From albuminuria to multi-omics signatures: emerging biomarkers and drug targets for early-stage chronic kidney disease

从蛋白尿到多组学特征:早期慢性肾脏病的新兴生物标志物和药物靶点

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Abstract

Chronic kidney disease (CKD) is highly prevalent worldwide, yet structural kidney injury often develops long before changes in estimated glomerular filtration rate (eGFR) or persistent albuminuria are detected. Albuminuria is a well-established prognostic marker and treatment target, but it captures only part of the biological diversity of early kidney damage, shows substantial within-person variability, and may miss risk in predominantly tubulointerstitial or microvascular forms of disease. Recent advances in high-throughput omics now allow detailed profiling of renal stress in urine, blood and tissue, yielding proteomic, metabolomic, transcriptomic, epigenetic and non-coding RNA signatures linked to tubular injury, inflammation, fibrosis, mitochondrial dysfunction and disturbed energy metabolism. When these molecular layers are analysed in combination, multi-omics signatures can improve risk stratification beyond conventional Kidney Disease: Improving Global Outcomes (KDIGO) staging, help to define mechanistically distinct patient subgroups and highlight candidate therapeutic targets in haemodynamic-metabolic, immune/complement and extracellular matrix pathways. In this mini-review, we summarise the emerging evidence supporting a move beyond an albuminuria-centred view of early CKD towards mechanistically informed, multi-omics-based biomarkers, and we outline key requirements for clinical translation, including analytical standardisation, longitudinal validation and proof that such markers deliver actionable gains in patient care.

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