AGEs and sRAGE Variations at Different Timepoints in Patients with Chronic Kidney Disease

Abstract

Patients with chronic kidney disease (CKD) are affected by enhanced oxidative stress and chronic inflammation, and these factors may contribute to increase advanced glycation end-products (AGEs). In this study we quantified AGEs and soluble receptors for AGE (sRAGE) isoforms and evaluated the association between their variations and eGFR at baseline and after 12 months. We evaluated 64 patients. AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer, and sRAGE by ELISA. Median age was 81 years, male patients accounted for 70%, 63% were diabetic, and eGFR was 27 ± 10 mL/min/1.73 m2. At follow up, sRAGE isoforms underwent a significant decrement (1679 [1393;2038] vs. 1442 [1117;2102], p < 0.0001), while AGEs/sRAGE ratios were increased (1.77 ± 0.92 vs. 2.24 ± 1.34, p = 0.004). Although AGEs and AGEs/sRAGE ratios were inversely related with eGFR, their basal values as well their variations did not show a significant association with eGFR changes. In a cohort of patients with a stable clinical condition at 1 year follow-up, AGEs/sRAGE was associated with renal function. The lack of association with eGFR suggests that other factors can influence its increase. In conclusion, AGEs/sRAGE can be an additional risk factor for CKD progression over a longer time, but its role as a prognostic tool needs further investigation.

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

“…sRAGE levels may be affected by numerous molecules in the AGE-RAGE pathway; however, many studies have only examined sRAGE or a combination of sRAGE, CML-AGE, and esRAGE, only capturing a fraction of the AGE-RAGE pathway [ 60 ]. The AGE/sRAGE ratio seems to be a better marker to estimate patient’s risk than AGEs or sRAGE alone [ 9 ].…”

“…sRAGE levels are linked to kidney function, AGEs, and inflammation, but they can also be altered genetically. An overview of human studies investigating the role of AGEs and sRAGE in CKD is presented in Table 2 [ 9 , 10 , 11 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ].…”

“…The increased AGE/sRAGE ratio at follow-up showed a higher risk of AGE-dependent development of both CKD and other co-morbidities. The potential usefulness of the AGE/sRAGE ratio as a prognostic tool should be examined further [ 9 ].…”

“…An increasing body of research indicates that AGEs may have a role in the development of a variety of illnesses. AGEs have a role in the development of diabetic, vascular, and uremic problems [ 9 , 10 , 11 ]. Although the precise mechanisms of action of AGEs are unknown, they are most likely the outcome of the interaction with their membrane-bound receptor (RAGE) [ 12 , 13 , 14 ].…”

In Patients with Chronic Kidney Disease Advanced Glycation End-Products Receptors Isoforms (sRAGE and esRAGE) Are Associated with Malnutrition

“…Nearly half of the patients had diabetes (56%), and, on average, they were overweight, with a mean BMI of 28 ± 5 kg/m 2 . Median malnutrition inflammation score was 4 [3][4][5][6][7][8], while eGFR ranged from 60 to 15 mL/min/1.73 m 2 , with a mean value of 25 ± 11 mL/min/1.73 m 2 (stage IV CKD). Nutritional metabolic markers were averagely normal (total cholesterol 168 ± 37 mg/dL; albumin 4.0 ± 0.4 gr/dL; prealbumin 28 ± 5 mg/dL).…”