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Diabetic kidney disease (DKD) is the most severe complication of diabetes mellitus and has poor prognosis, often progressing to end-stage renal disease, causing substantial morbidity and mortality globally. While the pathogenesis of DKD has been extensively characterised, including glomerular hyperfiltration, podocyte injury, and tubulointerstitial fibrosis, recent findings underscore renal tubular injury as a pivotal contributor to DKD progression. High glucose levels and lipid accumulation result in tubular injury, followed by oxidative stress, endoplasmic reticulum stress, inflammation, activation of the renin-angiotensin-aldosterone system, programmed cell death, epithelial-mesenchymal transition, and intercellular crosstalk, all of which exacerbate tubular dysfunction in DKD. Notably, biomarkers of renal tubular injury, including kidney injury molecule-1, cystatin C, neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, monocyte chemoattractant protein-1, N-acetyl-beta-glucosidase, and retinol-binding protein, along with other promising novel biomarkers, emerge earlier than microalbuminuria and serve as novel diagnostic indicators for early DKD detection. Therapeutically, we critically evaluate both established agents and emerging strategies, including hypoglycemic agents, anti-oxidative stress therapies, anti-inflammatory therapies, anti-cell death therapies, and stem cell therapy, showing promise for mitigating DKD-related tubular damage. This comprehensive review constructs a logical framework linking molecular mechanisms, novel biomarkers, and emerging therapeutic strategies for renal tubular injury in DKD. By bridging molecular mechanisms with actionable therapeutic strategies, this review highlights the pivotal role of tubulopathy in DKD pathogenesis and its implications for early diagnosis and intervention strategies.
Lv et al. (Wed,) studied this question.