Adel M. A. Assiri, Hala F. M. Kamel and Abeer A. EL-Refai
Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makah, KSA and Medical Biochemistry Department, Faculty of Medicine,Ain Shams University, Cairo, Egypt
AGEs are a heterogeneous group of compounds derived from non-enzymatic glycation of proteins, lipids and nuclic acids through complex reaction known as the Maillard reaction. AGEs interact with the receptor for AGEs (RAGE) on the membrane and induce harmfull effects through activation of nuclear factor kappa-B, and increased oxidative stress and inflammatory mediators. AGEs combine with membrane receptors (RAGEs) also combine with circulating soluble receptors (sRAGE) and act as a decay agent. AGEs are thought to be involved in many complications of angiopathy, cardiovascular diseases (CVD) and nephropathy in diabetes as well as those of end-stage renal failure. The aim of this study was to evaluate the changes of (AGEs), (sRAGE) and Oxidized Low-density Lipoproteins ( OxLDL) levels, in hemodialysis patients with different underlying causes and to evaluate them in relation to occurrence of CVD or with diabetic nephropathy as an underlying cause in relation to other glycemic, lipid profile and renal functions' biomarkers.Our study included 279 patients with end stage renal disease (ERD) who received maintenance hemodialysis (HD) (duration of HD, 6.7 ± 3.4 years.) and 112 sex and age matched healthy control subjects.The underlying casual disorders for them were as follows :diabetic nephropathy (56.9%) and non-diabetic nephropathy diseases (43.1%) including chronic hypertensive nephrosclerosis, glomerulonephritis, polycystic kidney disease, and rest of unknown etiology. We also categorized HD patients into 2 subgroups according to their positive medical history of CVD ( 52.09%) and another subgroups with no medical history of CVD (47,01%).We demonstrated significantly higher levels of oxLDL, AGES and sRAGE in HD than healthy control group ( P< 0.001). We found significant increase of OxLDL, AGEs and sRAGE in HD diabetic nephropathy subgroup when compared with non-diabetic subgroup as an underlying cause. Interestingly sRAGEs significantly decreased in HD patients who had positive history for CVD in comparison with those HD patients with no history of CVD (1970 ± 870, 2660 ± 908; P < 0.001). There was positive correlation between AGEs and sRAGE in whole HD patients (r =0.441;P = < 0.001, r = 0.395; P= < 0.05) while only in HD group with CVD There was negative correlation ( r = - 0.294 ; p = <0.01). We found that AGEs was an independent determine for diabetic nephropathy as an underlying cause for ESR (OR, 1.25; 95% CI, 1.04 to 1.49; P < 0.016). Another factor was the oxLDL level (OR, 1.10; 95% CI, 1.02 to 1.19, P < 0.018) and sRAGE (OR, 1.04; 95% CI, 1.01 to 1.06, P < 0.007). and we identified sRAGE as an independent factor associated with the prevalence of CVD(OR, -0. 49; 95% CI, -0.086 to 0.034; P < 0.001). The other factors were AGEs (OR, 2.81; 95% CI, 1.79 to 4.41; P < 0.001), ox LDL (OR, 1.04; 95% CI, 1.02 to 1.06; P < 0.001),and hs-CRP level (OR, 1.02; 95% CI, 1.00 to 1.05, P <0.046).Conclusions plasma OxLDL,AGEs and sRAGE levels are strongly associated with the prevalence of cardiovascular disease and diabetic nephropathy in hemodialysis patients and could be considered future markers for diabetic nephropathy and cardiovascular diseases in hemodialysis patients with end stage renal disease.