Update on the Pathogenesis, Diagnosis, and Treatment of Diabetic Tubulopathy

Abstract

Although diabetic glomerulopathy is a characteristic of diabetic kidney disease (DKD), manifesting as a thickened glomerular basement membrane, mesangial expansion with increased matrix, capillary microaneurysms, hypocellular nodules, and even glomerulosclerosis, accumulating data has shown that diabetic tubulopathy (DT) exists from the beginning of hyperglycemia and throughout the duration of diabetic mellitus (DM), playing a pivotal role in the pathogenesis of DKD. Under hyperglycemic conditions, proximal tubular epithelium cells (PTECs) disturbs the tubule-globular glucose, lipid, and protein feedback metabolism, then initiates a series of pathophysiological events, such as volume overload, glomerular hyperfiltration, reactive oxidative stress, and hyperoxide overproduction, which result in hypertrophy, senility, autophagy dysfunction, and PTEC apoptosis in the early stage of DM, as well as tubule atrophy, atherosclerosis tubulointerstitial inflammation, and fibrosis in the development of DKD. Clinically, DT contributes to hyperglycemia, hypertension, proteinuria, dyslipidemia, and hyperuricemia, which accelerate DKD. The biomarkers released from injured tubules are better able than albuminuria to predict early-stage DKD. Therapeutic approaches targeting tubulointerstitial disorders ( e.g. acute interstitial nephritis, chronic interstitial nephritis, acute tubular necrosis and tubulointerstitial fibrosis) in DKD have highlighted the comprehensive pathogenesis of DT and the need for early diagnosis of and intervention in DKD.