is presented in Table 8. Baseline scores across domains (Physical Functioning, Bodily Pain, Social Functioning, Role-Emotional, and Mental Health) were comparable (all P>0.05). After treatment, HD+HP recipients exhibited significantly higher scores in all domains relative to HP-only patients (all P<0.05).
Table 8.
Quality of life (SF-36) scores
| Indicators | HP group (n=52) | HD+HP group (n=66) | t | P |
|---|---|---|---|---|
| Physical Functioning (points) | ||||
| Before | 47.42±5.79 | 46.97±4.83 | 0.460 | 0.646 |
| After | 59.87±8.01* | 71.29±6.53** | 8.532 | <0.001 |
| Bodily Pain (points) | ||||
| Before | 48.77±4.85 | 47.73±5.33 | 1.095 | 0.276 |
| After | 63.56±6.61* | 70.70±7.29** | 5.502 | <0.001 |
| Social functioning (points) | ||||
| Before | 45.02±5.85 | 45.35±6.68 | 0.281 | 0.779 |
| After | 82.10±6.48* | 87.45±6.47** | 4.456 | <0.001 |
| Role-Emotional (points) | ||||
| Before | 50.46±5.65 | 48.68±5.08 | 1.798 | 0.075 |
| After | 74.23±6.66* | 79.14±7.46** | 3.719 | <0.001 |
| Mental health (points) | ||||
| Before | 49.04±5.14 | 50.73±6.57 | 1.523 | 0.130 |
| After | 77.67±5.90* | 82.91±6.42** | 4.560 | <0.001 |
P<0.05 for within-group comparisons to pre-treatment;
P<0.01 for within-group comparisons to pre-treatment.
Determinants of treatment outcomes in CGN
Univariate analysis (Table 9) revealed no significant association between therapeutic efficacy and sex, age, diagnostic type, or family history (P>0.05). However, longer disease duration and treatment modality were strongly associated with treatment outcome (P<0.05).
Table 9.
Factors affecting treatment efficacy in chronic glomerulonephritis: results from univariate analysis
| Indicators | Ineffective group (n=21) | Effective group (n=97) | χ2/t | P |
|---|---|---|---|---|
| Sex | 0.744 | 0.388 | ||
| Male (n=63) | 13 (61.90) | 50 (51.55) | ||
| Female (n=55) | 8 (38.10) | 47 (48.45) | ||
| Age (years) | 0.405 | 0.525 | ||
| <45 (n=58) | 9 (42.86) | 49 (50.52) | ||
| ≥45 (n=60) | 12 (57.14) | 48 (49.48) | ||
| Illness duration (years) | 6.956 | 0.008 | ||
| <5 (n=47) | 3 (14.29) | 44 (45.36) | ||
| ≥5 (n=71) | 18 (85.71) | 53 (54.64) | ||
| Diagnostic category | 1.702 | 0.427 | ||
| Membranous nephropathy (n=58) | 13 (61.90) | 45 (46.39) | ||
| Mesangial proliferative glomerulonephritis (n=43) | 6 (28.57) | 37 (38.14) | ||
| Immunoglobulin A nephropathy (n=17) | 2 (9.52) | 15 (15.46) | ||
| Family medical history | 2.290 | 0.130 | ||
| No (n=102) | 16 (76.19) | 86 (88.66) | ||
| Yes (n=16) | 5 (23.81) | 11 (11.34) | ||
| Treatment protocol | 5.293 | 0.021 | ||
| HP (n=52) | 14 (66.67) | 38 (39.18) | ||
| HD+HP (n=66) | 7 (33.33) | 59 (60.82) |
Multivariate logistic regression (Table 10) identified extended disease duration (OR=4.930, 95% CI: 1.339-18.147, P<0.05) and HP monotherapy (OR=3.069, 95% CI: 1.103-8.539, P<0.05) as independent predictors of inferior therapeutic efficacy.
Table 10.
Multivariate analysis of determinants for treatment outcomes in chronic glomerulonephritis
| Indicators | β | SE | Wald | P | Exp (B) | 95% CI |
|---|---|---|---|---|---|---|
| Illness duration (years) | 1.595 | 0.665 | 5.758 | 0.016 | 4.930 | 1.339-18.147 |
| Treatment protocol | 1.121 | 0.522 | 4.615 | 0.032 | 3.069 | 1.103-8.539 |
Note: Illness duration: Categorized as <5 years =0 and ≥5 years =1; Treatment protocol: Categorized as HD+HP =0 and HP =1; Efficacy: effective =0, ineffective =1.
Discussion
This study demonstrated that combining HD with HP yields greater therapeutic effectiveness than HP alone in managing CGN. Li J et al. [21] similarly reported that HD+HP therapy in elderly patients undergoing maintenance HD produced enhanced clinical outcomes, attenuated inflammation, and improved quality of life - findings consistent with the present study. Cheng W et al. [22], through a systematic review and meta-analysis, further confirmed that HD+HP improves survival in patients with ESRD. The enhanced efficacy likely arises from the complementary clearance mechanisms of HD and HP, which together facilitate metabolite removal, prevent HD-related complications, and improve internal homeostasis.
HD+HP therapy also favorably influenced bone metabolism (lower serum PTH and P, higher Ca), renal function (reduced 24 h Upro, BUN, and SCr; elevated eGFR), and systemic inflammation (suppressed IL-17, TNF-α, and hs-CRP). Declining renal function in CGN may result from active vitamin D deficiency and phosphate retention in residual nephrons - both potent stimulants of PTH secretion, which disrupt phosphate excretion and calcium reabsorption [23]. Elevated serum phosphorus independently accelerates IgA nephropathy progression [24]. Li W et al. [25] also reported that HD+HP increased serum Ca without compromising nutritional status, consistent with our findings. IL-17 and TNF-α act as central inflammatory mediators in glomerulonephritis [26,27], while hs-CRP reflects renal microcirculatory disturbance [28]. The NLRP3-ASC-caspase-1 inflammasome axis also contributes to renal inflammation and fibrosis [29]. Zhao D et al. [30] observed that prolonged HD+HP use in ESRD patients alleviated pruritus and improved renal function through PTH suppression.
Furthermore, HD+HP improved hemorheological indices by lowering whole blood viscosity under both high- and low-shear conditions. High-shear viscosity reflects erythrocyte deformability, whereas low-shear viscosity correlates with red blood cell aggregation and plasma protein concentration [31]. Hyperviscosity contributes to renal hypoperfusion, ischemia, and hypoxia, thereby accelerating CGN progression [32]. Consequently, reductions in abnormal viscosity indicate improved microcirculation and therapeutic response [33].
The combination therapy also modulated coagulation and fibrinolysis by decreasing PAI-1 and increasing t-PA levels. PAI-1 inhibits fibrinolysis and promotes fibrin accumulation, while t-PA activates plasminogen to degrade fibrin [34]. Dysregulation of this balance contributes to glomerulosclerosis, and reversing it - via reduced PAI-1 and elevated t-PA - helps delay CGN progression [35]. HD+HP further reduced uremic toxins (β2-MG, Hcy, and AGEs), which are implicated in tubulointerstitial inflammation, endothelial injury, and matrix deposition through the RAGE axis [36]. Although coagulation abnormalities are common in HD due to blood-membrane interactions [37], no increase in total adverse events was observed. Chen et al. [38] similarly reported no serious complications in maintenance HD patients treated with HD+HP. Additionally, the present study found significant improvements in quality-of-life indices among CGN patients receiving combined therapy. HD+HP has also been identified as more cost-effective than HD alone in ESRD populations [39], reinforcing its clinical utility.
Prolonged disease duration and HP monotherapy emerged as independent predictors of suboptimal response. This may reflect irreversible renal injury in long-standing cases and the limited detoxification scope of HP alone, which cannot fully restore internal homeostasis.
Several limitations should be acknowledged. First, the single-center, small-sample design may restrict generalizability. Future multicenter studies with larger, more diverse cohorts are warranted. Second, treatment costs were not assessed, and cost-effectiveness data would enhance clinical decision-making. Lastly, long-term prognostic differences between regimens were not examined; extended follow-up is needed to determine sustained benefits.
In conclusion, combined HD+HP therapy significantly improves bone metabolism, renal function, inflammatory control, and quality of life in CGN patients while maintaining an acceptable safety profile. However, therapeutic efficacy may be attenuated in those with prolonged disease duration or prior HP monotherapy.
Disclosure of conflict of interest
None.
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