Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

Abstract

The increase in the prevalence of diabetes mellitus (DM) and the secondary kidney damage produces diabetic nephropathy (DN). Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day), including normal glomerular filtration rate (GFR) or a mildly decreased GFR (60–89 mL/min/1.73 m2), with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is <30 mg/day. Albuminuria represents the excretion of >300 mg/day. Chronic kidney disease (CKD) is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs) with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β), producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS). The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase). The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

Crocin Protects Podocytes Against Oxidative Stress and Inflammation Induced by High Glucose Through Inhibition of NF-κB

“…Oxidative stress is emerging as a critical event and mediator of DN [29]. In diabetes, oxidative damage occurs when there is an imbalance between ROS generation and production of antioxidant enzyme [28].…”

“…The kidney remodeling and tissue fibrosis induced by hyperglycemia-induced oxidative damage contribute greatly to the development and progression of DN [28]. Miranda-Diaz et al reported an increase in reactive oxygen species (ROS) in diabetic mice with nephropathy [29], and Siddiqi et al demonstrated oxidative injury in podocytes cultured under high-glucose conditions [30]. In addition, altered secretion of pro-inflammatory factors, including interleukin (IL)-8 and IL-10, is observed during the early stages of DN, and these factors are major contributors to the pathogenesis of DN [31].…”

Mitochondrial energetics in the kidney

“…It is characterized by hyperglycaemia, albuminuria, the accumulation of extracellular matrix proteins, and glomerular and tubular epithelial hypertrophy, as well as a reduced glomerular filtration rate following an initial period of hyperfiltration 179 . Mitochondrial energetics are altered in diabetic nephropathy owing to increased ROS and hyperglycae-mia 180 , both of which induce changes in the ETC that cause a decrease in ATP production and an increase in apoptosis 180 .…”

High Glucose-Induced Podocyte Injury Involves Activation of Mammalian Target of Rapamycin (mTOR)-Induced Endoplasmic Reticulum (ER) Stress

“…Recently, it was found that decline of autophagy flux increases the ubiquitin-proteasome-dependent degradation pathway that is responsible for cell death in DN podocytes [14]. In addition, inflammatory pathways may be involved in podocyte loss in DN [15]. Notably, endoplasmic reticulum (ER) stress is an important cellular response that is required for process of unfolded and/or misfolded proteins in cell [16].…”