A lactate capture-sensing platform for facilitating early differential diagnosis of minimal change disease and focal segmental glomerulosclerosis in renal diseases

Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are primary glomerular disorders, and currently the invasive renal biopsy combined with gene sequencing are required for definitive diagnosis, which is apparently a suboptimal approach for patients with suspected early-stage disease. Given the central role of kidney in lactic acid (LA) metabolism and the emerging potential of LA as a predictor of renal pathology, a modular surface-enhanced Raman scattering (SERS) platform featuring with a simple "capture-detection" coordination mechanism was presented, facilitating a novel diagnostic strategy based on the identification and detection of urinary lactate enantiomers. Leveraging on the intermolecular hydrogen-bonding interactions, a precise enantiomeric resolution was achieved, yielding an exceptional enhancement factor (EF) of 2.45 × 10⁶ and a low limit of detection (LOD) of 10^-14.35 M and 10^-13.50 M for lactate enantiomers. It was notable that the aberrant urinary d-lactate (D-LA) levels enabled auxiliary discrimination between MCD and FSGS, enabling non-invasive discrimination with high diagnostic accuracy. To a certain extent, these findings established D-LA as a promising biomarker for chronic kidney disease (CKD). This SERS-based approach addresses the critical limitations of current traditional diagnosis, not only advancing chiral analysis but also offering a transformative opportunity for early diagnosis, disease monitoring, and mechanistic studies in nephrology.