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.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.