Circulating T lymphocyte subsets are associated clinical features and long-term prognosis in patients with hypertensive renal injury

Circulating T lymphocyte subsets are associated clinical features and long-term prognosis in patients with hypertensive renal injury | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Circulating T lymphocyte subsets are associated clinical features and long-term prognosis in patients with hypertensive renal injury Chenfeng Xu, Danni Liu, Zhi Zhao, Feng Yu, Wei Liu, Yanhua Wu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7665190/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim Although numerous studies have demonstrated the key role of immune system in hypertensive end organ damage, much less is known regarding the alterations of circulating immune cells in hypertensive renal injury.In this study, we examined the relationship between the distribution of T lymphocyte subsets and long-term clinical outcomes in patients with HRI. Methods In this study, a total of 431 patients (189 HRI patients and 242 hypertensions patients without renal injury) were recruited. Venous blood samples were used to detect for 15 distinct lymphocyte subsets by flow cytometry. T lymphocyte subsets and their correlations with clinical characteristics and long-term prognosis of patients were analyzed. Results A total of 431 patients (mean age 78.54 ± 14.23 years, 64.3% male) were enrolled. The median follow-up time was 16.54 months, range from 0.56 to 56.48 months. The overall mortality was 35.6% (144 cases). The age, gender, Scr (serum creatinine), level of urine protein, WBC (white blood cell) counts, levels of total lymphocytes, CD3 + CD8+, CD3 + HLADR+, CD3 + CD8 + CD28- and CD8 + CD95 + T cells were significantly higher in the HRI group compared to the non-HRI group (P < 0.05). Conversely, eGFR (estimated glomerular filtration rate) and CD3 + CD8 + CD28 + T cells were found to be lower in the HRI group (P < 0.05). As for the different CKD stages, patients with CKD "1 ~ 3" stages had higher levels of Hb, CD3+, CD3 + CD8+, CD3 + HLADR+, CD4 + CD69+, CD3 + CD8 + CD28-, CD4 + CD95 + and CD8 + CD95 + T cells than that of patients with "4 ~ 5" stages (P < 0.05). Multivariate COX regression analysis showed that age and CD3 + HLADR + T cells were independent risk factors for mortality [HR = 1.116(1.057,1.177), P < 0.001; HR = 8.676(1.887,39.886), P = 0.006]. However, CD3 + CD8 + and CD4 + CD25 + + CD127low T cells were independent protect factors for survive. [HR = 0.005(0.000,0.14), P = 0.002, HR = < 0.001(< 0.001,0.118), P = 0.03] Conclusions Patients with HRI showed lower levels of CD3+, CD3 + CD8+, CD3 + HLADR+, CD3 + CD8 + CD28- and CD8 + CD95 + T cells compared to non-HRI patients. Moreover, level of CD3 + HLADR + cells was independent risk factors for mortality in patients with HRI, while CD3 + CD8 + and CD4 + CD25 + + CD127low T cells were independent protect factors for survive. These results suggest that T lymphocyte differentiation and activation are associated with the progression and prognosis of HRI. T Lymphocyte hypertensive renal injury CD3+CD8+CD28- T cell CD8+CD95+T cell prognosis Introduction Hypertension is a leading cause of global morbidity and mortality1,2, and also a major risk factor for cardiovascular, cerebrovascular, and renal diseases3. Inadequately controlled essential hypertension can lead to renal insufficiency, which in turn contributes to the development of secondary hypertension. Both the magnitude of blood pressure fluctuations and the duration of hypertension are associated with an increased risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD). The underlying pathophysiology primarily involves progressive impairment of renal microvascular autoregulatory mechanisms. This impairment leads to abnormal dilation of the afferent arterioles, subsequently elevating intraglomerular pressure. Furthermore, the direct transmission of systemic hypertension to the glomerular vasculature induces arterial stretching and endothelial damage. Oxidative stress and inflammation trigger activation of the renin-angiotensin-aldosterone system (RAAS). Additionally, immune mechanisms are now recognized as significant contributors to the pathogenesis of arterial hypertension, promoting both its development and associated target organ damage4,5. Previous studies have demonstrated that T lymphocytes infiltrating the kidney contribute to the development of salt-sensitive hypertension and renal disease in Dahl salt-sensitive rats6. T cell-deficient mice exhibit resistance to blood pressure elevation, suggesting an important role for T lymphocytes in the pathogenesis of hypertension7. Further research revealed that inflammation is a characteristic feature of hypertensive renal disease, and infiltration of CD3⁺ T cells was observed in the kidneys of angiotensin II-treated mice6,8. Several clinical studies have demonstrated that Ang II-induced hypertension results in a 3- to 5-fold increase in mouse CD3⁺, CD4⁺, and CD8⁺ T cells within the lymph nodes of this model9. Furthermore, patients with renal injury associated with essential malignant hypertension exhibit a significant reduction in CD4⁺CD25⁺ cells10. Research by Brittany et al. identified CD8⁺ T cells as the primary source of IFN-γ, accumulating in the kidneys following hypertensive challenge. Recent studies have established crucial roles for cytotoxic T lymphocytes (CTLs, CD8⁺) and helper T cells (Th, CD4⁺) in hypertension11. Furthermore, CD4⁺ lymphocytes are key regulators of the Treg/Th17 balance, which is implicated in hypertension and hypertensive end-organ damage. Notably, regulatory T cells (Tregs) exert protective effects. Studies demonstrate that Treg deficiency exacerbates angiotensin II (Ang II)-induced microvascular damage through enhanced immune responses12. Additionally, Ang II promotes secretion of the pro-inflammatory cytokine IL-17 by Th17 cells, contributing to fibrosis progression13. In addition, innate immune cells play key roles in hypertension pathogenesis. Neutrophils, monocytes/macrophages, dendritic cells, myeloid-derived suppressor cells (MDSCs), and innate lymphoid cells (ILCs) are implicated in this process14. Cytokines released from these cells—including IL-17, IFN-γ, TNF-α, and IL-6—promote renal and vascular dysfunction, leading to enhanced sodium retention and elevated systemic vascular resistance. Through multiple pathways, these cytokines may stimulate angiotensinogen production, increase renal sodium reabsorption, and exacerbate renal fibrosis. Collectively, these findings suggest that T lymphocytes contribute to the initiation and progression of hypertension-associated kidney injury. However, the specific role of T lymphocyte gap junctions in regulating hypertension-mediated inflammation remains incompletely understood11,15.Further investigation is warranted to elucidate the interplay among hypertension, renal injury, and T-cell subsets. This study assessed alterations in circulating T-lymphocyte subpopulations in patients with hypertensive renal injury and their associations with clinical parameters and outcomes. Materials and Methods Patients Inclusion criteria As defined by the World Health Organization (WHO), hypertension is diagnosed when systolic blood pressure (SBP) measurements are ≥ 140 mmHg and/or diastolic blood pressure (DBP) measurements are ≥ 90 mmHg on two separate occasions in the absence of antihypertensive medication16.However, consensus diagnostic criteria for hypertensive kidney disease (HKD) remain undefined. In this study, hypertensive renal injury was diagnosed according to the following institutional protocol:(I) Documented primary hypertension;(II) Sustained hypertension (> 140/90 mmHg) for > 5 years preceding proteinuria onset;(III) Persistent proteinuria (urine protein > 300 mg/g creatinine) with bland urinary sediment;(IV) Exclusion of primary glomerular diseases;(V) Exclusion of secondary renal disorders (e.g., diabetic nephropathy, renovascular disease)17. CKD was staged according to estimated glomerular filtration rate (eGFR) as follows¹³: Stage 1: eGFR ≥ 90 mL/min/1.73 m² with kidney damage. Stage 2: eGFR 60–89 mL/min/1.73 m² with kidney damage. Stage 3a: eGFR 45–59 mL/min/1.73 m². Stage 3b: eGFR 30–44 mL/min/1.73 m². Stage 4: eGFR 15–29 mL/min/1.73 m². Stage 5: eGFR < 15 mL/min/1.73 m²13. The control group comprised hospitalized patients with hypertension but without renal injury (eGFR ≥ 60 mL/min/1.73 m² and absence of albuminuria or structural abnormalities). Exclusion criteria Patients were excluded if they met any of the following criteria: history of renal replacement therapy; diagnosis of solid tumors, leukemia, lymphoma, or AIDS; presence of connective tissue diseases; or acute infection. Clinical Data Collection This retrospective study included 431 patients with HRI (define acronym here if first use) admitted to Guangdong Provincial People's Hospital between January 2016 and July 2022. Clinical data collected for all patients comprised gender, age, hemoglobin, serum creatinine (Scr; measured enzymatically), urine protein-to-creatinine ratio (UPCR), 24-hour urinary protein excretion, white blood cell (WBC) count, and lymphocyte count. Definitions and Study Endpoints CKD was diagnosed and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Estimated glomerular filtration rate (eGFR; mL/min/1.73 m²) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Eq. 18. The primary endpoint was all-cause mortality. Statistical Analysis SPSS 26.0 statistical software was used for data collation and analysis. Continuous variables are expressed as mean ± standard deviation (SD) and compared using independent samples t-tests. Categorical variables are presented as frequency counts and percentages (%) and compared using chi-square tests. Univariate and multivariate Cox proportional hazards regression models were used to identify prognostic factors. A two-sided p-value < 0.05 was considered statistically significant. Result 1. Demographic characteristics and clinical data The study cohort comprised 431 participants, with males constituting 277 (64.3%). Mean age was 78.5 ± 14.2 years. At final follow-up (July 18, 2022), median follow-up duration was 16.5 months. Hypertensive renal injury was diagnosed in 189 patients (43.9%), among whom 122 (64.5%) had CKD stages 1–3. Detailed clinical characteristics are provided in Table 1 . Table 1 Demographic characteristics and clinical data (n = 431) Index n (%) or mean ± SD Age (years) 78.54 ± 14.23 Gender (M/F) 277/154 HRI, n (%) 189 (43.9%) Death, n (%) 144 (33.4%) Survive Times (days) 654.64 ± 444.66 CKD, n (%) 1 ~ 3 122(64.6%) 4 ~ 5 67(35.4%) eGFR 62.01 ± 28.30 24h urine protein 877.79 ± 1159.59 24h urine albumin 379.89 ± 640.06 PCR 732.18 ± 1022.19 ACR 271.50 ± 495.63 Scr mmol/l 130.62 ± 109.66 WBC 7.66 ± 3.09 Hb(g/l) 119.75 ± 19.95 Lymphocyte 1.75 ± 0.72 CD3 + T cells 1.20 ± 0.60 CD3 + CD4 + T cells 0.62 ± 0.33 CD3 + CD8 + T cells 0.52 ± 0.33 CD3 + HLADR + T cells 0.57 ± 0.40 CD4 + CD25 + T cells 0.29 ± 0.18 CD8 + CD25 + T cells 0.03 ± 0.03 CD4 + CD69 + T cells 0.04 ± 0.03 CD8 + CD69 + T cells 0.07 ± 0.06 CD3 + CD8 + CD28 + T cells 0.31 ± 0.17 CD3 + CD8 + CD28-T cells 0.43 ± 0.36 CD4 + CD28 + T cells 0.54 ± 0.28 CD8 + CD28 + T cells 0.18 ± 0.11 CD4 + CD95 + T cells 0.53 ± 0.29 CD8 + CD95 + T cells 0.52 ± 0.33 CD4 + CD25 + + CD127low T cells 0.02 ± 0.01 PCR: protein creatinine ratio. ACR: albumin creatinine ratio. HRI: hypertensive renal injury. eGFR: estimated glomerular filtration rate. CKD: chronic kidney disease. Scr: serum creatinine. WBC: white blood cell. Hb: hemoglobin. 2. Comparison of T lymphocyte subpopulations in patients with HRI and Non-HRI T lymphocyte profiles were compared between the HRI and Non-HRI groups. Compared with the Non-HRI group, the HRI group exhibited significantly higher values in: age, male proportion, Scr, 24-h urinary protein, 24-h urinary albumin, protein-to-creatinine ratio (PCR), albumin-to-creatinine ratio (ACR), WBC, lymphocyte count, CD3⁺ cells, CD3⁺CD8⁺ cells, CD3⁺HLA-DR⁺ cells, CD3⁺CD8⁺CD28⁻ cells, and CD8⁺CD95⁺ T cells (all P < 0.05). Conversely, the HRI group demonstrated significantly lower eGFR and CD3⁺CD8⁺CD28⁺ T cells (P < 0.05). Detailed comparisons are presented in Table 2 . Table 2 Comparison of T lymphocyte subpopulations in patients with HRI and Non-HRI Index HRI(n = 189) Non-HRI(n = 242) χ2/t P Age(years) 87.78 ± 5.9 71.34 ± 14.67 15.86 < 0.001 Gender, n (%) 22.722 < 0.001 Male 145(76.7%) 132(54.5%) Female 44(23.3%) 110(45.5%) eGFR 40.46 ± 21.80 78.84 ± 20.23 -18.720 0.172 24h urine protein 951.78 ± 1190.38 130.53 ± 91.01 6.737 0.031 24h urine albumin 416.32 ± 660.12 11.97 ± 10.12 6.149 0.023 PCR 993.21 ± 1120.78 114.54 ± 73.01 10.111 < 0.001 ACR 381.70 ± 555.82 10.73 ± 7.53 8.649 < 0.001 Scr(mmol/l) 186.96 ± 139.33 86.61 ± 43.37 9.547 < 0.001 WBC 7.80 ± 2.16 7.55 ± 3.66 0.891 0.011 Hb(g/l) 112.47 ± 17.66 125.37 ± 19.83 -7.094 0.797 Lymphocytes 1.77 ± 0.82 1.74 ± 0.63 0.386 0.004 CD3 + T cells 1.30 ± 0.46 1.04 ± 0.42 4.005 < 0.001 CD3 + CD4 + T cells 0.64 ± 0.35 0.57 ± 0.29 1.765 0.313 CD3 + CD8 + T cells 0.59 ± 0.36 0.38 ± 0.23 5.817 < 0.001 CD3 + HLADR + T cells 0.64 ± 0.42 0.38 ± 0.25 6.07 < 0.001 CD4 + CD25 + T cells 0.30 ± 0.20 0.26 ± 0.13 1.465 0.474 CD8 + CD25 + T cells 0.03 ± 0.03 0.03 ± 0.04 0.711 0.390 CD4 + CD69 + T cells 0.04 ± 0.04 0.04 ± 0.03 0.643 0.205 CD8 + CD69 + T cells 0.78 ± 0.57 0.06 ± 0.47 2.241 0.815 CD3 + CD8 + CD28 + T cells 0.27 ± 0.13 0.37 ± 0.20 -4.758 < 0.001 CD3 + CD8 + CD28-T cells 0.55 ± 0.39 0.25 ± 0.20 9.016 < 0.001 CD4 + CD28 + T cells 0.53 ± 0.30 0.55 ± 0.21 -0.473 0.058 CD8 + CD28 + T cells 0.18 ± 0.11 0.18 ± 0.10 -0.195 0.996 CD4 + CD95 + T cells 0.53 ± 0.31 0.52 ± 0.20 0.355 0.111 CD8 + CD95 + T cells 0.53 ± 0.34 0.44 ± 0.22 1.998 0.030 CD4 + CD25 + + CD127low T cells 0.03 ± 0.01 0.02 ± 0.01 0.543 0.967 PCR: protein creatinine ratio. ACR: albumin creatinine ratio. HRI: hypertensive renal injury. eGFR: estimated glomerular filtration rate. CKD: chronic kidney disease. Scr: serum creatinine. WBC: white blood cell. Hb: hemoglobin. 3. Comparison of T lymphocyte subpopulations in patients with different CKD stages Independent samples t-tests and χ² tests revealed significant intergroup differences: compared to CKD stages 4–5, patients with CKD stages 1–3 demonstrated significantly lower Scr, 24-hour urinary protein, 24-hour urinary albumin, PCR, and ACR (P < 0.05), but higher proportions of males, Hb levels, and percentages of CD3⁺ cells, CD3⁺CD8⁺ cells, CD3⁺HLA-DR⁺ cells, CD4⁺CD69⁺ cells, CD3⁺CD8⁺CD28⁻ T cells, CD4⁺CD95⁺ T cells, and CD8⁺CD95⁺ T cells (P < 0.05), with complete statistical comparisons detailed in Table 3. Table.3 Comparison of T lymphocyte subpopulations in patients with different CKD stages Index 1 ~ 3(n = 122) 4 ~ 5(n = 67) χ2/t P Age(years) 85.97 ± 10.31 84.61 ± 10.64 0.851 0.69 Gender, n (%) 16.831 < 0.001 Male 96(78.7%) 37(55.2%) Female 26(21.3%) 30(44.8%) eGFR 56.70 ± 21.67 36.42 ± 28.48 5.077 0.107 24h urine protein 604.99 ± 509.61 1275.64 ± 1663.64 -2.007 < 0.001 24h urine albumin 190.48 ± 173.30 620.05 ± 933.08 -2.327 < 0.001 PCR 689.04 ± 751.78 1335.95 ± 1380.56 -2.951 0.001 ACR 209.58 ± 252.74 562.02 ± 683.61 -3.321 < 0.001 Scr mmol/l 115.85 ± 40.47 232.69 ± 183.36 -5.148 < 0.001 WBC 8.04 ± 2.31 7.64 ± 2.44 1.106 0.959 Hb(g/l) 117.89 ± 15.45 113.22 ± 19.28 1.7 < 0.001 Lymphocytes 1.98 ± 0.76 1.59 ± 0.61 3.84 0.091 CD3 + T cells 1.44 ± 0.64 1.11 ± 0.47 3.894 0.005 CD3 + CD4 + T cells 0.68 ± 0.32 0.57 ± 0.28 2.34 0.098 CD3 + CD8 + T cells 0.68 ± 0.38 0.47 ± 0.25 4.45 < 0.001 CD3 + HLADR + T cells 0.77 ± 0.45 0.5 ± 0.29 4.73 < 0.001 CD4 + CD25 + T cells 0.3 ± 0.12 0.26 ± 0.13 1.93 0.718 CD8 + CD25 + T cells 0.04 ± 0.04 0.03 ± 0.02 1.723 0.305 CD4 + CD69 + T cells 0.04 ± 0.04 0.03 ± 0.02 2.862 0.003 CD8 + CD69 + T cells 0.08 ± 0.05 0.07 ± 0.05 1.151 0.987 CD3 + CD8 + CD28 + T cells 0.3 ± 0.14 0.25 ± 0.12 2.373 0.261 CD3 + CD8 + CD28-T cells 0.66 ± 0.42 0.42 ± 0.26 4.603 < 0.001 CD4 + CD28 + T cells 0.56 ± 0.24 0.46 ± 0.24 2.291 0.578 CD8 + CD28 + T cells 0.19 ± 0.11 0.16 ± 0.92 2.284 0.371 CD4 + CD95 + T cells 0.59 ± 0.27 0.45 ± 0.22 3.335 0.03 CD8 + CD95 + T cells 0.66 ± 0.36 0.42 ± 0.23 4.949 < 0.001 CD4 + CD25 + + CD127low T cells 0.03 ± 0.01 0.02 ± 0.01 1.468 0.756 PCR: protein creatinine ratio. ACR: albumin creatinine ratio. HRI: hypertensive renal injury. eGFR: estimated glomerular filtration rate. CKD: chronic kidney disease. Scr: serum creatinine. WBC: white blood cell. Hb: hemoglobin. 4. Univariate COX regression analysis for mortality Univariate Cox regression identified age, elevated WBC count, and increased proportions of CD3⁺ T cells, CD3⁺CD8⁺ T cells, CD3⁺HLA-DR⁺ T cells, CD8⁺CD69⁺ T cells, CD3⁺CD8⁺CD28⁻ T cells, and CD8⁺CD95⁺ T cells as significant risk factors for all-cause mortality (P < 0.05). Conversely, CD4⁺CD25highCD127low regulatory T cells demonstrated a marked protective association with survival (P = 0.022). Complete hazard ratios with 95% confidence intervals are detailed in Table 4 . Table 4 Univariate COX regression analysis for survival prognosis Index β SE Wald P HR (95% CI) Age 0.095 0.020 22.063 < 0.001 1.1(1.057, 1.144) Gender -0.378 0.207 3.319 0.068 0.686(0.457, 1.029) eGFR 0.002 0.004 0.359 0.549 1.002(0.994, 1.011) CKD stage -0.021 0.067 0.099 0.753 0.979(0.859, 1.117) 24h urine protein < 0.001 < 0.001 1.342 0.247 1.000(1.000, 1.000) 24h urine albumin -0.001 < 0.001 3.159 0.075 0.999(0.999, 1.000) PCR < 0.001 < 0.001 0.010 0.919 1.000(1.000, 1.000) ACR < 0.001 < 0.001 2.381 0.123 1.000(0.999, 1.000) Scr -0.001 0.001 0.853 0.356 0.999(0.998, 1.001) WBC 0.134 0.033 16.746 < 0.001 1.144(1.072, 1.219) Hb -0.004 0.005 0.592 0.442 0.996(0.987, 1.006) Lymphocytes 0.112 0.079 2.036 0.154 1.119(0.959, 1.306) CD3 + T cells 0.199 0.101 3.904 0.048 1.22(1.002, 1.485) CD3 + CD4 + T cells -0.046 0.202 0.052 0.820 0.955(0.642, 1.420) CD3 + CD8 + T cells 0.815 0.202 16.242 < 0.001 2.260(1.520, 3.360) CD3 + HLADR + T cells 0.998 0.183 29.863 < 0.001 2.713(1.897,3.881) CD4 + CD25 + T cells -0.832 0.497 2.799 0.094 0.435(0.164, 1.153) CD8 + CD25 + T cells -3.148 3.126 1.014 0.314 0.043(< 0.001, 19.645) CD4 + CD69 + T cells -2.831 2.229 1.613 0.204 0.059(0.001, 4.655) CD8 + CD69 + T cells 5.456 1.286 17.998 < 0.001 234.093(18.825,2910.954) CD3 + CD8 + CD28 + T cells -0.981 .647 2.302 0.129 0.375(0.106,1.331) CD3 + CD8 + CD28-T cells 1.028 0.186 30.443 < 0.001 2.795(1.940, 4.026) CD4 + CD28 + T cells -0.463 0.290 2.547 0.111 0.629(0.356, 1.111) CD8 + CD28 + T cells 0.374 0.711 0.277 0.598 1.454(0.361, 5.853) CD4 + CD95 + T cells 0.062 0.210 0.086 0.769 1.063(0.705, 1.605) CD8 + CD95 + T cells 0.867 0.213 16.533 < 0.001 2.380(1.567, 3.614) CD4 + CD25 + + CD127low T cells -14.931 6.506 5.267 0.022 < 0.001(< 0.001,0.113) PCR: protein creatinine ratio. ACR: albumin creatinine ratio. HRI: hypertensive renal injury. eGFR: estimated glomerular filtration rate. CKD: chronic kidney disease. Scr: serum creatinine. WBC: white blood cell. Hb: hemoglobin. 5. Multivariate COX regression analysis for survival prognosis Multivariate Cox regression identified age (HR 1.116, 95% CI 1.057–1.177; P < 0.001) and CD3⁺HLA-DR⁺ T cells (HR 8.676, 95% CI 1.887–39.886; P = 0.006) as independent risk factors for all-cause mortality. Conversely, CD3⁺CD8⁺ T cells and CD4⁺CD25highCD127low regulatory T cells demonstrated protective associations with survival (P = 0.002 and P = 0.03, respectively). Complete regression results are presented in Table 5 . Table 5 Multivariate COX regression analysis for survival prognosis Index β SE Wald P HR (95% CI) Age 0.109 0.027 16.044 < 0.001 1.116(1.057,1.177) WBC 0.052 0.04 1.703 0.192 1.053(0.974,1.138) CD3 + T cells 0.368 0.404 0.827 0.363 1.444(0.654,3.188) CD3 + CD8 + T cells -6.169 1.708 13.048 < 0.001 0.002(< 0.001,0.059) CD3 + HLADR + T cells 2.161 0.778 7.706 0.006 8.676(1.887,39.886) CD8 + CD69 + T cells 3.502 2.306 2.306 0.129 33.18(0.361,3045.825) CD3 + CD8 + CD28-T cells 1.187 0.718 2.731 0.098 3.277(0.802,13.394) CD8 + CD95 + T cells 2.716 1.454 3.486 0.062 15.112(0.874,261.455) CD4 + CD25 + + CD127low T cells -22.167 10.221 4.703 0.03 < 0.001(< 0.001,0.118) WBC: white blood cell. Discussion Hypertensive renal injury (HRI), a kidney disorder secondary to chronic hypertension, manifests as impaired glomerular filtration, tubular damage, and renal vascular remodeling. This condition evolves through complex pathological mechanisms involving altered renal hemodynamics, arteriolar constriction, elevated glomerular filtration pressure, and progressive interstitial fibrosis. Notably, T lymphocytes contribute significantly to HRI pathogenesis. Renal-infiltrating T cells drive inflammation, promote fibrotic processes, and induce endothelial dysfunction, culminating in progressive renal functional decline19,20. This longitudinal cohort study investigated T lymphocyte subset distributions and their clinical correlates in hypertensive patients with and without renal injury, focusing particularly on elderly individuals. With 64.3% male predominance (mean age 78.5 years), our cohort analysis revealed distinct immunophenotypic patterns predictive of outcomes. The extended follow-up period enabled robust assessment of T-cell profiles' relationship to clinical features and all-cause mortality, providing clinically applicable prognostic indicators for geriatric HRI management. Our analysis revealed significantly elevated values in the HRI group versus Non-HRI group for: age, male proportion, Scr, 24-hour urinary protein, 24-hour urinary albumin, PCR, ACR, WBC, lymphocyte count, CD3⁺ T cells, CD3⁺CD8⁺ T cells, CD3⁺HLA-DR⁺ T cells, CD3⁺CD8⁺CD28⁻ T cells, and CD8⁺CD95⁺ T cells (all P < 0.05). Conversely, eGFR and CD3⁺CD8⁺CD28⁺ T cells were significantly reduced in HRI patients.Compared to CKD stages 4–5, patients with CKD stages 1–3 demonstrated significantly lower Scr, 24-hour urinary protein, 24-hour urinary albumin, PCR, and ACR, but higher male proportion, Hb, CD3⁺ T cells, CD3⁺CD8⁺ T cells, CD3⁺HLA-DR⁺ T cells, CD4⁺CD69⁺ T cells, CD3⁺CD8⁺CD28⁻ T cells, CD4⁺CD95⁺ T cells, and CD8⁺CD95⁺ T cells (all P < 0.05). Multivariate Cox regression identified age (HR 1.116, 95% CI 1.057–1.177; P < 0.001) and CD3⁺HLA-DR⁺ T cells (HR 8.676, 95% CI 1.887–39.886; P = 0.006) as independent mortality risk factors, while CD3⁺CD8⁺ T cells and CD4⁺CD25highCD127low regulatory T cells showed protective associations (P = 0.002 and P = 0.03, respectively). These immunophenotypic alterations demonstrate the broad involvement of T cell-mediated immune activation, early response coordination, immunosenescence, and apoptotic pathways in the pathogenesis of HRI. CD3, a pan-T cell surface marker expressed on mature T lymphocytes, forms an essential component of the T cell receptor (TCR) signaling complex that facilitates antigen recognition. We observed significantly elevated CD3⁺ T cell levels in both HRI and CKD stage 1–3 cohorts (P < 0.05), though multivariate analysis did not identify them as independent mortality risk factors. This finding aligns with established reports of renal CD3⁺ T cell infiltration in salt-sensitive hypertension and renal injury21. Moreover, it’s reported a decreased absolute count of lymphocyte along with the renal insufficiency22,23,23. In patients with end-stage renal disease (ESRD), T lymphocytes show a downward trend24,25. The decrease in T cells may be associated with T cell immune function impaired26, premature aging, loss of naive T cells and lymphocyte apoptosis22. Human leukocyte antigen DR (HLA-DR), a class II molecule of the major histocompatibility complex (MHC), is indispensable in antigen presentation and initiates immune responses by interacting with T-cell receptors (TCRs)27. Previous studies have highlighted the CD3⁺HLA-DR⁺ cell subset as key players in immune activation and antigen presentation. Increased frequency and activity of CD3⁺HLA-DR⁺ cells have been observed in certain immune disorders, infections, and inflammatory conditions28,29. Limited research has been conducted on CD3⁺HLA-DR⁺ cells in hypertension. Available evidence indicates elevated levels of activated T lymphocytes (CD3⁺CD25⁺ and CD3⁺HLA-DR⁺) in the peripheral blood of hypertensive patients30. Another study also reported a significant reduction in CD3⁺HLA-DR⁺ cells following renal denervation in patients with resistant hypertension31. Our findings, along with these previous data, suggest a potential association between elevated CD3⁺HLA-DR⁺ cell levels and hypertension. Interestingly, our study demonstrated significantly higher levels of CD3⁺HLA-DR⁺ T cells in both the HRI group and the stage 1–3 CKD group. Moreover, HLA-DR⁺ T cells were identified as an independent risk factor for all-cause mortality. Our results indicate that CD3⁺HLA-DR⁺ T cells are not only associated with hypertension but also correlated with hypertensive renal injury and long-term prognosis. Human CD8⁺ T cells, also known as cytotoxic T lymphocytes, are effector cells in cell-mediated immunity. CD3⁺CD8⁺ T cells are typically activated through interaction with professional antigen-presenting cells—primarily dendritic cells in lymph nodes or follicles—leading to the acquisition of effector functions32. CD8⁺ T cells have been implicated as mediators in angiotensin II-induced endothelial dysfunction, rarefaction of blood vessels, and hypertension33. Youn et al. reported an increase in immunosenescent CD8⁺ T cells and CXCR3-type chemokines in human hypertension34. Renal biopsies from patients with hypertensive nephrosclerosis have shown enhanced infiltration of T cells and their subsets, including both CD4⁺ and CD8⁺ T cells35. Based on existing literature, it remains unclear whether CD3⁺CD8⁺ T cells constitute a protective or risk factor for mortality in patients with hypertensive renal injury. While ESRD patients often exhibit immunodeficiency and lymphopenia, our data also revealed a reduction in CD8⁺ T cells in advanced CKD. Notably, our study demonstrated that CD3⁺CD8⁺ T cells were significantly elevated in the HRI group compared with the non-HRI group. Furthermore, we identified this T-cell subset as an independent protective factor for survival. These findings reveal a novel association between CD3⁺CD8⁺ T cells and HRI, underscoring their potential role in long-term prognosis. Further investigations are warranted to elucidate the underlying mechanisms and clinical implications of these observations. As known, Tc cells labeled with CD3 + CD8 + CD28+, representing cytotoxic T cells, and Ts cells labeled with CD3 + CD8 + CD28-, denoting suppressor T cells. CD28, a critical co-stimulatory molecule, binds to CD80 and CD86 on the surface of antigen-presenting cells. It is essential for the activation of native T cells and the amplification of immune responses15, promoting T cell proliferation, differentiation, and cytokine production36,37. Antony et al. demonstrated that B7/CD28 co-stimulatory signaling plays a major role in the development of hypertension. Inhibition of T cell activation using CTLA4-Ig or deficiency in CD80/CD86 resulted in reduced blood pressure38. Previous studies have observed an elevation of CD8⁺CD28null T cells in hypertensive patients. Youn et al. reported an increased proportion of CD8⁺CD28null T cells in a cohort of newly diagnosed, untreated hypertensive adults compared with age- and sex-matched normotensive controls34(p3). Furthermore, elevated levels of CD8⁺CD28⁻ cells have been associated with hypertensive left ventricular hypertrophy39. Our study reveals a novel observation: the abundance of CD3⁺CD8⁺CD28⁻ T cells was increased in the HRI group compared with the control group. This finding adds a new dimension to the understanding of the immune landscape associated with hypertensive kidney damage. However, this T cell subset was not identified as an independent risk factor for mortality. Additionally, we observed a general increase in T lymphocytes (including various T cell subsets) in early-stage CKD compared with advanced stages. This phenomenon may be related to the migration of senescent CD28⁻ cells toward myeloid lineages, potentially competing with the output of T progenitor cells in the lymphoid niche22. In summary, these results indicate that CD8⁺CD28⁻ T cells are associated with the development of both hypertension and HRI. Coordinated and amplified T cell immune responses, along with cellular senescence and loss of normal function, may collectively contribute to the initiation and progression of hypertensive renal injury. CD4⁺CD25⁺⁺CD127[low] refers to a specific population of T cells in human peripheral blood that has been identified as naturally occurring regulatory T cells (nTreg cells)40. These cells are involved in controlling autoimmune responses and preventing excessive immune activation. CD4⁺CD25⁺⁺CD127low T cells express high levels of Foxp3, a transcription factor essential for their suppressive function41. Studies have shown that CD4⁺CD25⁺⁺CD127low T cells play a role in vascular dysfunction associated with hypertension42. Another study revealed a significantly reduced frequency of CD4⁺CD25⁺CD127low Foxp3⁺ regulatory T cells—including CD4⁺CD25⁺⁺CD127low T cells—in patients with CKD compared with healthy controls43. Furthermore, Huang and colleagues demonstrated a marked reduction in CD4⁺CD25⁺ cells among patients with renal injury due to primary malignant hypertension compared to control subjects10. These findings suggest that CD4⁺CD25⁺⁺CD127low T cells may be implicated in the pathogenesis of hypertension and target organ damage. In our study, no significant differences were observed in either CD4⁺CD25⁺ or CD4⁺CD25⁺⁺CD127low T cells between the HRI group and across different stages of CKD. However, multivariate COX regression analysis identified CD4⁺CD25⁺⁺CD127low T cells as a protective factor for survival. This represents a novel finding regarding the association between CD4⁺CD25⁺⁺CD127low T cells and long-term prognosis in hypertensive renal injury. Further studies are warranted to validate and expand upon these observations. However, several limitations of our study should be acknowledged. First, this was a retrospective study. Second, the mechanisms underlying the interactions between hypertension, uremic toxins, and their potential effects on T cell growth, differentiation, or survival were not explored. Further research is needed to elucidate these mechanisms and to build upon the insights gained from our study in order to achieve a more comprehensive understanding. Conclusions Compared with non-HRI patients, those with HRI exhibited decreased levels of CD3⁺, CD3⁺CD8⁺, CD3⁺HLA-DR⁺, CD3⁺CD8⁺CD28⁻, and CD8⁺CD95⁺ T cells. Furthermore, the level of CD3⁺HLA-DR⁺ cells was identified as an independent risk factor for mortality in HRI patients, whereas CD3⁺CD8⁺ and CD4⁺CD25⁺⁺CD127low T cells were independent protective factors for survival. These findings suggest that the differentiation and activation of T lymphocytes are associated with the progression and long-term prognosis of HRI. Abbreviations CKD: chronic kidney disease; ESRD: end-stage renal disease; RAAS: renin-angiotensin-aldosterone system; eGFR: estimated glomerular filtration rate; Scr: serum creatinine; WBC: white blood cell; KDIGO: Kidney Disease Improving Global Outcomes; CKD-EPI: Chronic Kidney Disease Epidemiology collaboration equation; PCR: protein creatinine ratio; ACR: albumin creatinine ratio; HRI: hypertensive renal injury; Hb: hemoglobin; HLADR: Human Leukocytes Antigen DR; TCR: T cell receptors Declarations Acknowledgements We are grateful to the patients who kindly consented to join the study. Authors’ contributions XCF and LW acquired the data. XCF, LDN, ZZ, and WYH analyzed and interpreted the data. XCF, LDN, and YF performed the statistical analysis. HWK and HWX supervised the study and provided mentorship. HWK and HWX conceived the research idea and designed the study. All authors read and approved the final manuscript. Funding This work was supported by the General Program of National Natural Science Foundation of China [grant numbers: 82270780], National Natural Science Foundation of China[grant numbers: 82470773], Natural Science Foundation of Guangdong Province [grant numbers: 2024A1515013139] , Guangdong Provincial Science and Technology Planning Project [grant numbers: KS012023323], Guangdong Basic and Applied Basic Research Foundation [grant numbers: 2024A1515010692], and the Basic research program of Guangzhou Science and Technology Project, China [grant numbers: 2024A04J5130] Availability of data and materials The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate. This study was performed in line with the principles of the Declaration of Helsinki. The approval was granted by the Ethics Committees of Guangdong Provincial People’s Hospital. The patient provided written informed consent before participation. Consent for publication The patient has signed the informed consent form. Competing interests The authors declare that they have no competing interests. Author details Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Southern Medical University, Guangzhou, China The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China. References Poulter NR, Prabhakaran D, Caulfield M. Hypertension. The Lancet. 2015;386(9995):801-812. doi:10.1016/S0140-6736(14)61468-9 Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet Lond Engl. 2012;380(9859):2224-2260. doi:10.1016/S0140-6736(12)61766-8 Iqbal AM, Jamal SF. 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Inflammation. 2012;35(6):1773-1780. doi:10.1007/s10753-012-9496-8 CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells | Journal of Experimental Medicine | Rockefeller University Press. Accessed September 14, 2023. https://rupress.org/jem/article/203/7/1701/46415/CD127-expression-inversely-correlates-with-FoxP3 Kassan M, Wecker A, Kadowitz P, Trebak M, Matrougui K. CD4+CD25+Foxp3 regulatory T cells and vascular dysfunction in hypertension. J Hypertens. 2013;31(10):1939-1943. doi:10.1097/HJH.0b013e328362feb7 Aly MG, Ibrahim EH, Karakizlis H, et al. CD4+CD25+CD127-Foxp3+ and CD8+CD28- Tregs in Renal Transplant Recipients: Phenotypic Patterns, Association With Immunosuppressive Drugs, and Interaction With Effector CD8+ T Cells and CD19+IL-10+ Bregs. Front Immunol. 2021;12. Accessed September 14, 2023. https://www.frontiersin.org/articles/10.3389/fimmu.2021.716559 Additional Declarations No competing interests reported. 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09:54:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1085763,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7665190/v1/e5c7aeb5-8fec-423b-bbb3-6f676751163d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Circulating T lymphocyte subsets are associated clinical features and long-term prognosis in patients with hypertensive renal injury","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHypertension is a leading cause of global morbidity and mortality1,2, and also a major risk factor for cardiovascular, cerebrovascular, and renal diseases3. Inadequately controlled essential hypertension can lead to renal insufficiency, which in turn contributes to the development of secondary hypertension. Both the magnitude of blood pressure fluctuations and the duration of hypertension are associated with an increased risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD). The underlying pathophysiology primarily involves progressive impairment of renal microvascular autoregulatory mechanisms. This impairment leads to abnormal dilation of the afferent arterioles, subsequently elevating intraglomerular pressure. Furthermore, the direct transmission of systemic hypertension to the glomerular vasculature induces arterial stretching and endothelial damage. Oxidative stress and inflammation trigger activation of the renin-angiotensin-aldosterone system (RAAS). Additionally, immune mechanisms are now recognized as significant contributors to the pathogenesis of arterial hypertension, promoting both its development and associated target organ damage4,5.\u003c/p\u003e\u003cp\u003ePrevious studies have demonstrated that T lymphocytes infiltrating the kidney contribute to the development of salt-sensitive hypertension and renal disease in Dahl salt-sensitive rats6. T cell-deficient mice exhibit resistance to blood pressure elevation, suggesting an important role for T lymphocytes in the pathogenesis of hypertension7. Further research revealed that inflammation is a characteristic feature of hypertensive renal disease, and infiltration of CD3⁺ T cells was observed in the kidneys of angiotensin II-treated mice6,8. Several clinical studies have demonstrated that Ang II-induced hypertension results in a 3- to 5-fold increase in mouse CD3⁺, CD4⁺, and CD8⁺ T cells within the lymph nodes of this model9. Furthermore, patients with renal injury associated with essential malignant hypertension exhibit a significant reduction in CD4⁺CD25⁺ cells10. Research by Brittany et al. identified CD8⁺ T cells as the primary source of IFN-γ, accumulating in the kidneys following hypertensive challenge. Recent studies have established crucial roles for cytotoxic T lymphocytes (CTLs, CD8⁺) and helper T cells (Th, CD4⁺) in hypertension11. Furthermore, CD4⁺ lymphocytes are key regulators of the Treg/Th17 balance, which is implicated in hypertension and hypertensive end-organ damage. Notably, regulatory T cells (Tregs) exert protective effects. Studies demonstrate that Treg deficiency exacerbates angiotensin II (Ang II)-induced microvascular damage through enhanced immune responses12. Additionally, Ang II promotes secretion of the pro-inflammatory cytokine IL-17 by Th17 cells, contributing to fibrosis progression13. In addition, innate immune cells play key roles in hypertension pathogenesis. Neutrophils, monocytes/macrophages, dendritic cells, myeloid-derived suppressor cells (MDSCs), and innate lymphoid cells (ILCs) are implicated in this process14. Cytokines released from these cells\u0026mdash;including IL-17, IFN-γ, TNF-α, and IL-6\u0026mdash;promote renal and vascular dysfunction, leading to enhanced sodium retention and elevated systemic vascular resistance. Through multiple pathways, these cytokines may stimulate angiotensinogen production, increase renal sodium reabsorption, and exacerbate renal fibrosis.\u003c/p\u003e\u003cp\u003eCollectively, these findings suggest that T lymphocytes contribute to the initiation and progression of hypertension-associated kidney injury. However, the specific role of T lymphocyte gap junctions in regulating hypertension-mediated inflammation remains incompletely understood11,15.Further investigation is warranted to elucidate the interplay among hypertension, renal injury, and T-cell subsets. This study assessed alterations in circulating T-lymphocyte subpopulations in patients with hypertensive renal injury and their associations with clinical parameters and outcomes.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cdiv id=\"Sec4\" class=\"Section3\"\u003e\u003ch2\u003eInclusion criteria\u003c/h2\u003e\u003cp\u003eAs defined by the World Health Organization (WHO), hypertension is diagnosed when systolic blood pressure (SBP) measurements are ≥ 140 mmHg and/or diastolic blood pressure (DBP) measurements are ≥ 90 mmHg on two separate occasions in the absence of antihypertensive medication16.However, consensus diagnostic criteria for hypertensive kidney disease (HKD) remain undefined. In this study, hypertensive renal injury was diagnosed according to the following institutional protocol:(I) Documented primary hypertension;(II) Sustained hypertension (\u0026gt; 140/90 mmHg) for \u0026gt; 5 years preceding proteinuria onset;(III) Persistent proteinuria (urine protein \u0026gt; 300 mg/g creatinine) with bland urinary sediment;(IV) Exclusion of primary glomerular diseases;(V) Exclusion of secondary renal disorders (e.g., diabetic nephropathy, renovascular disease)17. CKD was staged according to estimated glomerular filtration rate (eGFR) as follows¹³: Stage 1: eGFR ≥ 90 mL/min/1.73 m² with kidney damage. Stage 2: eGFR 60–89 mL/min/1.73 m² with kidney damage. Stage 3a: eGFR 45–59 mL/min/1.73 m². Stage 3b: eGFR 30–44 mL/min/1.73 m². Stage 4: eGFR 15–29 mL/min/1.73 m². Stage 5: eGFR \u0026lt; 15 mL/min/1.73 m²13. The control group comprised hospitalized patients with hypertension but without renal injury (eGFR ≥ 60 mL/min/1.73 m² and absence of albuminuria or structural abnormalities).\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003ePatients were excluded if they met any of the following criteria: history of renal replacement therapy; diagnosis of solid tumors, leukemia, lymphoma, or AIDS; presence of connective tissue diseases; or acute infection.\u003c/p\u003e\n\u003ch3\u003eClinical Data Collection\u003c/h3\u003e\n\u003cp\u003eThis retrospective study included 431 patients with HRI (define acronym here if first use) admitted to Guangdong Provincial People's Hospital between January 2016 and July 2022. Clinical data collected for all patients comprised gender, age, hemoglobin, serum creatinine (Scr; measured enzymatically), urine protein-to-creatinine ratio (UPCR), 24-hour urinary protein excretion, white blood cell (WBC) count, and lymphocyte count.\u003c/p\u003e\n\u003ch3\u003eDefinitions and Study Endpoints\u003c/h3\u003e\n\u003cp\u003e CKD was diagnosed and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Estimated glomerular filtration rate (eGFR; mL/min/1.73 m²) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Eq.\u0026nbsp;18. The primary endpoint was all-cause mortality.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eSPSS 26.0 statistical software was used for data collation and analysis. Continuous variables are expressed as mean ± standard deviation (SD) and compared using independent samples t-tests. Categorical variables are presented as frequency counts and percentages (%) and compared using chi-square tests. Univariate and multivariate Cox proportional hazards regression models were used to identify prognostic factors. A two-sided p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Result","content":"\u003cp\u003e\u003cb\u003e1. Demographic characteristics and clinical data\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe study cohort comprised 431 participants, with males constituting 277 (64.3%). Mean age was 78.5 ± 14.2 years. At final follow-up (July 18, 2022), median follow-up duration was 16.5 months. Hypertensive renal injury was diagnosed in 189 patients (43.9%), among whom 122 (64.5%) had CKD stages 1–3. Detailed clinical characteristics are provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic characteristics and clinical data (n = 431)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en (%) or mean ± SD\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78.54 ± 14.23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (M/F)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e277/154\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHRI, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e189 (43.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeath, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e144 (33.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurvive Times (days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e654.64 ± 444.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCKD, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1 ~ 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e122(64.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4 ~ 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67(35.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62.01 ± 28.30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e877.79 ± 1159.59\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e379.89 ± 640.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e732.18 ± 1022.19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e271.50 ± 495.63\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScr mmol/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e130.62 ± 109.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.66 ± 3.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb(g/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e119.75 ± 19.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocyte\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.75 ± 0.72\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.20 ± 0.60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD4 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.62 ± 0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.52 ± 0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + HLADR + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.57 ± 0.40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.29 ± 0.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD25 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.03 ± 0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.04 ± 0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.07 ± 0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.31 ± 0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28-T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.43 ± 0.36\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.54 ± 0.28\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.18 ± 0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.53 ± 0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.52 ± 0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + + CD127low T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.02 ± 0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003ePCR: protein creatinine ratio. ACR: albumin creatinine ratio. HRI: hypertensive renal injury. eGFR: estimated glomerular filtration rate. CKD: chronic kidney disease. Scr: serum creatinine. WBC: white blood cell. Hb: hemoglobin.\u003c/p\u003e\u003cp\u003e\u003cb\u003e2. Comparison of T lymphocyte subpopulations in patients with HRI and Non-HRI\u003c/b\u003e\u003c/p\u003e\u003cp\u003eT lymphocyte profiles were compared between the HRI and Non-HRI groups. Compared with the Non-HRI group, the HRI group exhibited significantly higher values in: age, male proportion, Scr, 24-h urinary protein, 24-h urinary albumin, protein-to-creatinine ratio (PCR), albumin-to-creatinine ratio (ACR), WBC, lymphocyte count, CD3⁺ cells, CD3⁺CD8⁺ cells, CD3⁺HLA-DR⁺ cells, CD3⁺CD8⁺CD28⁻ cells, and CD8⁺CD95⁺ T cells (all P \u0026lt; 0.05). Conversely, the HRI group demonstrated significantly lower eGFR and CD3⁺CD8⁺CD28⁺ T cells (P \u0026lt; 0.05). Detailed comparisons are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of T lymphocyte subpopulations in patients with HRI and Non-HRI\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHRI(n = 189)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-HRI(n = 242)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ2/t\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge(years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e87.78 ± 5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71.34 ± 14.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e15.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e22.722\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e145(76.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e132(54.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44(23.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e110(45.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40.46 ± 21.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.84 ± 20.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-18.720\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.172\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e951.78 ± 1190.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130.53 ± 91.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6.737\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e416.32 ± 660.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.97 ± 10.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6.149\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.023\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e993.21 ± 1120.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e114.54 ± 73.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e381.70 ± 555.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.73 ± 7.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.649\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScr(mmol/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e186.96 ± 139.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86.61 ± 43.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.547\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.80 ± 2.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.55 ± 3.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.891\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb(g/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e112.47 ± 17.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e125.37 ± 19.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-7.094\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.797\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.77 ± 0.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.74 ± 0.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.386\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.30 ± 0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.04 ± 0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD4 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.64 ± 0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.57 ± 0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.765\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.313\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.59 ± 0.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.38 ± 0.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.817\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + HLADR + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.64 ± 0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.38 ± 0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.30 ± 0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.26 ± 0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.465\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.474\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD25 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.03 ± 0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.03 ± 0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.711\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.390\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.04 ± 0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.04 ± 0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.643\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.205\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.78 ± 0.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.06 ± 0.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.241\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.815\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.27 ± 0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.37 ± 0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-4.758\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28-T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.55 ± 0.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.25 ± 0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.53 ± 0.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.55 ± 0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.473\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.058\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.18 ± 0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.18 ± 0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.195\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.996\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.53 ± 0.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.52 ± 0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.355\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.111\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.53 ± 0.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.44 ± 0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.998\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + + CD127low T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.03 ± 0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.02 ± 0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.543\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.967\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003ePCR: protein creatinine ratio. ACR: albumin creatinine ratio. HRI: hypertensive renal injury. eGFR: estimated glomerular filtration rate. CKD: chronic kidney disease. Scr: serum creatinine. WBC: white blood cell. Hb: hemoglobin.\u003c/p\u003e\u003cp\u003e\u003cb\u003e3. Comparison of T lymphocyte subpopulations in patients with different CKD stages\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIndependent samples t-tests and χ² tests revealed significant intergroup differences: compared to CKD stages 4–5, patients with CKD stages 1–3 demonstrated significantly lower Scr, 24-hour urinary protein, 24-hour urinary albumin, PCR, and ACR (P \u0026lt; 0.05), but higher proportions of males, Hb levels, and percentages of CD3⁺ cells, CD3⁺CD8⁺ cells, CD3⁺HLA-DR⁺ cells, CD4⁺CD69⁺ cells, CD3⁺CD8⁺CD28⁻ T cells, CD4⁺CD95⁺ T cells, and CD8⁺CD95⁺ T cells (P \u0026lt; 0.05), with complete statistical comparisons detailed in Table\u0026nbsp;3.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTable.3 Comparison of T lymphocyte subpopulations in patients with different CKD stages\u003c/b\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 ~ 3(n = 122)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 ~ 5(n = 67)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ2/t\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge(years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e85.97 ± 10.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e84.61 ± 10.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.851\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.831\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96(78.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37(55.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26(21.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30(44.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56.70 ± 21.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.42 ± 28.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.077\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.107\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e604.99 ± 509.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1275.64 ± 1663.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-2.007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e190.48 ± 173.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e620.05 ± 933.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-2.327\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e689.04 ± 751.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1335.95 ± 1380.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-2.951\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e209.58 ± 252.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e562.02 ± 683.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-3.321\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScr mmol/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e115.85 ± 40.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e232.69 ± 183.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-5.148\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.04 ± 2.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.64 ± 2.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.106\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.959\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb(g/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e117.89 ± 15.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e113.22 ± 19.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.98 ± 0.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.59 ± 0.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.091\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.44 ± 0.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.11 ± 0.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.894\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD4 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.68 ± 0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.57 ± 0.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.098\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.68 ± 0.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.47 ± 0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + HLADR + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.77 ± 0.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5 ± 0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.3 ± 0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.26 ± 0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.718\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD25 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.04 ± 0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.03 ± 0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.723\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.305\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.04 ± 0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.03 ± 0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.862\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.08 ± 0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.07 ± 0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.151\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.987\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.3 ± 0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.25 ± 0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.373\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.261\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28-T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.66 ± 0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.42 ± 0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.603\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.56 ± 0.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.46 ± 0.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.291\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.578\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.19 ± 0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.16 ± 0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.284\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.371\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.59 ± 0.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.45 ± 0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.335\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.66 ± 0.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.42 ± 0.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.949\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + + CD127low T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.03 ± 0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.02 ± 0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.468\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.756\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003ePCR: protein creatinine ratio. ACR: albumin creatinine ratio. HRI: hypertensive renal injury. eGFR: estimated glomerular filtration rate. CKD: chronic kidney disease. Scr: serum creatinine. WBC: white blood cell. Hb: hemoglobin.\u003c/p\u003e\u003cp\u003e\u003cb\u003e4. Univariate COX regression analysis for mortality\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUnivariate Cox regression identified age, elevated WBC count, and increased proportions of CD3⁺ T cells, CD3⁺CD8⁺ T cells, CD3⁺HLA-DR⁺ T cells, CD8⁺CD69⁺ T cells, CD3⁺CD8⁺CD28⁻ T cells, and CD8⁺CD95⁺ T cells as significant risk factors for all-cause mortality (P \u0026lt; 0.05). Conversely, CD4⁺CD25highCD127low regulatory T cells demonstrated a marked protective association with survival (P = 0.022). Complete hazard ratios with 95% confidence intervals are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate COX regression analysis for survival prognosis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWald\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.095\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e22.063\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.1(1.057, 1.144)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.378\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.207\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.319\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.068\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.686(0.457, 1.029)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.359\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.549\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.002(0.994, 1.011)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCKD stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.099\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.753\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.979(0.859, 1.117)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.342\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.247\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.000(1.000, 1.000)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24h urine albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.159\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.075\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.999(0.999, 1.000)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.919\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.000(1.000, 1.000)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.381\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.000(0.999, 1.000)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScr\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.853\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.356\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.999(0.998, 1.001)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.134\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.746\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.144(1.072, 1.219)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.592\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.442\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.996(0.987, 1.006)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.112\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.079\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.036\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.154\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.119(0.959, 1.306)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.199\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.101\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.904\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.048\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.22(1.002, 1.485)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD4 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.046\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.202\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.052\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.820\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.955(0.642, 1.420)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.815\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.202\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.242\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.260(1.520, 3.360)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + HLADR + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.998\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e29.863\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.713(1.897,3.881)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.832\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.497\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.799\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.435(0.164, 1.153)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD25 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-3.148\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.126\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.314\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.043(\u0026lt; 0.001, 19.645)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-2.831\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.229\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.613\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.204\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.059(0.001, 4.655)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5.456\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.286\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e17.998\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e234.093(18.825,2910.954)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.981\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e.647\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.302\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.129\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.375(0.106,1.331)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28-T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.186\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30.443\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.795(1.940, 4.026)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.463\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.290\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.547\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.629(0.356, 1.111)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD28 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.374\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.711\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.277\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.598\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.454(0.361, 5.853)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.210\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.086\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.769\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.063(0.705, 1.605)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.867\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.213\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.533\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.380(1.567, 3.614)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + + CD127low T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-14.931\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.506\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.267\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt; 0.001(\u0026lt; 0.001,0.113)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003ePCR: protein creatinine ratio. ACR: albumin creatinine ratio. HRI: hypertensive renal injury. eGFR: estimated glomerular filtration rate. CKD: chronic kidney disease. Scr: serum creatinine. WBC: white blood cell. Hb: hemoglobin.\u003c/p\u003e\u003cp\u003e\u003cb\u003e5. Multivariate COX regression analysis for survival prognosis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMultivariate Cox regression identified age (HR 1.116, 95% CI 1.057–1.177; P \u0026lt; 0.001) and CD3⁺HLA-DR⁺ T cells (HR 8.676, 95% CI 1.887–39.886; P = 0.006) as independent risk factors for all-cause mortality. Conversely, CD3⁺CD8⁺ T cells and CD4⁺CD25highCD127low regulatory T cells demonstrated protective associations with survival (P = 0.002 and P = 0.03, respectively). Complete regression results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate COX regression analysis for survival prognosis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWald\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.109\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.044\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.116(1.057,1.177)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.052\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.703\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.053(0.974,1.138)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.368\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.404\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.827\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.363\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.444(0.654,3.188)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-6.169\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.708\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13.048\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.002(\u0026lt; 0.001,0.059)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + HLADR + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.161\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.778\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.706\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e8.676(1.887,39.886)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD69 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.502\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.306\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.306\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.129\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e33.18(0.361,3045.825)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3 + CD8 + CD28-T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.187\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.718\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.731\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.098\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e3.277(0.802,13.394)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD8 + CD95 + T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.716\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.454\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.486\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e15.112(0.874,261.455)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD4 + CD25 + + CD127low T cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-22.167\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.221\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.703\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt; 0.001(\u0026lt; 0.001,0.118)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eWBC: white blood cell.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHypertensive renal injury (HRI), a kidney disorder secondary to chronic hypertension, manifests as impaired glomerular filtration, tubular damage, and renal vascular remodeling. This condition evolves through complex pathological mechanisms involving altered renal hemodynamics, arteriolar constriction, elevated glomerular filtration pressure, and progressive interstitial fibrosis. Notably, T lymphocytes contribute significantly to HRI pathogenesis. Renal-infiltrating T cells drive inflammation, promote fibrotic processes, and induce endothelial dysfunction, culminating in progressive renal functional decline19,20.\u003c/p\u003e\u003cp\u003eThis longitudinal cohort study investigated T lymphocyte subset distributions and their clinical correlates in hypertensive patients with and without renal injury, focusing particularly on elderly individuals. With 64.3% male predominance (mean age 78.5 years), our cohort analysis revealed distinct immunophenotypic patterns predictive of outcomes. The extended follow-up period enabled robust assessment of T-cell profiles' relationship to clinical features and all-cause mortality, providing clinically applicable prognostic indicators for geriatric HRI management.\u003c/p\u003e\u003cp\u003eOur analysis revealed significantly elevated values in the HRI group versus Non-HRI group for: age, male proportion, Scr, 24-hour urinary protein, 24-hour urinary albumin, PCR, ACR, WBC, lymphocyte count, CD3⁺ T cells, CD3⁺CD8⁺ T cells, CD3⁺HLA-DR⁺ T cells, CD3⁺CD8⁺CD28⁻ T cells, and CD8⁺CD95⁺ T cells (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Conversely, eGFR and CD3⁺CD8⁺CD28⁺ T cells were significantly reduced in HRI patients.Compared to CKD stages 4\u0026ndash;5, patients with CKD stages 1\u0026ndash;3 demonstrated significantly lower Scr, 24-hour urinary protein, 24-hour urinary albumin, PCR, and ACR, but higher male proportion, Hb, CD3⁺ T cells, CD3⁺CD8⁺ T cells, CD3⁺HLA-DR⁺ T cells, CD4⁺CD69⁺ T cells, CD3⁺CD8⁺CD28⁻ T cells, CD4⁺CD95⁺ T cells, and CD8⁺CD95⁺ T cells (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Multivariate Cox regression identified age (HR 1.116, 95% CI 1.057\u0026ndash;1.177; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and CD3⁺HLA-DR⁺ T cells (HR 8.676, 95% CI 1.887\u0026ndash;39.886; P\u0026thinsp;=\u0026thinsp;0.006) as independent mortality risk factors, while CD3⁺CD8⁺ T cells and CD4⁺CD25highCD127low regulatory T cells showed protective associations (P\u0026thinsp;=\u0026thinsp;0.002 and P\u0026thinsp;=\u0026thinsp;0.03, respectively). These immunophenotypic alterations demonstrate the broad involvement of T cell-mediated immune activation, early response coordination, immunosenescence, and apoptotic pathways in the pathogenesis of HRI. CD3, a pan-T cell surface marker expressed on mature T lymphocytes, forms an essential component of the T cell receptor (TCR) signaling complex that facilitates antigen recognition. We observed significantly elevated CD3⁺ T cell levels in both HRI and CKD stage 1\u0026ndash;3 cohorts (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), though multivariate analysis did not identify them as independent mortality risk factors. This finding aligns with established reports of renal CD3⁺ T cell infiltration in salt-sensitive hypertension and renal injury21. Moreover, it\u0026rsquo;s reported a decreased absolute count of lymphocyte along with the renal insufficiency22,23,23. In patients with end-stage renal disease (ESRD), T lymphocytes show a downward trend24,25. The decrease in T cells may be associated with T cell immune function impaired26, premature aging, loss of naive T cells and lymphocyte apoptosis22.\u003c/p\u003e\u003cp\u003eHuman leukocyte antigen DR (HLA-DR), a class II molecule of the major histocompatibility complex (MHC), is indispensable in antigen presentation and initiates immune responses by interacting with T-cell receptors (TCRs)27. Previous studies have highlighted the CD3⁺HLA-DR⁺ cell subset as key players in immune activation and antigen presentation. Increased frequency and activity of CD3⁺HLA-DR⁺ cells have been observed in certain immune disorders, infections, and inflammatory conditions28,29. Limited research has been conducted on CD3⁺HLA-DR⁺ cells in hypertension. Available evidence indicates elevated levels of activated T lymphocytes (CD3⁺CD25⁺ and CD3⁺HLA-DR⁺) in the peripheral blood of hypertensive patients30. Another study also reported a significant reduction in CD3⁺HLA-DR⁺ cells following renal denervation in patients with resistant hypertension31. Our findings, along with these previous data, suggest a potential association between elevated CD3⁺HLA-DR⁺ cell levels and hypertension. Interestingly, our study demonstrated significantly higher levels of CD3⁺HLA-DR⁺ T cells in both the HRI group and the stage 1\u0026ndash;3 CKD group. Moreover, HLA-DR⁺ T cells were identified as an independent risk factor for all-cause mortality. Our results indicate that CD3⁺HLA-DR⁺ T cells are not only associated with hypertension but also correlated with hypertensive renal injury and long-term prognosis.\u003c/p\u003e\u003cp\u003eHuman CD8⁺ T cells, also known as cytotoxic T lymphocytes, are effector cells in cell-mediated immunity. CD3⁺CD8⁺ T cells are typically activated through interaction with professional antigen-presenting cells\u0026mdash;primarily dendritic cells in lymph nodes or follicles\u0026mdash;leading to the acquisition of effector functions32. CD8⁺ T cells have been implicated as mediators in angiotensin II-induced endothelial dysfunction, rarefaction of blood vessels, and hypertension33. Youn et al. reported an increase in immunosenescent CD8⁺ T cells and CXCR3-type chemokines in human hypertension34. Renal biopsies from patients with hypertensive nephrosclerosis have shown enhanced infiltration of T cells and their subsets, including both CD4⁺ and CD8⁺ T cells35. Based on existing literature, it remains unclear whether CD3⁺CD8⁺ T cells constitute a protective or risk factor for mortality in patients with hypertensive renal injury. While ESRD patients often exhibit immunodeficiency and lymphopenia, our data also revealed a reduction in CD8⁺ T cells in advanced CKD. Notably, our study demonstrated that CD3⁺CD8⁺ T cells were significantly elevated in the HRI group compared with the non-HRI group. Furthermore, we identified this T-cell subset as an independent protective factor for survival. These findings reveal a novel association between CD3⁺CD8⁺ T cells and HRI, underscoring their potential role in long-term prognosis. Further investigations are warranted to elucidate the underlying mechanisms and clinical implications of these observations.\u003c/p\u003e\u003cp\u003eAs known, Tc cells labeled with CD3\u0026thinsp;+\u0026thinsp;CD8\u0026thinsp;+\u0026thinsp;CD28+, representing cytotoxic T cells, and Ts cells labeled with CD3\u0026thinsp;+\u0026thinsp;CD8\u0026thinsp;+\u0026thinsp;CD28-, denoting suppressor T cells. CD28, a critical co-stimulatory molecule, binds to CD80 and CD86 on the surface of antigen-presenting cells. It is essential for the activation of native T cells and the amplification of immune responses15, promoting T cell proliferation, differentiation, and cytokine production36,37. Antony et al. demonstrated that B7/CD28 co-stimulatory signaling plays a major role in the development of hypertension. Inhibition of T cell activation using CTLA4-Ig or deficiency in CD80/CD86 resulted in reduced blood pressure38. Previous studies have observed an elevation of CD8⁺CD28null T cells in hypertensive patients. Youn et al. reported an increased proportion of CD8⁺CD28null T cells in a cohort of newly diagnosed, untreated hypertensive adults compared with age- and sex-matched normotensive controls34(p3). Furthermore, elevated levels of CD8⁺CD28⁻ cells have been associated with hypertensive left ventricular hypertrophy39. Our study reveals a novel observation: the abundance of CD3⁺CD8⁺CD28⁻ T cells was increased in the HRI group compared with the control group. This finding adds a new dimension to the understanding of the immune landscape associated with hypertensive kidney damage. However, this T cell subset was not identified as an independent risk factor for mortality. Additionally, we observed a general increase in T lymphocytes (including various T cell subsets) in early-stage CKD compared with advanced stages. This phenomenon may be related to the migration of senescent CD28⁻ cells toward myeloid lineages, potentially competing with the output of T progenitor cells in the lymphoid niche22. In summary, these results indicate that CD8⁺CD28⁻ T cells are associated with the development of both hypertension and HRI. Coordinated and amplified T cell immune responses, along with cellular senescence and loss of normal function, may collectively contribute to the initiation and progression of hypertensive renal injury.\u003c/p\u003e\u003cp\u003eCD4⁺CD25⁺⁺CD127[low] refers to a specific population of T cells in human peripheral blood that has been identified as naturally occurring regulatory T cells (nTreg cells)40. These cells are involved in controlling autoimmune responses and preventing excessive immune activation. CD4⁺CD25⁺⁺CD127low T cells express high levels of Foxp3, a transcription factor essential for their suppressive function41. Studies have shown that CD4⁺CD25⁺⁺CD127low T cells play a role in vascular dysfunction associated with hypertension42. Another study revealed a significantly reduced frequency of CD4⁺CD25⁺CD127low Foxp3⁺ regulatory T cells\u0026mdash;including CD4⁺CD25⁺⁺CD127low T cells\u0026mdash;in patients with CKD compared with healthy controls43. Furthermore, Huang and colleagues demonstrated a marked reduction in CD4⁺CD25⁺ cells among patients with renal injury due to primary malignant hypertension compared to control subjects10. These findings suggest that CD4⁺CD25⁺⁺CD127low T cells may be implicated in the pathogenesis of hypertension and target organ damage. In our study, no significant differences were observed in either CD4⁺CD25⁺ or CD4⁺CD25⁺⁺CD127low T cells between the HRI group and across different stages of CKD. However, multivariate COX regression analysis identified CD4⁺CD25⁺⁺CD127low T cells as a protective factor for survival. This represents a novel finding regarding the association between CD4⁺CD25⁺⁺CD127low T cells and long-term prognosis in hypertensive renal injury. Further studies are warranted to validate and expand upon these observations.\u003c/p\u003e\u003cp\u003eHowever, several limitations of our study should be acknowledged. First, this was a retrospective study. Second, the mechanisms underlying the interactions between hypertension, uremic toxins, and their potential effects on T cell growth, differentiation, or survival were not explored. Further research is needed to elucidate these mechanisms and to build upon the insights gained from our study in order to achieve a more comprehensive understanding.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCompared with non-HRI patients, those with HRI exhibited decreased levels of CD3⁺, CD3⁺CD8⁺, CD3⁺HLA-DR⁺, CD3⁺CD8⁺CD28⁻, and CD8⁺CD95⁺ T cells. Furthermore, the level of CD3⁺HLA-DR⁺ cells was identified as an independent risk factor for mortality in HRI patients, whereas CD3⁺CD8⁺ and CD4⁺CD25⁺⁺CD127low T cells were independent protective factors for survival. These findings suggest that the differentiation and activation of T lymphocytes are associated with the progression and long-term prognosis of HRI.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCKD: chronic kidney disease; ESRD: end-stage renal disease; RAAS: renin-angiotensin-aldosterone system; eGFR: estimated glomerular filtration rate; Scr: serum creatinine; WBC: white blood cell; KDIGO: Kidney Disease Improving Global Outcomes; CKD-EPI: Chronic Kidney Disease Epidemiology collaboration equation; PCR: protein creatinine ratio; ACR: albumin creatinine ratio; HRI: hypertensive renal injury; Hb: hemoglobin; HLADR: Human Leukocytes Antigen DR; TCR: T cell receptors\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to the patients who kindly consented to join the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXCF and LW acquired the data. XCF, LDN, ZZ, and WYH analyzed and interpreted the data. XCF, LDN, and YF performed the statistical analysis. HWK and HWX supervised the study and provided mentorship. HWK and HWX conceived the research idea and designed the study. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the General Program of National Natural Science Foundation of China [grant numbers: 82270780], National Natural Science Foundation of China[grant numbers: 82470773], Natural Science Foundation of Guangdong Province [grant numbers: 2024A1515013139] , Guangdong Provincial Science and Technology Planning Project [grant numbers: KS012023323], Guangdong Basic and Applied Basic Research Foundation [grant numbers: 2024A1515010692], and the Basic research program of Guangzhou Science and Technology Project, China [grant numbers: 2024A04J5130]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate.\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. The approval was granted by the Ethics Committees of Guangdong Provincial People’s Hospital. The patient provided written informed consent before participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient has signed the informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGuangdong Provincial Geriatrics Institute, Southern Medical University, Guangzhou,\u0026nbsp;\nChina\u003c/p\u003e\n\u003cp\u003eThe Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePoulter NR, Prabhakaran D, Caulfield M. 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J Exp Med. 2007;204(10):2449-2460. doi:10.1084/jem.20070657\u003c/li\u003e\n\u003cli\u003eMattson DL. Infiltrating immune cells in the kidney in salt-sensitive hypertension and renal injury. Am J Physiol-Ren Physiol. 2014;307(5):F499-F508. doi:10.1152/ajprenal.00258.2014\u003c/li\u003e\n\u003cli\u003eSaad K, Elsayh KI, Zahran AM, Sobhy KM. Lymphocyte populations and apoptosis of peripheral blood B and T lymphocytes in children with end stage renal disease. Ren Fail. 2014;36(4):502-507. doi:10.3109/0886022X.2013.875833\u003c/li\u003e\n\u003cli\u003eMeijers RW, Betjes MG, Baan CC, Litjens NH. T-cell ageing in end-stage renal disease patients: Assessment and clinical relevance. World J Nephrol. 2014;3(4):268-276. doi:10.5527/wjn.v3.i4.268\u003c/li\u003e\n\u003cli\u003eLisowska KA, Storoniak H, Dębska-Ślizień A. T cell subpopulations and cytokine levels in hemodialysis patients. Hum Immunol. 2022;83(2):134-143. doi:10.1016/j.humimm.2021.11.003\u003c/li\u003e\n\u003cli\u003eWinterberg PD, Ford ML. The Effect of Chronic Kidney Disease on T Cell Alloimmunity. Curr Opin Organ Transplant. 2017;22(1):22-28. doi:10.1097/MOT.0000000000000375\u003c/li\u003e\n\u003cli\u003eXiaoyan J, Rongyi C, Xuesen C, et al. The difference of T cell phenotypes in end stage renal disease patients under different dialysis modality. BMC Nephrol. 2019;20(1):301. doi:10.1186/s12882-019-1475-y\u003c/li\u003e\n\u003cli\u003eLaSalle JM, Tolentino PJ, Freeman GJ, Nadler LM, Hafler DA. Early signaling defects in human T cells anergized by T cell presentation of autoantigen. J Exp Med. 1992;176(1):177-186. doi:10.1084/jem.176.1.177\u003c/li\u003e\n\u003cli\u003eHoshino Y, Morishima T, Kimura H, Nishikawa K, Tsurumi T, Kuzushima K. Antigen-driven expansion and contraction of CD8+-activated T cells in primary EBV infection. J Immunol Baltim Md 1950. 1999;163(10):5735-5740.\u003c/li\u003e\n\u003cli\u003eStarska K, Głowacka E, Kulig A, Lewy-Trenda I, Bryś M, Lewkowicz P. The role of tumor cells in the modification of T lymphocytes activity--the expression of the early CD69+, CD71+ and the late CD25+, CD26+, HLA/DR+ activation markers on T CD4+ and CD8+ cells in squamous cell laryngeal carcinoma. Part I. Folia Histochem Cytobiol. 2011;49(4):579-592.\u003c/li\u003e\n\u003cli\u003eTrushina \u0026Eacute;N, Mustafina OK, Soto SK, et al. [The cell immunity in patients with arterial hypertension and obesity]. Vopr Pitan. 2012;81(6):19-26.\u003c/li\u003e\n\u003cli\u003eDelgado Silva J, Almeida JS, Rodrigues-Santos P, Santos Rosa M, Gon\u0026ccedil;alves L. Activated double-negative T cells (CD3+CD4-CD8-HLA-DR+) define response to renal denervation for resistant hypertension. 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Nat Rev Immunol. 2003;3(12). doi:10.1038/nri1248\u003c/li\u003e\n\u003cli\u003eEsensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA. CD28 costimulation: from mechanism to therapy. Immunity. 2016;44(5):973-988. doi:10.1016/j.immuni.2016.04.020\u003c/li\u003e\n\u003cli\u003eVinh A, Chen W, Blinder Y, et al. Inhibition and Genetic Ablation of the B7/CD28 T cell Costimulation Axis Prevents Experimental Hypertension. Circulation. 2010;122(24):2529. doi:10.1161/CIRCULATIONAHA.109.930446\u003c/li\u003e\n\u003cli\u003eGackowska L, Michałkiewicz J, Niemirska A, et al. Loss of CD31 receptor in CD4+ and CD8+ T-cell subsets in children with primary hypertension is associated with hypertension severity and hypertensive target organ damage. J Hypertens. 2018;36(11):2148-2156. doi:10.1097/HJH.0000000000001811\u003c/li\u003e\n\u003cli\u003eYu N, Li X, Song W, et al. CD4(+)CD25 (+)CD127 (low/-) T cells: a more specific Treg population in human peripheral blood. Inflammation. 2012;35(6):1773-1780. doi:10.1007/s10753-012-9496-8\u003c/li\u003e\n\u003cli\u003eCD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells | Journal of Experimental Medicine | Rockefeller University Press. Accessed September 14, 2023. https://rupress.org/jem/article/203/7/1701/46415/CD127-expression-inversely-correlates-with-FoxP3\u003c/li\u003e\n\u003cli\u003eKassan M, Wecker A, Kadowitz P, Trebak M, Matrougui K. CD4+CD25+Foxp3 regulatory T cells and vascular dysfunction in hypertension. J Hypertens. 2013;31(10):1939-1943. doi:10.1097/HJH.0b013e328362feb7\u003c/li\u003e\n\u003cli\u003eAly MG, Ibrahim EH, Karakizlis H, et al. CD4+CD25+CD127-Foxp3+ and CD8+CD28- Tregs in Renal Transplant Recipients: Phenotypic Patterns, Association With Immunosuppressive Drugs, and Interaction With Effector CD8+ T Cells and CD19+IL-10+ Bregs. Front Immunol. 2021;12. Accessed September 14, 2023. https://www.frontiersin.org/articles/10.3389/fimmu.2021.716559\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"T Lymphocyte, hypertensive renal injury, CD3+CD8+CD28- T cell, CD8+CD95+T cell, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-7665190/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7665190/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eAim\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAlthough numerous studies have demonstrated the key role of immune system in hypertensive end organ damage, much less is known regarding the alterations of circulating immune cells in hypertensive renal injury.In this study, we examined the relationship between the distribution of T lymphocyte subsets and long-term clinical outcomes in patients with HRI.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn this study, a total of 431 patients (189 HRI patients and 242 hypertensions patients without renal injury) were recruited. Venous blood samples were used to detect for 15 distinct lymphocyte subsets by flow cytometry. T lymphocyte subsets and their correlations with clinical characteristics and long-term prognosis of patients were analyzed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 431 patients (mean age 78.54\u0026thinsp;\u0026plusmn;\u0026thinsp;14.23 years, 64.3% male) were enrolled. The median follow-up time was 16.54 months, range from 0.56 to 56.48 months. The overall mortality was 35.6% (144 cases). The age, gender, Scr (serum creatinine), level of urine protein, WBC (white blood cell) counts, levels of total lymphocytes, CD3\u0026thinsp;+\u0026thinsp;CD8+, CD3\u0026thinsp;+\u0026thinsp;HLADR+, CD3\u0026thinsp;+\u0026thinsp;CD8\u0026thinsp;+\u0026thinsp;CD28- and CD8\u0026thinsp;+\u0026thinsp;CD95\u0026thinsp;+\u0026thinsp;T cells were significantly higher in the HRI group compared to the non-HRI group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Conversely, eGFR (estimated glomerular filtration rate) and CD3\u0026thinsp;+\u0026thinsp;CD8\u0026thinsp;+\u0026thinsp;CD28\u0026thinsp;+\u0026thinsp;T cells were found to be lower in the HRI group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). As for the different CKD stages, patients with CKD \"1\u0026thinsp;~\u0026thinsp;3\" stages had higher levels of Hb, CD3+, CD3\u0026thinsp;+\u0026thinsp;CD8+, CD3\u0026thinsp;+\u0026thinsp;HLADR+, CD4\u0026thinsp;+\u0026thinsp;CD69+, CD3\u0026thinsp;+\u0026thinsp;CD8\u0026thinsp;+\u0026thinsp;CD28-, CD4\u0026thinsp;+\u0026thinsp;CD95\u0026thinsp;+\u0026thinsp;and CD8\u0026thinsp;+\u0026thinsp;CD95\u0026thinsp;+\u0026thinsp;T cells than that of patients with \"4\u0026thinsp;~\u0026thinsp;5\" stages (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Multivariate COX regression analysis showed that age and CD3\u0026thinsp;+\u0026thinsp;HLADR\u0026thinsp;+\u0026thinsp;T cells were independent risk factors for mortality [HR\u0026thinsp;=\u0026thinsp;1.116(1.057,1.177), P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; HR\u0026thinsp;=\u0026thinsp;8.676(1.887,39.886), P\u0026thinsp;=\u0026thinsp;0.006]. However, CD3\u0026thinsp;+\u0026thinsp;CD8\u0026thinsp;+\u0026thinsp;and CD4\u0026thinsp;+\u0026thinsp;CD25\u0026thinsp;+\u0026thinsp;+\u0026thinsp;CD127low T cells were independent protect factors for survive. [HR\u0026thinsp;=\u0026thinsp;0.005(0.000,0.14), P\u0026thinsp;=\u0026thinsp;0.002, HR\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001(\u0026lt;\u0026thinsp;0.001,0.118), P\u0026thinsp;=\u0026thinsp;0.03]\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePatients with HRI showed lower levels of CD3+, CD3\u0026thinsp;+\u0026thinsp;CD8+, CD3\u0026thinsp;+\u0026thinsp;HLADR+, CD3\u0026thinsp;+\u0026thinsp;CD8\u0026thinsp;+\u0026thinsp;CD28- and CD8\u0026thinsp;+\u0026thinsp;CD95\u0026thinsp;+\u0026thinsp;T cells compared to non-HRI patients. Moreover, level of CD3\u0026thinsp;+\u0026thinsp;HLADR\u0026thinsp;+\u0026thinsp;cells was independent risk factors for mortality in patients with HRI, while CD3\u0026thinsp;+\u0026thinsp;CD8\u0026thinsp;+\u0026thinsp;and CD4\u0026thinsp;+\u0026thinsp;CD25\u0026thinsp;+\u0026thinsp;+\u0026thinsp;CD127low T cells were independent protect factors for survive. These results suggest that T lymphocyte differentiation and activation are associated with the progression and prognosis of HRI.\u003c/p\u003e","manuscriptTitle":"Circulating T lymphocyte subsets are associated clinical features and long-term prognosis in patients with hypertensive renal injury","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-16 16:06:05","doi":"10.21203/rs.3.rs-7665190/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"32197442-f89d-4338-832c-a8fab4171e90","owner":[],"postedDate":"October 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-13T21:23:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-16 16:06:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7665190","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7665190","identity":"rs-7665190","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}