Diabetic nephropathy: Progression and pathophysiology

Abstract

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ~30% of type 1 and type 2 diabetic patients. This review focuses on the progression and pathophysiological aspects of the condition. The natural history of diabetic nephropathy is characterized by specific renal morphological and functional alterations. Features of early diabetic renal changes are microalbuminuria (30-300mg/day), glomerular hyperfiltration, glomerular and renal hypertrophy, increased basement membrane thickness, and mesangial expansion with the accumulation of extracellular matrix proteins such as collagen, fibronectin, and laminin. Advanced diabetic nephropathy is characterized by macroalbuminuria (>300mg/day), a progressive decline in glomerular filtration rate, decreasing creatinine clearance, glomerulosclerosis, and interstitial fibrosis. Although poor glycemic control is an important risk factor, glycemia does not fully explain why only a subset of diabetic patients progress to end stage renal disease. Several decades of extensive research has elucidated various pathways to be implicated in the development of diabetic kidney disease such as systemic and glomerular hypertension, advanced glycation endproducts and the aldose reductase system. Furthermore, hemodynamic factors, the reninangiotensin system, the endothelin system, the intracellular signaling molecule protein kinase C, transforming growth factor-ß, growth hormone, insulin like growth factors, vascular endothelial growth factor, and platelet-derived growth factor are believed to be involved in the pathogenesis. Thus, there are clearly many points at which therapeutic approaches could be tried to provide renoprotection in diabetes. It is likely that due to its complexity, targeting multiple points in altered metabolism in the diabetic kidney will be more successful in attenuating the development of diabetic nephropathy, rather than a single approach.

Association of serum sestrin 2 and betatrophin with serum neutrophil gelatinase associated lipocalin levels in type 2 diabetic patients with diabetic nephropathy

“…They were categorized into: G1; control, 20 non-diabetic individuals and cases (76 T2DM patients; treated by life style-modifications and oral hypoglycemic drugs). According to urinary albumintocreatinineratio (ACR), the cases were categorized into 3 groups:G2;22 normoalbuminuric case (ACR >20 mg/g), G3: 35 microalbuminuric case (ACR = 20 to 200 mg/g) and G4: 19 macroalbuminuric case (ACR < 200 mg/g) [29,30]. Exclusion criteria included subjects with type 1 diabetes mellitus or when the participant presented with any systemic or endocrinal diseases(e.g.…”

EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress

“…The metabolic abnormality and microvascular complications caused by the sustained hyperglycemia lead to diabetic nephropathy (DN) [1]. Diabetic kidney disease is the leading cause of morbidity and end-stage renal disease (ESRD) [2–4]. However, effective clinical interventions for DN have not yet been elucidated.…”

Plasma endothelin-1 level, measured glomerular filtration rate and effective renal plasma flow in diabetic nephropathy

“…1,2 During the past two decades, numerous research papers have lightened a few new paths explaining the development and progression of DN. Systemic hypertension, as well as intraglomerular hypertension, and the activation of vasoactive systems including renin-angiotensin system and endothelin system are well known hemodynamic factors that contribute to the development of DN.…”