肾素-血管紧张素系统可预测腹腔镜肾根治术后的急性肾损伤

doi:10.12122/j.issn.1673-4254.2024.11.19

摘要/Abstract

摘要：

目的分析患者围术期肾素-血管紧张素系统（RAS）的变化来探讨腹腔镜根治性肾切除术（LRN）术后急性肾损伤（AKI）的发病机制及其对AKI的预测作用。方法纳入2023年12月至2024年3月解放军总医院第三医学中心接受LRN患者82例，依据国际肾病改善全球预后（KDIGO）标准，根据术后是否发生AKI将患者分为AKI组（n=57）和非AKI组（n=25）。在术前、术后24 h留取血液、尿液标本，检测RAS常规通路尿醛固酮，RAS非常规通路血浆血管紧张素转换酶2（ACE 2）、血管紧张素1-7（Ang 1-7）、核因子E2相关因子-2（Nrf-2）和IL-10水平，分析其与AKI发生的相关性，单因素和多因素Logistic回归分析术后AKI的危险因素，采用受试者工作特征（ROC）曲线分析其对AKI的预测价值。结果 LRN术后AKI的发生率为69.5%。AKI组术后24 h尿醛固酮水平显著高于非AKI组（P=0.022），血浆ACE 2、Ang1-7、Nrf-2、IL-10水平显著低于非AKI组（P<0.05）。相关分析显示，术后24 h尿醛固酮水平与AKI成正相关（P=0.029）、与eGFR成负相关（P=0.007），血浆ACE 2、Nrf-2、IL-10水平与AKI成负相关（P<0.05）、与eGFR成正相关（P=0.029，P=0.013，P=0.008）。单因素Logistic回归分析显示，尿醛固酮是AKI发生的危险因素（OR=1.01，95% CI 1.00~1.001，P=0.026），血浆ACE2、Ang1-7、Nrf-2和IL-10是AKI发生的保护因素（OR=0.98，95% CI 0.97~0.998，P=0.030；OR=0.98，95% CI 0.96~0.998，P=0.041；OR=0.99，95% CI 0.99~0.999，P=0.023；OR=0.99，95% CI 0.97~0.999，P=0.044）。多因素Logistic回归分析显示，尿醛固酮是AKI的独立危险因素（OR=1.002，95% CI 1.000~1.004，P=0.030），血浆Nrf-2是AKI的独立保护因素（OR=0.999，95% CI 0.999~1.000，P=0.042），曲线下面积（AUC）分别为0.651和0.679；联合分析非常规通路各个指标，AUC为0.758，联合分析醛固酮和非常规通路各个指标，AUC为0.788。结论 AKI患者术后24 h RAS常规通路活性增强，非常规通路活性减弱，RAS系统可能通过影响eGFR参与了AKI的发生；醛固酮联合非常规通路各指标可用于预测LRN术后AKI。

关键词: 急性肾损伤, 根治性肾切除术, 肾素-血管紧张素系统

Abstract:

Objective To investigate the role of the renin-angiotensin system (RAS) in the pathogenesis of acute kidney injury (AKI) after laparoscopic radical nephrectomy (LRN) and the predictive value of RAS activation status for AKI. Methods Eighty-two patients undergoing LRN at the Third Medical Center of General Hospital of PLA from December, 2023 to March, 2024 were enrolled, including 57 with postoperative AKI and 25 without AKI according to KDIGO criteria. Blood and urine samples were collected from the patients before and at 24 h after the operation for analyzing the correlation of urinary aldosterone, plasma ACE2, Ang1-7, Nrf-2, and IL-10 levels with postoperative AKI. Univariate and multivariate logistic regression analyses and ROC curve were employed to identify the risk factors for postoperative AKI and their predictive value for AKI. Results Compared with those without postoperative AKI, the patients with AKI had significantly higher postoperative urinary aldosterone levels and lower plasma ACE 2, Ang 1-7, Nrf-2, and IL-10 levels (P<0.05). Postoperative urinary aldosterone level was positively correlated with AKI and negatively with estimated glomerular filtration rate (eGFR) (P<0.05); plasma levels of ACE 2, Nrf-2, and IL-10 were all negatively correlated with AKI and positively with eGFR. Urinary aldosterone was a risk factor and plasma ACE 2, Ang 1-7, Nrf-2 and IL-10 were protective factors for AKI, and among them urinary aldosterone was an independent risk factor (AUC=0.651) and plasma Nrf-2 was an independent protective factor (AUC=0.679). The unconventional RAS pathway indices had an AUC of 0.758, and aldosterone combined with the unconventional pathway indices had an AUC of 0.788 for predicting postoperative AKI. Conclusion Activation of the conventional RAS pathway and suppression of the unconventional pathway contribute to AKI following LRA possibly by affecting eGFR. Aldosterone combined with the unconventional pathway indicators can predict the occurrence of AKI after LRN.

Key words: acute kidney injury, radical nephrectomy, renin-angiotensin system

李佳馨, 刘毅, 刘向杰, 徐龙河, 刘永哲. 肾素-血管紧张素系统可预测腹腔镜肾根治术后的急性肾损伤[J]. 南方医科大学学报, 2024, 44(11): 2220-2226.

Jiaxin LI, Yi LIU, Xiangjie LIU, Longhe XU, Yongzhe LIU. Acute kidney injury after laparoscopic radical nephrectomy: role of the renin-angiotensin system and the predictive value of its activation status[J]. Journal of Southern Medical University, 2024, 44(11): 2220-2226.

图/表 6

参考文献 33

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Characteristics	AKI group (n=57)	Non-AKI group (n=25)	t /χ²/Z	P
Age (year)	59.65±9.71	58.32±8.59	0.58	0.56
Gender (male/female)	41/16	11/14	5.84	0.02
BMI (kg/m²)	25.58±3.29	25.04±2.60	-0.72	0.48
Smoking [n (%)]	16 (28.1%)	6 (4%)	0.15	0.70
Alcohol consumption[n (%)]	12 (21.1%)	8 (32%)	1.13	0.29
Combined disease [n (%)]
Diabetes	6 (10.5%)	2 (8%)	0.13	0.72
Cardiovascular disease	3 (5.3%)	1 (4%)	0.06	0.81
blood volume	100 (50, 200)	100 (50, 250)	-0.67	0.50
urine output	100 (50, 175)	100 (50, 100)	-0.85	0.40
Crystalloid solution (mL)	1000 (1000, 1500)	1500 (1000, 1500)	-1.57	0.12
Surgery time (min)	160 (111.5, 222)	170 (111.5, 195)	-0.08	0.94
sCr (mmol/L)	70.29±11.67	65.48±12.59	-1.68	0.09
eGFR (mL/min/1.73 m² )	94.42±12.97	97.68±15.89	0.54	0.60

Characteristics	AKI group (n=57)	Non-AKI group (n=25)	t /χ²/Z	P
Age (year)	59.65±9.71	58.32±8.59	0.58	0.56
Gender (male/female)	41/16	11/14	5.84	0.02
BMI (kg/m²)	25.58±3.29	25.04±2.60	-0.72	0.48
Smoking [n (%)]	16 (28.1%)	6 (4%)	0.15	0.70
Alcohol consumption[n (%)]	12 (21.1%)	8 (32%)	1.13	0.29
Combined disease [n (%)]
Diabetes	6 (10.5%)	2 (8%)	0.13	0.72
Cardiovascular disease	3 (5.3%)	1 (4%)	0.06	0.81
blood volume	100 (50, 200)	100 (50, 250)	-0.67	0.50
urine output	100 (50, 175)	100 (50, 100)	-0.85	0.40
Crystalloid solution (mL)	1000 (1000, 1500)	1500 (1000, 1500)	-1.57	0.12
Surgery time (min)	160 (111.5, 222)	170 (111.5, 195)	-0.08	0.94
sCr (mmol/L)	70.29±11.67	65.48±12.59	-1.68	0.09
eGFR (mL/min/1.73 m² )	94.42±12.97	97.68±15.89	0.54	0.60

Variable	Time	AKI group (n=57)	Non-AKI group (n=25)	P
Urinary aldosterone (pg/mL)	T₁	362.63±53.87	381.27±38.26	0.122
Urinary aldosterone (pg/mL)	T₂	433.65±44.95	407.34±51.29	0.022
Plasma ACE 2 (pg/mL)	T₁	219.74±29.84	210.82±33.05	0.233
Plasma ACE 2 (pg/mL)	T₂	210.88±36.68	230.60±35.13	0.026
Plasma Ang 1-7 (pg/mL)	T₁	176.15±24.46	172.63±24.71	0.551
Plasma Ang 1-7 (pg/mL)	T₂	191.71±31.22	206.82±25.45	0.036
Plasma Nrf-2 (ng/mL)	T₁	1024.12±245.77	978.27±204.63	0.417
Plasma Nrf-2 (ng/mL)	T₂	1213.26±177.50	1314.99±172.10	0.018
Plasma IL-10 (pg/mL)	T₁	361.55±41.98	360.01±42.52	0.879
Plasma IL-10 (pg/mL)	T₂	331.06±40.14	351.49±40.67	0.038

Variable	Time	AKI group (n=57)	Non-AKI group (n=25)	P
Urinary aldosterone (pg/mL)	T₁	362.63±53.87	381.27±38.26	0.122
Urinary aldosterone (pg/mL)	T₂	433.65±44.95	407.34±51.29	0.022
Plasma ACE 2 (pg/mL)	T₁	219.74±29.84	210.82±33.05	0.233
Plasma ACE 2 (pg/mL)	T₂	210.88±36.68	230.60±35.13	0.026
Plasma Ang 1-7 (pg/mL)	T₁	176.15±24.46	172.63±24.71	0.551
Plasma Ang 1-7 (pg/mL)	T₂	191.71±31.22	206.82±25.45	0.036
Plasma Nrf-2 (ng/mL)	T₁	1024.12±245.77	978.27±204.63	0.417
Plasma Nrf-2 (ng/mL)	T₂	1213.26±177.50	1314.99±172.10	0.018
Plasma IL-10 (pg/mL)	T₁	361.55±41.98	360.01±42.52	0.879
Plasma IL-10 (pg/mL)	T₂	331.06±40.14	351.49±40.67	0.038

Characteristics	r	P
Urinary aldosterone (pg/mL)	-0.294	0.007
Plasma ACE 2 (pg/mL)	0.241	0.029
Plasma Ang 1-7 (pg/mL)	0.179	0.108
Plasma Nrf-2 (ng/mL)	0.274	0.013
Plasma IL-10 (pg/mL)	0.293	0.008