Is there any evidence that AGE/sRAGE is a universal biomarker/risk marker for diseases?

Advanced glycation end products (AGE) and its cell-bound receptor called receptor for AGE (RAGE) are implicated in the pathogenesis of numerous diseases. Soluble receptor for AGE (sRAGE) counteracts the adverse effects of AGE-RAGE interaction by competing with RAGE for binding with AGE. Low levels of serum sRAGE have been proposed as a biomarker for diseases. However, the serum levels of sRAGE in diabetes and end-stage renal disease (ESRD) are elevated. Thus, low levels of sRAGE cannot be a universal biomarker. An elevated ratio of AGE/sRAGE was then proposed as a universal biomarker. However, evidence was not provided for this new biomarker. The objective of this paper is to provide evidence in support of elevated AGE/sRAGE being a universal biomarker. The data for serum levels of AGE, sRAGE, and ratio of AGE/sRAGE were collected from patients with low serum sRAGE [non-ST-elevation myocardial infarction (NSTEMI), hyperthyroidism (HT), thoracic aortic aneurysm (TAA),and hypercholesterolemia (HC)], and with high serum levels of sRAGE [type-2 diabetes (T2D) and ESRD], and control subjects. The serum levels of AGE and ratio of AGE/sRAGE were higher in all types of patients irrespective of low or high serum sRAGE as compared to control subjects. Reasons are provided as to why AGE or sRAGE individually cannot be considered as a universal biomarker. In conclusion, the evidence supports the validity of the high ratio AGE/sRAGE as a universal biomarker/risk marker for diseases.