Renal venous density in the arterial phase of contrast-enhanced CT predicts prognosis in septic shock

Abstract

Objective:

To evaluate a series of vascular parameters derived from abdominal dual-phase contrast-enhanced CT as predictors of 14-day mortality and AKI within 7 days in septic shock.

Methods:

144 patients with septic shock and 60 negative cases were included. The vascular parameters from CT were measured and calculated, including aortic density in arterial (Den_a-A) and venous phase (Den_a-V), renal vein density in arterial (Den_rv-A) and venous phase (Den_rv-V), and renal vein-to-aortic density ratio in arterial (DenR_rv/a-A) and venous phase (DenR_rv/a-V). The parameters were compared between patients and controls, and between patients with different clinical outcomes, and assessed for predictive value of 14-day mortality and AKI within 7 days.

Results:

Patients with septic shock presented significantly lower Den_rv-A (p < 0.001) and DenR_rv/a-A (p = 0.002) levels than the controls. In the septic shock group, patients who died had significantly lower Den_rv-A (p = 0.001) and lower DenR_rv/a-A (p < 0.001) than those who survived. Patients who developed AKI had significantly lower Den_rv-A (p < 0.001) and DenR_rv/a-A (p = 0.011) than those who did not. Multivariate analysis suggested DenR_rv/a-A as an independent predictor of 14-day mortality (OR 0.012; 95% confidence interval [CI]:0.002,0.086; p < 0.001) and Den_rv-A as an independent predictor of AKI (OR 0.989;95% CI:0.982,0.997; p = 0.006).

Conclusion:

In septic shock, significant decreases in Den_rv-A and DenR_rv/a-A were associated with the onset of AKI and predicted higher 14-day mortality.

Advances in knowledge:

The renal vein density and renal vein-aortic density ratio in arterial phase of dual-phase contrast-enhanced CT may serve as good predictors of AKI and mortality in septic shock.

Introduction

Septic shock, the most severe complication of sepsis, is a life-threatening disorder characterized by circulatory and cellular/metabolic dysfunction. ^1,2 Despite standard fluid resuscitation and the use of vasopressors, potential circulatory dysfunction may still involve vital organs and lead to multiorgan injury, including acute kidney injury (AKI), and a higher risk of mortality. ^3–5 The pathogenic mechanisms of septic AKI are complicated and involve systemic and intrarenal haemodynamic effects of the syndrome, as well as immunological and inflammatory mechanisms. ^6,7 Among them, microcirculatory dysfunction of the kidneys may play a crucial role. ⁸

Abdominal dual-phase contrast-enhanced CT is a widely used imaging modality for aetiological diagnosis and evaluation in septic shock, especially that caused by abdominal infections. ^9–11 Specific signs on CT could reflect systemic and focal haemodynamic changes during septic shock and predict the prognosis. ^12,13 For example, flattening of the inferior vena cava (IVC) (reduced anterior–posterior diameter) ^12,14 and a small-calibre abdominal aorta ^15,16 were reported to be signs of systemic circulatory dysfunction, which indicates poor prognosis. For renal haemodynamics, abnormal renal enhancement, which typically manifests as increased and prolonged parenchymal enhancement, could be observed in the context of hypoperfusion. ¹⁶ However, the pattern of renal enhancement can vary widely depending on the severity of circulatory dysfunction, ¹⁰ making qualitative or quantitative evaluation difficult in practice. Nevertheless, there is no well-established CT parameter for the quantitative evaluation of renal haemodynamics in septic shock. Therefore, we defined a series of vascular parameters (detailed below) derived from abdominal dual-phase contrast-enhanced CT and investigated the differences in them between patients with septic shock and healthy controls and among patients with different outcomes. We also evaluated the predictive ability of these parameters in short-term mortality and AKI.

Methods and materials

Study participants

From July 2018 to July 2021, 284 consecutive patients who were clinically diagnosed as septic shock (diagnostic criteria as defined by Singer et al ¹ ) were retrospectively enrolled. All patients were hospitalized in the intensive care unit (ICU) of our institution and underwent abdominal dual-phase contrast-enhanced CT scan after the diagnosis of septic shock. The exclusion criteria were (1) age under 18 years old; (2) known or newly diagnosed advanced chronic kidney disease (CKD, Stages 3–5); (3) congestive heart failure or a mean arterial pressure (MAP) of less than 65 mm Hg during the examination; (4) severe aortic or renal artery disease (aortic or renal artery dissection, aortic or renal artery aneurysm, aortic or renal artery stenosis of more than 50%); 5) structural abnormalities of renal circulation, including arteriovenous malformations, fistula and shunt, or prominent developmental variations that may significantly alter renal circulation, including large accessory renal artery, retroaortic renal vein, and circumaortic renal collar; and 6) data missing from clinical records or CT images. All patients’ clinical records and CT images were collected. According to the principal diagnosis, the patients were further divided into four categories: digestive tract diseases (DTDs; including intestinal obstruction, digestive tract perforation, and intestinal necrosis), biliary pancreatic disease (BPD; including biliary infection and pancreatitis), postsurgical infection (PI), and other diseases (ODs; including pulmonary infection, urinary tract infection, complex abdominal infection, liver abscess, and graft-versus-host response). The primary endpoint of the study was 14-day mortality after the CT examination. ¹⁷ The secondary endpoint of the study was the onset of AKI within 7 days after the CT scan. The definition of AKI was an abrupt decrease in kidney function that occurs over a period of 7 days or less by Kidney Disease Improving Global Outcomes [KDIGO] clinical practice guideline. ¹⁸ The onset of AKI in patients who died within 7 days was confirmed according to clinical records from after the CT scan to death. The selection process for the study population is depicted in Figure 1.

Figure 1.

Study inclusion flowchart. CKD = chronic kidney disease. MAP = mean arterial pressure.

Another 60 patients with mild clinical symptoms were carefully matched for age and sex composition as the control group. All these patients underwent abdominal dual-phase contrast-enhanced CT and had no significant findings.

Our institutional review board approved this observational retrospective study. Written informed consent was not required because of the retrospective nature. All procedures in the study were carried out in accordance with approved guidelines.

CT protocol

Abdominal CT was performed on a multislice spiral CT scanner (Aquilion 64, Canon Medical System) using the following scanning parameters: slice thickness, 0.5 mm; slice increments, 0.5 mm; pitch, 0.9; voltage, 120 kV; current, 180–250 mAs; and collimation, 64 × 0.5 mm. The contrast agent used in this study was iodinated contrast (Ultravist 300, Bayer-Schering), and the dose was 70–90 ml based on the patient’s body weight with an injection flow rate of 3.0 ml s⁻¹ through an automatic injector, followed by a 40 ml bolus of saline solution. After contrast injection, images were acquired with a 35 s delay (arterial phase) and a 65 s delay (venous phase).

Vascular parameters from CT

A series of vascular parameters were derived from CT, including aortic diameter (D_a), anteroposterior diameter of the inferior vena cava (D_ivc), renal artery diameter (D_ra), aortic density in the arterial phase and venous phase (Den_a-A and Den_a-V), renal artery density in the arterial phase and venous phase (Den_ra-A and Den_ra-V), renal vein density in the arterial phase and venous phase (Den_rv-A and Den_rv-V), and renal vein-to-aortic density ratio in the arterial phase and venous phase (DenR_rv/a-A and DenR_rv/a-V). D_a, Den_a-A and Den_a-V were measured at three segments: the level of the left renal artery ostium, as well as 20 mm above and below; the average measurement was obtained. D_ivc was measured at three segments–20 mm above and below the renal veins and at the level of the perihepatic portion–and the average was calculated. D_ra, Den_ra-A and Den_ra-V were measured bilaterally at 30 mm proximal to the renal hilus and averaged. Den_rv-A and Den_rv-V were measured bilaterally at the confluence and averaged. D_a and D_ra were measured in the arterial phase, and D_ivc was measured in the venous phase. DenR_rv/a-A and DenR_rv/a-V were calculated with the following equations:

$${\mathrm{D}\mathrm{e}\mathrm{n}\mathrm{R}}_{rv/a}-\mathrm{A}=\frac{{\mathrm{D}\mathrm{e}\mathrm{n}}_{rv}-\mathrm{A}\mathrm{}}{{\mathrm{D}\mathrm{e}\mathrm{n}}_a-\mathrm{A}}$$

$${\mathrm{D}\mathrm{e}\mathrm{n}\mathrm{R}}_{rv/a}-\mathrm{V}=\frac{{\mathrm{D}\mathrm{e}\mathrm{n}}_{rv}-\mathrm{V}\mathrm{}}{{\mathrm{D}\mathrm{e}\mathrm{n}}_a-\mathrm{V}}$$

All the regions of interest (ROIs) were round circles placed centrally within the vessels, and the area should be no less than 10 mm². The ROIs are also illustrated in Figure 2.

Figure 2.

ROI placement for measurement of vascular parameters on CT. (a) The diameter (D_a) (distance between blue lines) and density (Den_a-A and Den_a-V) (red circle) of the aorta were measured at the level of the left renal artery ostium. Then, measurements at 20 mm above and below were performed similarly, and an average was taken. (b) The anteroposterior diameter of the inferior vena cava (D_ivc) (distance between blue lines) was measured at the level of 20 mm above the renal veins. It was also measured at the level of 20 mm below the renal veins and at the level of the perihepatic portion. An average of the three measurements was then taken. (c, d) Renal artery diameter (D_ra) (red arrows) and renal artery density in the arterial phase and venous phase (Den_ra-A and Den_ra-V) (red circle) were measured at 30 mm proximal to the renal hilus of both sides and averaged. (e, f) Renal vein density in the arterial phase and venous phase (Den_rv-A and Den_rv-V) (red circle) was measured at the confluence bilaterally and averaged.

Among these parameters, D_a and D_ivc were regarded as markers of systemic hypoperfusion in previous studies, ^14,15 while other parameters were self-defined to evaluate renal haemodynamics.

All the parameters were independently measured by two radiologists (one with 5 years of experience and another with 15 years of experience) and then averaged. Both radiologists were blinded to the clinical outcomes of the patients.

Statistical analysis

Continuous variables are expressed as the mean ± standard deviation or median and interquartile range. Categorical variables are displayed as counts. Independent-samples t tests, the Mann–Whitney test, and the chi-squared test were applied to compare the demographic and vascular parameters between patients with septic shock and the controls and among septic shock patients with different outcomes. Uni- and multivariate binary logistic regression analyses were utilized to assess predictors of 14 day mortality and AKI. The variance inflation factor (VIF) was utilized to evaluate multicollinearity. In univariate analysis, the parameters with VIFs of more than five were thought to be largely collinear. Only the parameter with the lowest P value was incorporated into the model for multivariate analysis so that all VIFs of the included parameters were less than 5. The parameters with P values of less than 0.05 in univariate analysis were also excluded from the model for multivariate analysis. Receiver operating characteristic (ROC) analysis and the area under the ROC curve (AUC) were used to evaluate the vascular parameters for predicting prognosis.

In 30 randomly selected data sets, both reviewers measured the vascular parameters (D_a, D_ivc, D_ra, Den_a-A, Den_a-V, Den_ra-A, Den_ra-V, Den_rv-A, Den_rv-V). The reproducibility of measurements was evaluated with the intraclass correlation coefficient (ICC) and coefficient of variation (CV, which is equal to standard deviation between measurements/mean × 100%).

Statistical analyses were performed by using SPSS version 20 (IBM, Armonk, NY). A P value of 0.05 or less was considered to indicate a statistically significant difference.

Results

Characteristics of participants with and without septic shock

A total of 144 patients with septic shock and 60 controls were included in this study. Their demographic characteristics and vascular parameters are reported in Table 1. Patients with septic shock had significantly smaller D_ivc (p = 0.003) and D_ra (p < 0.001) and lower Den_ra-A (p = 0.016), Den_rv-A (p < 0.001), DenR_rv/a-A (p = 0.002), and Den_ra-V (p = 0.005) than the controls.

Table 1.

Characteristics of participants with and without septic shock

Parameter	Septic Shock Group (n = 144)	Control Group (n = 60)	P Value
Age (y)	62 (41, 83)	66 (36, 86)	0.519
Sex			0.697
Male	100	40
Female	44	20
Da (mm)	16.75 ± 2.28	16.67 ± 2.59	0.840
Divc (mm)	14.46 ± 4.43	16.79 ± 3.46	0.003
Dra (mm)	4.81 ± 0.83	5.65 ± 0.74	< 0.001
Dena-A (Hu)	254.95 ± 84.14	268.72 ± 63.41	0.352
Denra-A (Hu)	217.57 ± 71.59	247.43 ± 55.15	0.016
Denrv-A (Hu)	165.89 ± 55.79	205.01 ± 38.84	< 0.001
DenRrv/a-A	0.70 ± 0.27	0.79 ± 0.20	0.002
Dena-V (Hu)	157.13 ± 31.50	165.22 ± 21.63	0.081
Denra-V (Hu)	136.07 ± 27.13	146.97 ± 20.56	0.005
Denrv-V (Hu)	149.52 ± 33.84	154.23 ± 20.50	0.283
DenRrv/a-V	0.95 ± 0.09	0.93 ± 0.05	0.350

D_a: diameter of abdominal aorta; DenR_rv/a-A and DenR_rv/a-V: renal vein-to-aortic density ratio in the arterial phase and venous phase; Den_a-A and Den_a-V: aortic density in the arterial phase and venous phase; Den_ra-A and Den_ra-V: renal artery density in the arterial phase and venous phase; Den_rv-A and Den_rv-V: renal vein density in the arterial phase and venous phase; D_ivc: anteroposterior diameter of the inferior vena cava; D_ra: diameter of renal artery.

Predictors of 14-day mortality in patients with septic shock

In the septic shock group, 85 patients died within 14 days after the CT examination, and 59 survived. Their demographic and clinical characteristics, as well as vascular parameters, are reported in Table 2. Patients who died within 14 days were older (p < 0.001), presented with significantly smaller D_ra (p = 0.017), higher Den_a-A (p < 0.001), higher Den_ra-A (p = 0.002), higher Den_a-V (p = 0.018), higher Den_rv-V (p = 0.038), lower Den_rv-A (p = 0.001), and lower DenR_rv/a-A (p < 0.001) than those who survived.

Table 2.

Characteristics of patients who died within 14 days and those who survived in the septic shock group

Parameter	Patients with Septic Shock		P Value
	Died (n = 85)	Survived (n = 59)
Age (y)	67 (42, 92)	60 (39, 81)	< 0.001
Sex			0.358
Male	62	38
Female	23	21
Principal Diagnosis			0.065
DTD	22	21
BPD	17	16
PI	36	12
OD	10	10
Da (mm)	17.01 ± 2.27	16.39 ± 2.27	0.108
Divc (mm)	14.13 ± 4.76	14.94 ± 3.89	0.262
Dra (mm)	4.68 ± 0.83	5.01 ± 0.79	0.017
Dena-A (Hu)	276.10 ± 88.65	224.47 ± 66.87	< 0.001
Denra-A (Hu)	232.62 ± 75.89	196.34 ± 59.20	0.002
Denrv-A (Hu)	153.74 ± 59.30	183.40 ± 45.31	0.001
DenRrv/a-A	0.59 ± 0.24	0.86 ± 0.23	< 0.001
Dena-V (Hu)	162.26 ± 29.91	149.74 ± 32.51	0.018
Denra-V (Hu)	137.66 ± 25.69	133.76 ± 29.14	0.398
Denrv-V (Hu)	154.38 ± 35.27	142.52 ± 30.61	0.038
DenRrv/a-V	0.95 ± 0.10	0.95 ± 0.08	0.818

Univariate and multivariate analyses were performed to identify factors associated with 14-day mortality (Supplementary Table 1). In univariate analysis, age, Den_a-A, Den_ra-A, Den_a-V, and Den_rv-V were positively related to 14-day mortality, while D_ra, Den_rv-A and DenR_rv/a-A were negatively associated with 14-day mortality. In multivariate analysis, age was independently positively related to 14-day mortality (odds ratio, 1.029; 95% confidence interval [CI]: 1.002, 1.054; p = 0.038), while DenR_rv/a-A was negatively independently associated with 14-day mortality (odds ratio, 0.012; 95% confidence interval: 0.002, 0.086; p < 0.001).

ROC curves for predicting 14-day mortality with DenR_rv/a-A, age, and DenR_rv/a-A combined with age are shown in Figure 3. DenR_rv/a-A alone showed an area under the ROC curve that was comparable to that of DenR_rv/a-A combined with age (0.792 vs 0.799, p = 0.600) and significantly greater than that of age alone (0.792 vs 0.674, p = 0.025). When the cut-off value was 0.76, the sensitivity and specificity of DenR_rv/a-A for the prediction of 14-day mortality were 0.678 and 0.812, respectively.

Figure 3.

Receiver operating characteristic analysis for the prediction of 14-day mortality. The areas under the receiver operating characteristic curve (AUCs) for DenR_rv/a-A alone were comparable to the AUCs for DenR_rv/a-A combined with age and significantly greater than the AUCs for age. DenR_rv/a-A: renal vein-to-aortic density ratio in arterial phase. *P, .05, compared with DenR_rv/a-A combined with age. P value obtained from significance test of Uno C statistic.

Illustrations and examples of control patients, patients with septic shock who survived, and patients with septic shock who died within 14 days are shown in Figure 4.

Figure 4.

Illustrations and examples of renal circulation in patients without septic shock (a), patients with septic shock who survived (b), and patients with septic shock who died within 14 days (c). The darkening of renal vein in the schematic diagram indicates a decrease in renal vein density (the delay of renal circulation). The darkening of renal cortex suggests the renal haemodynamic dysfunction in septic shock patients. Compared with that of patients without septic shock (a), the density of the aorta (Den_a-A), renal artery (Den_ra-A) and renal vein (Den_rv-A) in the arterial Phase in patients with septic shock who survived (b) were all decreased, while the ratio of Den_rv-A and Den_a-A (DenR_rv/a-A) were similar. In patients with septic shock who died (c), the further decrease in Den_rv-A and the relative recovery of Den_a-A and Den_ra-A led to a more serious significantly decreased DenR_rv/a-A and suggested a haemodynamic delay compared with patients who survived or did not have septic shock.

Predictors of AKI in patients with septic shock

Ninety-one of 144 patients with septic shock developed AKI in the 7 days following the CT examination, while 53 patients did not have AKI. Their demographic, clinical and imaging data are listed in Table 3. In septic shock group, the onset of AKI was more common in elderly (p = 0.025) and female (p = 0.011) patients. Patients who developed AKI had a significantly greater D_a (p = 0.030), lower Den_rv-A (p < 0.001), and lower DenR_rv/a-A (p = 0.011) than those who did not.

Table 3.

Characteristics of patients with and without AKI at 7 days in the septic shock group

Parameter	Patients with Septic Shock		P Value
	With AKI (n = 91)	Without AKI (n = 53)
Age (y)	63 (41, 85)	58 (41, 75)	0.025
Sex			0.011
Male	70	30
Female	21	23
Principal Diagnosis			0.740
DTD	20	23
BPD	19	14
PI	28	20
OD	11	9
Da (mm)	17.07 ± 2.19	16.22 ± 2.35	0.030
Divc (mm)	14.50 ± 4.51	14.40 ± 4.33	0.895
Dra (mm)	4.94 ± 1.20	4.75 ± 0.94	0.334
Dena-A (Hu)	253.99 ± 84.69	256.59 ± 83.96	0.859
Denra-A (Hu)	215.24 ± 72.43	222.08 ± 70.58	0.582
Denrv-A (Hu)	153.55 ± 53.13	187.08 ± 54.31	< 0.001
DenRrv/a-A	0.66 ± 0.28	0.78 ± 0.24	0.011
Dena-V (Hu)	156.56 ± 33.14	158.11 ± 28.75	0.777
Denra-V (Hu)	135.25 ± 28.98	137.46 ± 23.81	0.639
Denrv-V (Hu)	149.64 ± 36.11	149.32 ± 29.87	0.956
DenRrv/a-V	0.95 ± 0.10	0.95 ± 0.08	0.564

Uni- and multivariate analyses of the demographic, clinical and imaging parameters identified sex and Den_rv-A as independent predictors of AKI at 7 days (Supplementary Table 2). Female sex was a risk factor for AKI at 7 days (odds ratio, 2.258; 95% confidence interval: 1.074, 5.128; p = 0.033), while Den_rv-A was negatively associated with AKI at 7 days (odds ratio, 0.989; 95% CI: 0.982, 0.997; p = 0.006).

Reproducibility

Agreement between the two reviewers was excellent for measurement of all the vascular parameters (Table 4).

Table 4.

Inter observer reproducibility for measurement of vascular parameters

	Observer A	Observer B	P value	ICC	CV
Da (mm)	16.53 ± 2.71	16.46 ± 2.67	0.915	0.99	1.94%
Divc (mm)	14.65 ± 4.26	14.61 ± 4.16	0.968	0.99	1.98%
Dra (mm)	4.90 ± 0.80	4.86 ± 0.75	0.837	0.98	3.48%
Dena-A (Hu)	293.82 ± 87.22	294.12 ± 86.81	0.978	0.99	1.81%
Denra-A (Hu)	161.68 ± 30.33	163.24 ± 30.32	0.841	0.99	2.73%
Denrv-A (Hu)	253.40 ± 72.02	256.35 ± 73.02	0.876	0.98	3.61%
Dena-V (Hu)	144.83 ± 27.41	145.12 ± 27.04	0.966	0.97	3.94%
Denra-V (Hu)	175.98 ± 64.69	174.22 ± 64.30	0.917	0.98	3.71%
Denrv-V (Hu)	163.66 ± 38.68	165.60 ± 38.13	0.837	0.99	3.36%

CV: coefficient of variation;ICC: Intraclass correlation coefficient.

Discussion

AKI is a frequent complication in patients with septic shock and contributes to high mortality. ^5,19 Renal haemodynamic dysfunction is believed to play an important role in septic AKI. ^20,21 Via conventional dual-phase contrast-enhanced CT, our study investigated the differences in a series of readily accessible vascular parameters in septic shock, including D_a, D_ivc, D_ra, Den_a-A, Den_a-V, Den_rv-A, Den_rv-V, DenR_rv/a-A and DenR_rv/a-V, and evaluated them as markers of renal haemodynamic disorder and predictors of subsequent AKI and mortality. The main results could be simply summarized to the following four points: 1) Patients with septic shock presented significantly smaller D_ivc and D_ra, and lower Den_rv-A and DenR_rv/a-A than age- and sex-matched negative controls. 2) Patients who died within 14 days were significantly older and had smaller D_ra, lower Den_rv-A, and lower DenR_rv/a-A than the survivors. Similarly, patients who developed AKI within 7 days were also older and had significantly lower Den_rv-A and lower DenR_rv/a-A than those who did not. 3) DenR_rv/a-A and age were identified as independent predictors of 14-day mortality, while Den_rv-A and female sex were identified as independent predictors of AKI within 7 days. 4) DenR_rv/a-A alone acted as a good predictor of 14-day mortality at a cut-off value of 0.76 (sensitivity: 0.678; specificity: 0.812).

Generally, arterial Phase images obtained after a > 25 s delay after contrast injection can adequately show opacified bilateral renal veins, ^22,23 which makes it possible to quantitatively evaluate renal vein density in the arterial phase. Our study revealed significantly delays in renal circulation in septic shock, especially in critically ill patients (who died within 14 days or developed AKI within 7 days), through a significantly decreased density of the renal vein in the arterial phase (Den_rv-A) with relative venous phase (Den_rv-V) recovery. Moreover, a comparable or increased density of the aorta and renal artery, as well as a significantly decreased renal vein-aortic density ratio in the arterial phase (DenR_rv/a-A), further suggested that haemodynamic delay may occur at the level of the renal parenchyma (Figure 4).

Septic AKI was once presumed to be caused by renal hypoperfusion and the consequent acute tubular necrosis. ^24,25 However, there is increasing evidence that renal blood flow is normal or even increased in septic AKI, ^26,27 suggesting that renal ischaemia is not a leading cause. This finding also explains the abnormally increased renal parenchymal enhancement in septic shock on CT imaging. ^10,16 Dysfunction of the renal microvascular system is now regarded as an important pathogenic factor in septic AKI. ^7,8 Hypotheses include a redistributed parenchymal blood flow of relative cortical hypoperfusion and medullary overflow, ²⁸ relative venous hypertension-induced microvascular congestion and tissue oedema, ^8,29 the presence of efferent arteriole overdilation, ²⁶ inflammation-activated shunt systems connecting afferent and efferent arterioles, ²⁸ and tubular cell dysfunction-induced back leakage. ³⁰ However, the specific mechanism is not fully understood. Previous studies have reported various patterns of renal parenchyma enhancement on contrast-enhanced CT, from typical increased and prolonged enhancement ^10,16 to focal and heterogeneous enhancement ¹⁰ or even decreased enhancement in some critically ill patients, ¹⁶ making these findings rather unspecific. ³¹ In our study, we investigated the difference in renal vein density between patients who survived and those who died from septic shock and found that a haemodynamic delay at the level of the renal parenchyma could be associated with AKI and poor prognosis. Among the hypotheses mentioned above, this result may support the hypothesis of relative venous hypertension which could lead to renal microvascular congestion and delayed venous drainage, while it seems contradictory to the hypothesis of an inflammation-activated shunt which might lead to earlier venous drainage rather than delay.

Contrast-enhanced CT can play an important role in the diagnosis and evaluation of septic shock, not only for structural abnormalities and lesions but also for haemodynamic changes. ^12,13 With a standardized scanning protocol and strict quality control, quantitative assessment of haemodynamic changes based on basic parameters such as vascular density and diameter is possible. Flattening of the inferior vena cava and a small-calibre aorta were reported to be signs of systemic hypoperfusion in septic shock. ^14,15 In our study, patients with septic shock had a smaller anteroposterior diameter of the IVC than the controls, but the diameter of the aorta in both groups was not significantly different, probably due to the low sensitivity and specificity of this sign. ¹⁰ In addition, neither sign was predictive of prognosis, while DenR_rv/a-A alone could act as a good predictor of 14-day mortality. In a previous study, the hollow adrenal gland sign (HAGS) was proposed as a predictor of poor prognosis in septic shock. ³² Its overall sensitivity and specificity for death were 0.44 and 0.86, respectively. DenR_rv/a-A seemed to have better sensitivity (0.678 vs 0.44) and comparative specificity (0.812 vs 0.86) than HAGS. More importantly, the measurement of renal vein density and diameter is achievable in the routine work, and the calculation of DenR_rv/a-A is simple and independent of the observer’s experience with good reproducibility, which makes it more convenient and applicable than HAGS (accurate recognition requires experienced radiologists) by both radiologists and clinicians in screening critically ill patients with septic shock. Early recognition of the patients in danger would remind clinicians to pay more attention to the potential progression of the disease and choose appropriate treatments.

Our study had some limitations. First, because of its retrospective nature and relatively small sample size at a single institution, further prospective multicentre studies are needed for validation. Second, the majority of patients in this study had abdominal infections, which may lead to selection bias. Thus, the application of our findings should be carefully limited to septic shock with abdominal infections. Finally, contrast agent use may increase the risk of AKI and act as a confounding factor. However, since we excluded patients with a history of CKD, evidence has shown that intravenous administration of iodinated contrast media might add little risk of AKI in patients with normal renal function. ^33,34 The influence of contrast agent-induced AKI was probably well controlled.

In conclusion, our results suggested a tendency of delayed renal circulation in septic shock, especially in critically ill patients. Among the vascular parameters derived from abdominal dual-phase contrast-enhanced CT, Den_rv-A and DenR_rv/a-A were the strongest predictors of short-term AKI and mortality, respectively. Therefore, measurement of Den_rv-A and DenR_rv/a-A on contrast-enhanced CT may serve as a useful and convenient method for screening critically ill patients with septic shock.