Advanced glycation end products in kidney transplant patients:A putative role in the development of chronic renal transplant dysfunction

Chronic renal transplant dysfunction is one of the leading causes of graft failure in kidney transplantation. A complex interplay of both alloantigen-related and alloantigen-unrelated risk factors is believed to underlie its development. We propose that advanced glycation end products (AGEs) are involved in the development of chronic renal transplant dysfunction. AGE formation is associated with different alloantigen-unrelated risk factors for chronic renal transplant dysfunction, such as recipient age, diabetes, proteinuria, hypertension, and hyperlipidemia. In vitro studies have shown that AGEs induce the expression of various mediators associated with chronic renal transplant dysfunction. Furthermore, AGE-induced renal damage has been found in multiple experimental studies. This renal damage shows similarity to the damage found in chronic renal transplant dysfunction. Together, several lines of evidence support a role of AGEs in the development of chronic renal transplant dysfunction and suggest that preventive therapy with AGE inhibitors may be helpful in preserving renal function in transplant recipients

Advanced glycation end products in kidney transplant patients:A putative role in the development of chronic renal transplant dysfunction

Chronic renal transplant dysfunction is one of the leading causes of graft failure in kidney transplantation. A complex interplay of both alloantigen-related and alloantigen-unrelated risk factors is believed to underlie its development. We propose that advanced glycation end products (AGEs) are involved in the development of chronic renal transplant dysfunction. AGE formation is associated with different alloantigen-unrelated risk factors for chronic renal transplant dysfunction, such as recipient age, diabetes, proteinuria, hypertension, and hyperlipidemia. In vitro studies have shown that AGEs induce the expression of various mediators associated with chronic renal transplant dysfunction. Furthermore, AGE-induced renal damage has been found in multiple experimental studies. This renal damage shows similarity to the damage found in chronic renal transplant dysfunction. Together, several lines of evidence support a role of AGEs in the development of chronic renal transplant dysfunction and suggest that preventive therapy with AGE inhibitors may be helpful in preserving renal function in transplant recipients.</p

Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients

Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic stress and trigger cytokines driven inflammatory reactions. AGE are thought to contribute to the chronic complications of diabetes and ESRD. Tissue autofluorescence is related to the accumulation of AGE. Therefore, skin autofluorescence (AF) may provide prognostic information on mortality in hemodialysis (HD) patients. Skin AF was measured noninvasively with an AF reader at baseline in 109 HD patients. Overall and cardiovascular mortality was monitored prospectively during a period of 3 yr. The AF reader was validated against AGE contents in skin biopsies from 29 dialysis patients. Forty-two of the 109 (38.5%) HD patients died. Cox regression analysis showed that AF was an independent predictor of overall and cardiovascular mortality (for overall mortality odds ratio [OR] 3.9), as were pre-existing cardiovascular disease (CVD; OR 3.1), C-reactive protein (OR 1.1), and serum albumin (OR 0.3). Multivariate analysis revealed that 65% of the variance in AF could be attributed to the independent effects of age, dialysis and renal failure duration, presence of diabetes, triglycerides levels, and C-reactive protein. AF was also independently linked to the presence of CVD at baseline (OR 8.8; P <0.001). AF correlated with collagen-linked fuorescence (r = 0.71, P <0.001), pentosidine (r = 0.75, P <0.001), and carboxy(m)ethyllysine (both r = 0.45, P <0.01). Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation

Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease

Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age, 52 years; range, 41 to 60 years), 32 dialysis patients (mean age, 56 years; range, 43 to 65 years), and 231 normal control subjects (mean age, 51 years; range, 40 to 65 years). Measurements in transplant recipients were performed for a mean of 73 months (range, 32 to 143 months) after transplantation. Dialysis patients were on dialysis therapy for a mean of 42 months (range, 17 to 107 months). Fluorescence was significantly increased in dialysis patients compared with normal control subjects (2.8 vs. 2.0 arbitrary units [a.u.],