Hypertension remains a leading cause of morbidity and mortality worldwide, with target organ damage being a major concern in its progression. Among the organs affected, the kidneys are particularly vulnerable due to their role in long-term blood pressure regulation and fluid homeostasis. Renal perfusion abnormalities can occur early in the course of essential hypertension, even before structural damage becomes evident. Evaluating renal cortical perfusion is thus essential for early identification of subclinical renal involvement and for understanding the hemodynamic mechanisms contributing to hypertensive nephropathy [1,2].

Conventional imaging modalities such as Doppler ultrasound provide limited information about microvascular flow within the renal cortex. In recent years, contrast-enhanced ultrasound (CEUS) has emerged as a valuable tool for assessing real-time renal microvascular perfusion with high spatial and temporal resolution, without the risks of ionizing radiation or nephrotoxic contrast agents [3,4]. CEUS utilizes microbubble contrast agents to enhance the echogenicity of blood, thereby allowing dynamic assessment of perfusion kinetics in the renal cortex. Parameters such as time to peak (TTP), peak intensity (PI), and area under the curve (AUC) have shown promise in quantifying renal cortical perfusion [5].

The renin–angiotensin system (RAS) plays a pivotal role in the pathophysiology of hypertension and in modulating renal hemodynamics. Activation of the RAS leads to vasoconstriction, sodium retention, and ultimately structural changes within the kidney, including glomerulosclerosis and tubulointerstitial fibrosis [6,7]. Previous studies have shown a correlation between elevated RAS activity and impaired renal perfusion, suggesting that CEUS-based perfusion parameters may serve as surrogate markers of intrarenal RAS activation [8]. Understanding this relationship could be crucial for risk stratification and for tailoring antihypertensive therapies aimed at renal protection [9].

This study aims to assess renal cortical perfusion using CEUS in patients with essential hypertension and to correlate perfusion parameters with systemic markers of RAS activity, thereby elucidating potential early indicators of renal dysfunction in hypertensive patients [10].

Search Strategy

Databases searched: PubMed, Embase, Scopus, and Cochrane Library
Search terms:

• “Contrast-Enhanced Ultrasound” OR “CEUS”
• “Renal Cortical Perfusion” OR “Kidney Perfusion”
• “Hypertension” OR “High Blood Pressure”
• “Renin–Angiotensin System” OR “Plasma Renin Activity” OR “Aldosterone”

Inclusion Criteria

• Human studies (age >18)
• Hypertensive patients assessed with CEUS
• Correlation with at least one RAS parameter
• Full-text available in English
• Prospective/retrospective studies, RCTs

Exclusion Criteria

• Animal studies
• Case reports
• Studies not reporting perfusion metrics or RAS biomarkers

Data Extraction

Extracted: sample size, demographics, CEUS technique, perfusion parameters (e.g., AUC, TTP), RAS biomarker levels, correlation coefficients, and clinical outcomes.

Quality Assessment

• NOS (Newcastle–Ottawa Scale) for observational studies
• Cochrane RoB2 tool for RCTs
• Grading of Recommendations Assessment, Development and Evaluation (GRADE) for evidence strength.

The use of contrast-enhanced ultrasound (CEUS) for evaluating renal cortical perfusion offers a promising, non-invasive imaging modality, especially in hypertensive populations where microvascular dysfunction is often implicated. CEUS enables real-time visualization of cortical microcirculation, potentially reflecting alterations in renal hemodynamics associated with the overactivation of the renin–angiotensin system (RAS). In hypertensive patients, increased renin and angiotensin II levels lead to vasoconstriction, sodium retention, and sympathetic nervous system activation, all of which contribute to impaired renal perfusion and target organ damage [31,32]. Studies using CEUS have demonstrated reduced time-to-peak intensity and prolonged washout times in the renal cortex of hypertensive individuals compared to normotensive controls, indicating delayed and diminished perfusion, possibly linked with intrarenal RAS activation [33,34]. These perfusion deficits were found to correlate positively with plasma renin activity and aldosterone levels, underscoring the physiological role of systemic and intrarenal RAS in modulating cortical microcirculation [35].

Furthermore, RAS inhibitors, including ACE inhibitors and ARBs, have shown to reverse some of these perfusion deficits as assessed by CEUS, suggesting that CEUS might serve as a valuable tool for monitoring therapeutic responses [36,37]. Several experimental models and clinical studies also support the role of angiotensin II in promoting cortical hypoperfusion through afferent and efferent arteriolar constriction and by modulating endothelial dysfunction and inflammatory pathways [38,39]. CEUS parameters, such as peak enhancement and area under the curve (AUC), have been correlated with renal resistive index (RRI) and urinary albumin excretion, further emphasizing the microvascular implications of hypertension [40,41]. Importantly, unlike Doppler-based assessments, CEUS provides a more direct visualization of the cortical capillary bed, thus offering superior sensitivity in detecting early microvascular alterations [42].

Longitudinal studies have also identified that worsening CEUS-derived perfusion metrics precede the development of hypertensive nephropathy and albuminuria, suggesting potential prognostic value [43]. In elderly hypertensive patients, cortical hypoperfusion detected on CEUS was associated with cognitive decline and vascular dementia, indicating systemic consequences of renal microvascular compromise [44,45]. Moreover, CEUS studies in animal models have elucidated the role of oxidative stress and angiotensin II–mediated apoptosis in cortical perfusion heterogeneity, which could translate into future therapeutic targets [46]. The reproducibility and safety of CEUS, with no nephrotoxicity and minimal adverse effects, make it particularly attractive for repeated assessments in chronic hypertensive states [47]. Novel CEUS techniques, such as time–intensity curve analysis and quantitative perfusion software, have further refined the sensitivity of this modality [48].

Finally, integration of CEUS findings with circulating RAS biomarkers and renal function tests could lead to a comprehensive diagnostic approach that not only assesses anatomical changes but also captures dynamic renal vascular physiology [49]. This multidisciplinary diagnostic paradigm may facilitate earlier detection of renal damage, optimize antihypertensive therapy, and ultimately improve outcomes in patients with essential hypertension [50].

Contrast-Enhanced Ultrasound is an effective, non-invasive method to assess renal cortical perfusion and offers valuable insights into RAS activity in hypertensive patients. Integrating CEUS into clinical workflows can improve risk stratification, guide RAS-targeted therapies, and potentially delay hypertensive kidney damage.

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