Precisely Staging Diabetic Nephropathy by a Gold-Based Artificial Filtration Biomarker through Computed Tomography and Blood Testing of the Glomerular Filtration Rate

Diabetic nephropathy (DN) has become a global health burden associated with high morbidity and mortality. Quantitative staging of DN is crucial for its timely and stage-matched therapeutic intervention. Given that glomerular dysfunction is the pathological hallmark of DN progression, the glomerular filtration rate (GFR) is the most comprehensive indicator of DN. However, estimated GFR derived from endogenous serum creatinine is inaccurate for precise staging of DN. To address this issue, we developed an exogenous gold-based artificial filtration biomarker (Gold-AFB), realizing accurate measurement of GFR alteration during DN progression through computed tomography (CT) imaging or simple blood testing. The Gold-AFB comprised an ultrasmall gold core and a strongly antifouling phosphatidylcholine shell, which enabled its rapid and free glomerular filtration (>90%@2 h, ∼100%@24 h) without tubular interactions. Leveraging the high X-ray attenuation properties of Gold-AFB, we achieved accurate quantification of GFR via rapid renal CT imaging and realized the differentiation of three DN stages, covering phases from glomerular hyperfiltration to mild and severe glomerulosclerosis, which were hardly distinguished by endogenous biomarkers. Furthermore, we also established a blood-based assay using Gold-AFB, realizing a convenient GFR report in murine and rabbit models at a 100-fold lower dose than FITC-inulin, the current "gold" standard for GFR measurement.