Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis

Abstract

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease. The natural history of DKD includes glomerular hyperfiltration, progressive albuminuria, declining estimated glomerular filtration rate, and, ultimately, kidney failure. It is known that DKD is associated with metabolic changes caused by hyperglycemia, resulting in glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Hyperglycemia is also known to cause programmed epigenetic modification. However, the detailed mechanisms involved in the onset and progression of DKD remain elusive. In this review, we discuss recent advances regarding the pathogenic mechanisms involved in DKD.

The Histone Demethylase Inhibitor GSK-J4 Is a Therapeutic Target for the Kidney Fibrosis of Diabetic Kidney Disease via DKK1 Modulation

“…The pathological and clinical features of DKD are glomerular basement membrane thickening, mesangial cell aggregation, renal fibrosis, and proteinuria, as well as multiple mechanisms known to be involved [ 1 ]. Multiple signaling pathways are involved in the pathological process of nephritis and renal fibrosis during DKD.…”

“…Diabetic kidney disease (DKD) leads to chronic kidney disease (CKD) and end-stage renal disease (ESRD), which is a microvascular complication in patients with diabetes that results in the chronic loss of renal function [ 1 , 2 ]. DKD has high morbidity and mortality in patients with diabetes mellitus (DM) [ 3 ].…”

“…One of the main features of DKD is chronic renal inflammation and fibrosis, in which inflammatory cytokines stimulate tubular epithelial cells to secrete collagen I and fibronectin. Additionally, inflammatory cytokines also lead to interstitial ECM deposition and basement membrane thickening, accelerating tubulointerstitial fibrosis [ 1 ].…”

“…Epigenetic alterations in abnormal DNA methylation or histone modifications also play a key role in causing renal injury [ 1 ]. Histone methylation tightens the chromatin structure and inhibits the binding of transcription factors to promoters [ 21 ]; the extent of histone methylation can regulate gene transcription [ 22 ] and affects the pathogenesis of DKD [ 23 ].…”

Decoy receptor 2 mediates the apoptosis-resistant phenotype of senescent renal tubular cells and accelerates renal fibrosis in diabetic nephropathy

“…Diabetic nephropathy (DN) occurs in 20–40% of patients with diabetes and is the leading cause of end-stage renal disease [ 1 , 2 ]. Accumulating evidence suggests that renal fibrosis is an essential mediator in the progression of DN [ 3 , 4 ]. Although renal fibrosis scores are positively correlated with renal dysfunction, which is a powerful predictor of prognosis in patients with DN [ 5 ], the mechanisms underlying this association remain to be fully clarified.…”