Super-Resolution Contrast-Enhanced Ultrasound Detects Renal Microvascular Impairment in Early Chronic Kidney Disease with Preserved Estimated Glomerular Filtration Rate: A Comparative Study with Conventional Contrast-enhanced Ultrasound and Serum Biomarkers

Renal microvascular rarefaction is an early pathological event in chronic kidney disease (CKD) that may precede a measurable decline in renal function. However, currently available non-invasive tools remain limited in detecting these early structural alterations. This study aimed to evaluate the value of super-resolution contrast-enhanced ultrasound (SR-CEUS) for assessing renal cortical microvascular impairment in early CKD with preserved estimated glomerular filtration rate (eGFR), and to compare its performance with conventional contrast-enhanced ultrasound (CEUS) and serum biomarkers.

In this prospective study, 39 patients with early CKD scheduled for renal biopsy and 41 healthy controls were enrolled. All participants underwent CEUS and SR-CEUS imaging during the same contrast-enhanced examination. Quantitative SR-CEUS parameters, including vessel density (VD), mean velocity (MV) and perfusion index (PI), as well as conventional CEUS time-intensity curve parameters, were analyzed. Logistic regression models were constructed based on variables with significant between-group differences, and diagnostic performance was assessed using receiver operating characteristic analysis. DeLong tests were used to compare model performance. Correlations between imaging-derived parameters and renal functional biomarkers across all participants, as well as histopathological interstitial fibrosis and tubular atrophy scores in the CKD group, were evaluated.

Compared with healthy controls, patients with early CKD showed significantly lower VD, MV and PI (all p < 0.001). Among CEUS-derived time-intensity curve parameters, peak enhancement and wash-in perfusion were also significantly reduced (both p < 0.001), whereas time-related parameters showed no significant between-group differences. Among individual variables, VD yielded the best diagnostic performance (area under the receiver operating characteristic curve [AUC] = 0.86; 95% confidence interval [CI]: 0.74-0.95). The SR-CEUS model (VD + MV + PI) achieved the highest diagnostic accuracy (AUC = 0.94; 95% CI: 0.88-0.99), significantly outperforming the CEUS model (AUC = 0.82, p = 0.030) and eGFR (AUC = 0.75, p = 0.003). Across all participants, VD showed the strongest positive correlation with eGFR (r = 0.58, p < 0.001). In the CKD group, VD (r = -0.61), MV (r = -0.44), peak enhancement (r = -0.44) and wash-in perfusion (r = -0.36) were significantly negatively correlated with interstitial fibrosis and tubular atrophy scores.

SR-CEUS enables non-invasive visualization and quantitative assessment of renal cortical microvascular alterations in early CKD. Compared with conventional CEUS and serum biomarkers, SR-CEUS demonstrated superior diagnostic performance for detecting microvascular impairment in patients with preserved eGFR. These findings suggest that SR-CEUS may serve as a sensitive imaging biomarker for the early non-invasive assessment of CKD-related microvascular injury.