Related Experiment Videos
AGEs and carbonyl stress: potential pathogenetic factors of long-term uraemic complications
C Zoccali1, F Mallamaci, G Tripepi
1CNR Centro Fisiologia Clinica, Reggio Calabria, Italy.
Insights
Advanced glycation end products (AGEs) and carbonyl stress are elevated in chronic renal failure, potentially driving complications. These markers, including pentosidine, are linked to cardiovascular issues and dialysis amyloidosis in uraemic patients.
Area of Science:
- Nephrology
- Biochemistry
- Cardiology
Background:
- Advanced glycation end products (AGEs) and advanced lipoxidation end products accumulate in uraemia.
- Pentosidine, a specific AGE, is elevated and serves as a marker for AGE precursors.
- Accumulation of these compounds may not solely depend on declining renal function.
Purpose of the Study:
- To explore the role of AGEs and carbonyl stress in the pathogenesis of chronic renal failure complications.
- To investigate the association between AGEs, carbonyl stress, and cardiovascular alterations in haemodialysis patients.
Main Methods:
- Analysis of AGEs and advanced lipoxidation end products in uraemic patients.
- Assessment of carbonyl precursors.
- Cross-sectional studies in haemodialysis patients focusing on left ventricular geometry and function.
Main Results:
- Uraemic patients exhibit elevated levels of AGE precursors and advanced lipoxidation end products.
- The 'carbonyl stress' theory proposes these elevations contribute to end-stage renal disease complications.
- Preliminary findings suggest AGEs and carbonyl stress are implicated in left ventricular alterations in haemodialysis patients.
Conclusions:
- Carbonyl stress is a significant factor in uraemia, contributing to complications like dialysis amyloidosis and cardiovascular disease.
- AGEs and carbonyl stress are potentially involved in the pathogenesis of cardiac dysfunction in end-stage renal disease.
- Further research is warranted to elucidate the precise mechanisms and therapeutic implications.
Abstract:
Advanced glycation end products (AGEs) may be involved in the pathogenesis of complications of chronic renal failure. Pentosidine, a carbohydrate-derived AGE, is considerably elevated in uraemic patients. This compound per se has no biological activities but is highly correlated to the levels of precursors of carbonyl compounds, and for this reason is considered a reliable surrogate marker for AGEs. The modification of proteins in uraemia is not limited to AGEs, since advanced lipoxidation end products are also demonstrable in plasma proteins in uraemia. The accumulation of these compounds does not seem to be dependent only on the decline of renal function. Carbonyl precursors of AGEs and advanced lipoxidation end products are markedly elevated in uraemic patients. On this basis, the 'carbonyl stress' theory has been formulated. This theory holds that increased oxidation of carbohydrates and lipids and/or inadequate detoxification of carbonyl compounds may contribute to long-term complications of end-stage renal disease such as dialysis amyloidosis and cardiovascular diseases. Preliminary cross-sectional studies in haemodialysis patients seem to indicate that the AGEs and carbonyl stress may be involved in the pathogenesis of alterations in left ventricular geometry and function in these patients.