Contrast-enhanced ultrasonography quantitative parameters for evaluation of renal perfusion in septic rats with acute renal injury and their correlation with inflammatory factors

doi:10.3877/cma.j.issn.1672-6448.2022.01.012

Abstract

Abstract:

Objective

To explore the value of contrast-enhanced ultrasonography (CEUS) quantitative parameters in evaluating renal perfusion and monitoring inflammatory response in sepsis-induced acute renal injury (S-AKI).

Methods

Thirty-two healthy Sprague Dawley rats were selected and divided into either a model group or a control group. Sepsis was induced in rats by cecal ligation and puncture. For control rats, the abdominal cavity was only opened and closed, and cecal ligation and puncture were not performed. At 12 h and 24 h after modeling, eight rats from each group were taken to perform contrast-enhanced ultrasonography, and region of interest (ROI) was selected to draw time intensity curve (TIC) and perform quantitative analysis. Blood samples were taken from the inferior vena cava (IVC) to test serum creatinine (SCr), urea, interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10, and the kidney was taken for pathological examination. Independent sample t test and non-parametric test (Mann-Whitney U) were used to analyze the differences between the two groups at different time points, and Spearman correlation test was used to analyze the correlation between quantitative parameters of CEUS [arrival time (AT), time to peak (TTP), ascending slope (AS), peak intensity (PI), half of descending time (DT/2), descending slope (DS), and area under curve (AUC)] and inflammatory factors.

Results

Renal function indexes (Scr and urea) and inflammatory factors (IL-6, TNF-α, and IL-10) in the model group were significantly higher than those of the control group at both time points (P＜0.05). At 2-4 s after SonoVue bolus injection, the blood vessels of the kidney were enhanced at first, then the cortex and medulla developed successively, and the medulla and cortex disappeared in turn. Compared with the control group, in the model group at 12 h, the TTP of the renal cortex significantly increased [(10.47±1.25) s vs (8.30±1.53) s, t=-3.105, P=0.008], the DS and PI of the renal cortex significantly decreased [(-0.13±0.02) dB/s vs (-0.17±0.04) dB/s, t=-3.121, P=0.008; (23.90±1.36) dB vs (27.26±1.88) dB, t=4.102, P=0.001], TTP and DT/2 of the medulla significantly increased [(11.66±1.99) s vs (9.00±1.28) s, t=-3.180, P=0.007; (62.49±4.56) s vs (52.15±7.70) s, t=-3.268, P=0.007], and DS of the medulla significantly decreased [(-0.13±0.02) s dB/s vs (-0.17±0.03) dB/s, t=-2.915, P=0.011]. Compared with the control group, in the model group at 24 h, AS and DS of the renal cortex significantly increased [(0.99±0.17) dB/s vs (0.61±0.19) dB/s, t=-4.262, P=0.001; (-0.23±0.03) dB/s vs (-0.15±0.04) dB/s, t=5.138, P＜0.001], and DT/2 and AUC of the renal cortex significantly decreased [(42.41±3.03) s vs (61.07±6.52) s, t=7.344, P＜0.001; (2477.89±113.37) dB?s vs (3024.93±253.81) dB?s, t=5.566, P＜0.001]; AS, DS, and AT of the renal medulla significantly increased [(1.00±0.27) dB/s vs (0.66±0.17) dB/s, t=-3.061, P=0.008; (-0.23±0.06) dB/s vs (-0.15±0.04) dB/s, t=3.108, P=0.008; (4.30±0.34) s vs (3.77±0.29) s, t=-3.349, P=0.005], and DT/2 and AUC of the renal medulla significantly decreased [(42.73±7.02) s vs (59.64±9.23) s, t=4.124, P=0.001; (2335.75±189.77) dB?s vs (2689.72±285.45) dB?s, t=2.921, P=0.011]. The CEUS quantitative parameters PI and AUC in the renal cortex were significantly correlated with serum IL-6, TNF-α, and IL-10 (r=-0.562, -0.398, -0.512, -0.540, -0.638, and -0.430, respectively, P＜0.05). Renal PAS staining showed that the kidney of rats in the model group showed unclear outline of renal tubules, dilatation, shedding of brush margin, and flattening and shedding of renal tubular epithelial cells, and part of renal tubules were formed in 24 h in the model group.

Conclusion

CEUS can be used to dynamically assess the blood perfusion process of the rat kidney in real time, quantitative evaluate the blood perfusion level, and monitor the inflammatory reaction state of the body.

Key words: Contrast-enhanced ultrasound, Quantitative parameters, Sepsis, Acute renal injury, Blood perfusion, Inflammatory factors

Shuo Wang, Ping Zhao, Qiuyang Li, Ying Zhang, Qing Song, Jianing Zhu, Lianhua Zhu, Yukun Luo. Contrast-enhanced ultrasonography quantitative parameters for evaluation of renal perfusion in septic rats with acute renal injury and their correlation with inflammatory factors[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2022, 19(01): 59-65.

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URL: https://chaosheng.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1672-6448.2022.01.012

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Figures/Tables 6

组别	只数	12 h
组别	只数	Scr（μmol/L， $x ¯$ ±s）	Urea（mmol/L， $x ¯$ ±s）	IL-6［pg/L，M（Q_R）］	TNF-α［pg/ml，M（Q_R）］	IL-10［pg/ml，M（Q_R）］
对照组	8	26.13±2.41	6.21±1.71	2.01（1.12，6.35）	13.52（11.22，16.36）	7.26（2.37，17.76）
模型组	8	52.50±14.01	20.21±2.78	2006.24（783.12，4045.64）	38.60（36.95，56.34）	541.13（392.35，815.77）
统计值		t=-5.241	t=-12.093	U=0.000	t=-6.497	t=-9.334
P值		0.001	0.007	＜0.001	0.001	＜0.001
组别	只数	24 h
组别	只数	Scr（μmol/L， $x ¯$ ±s）	Urea（mmol/L）	IL-6［pg/L，M（Q_R）］	TNF-α［pg/ml，M（Q_R）］	IL-10［pg/ml，M（Q_R）］
对照组	8	26.68±2.69	5.94±1.79	4.88（4.88，9.76）	9.83（2.33，9.83）	3.40（2.41，7.93）
模型组	8	109.23±22.30	14.88（12.40，26.47）	2926.04（223.98，5257.40）	74.71（44.48，104.30）	282.87（54.65，371.56）
统计值		t=-10.397	t=-4.734	U=0.000	t=-6.543	t=-6.342
P值		＜0.001	0.002	＜0.001	＜0.001	＜0.001

组别	只数	12 h
组别	只数	Scr（μmol/L， $x ¯$ ±s）	Urea（mmol/L， $x ¯$ ±s）	IL-6［pg/L，M（Q_R）］	TNF-α［pg/ml，M（Q_R）］	IL-10［pg/ml，M（Q_R）］
对照组	8	26.13±2.41	6.21±1.71	2.01（1.12，6.35）	13.52（11.22，16.36）	7.26（2.37，17.76）
模型组	8	52.50±14.01	20.21±2.78	2006.24（783.12，4045.64）	38.60（36.95，56.34）	541.13（392.35，815.77）
统计值		t=-5.241	t=-12.093	U=0.000	t=-6.497	t=-9.334
P值		0.001	0.007	＜0.001	0.001	＜0.001
组别	只数	24 h
组别	只数	Scr（μmol/L， $x ¯$ ±s）	Urea（mmol/L）	IL-6［pg/L，M（Q_R）］	TNF-α［pg/ml，M（Q_R）］	IL-10［pg/ml，M（Q_R）］
对照组	8	26.68±2.69	5.94±1.79	4.88（4.88，9.76）	9.83（2.33，9.83）	3.40（2.41，7.93）
模型组	8	109.23±22.30	14.88（12.40，26.47）	2926.04（223.98，5257.40）	74.71（44.48，104.30）	282.87（54.65，371.56）
统计值		t=-10.397	t=-4.734	U=0.000	t=-6.543	t=-6.342
P值		＜0.001	0.002	＜0.001	＜0.001	＜0.001

组别	只数	12 h
组别	只数	AT（s）	TTP（s）	PI（dB）	AS（dB/s）	DT/2（s）	DS（dB/s）	AUC（dB•s）
对照组	8	3.73±0.52	8.30±1.53	27.26±1.88	0.71±0.12	56.03±9.96	-0.17±0.04	2965.47±319.25
模型组	8	3.64±0.74	10.47±1.25	23.90±1.36	0.60±0.11	63.24±4.32	-0.13±0.02	2779.59±148.73
t值		0.263	-3.105	4.102	1.932	-1.879	-3.121	1.493
P值		0.796	0.008	0.001	0.074	0.081	0.008	0.158
组别	只数	24 h
组别	只数	AT（s）	TTP（s）	PI（dB）	AS（dB/s）	DT/2（s）	DS（dB/s）	AUC（dB•s）
对照组	8	3.73±0.27	8.19±0.9	26.79±2.25	0.61±0.19	61.07±6.52	-0.15±0.04	3024.93±253.81
模型组	8	3.78±0.51	8.21±1.29	25.54±1.41	0.99±0.17	42.41±3.03	-0.23±0.03	2477.89±113.37
t值		-0.279	-0.025	1.334	-4.262	7.344	5.138	5.566
P值		0.784	0.981	0.204	0.001	＜0.001	＜0.001	＜0.001

组别	只数	12 h
组别	只数	AT（s）	TTP（s）	PI（dB）	AS（dB/s）	DT/2（s）	DS（dB/s）	AUC（dB•s）
对照组	8	3.87±0.52	9.00±1.28	24.66±2.16	0.73±0.12	52.15±7.70	-0.17±0.03	2701.66±243.90
模型组	8	3.66±0.64	11.66±1.99	23.38±2.26	0.64±0.11	62.49±4.56	-0.13±0.02	2685.35±225.17
t值		0.728	-3.180	1.315	1.577	-3.268	-2.915	0.139
P值		0.479	0.007	0.270	0.137	0.007	0.011	0.891
组别	只数	24 h
组别	只数	AT（s）	TTP（s）	PI（dB）	AS（dB/s）	DT/2（s）	DS（dB/s）	AUC（dB•s）
对照组	8	3.77±0.29	9.91±2.20	24.27±1.76	0.66±0.17	59.64±9.23	-0.15±0.04	2689.72±285.45
模型组	8	4.30±0.34	10.07±1.62	23.62±2.38	1.00±0.27	42.73±7.02	-0.23±0.06	2335.75±189.77
t值		-3.349	-0.167	0.63	-3.061	4.124	3.108	2.921
P值		0.005	0.870	0.539	0.008	0.001	0.008	0.011

炎症因子	肾皮质
炎症因子	AT	TTP	PI	AS	DT/2	DS	AUC
IL-6	0.153	0.317	-0.562^a	0.158	-0.206	-0.110	-0.540^a
TNF-α	-0.141	0.202	-0.398^a	0.439^a	-0.417^a	-0.413^a	-0.638^a
IL-10	-0.204	0.373^a	-0.512^a	0.072	-0.064	-0.024	-0.430^a
炎症因子	肾髓质
炎症因子	AT	TTP	PI	AS	DT/2	DS	AUC
IL-6	0.216	0.379^a	-0.241	0.131	-0.071	-0.033	-0.331
TNF-α	0.100	0.240	-0.076	0.364^a	-0.314	-0.277	-0.256
IL-10	-0.058	0.348	-0.125	0.081	-0.001	-0.018	-0.110

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