To the best of our knowledge, this is the first study to investigate various venous reflux patterns and their role in assessing renal prognosis in both PRVF and IRVF. Our research team demonstrated that in sepsis-associated AKI, PRVF may be more sensitive than IRVF for renal prognosis assessment and combining PRVF and IRVF can improve the prediction of renal prognosis. Variations in venous flow patterns, the resolution of obstructed patterns, and the duration of the discontinuous monophasic pattern significantly influenced the 28-day renal prognosis. In PRVF, all subtypes of discontinuous patterns were associated with CVP, while in IRVF, the RVSI was positively correlated with CVP exclusively in the discontinuous pulsatile pattern.

The patterns of PRVF and IRVF were not entirely identical in the study population. Under physiological conditions, renal veins maintain a continuous flow independent of renal function [18, 19]. As venous load increases, cardiac pressure waves propagate further, leading to alterations in the venous blood flow spectrum. Consequently, RVF patterns vary with the severity of venous reflux disorder [20]. The inconsistency between PRVF and IRVF patterns was observed in 31.9% of cases, with the PRVF pattern being more severe in 88% of these instances. Several factors might explain these observations: Firstly, distance plays a role. The proximity of PRVF to the heart often results in a pulsatile flow, whereas IRVF demonstrates a less severe pattern owing to the “ripple” effect. If renal venous reflux impairment is solely as a result of increased right heart pressure, this typically results in either a consistent pattern or PRVF being more severe than IRVF [21]. Second, the possibility of false negatives should be considered. When renal interstitial pressure significantly increases for various reasons, leading to a marked reduction in intrarenal venous compliance, IRVF often fails to respond to downstream pressure changes. This results in a persistent flat flow without pulsatility [21,22,23], which might be incorrectly classified as continuous, masking a significantly impaired reflux state. Our study also identified a minority of cases where IRVF patterns were more severe than those of PRVF. This discrepancy could be attributed to renal interstitial edema without hydrostatic pressure increase, which is often caused by the destruction of renal endothelial glycocalyx and increased endothelial permeability due to factors like sepsis, inflammation, stress, and trauma [24]. Therefore, a persistent flat flow in IRVF does not necessarily imply optimal renal function. This could explain the weak correlation between IRVF and PRVF, particularly in cases of severe obstruction. As PRVF and IRVF are influenced by different factors, a stepwise evaluation of venous reflux status across various renal regions is crucial for determining the optimal site for hemodynamic intervention.

Elevation in CVP impacts venous reflux as it reflects the pressure within the right heart, the endpoint for venous reflux. Therefore, we compared the RVSI with CVP in patients with PRVF and IRVF, respectively. The results of the study indicated distinct patterns between PRVF and IRVF, with their relationship to CVP also varying. In PRVF, RVSI exhibited a significant correlation with CVP across all reflux patterns. However, in IRVF, a significant correlation was observed only in the discontinuous pulsatile pattern. Previous studies primarily targeting IRVF did not reach the same conclusions. The direct connection of the proximal renal vein to the inferior vena cava facilitates easier pressure transmission [21], with its flow pattern largely influenced by downstream pressure (indicated by CVP) and changes in vascular compliance. Moreover, the intrarenal vein’s function is altered by additional factors, such as interstitial edema from enhanced endothelial permeability [25], sensitivity to sympathetic nervous system activation, and the risk of false negatives [26,27,28,29]. This can explain why earlier studies on IRVF found associations between cardiac dysfunction patients and CVP (attributable to increased downstream pressure) [11], whereas sepsis patients showed no CVP association (due to concurrent increased endothelial permeability and downstream pressure) [10]. Based on the above information, our research results suggest that high CVP may lead to renal congestion, with a positive linear relationship between them. Under certain conditions, the higher the CVP, the more severe the renal venous flow congestion assessed by ultrasonography. However, renal congestion is not only influenced by downstream pressure but also by local vascular elasticity. In septic or septic shock states, due to widespread endothelial leakage, interstitial pressure increases, leading to decreased local vascular elasticity and aggravated venous congestion. This means that in clinical practice, excessive resuscitation leading to high CVP should be avoided, as it serves as the downstream pressure for renal venous reflux and is closely related to renal congestion. Avoiding high CVP is beneficial to reducing renal congestion which is beneficial for improving adverse renal outcomes. Our study further demonstrated that the severity of obstruction escalation correlated with lactate levels. According to Guyton’s theory of venous reflux, increased right atrial pressure reduces venous return, leading to systemic venous congestion and impaired lactate clearance [30, 31]. Although few studies focused on the correlation between RVSI and lactate levels, evidence supporting a positive correlation between CVP, as a surrogate for RVSI, and lactate levels exists [32]. Higher CVP was associated with diminished lactate clearance [33].

In terms of renal prognosis, our research demonstrated that in sepsis-associated AKI, PRVF may be more sensitive than IRVF for renal prognosis assessment and combining PRVF and IRVF can improve the prediction of renal prognosis. The discontinuous monophasic pattern exhibited poorer outcomes compared with other patterns in PRVF. A similar pattern was observed in IRVF. Recent studies have focused on the prognostic assessment of renal function in IRVF. A study involving septic patients demonstrated that analyzing IRVF patterns after 24 h correlated with the future prognosis of renal function [10]. RVSI can independently predict morbidity and mortality in individuals with pulmonary hypertension [17]. In the context of ICU patients, monitoring IRVF within the first 24 h did not correlate with renal prognosis, attributed to a variety of factors [9]. Elevated CVP is linked to the discontinuous phenotypes of renal reflux mentioned previously. Concurrently, the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system are affected by renal venous congestion [29]. Venous tone, regulated by the SNS, is a critical determinant of effective circulatory volume [26]. SNS activation further leads to renal vasoconstriction and a decline in glomerular filtration rate [28, 34]. In addition, there is increasing interest in the roles of inflammation and endothelial cell activation [24]. These diverse mechanisms contribute to the potential irreversibility of impaired renal function.

In the context of PRVF phenotypes and their correlation with renal prognosis, we investigated the correlation between varying temporal patterns and renal prognosis in PRVF. Our study found that an inability to alleviate obstruction beyond 5 days poses a risk for chronic renal injury. Moreover, the persistence of a discontinuous monophasic pattern by day 5 is associated with a poorer renal prognosis. Immediate adjustment of venous reflux is beneficial. This finding aligns with prior research [35]. Based on our definition of adverse renal outcomes, and by examining the relationship between renal venous flow patterns and adverse renal outcomes, we found that when the renal venous flow exhibits a monophasic pattern, early AKI is more severe, with higher AKI stages, longer AKI recovery times, and a higher incidence of adverse renal outcomes. Conversely, when the pattern is non-monophasic, AKI stages are lower, indicating less AKI, shorter AKI recovery times, and a lower probability of adverse renal outcomes. Furthermore, early improvement in renal venous congestion facilitates early recovery from AKI and reduces the risk of adverse outcomes. However, we aim to highlight that any hemodynamic modification enhancing venous reflux is beneficial for renal outcomes. Minimally, transitioning patients away from the discontinuous monophasic type is crucial. Both PRVF and IRVF hold significant clinical relevance throughout the treatment process. Our results suggest considering PRVF as an indicator of systemic reflux and IRVF as reflective of organ-specific reflux. Even when systemic reflux normalizes, organ function may remain compromised. In addition to normal systemic reflux, it is critical to address organ-specific reflux. Hemodynamic interventions should be tailored accordingly. Enhancing both systemic and organ-specific reflux conditions is essential for the recovery of organ function.

Our study offers several advantages. First, it establishes the distinct differences between PRVF and IRVF in the kidney, with PRVF demonstrating a more pronounced degree of obstruction than IRVF. Furthermore, PRVF is closely associated with CVP, indicating that the severity of reflux obstruction correlates with the strength of this relationship. Second, our study illustrated that PRVF may be more sensitive than IRVF for renal prognosis assessment and combining PRVF and IRVF can improve the prediction of renal prognosis. We identified that phenotypes of PRVF and IRVF, the timeline for obstruction improvement in PRVF pattern, the discontinuous monophasic pattern, and its duration are significant factors affecting 28-day renal function prognosis. Third, the prognosis for 28-day renal function in cases of PRVF obstruction without improvement for over 5 days was less favorable compared to cases that showed improvement within 3 and 5 days, and outcomes were worse for those with a discontinuous monophasic pattern for 5 days than for the non-monophasic group. These findings offer new insights for intensivists and provide valuable guidance for clinical practice.

However, this study also has some limitations. First, it is a single-center study with a small sample size, and the subgroup with a discontinuous monophasic pattern is particularly limited. While our findings are promising, they require confirmation through further research with a larger cohort. Second, some of the results remain inadequately explained, indicating a need for more comprehensive studies in the future. Third, the absence of long-term follow-up might lead to an underestimation of renal function, suggesting the necessity for extended observation periods in subsequent studies. Finally, renal ultrasonography was performed by a single sonographer who were aware of the patients’ clinical information, which may lead to a high degree of subjectivity in the obtained ultrasound images and result in certain biases. However, we attempted to minimize bias from awareness of clinical information by adopting an assessment of the RVF patterns by two independent expert sonographers who were blind to the patients’ clinical data.