Microfluidic innovations in chronic kidney disease and renal fibrosis: from mechanistic insights to clinical applications.

Background: Chronic kidney disease (CKD) and renal fibrosis remain major global health burdens, with limited options for early diagnosis and effective therapy. Conventional approaches, such as kidney biopsy and imaging, are invasive or insensitive to early-stage changes. Microfluidic technology has emerged as a transformative platform that enables precise modeling of renal microenvironments, sensitive biomarker detection, and physiologically relevant drug testing. This review evaluates recent advances in microfluidics for CKD and fibrosis, with emphasis on mechanistic insights, diagnostic innovations, and therapeutic strategies. Discussion: Mechanistic studies using organ-on-a-chip systems, including glomerulus- and tubule-on-a-chip, have replicated critical pathophysiological processes such as proteinuria-induced podocyte injury, epithelial-mesenchymal transition, FAO dysregulation in tubular cells, and immune cell-mediated inflammation. These models provide superior resolution compared with 2D culture or animal models and have identified novel fibrotic pathways-how they work: by perfusing media through microchannels to simulate shear stress; advantages: dynamic real-time monitoring; disadvantages: high cost and limited throughput; limitations: often lack full multi-cellular integration; translational value: patient-specific modeling for precision nephrology. Diagnostic innovations include microfluidic biosensors for non-invasive, high-sensitivity detection of CKD biomarkers such as albumin and neutrophil gelatinase-associated lipocalin (NGAL), as well as multiplex platforms that analyze multiple analytes in urine or blood simultaneously. Wearable epidermal patches have further extended applications to continuous monitoring of electrolytes and metabolites, enhancing patient-centered management. Therapeutically, microfluidic systems support high-throughput drug screening under physiologically relevant perfusion, enabling more predictive antifibrotic testing. Microfluidic-assisted nanodelivery platforms improve drug targeting and bioavailability, while organoid-on-chip systems enhance stem cell differentiation and regenerative potential. Integration with artificial intelligence and multi-omics further refines data interpretation, biomarker discovery, and personalized therapy design. Conclusion: Microfluidic technologies bridge the gap between bench and bedside by enabling mechanistic discovery, sensitive biomarker detection, and translational therapeutic testing in CKD and fibrosis. Despite significant advances, challenges remain in scalability, reproducibility, and regulatory approval. Addressing these hurdles through interdisciplinary collaboration will be essential. With continued innovation, microfluidic systems hold strong promise for advancing precision nephrology and improving patient outcomes.