Advancements in the non-invasive diagnosis of renal fibrosis

Renal fibrosis is the central pathological pathway by which various primary and secondary kidney diseases progress to end-stage renal disease. It is characterized by excessive extracellular matrix deposition and destruction of the native renal parenchyma, ultimately leading to irreversible loss of nephrons. Currently, percutaneous renal biopsy with histopathological evaluation remains the diagnostic gold standard for renal fibrosis, allowing semiquantitative scoring of renal interstitial fibrosis and glomerulosclerosis (e.g., Banff grading). However, this invasive procedure carries a risk of bleeding and is limited by sampling error and inter-observer variability, making it impractical for dynamic disease monitoring. In recent years, significant advances have been made in noninvasive diagnostic techniques. These include: (1) blood and urine biomarkers such as markers of ECM metabolism, inflammatory factors, tubular injury markers, and extracellular vesicles; (2) imaging modalities including novel ultrasound techniques, shear wave elastography, functional magnetic resonance imaging (MRI) methods such as diffusion-weighted imaging, blood oxygen level-dependent MRI, magnetic resonance elastography, and positron emission tomography/computed tomography using radiotracers targeting fibrosis-associated molecules such as ⁶⁸Ga-FAPI. This review systematically summarizes the latest evidence on the above biomarkers and advanced imaging modalities, with an emphasis on their diagnostic performance (sensitivity/specificity), utility for dynamic monitoring, and bottlenecks in clinical translation. The aim is to develop a multimodal, noninvasive assessment system to enable earlier fibrosis detection, stratified disease management, and precise intervention targeting fibrogenic pathways, ultimately improving renal disease outcomes.