The Role of Advanced Glycation End Products and Its Soluble Receptor in Kidney Diseases

Abstract

Patients with chronic kidney disease (CKD) are more prone to oxidative stress and chronic inflammation, which may lead to an increase in the synthesis of advanced glycation end products (AGEs). Because AGEs are mostly removed by healthy kidneys, AGE accumulation is a result of both increased production and decreased kidney clearance. On the other hand, AGEs may potentially hasten decreasing kidney function in CKD patients, and are independently related to all-cause mortality. They are one of the non-traditional risk factors that play a significant role in the underlying processes that lead to excessive cardiovascular disease in CKD patients. When AGEs interact with their cell-bound receptor (RAGE), cell dysfunction is initiated by activating nuclear factor kappa-B (NF-κB), increasing the production and release of inflammatory cytokines. Alterations in the AGE-RAGE system have been related to the development of several chronic kidney diseases. Soluble RAGE (sRAGE) is a decoy receptor that suppresses membrane-bound RAGE activation and AGE-RAGE-related toxicity. sRAGE, and more specifically, the AGE/sRAGE ratio, may be promising tools for predicting the prognosis of kidney diseases. In the present review, we discuss the potential role of AGEs and sRAGE as biomarkers in different kidney pathologies.

Number of Teeth and Nutritional Status Parameters Are Related to Intima-Media Thickness in Dalmatian Kidney Transplant Recipients

“…Atherosclerosis is believed to be one of the major contributors to elevated CV risk in the CKD population [ 5 , 6 ]. Mechanisms connecting ESRD and atherosclerosis include mineral metabolism disturbances affecting vascular calcification, chronic volume overload through effects on hypertension and hypertrophy of the left ventricle, effects of advanced glycation end-products (AGEs) through endothelial dysfunction [ 7 ], chronic infectious disease, and angiopoietin-2 effects [ 8 ]. After KTX, the effects of pretransplantation risk factors on atherosclerosis are diminutive, but the post-transplant period bears challenges such as immunosuppressants, weight gain, post-transplantation diabetes mellitus, and chronic infections, also contributing to atherosclerosis and arterial stiffness [ 8 , 9 ] in this patient population.…”

“…In CKD, accumulation of AGEs is attributed to impaired renal clearance, increased endogenous formation, and excess dietary intake [ 7 , 26 ]. Although plasmatic clearance of AGEs dramatically improves after KTX, their removal from slow-turnover tissues might be difficult to achieve and may contribute to this high CVD burden in this population of patients [ 27 , 28 ].…”

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders

“…It appears that there is a dose-risk relationship between AGEs and adverse health outcomes. In both human and animal models, high levels of accumulated AGEs contribute to type-2 diabetes mellitus (T2DM), obesity, metabolic syndrome, retinopathy, diabetic neuropathy, cardiomyopathy, and kidney disease, as well as a reduced estimated glomerular filtration rate [12][13][14]. A meta-analysis of prospective studies also demonstrated increased risk of mortality from all causes and cardiovascular disease with higher circulating AGEs [15].…”

L-Lysine Ameliorates Diabetic Nephropathy in Rats with Streptozotocin-Induced Diabetes Mellitus

“…Besides, AGEs stimulate, through RAGE, the expression of interleukin 6, TNF- α , and TGF β 1 [ 7 ]. Stimulation of TGF β 1 is associated with more production of collagen types I and IV, prevents the expression of proteoglycans, and thereby leads to polymerization and abnormally increases extracellular matrix [ 8 ]. Functional and morphological analyses of the kidney in diabetic animals that carried the human AGER transgene showed the acceleration of diabetic nephropathy characterized by albuminuria, glomerular hypertrophy, nephromegaly, and glomerulosclerosis.…”