Detection of Kidney Fibrosis and Vascular Sclerosis Using Contrast Enhanced Ultrasonography

Chronic kidney disease (CKD) affects >10% of the adult US population, and leads to significant morbidity and mortality. A major barrier to therapeutics discovery is selection of the study population that is highly likely to experience CKD progression during the intervention period. Interstitial fibrosis/tubular atrophy (IFTA) and microvascular sclerosis are histopathologic hallmarks that are mechanistically linked to CKD progression.1-5 Identification of novel non-invasive markers of IFTA and microvascular sclerosis will enhance risk prediction and facilitate optimal selection of trial populations. Histopathological assessments inform investigators of injury severity and chronicity, but they necessitate a kidney biopsy, which carries non-negligible complication risks.6 The scientific premise of our proposal is based on the observations that structural injury to the tubulointerstitial and vascular space leads to fibrosis and disruption of the microvascular circulation, which results in intrarenal hypoxia and decreased renal perfusion.7 Our overarching goal is to advance contrast enhanced ultrasonography (CEUS), a novel renal perfusion imaging modality, as a non-invasive marker of CKD progression. CEUS uses gas-filled microbubbles as a tracer to assess the microcirculation with ultrasound. Previous studies in animals and humans demonstrated ability of CEUS to define renal blood flow, cortical perfusion, and kidney injury. We will now study the ability of CEUS to predict kidney function and severity of IFTA and microvascular sclerosis. In a pilot study, we plan to evaluate the relationship between microvascular perfusion and kidney function in patients who have undergone CEUS for evaluation of a renal mass, and newly recruit patients with CKD stages 2 and 3a undergoing clinically indicated native kidney biopsies to evaluate the association of microvascular perfusion measured by CEUS with histopathological lesions and kidney function.