Systemic inflammation, metabolic syndrome and progressive renal disease

Abstract

In conclusion, there is increasing evidence that systemic inflammation may increase the risk for CV outcomes and the progression of renal disease. One of the key driving forces for the systemic inflammatory response appears to be the presence of the metabolic syndrome. In turn, recent studies suggest that excessive intake of fructose may have a key role in inducing the metabolic syndrome and that it may be due to the unique role of this sugar to induce ATP depletion and uric acid generation. Furthermore, it appears that the fructose- and uric acid-mediated effects may involve the induction of leukocyte adhesion proteins (ICAM-1) and chemokines (MCP-1) that act in combination with oxidative stress and endothelial dysfunction to accelerate the renal lesion. This may theoretically be important not simply in CKD, but also in acute kidney injury. It may also represent an important mechanism by which fructose or uric acid may cause microvascular inflammation, metabolic syndrome and insulin resistance (Figure ​(Figure1).1). Thus, these studies suggest that we may be able to prevent and to slow the progression of renal disease by a variety of novel strategies, including dietary reduction of fructose, lowering of uric acid or treating downstream events including inflammatory proteins (MCP-1, ICAM-1) or the signalling pathways driving their response. Fig. 1 Potential role of inflammatory molecules in fructose/uric acid-related events. Acknowledgments This work was supported by Italian Society of Nephrology Grant (P.C.), by Italian Ministry of Health (Ex 56 grant, L.G.), the NIH HL-68607 (R.J.J.), the Gatorade foundation (Y.S.), the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (R01-2008-000-10845-0). Conflict of interest statement. R.J.J., Y.S. and T.N. are listed as inventors on patent applications by the University of Florida related to the role of fructose in hypertension and metabolic syndrome. Dr Johnson has also written a book on fructose for the lay public (Rodale Press, 2008).