Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Predicts Mortality in Hemodialysis Patients

Abstract

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 fluorescence (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.

Skin Autofluorescence–Indicated Advanced Glycation End Products as Predictors of Cardiovascular and All‐Cause Mortality in High‐Risk Subjects: A Systematic Review and Meta‐analysis

“…Of the 56 full‐text articles reviewed, only 10 studies25, 26, 27, 28, 29, 30, 31, 32, 33, 34 met the eligibility criteria (Figure 1). Seven studies25, 27, 28, 30, 33, 34 quantified the risk for all‐cause mortality, and 8 samples from 7 studies25, 26, 27, 29, 32, 34 quantified the risk for cardiovascular mortality.…”

“…Seven studies25, 27, 28, 30, 33, 34 quantified the risk for all‐cause mortality, and 8 samples from 7 studies25, 26, 27, 29, 32, 34 quantified the risk for cardiovascular mortality. The studies were conducted in 4 European countries25, 26, 27, 28, 30, 31, 32, 33, 34 and 1 Asian country 29. The reports were published between 2005 and 2015 (Table 1).…”

“…The studies included patients with renal disease,25, 27, 28, 29, 31, 33, 34 peripheral artery disease,26 and diabetes mellitus 30, 32. The percentage of male participants ranged from 39.3% to 73.0%, and the percentage of current smokers ranged from 10.0% to 50.0%.…”

“…The percentage of male participants ranged from 39.3% to 73.0%, and the percentage of current smokers ranged from 10.0% to 50.0%. Most studies included a normal weight population,25, 28, 29, 31, 32 and only 3 included an overweight population 26, 27, 31. The prevalence of hypertension ranged from 18.0% to 91.0%, and the prevalence of preexisting CVD ranged from 29.0% to 50.0%.…”

Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

“…In people with end-stage kidney disease on dialysis, skin AF is associated with arterial stiffness (19). Skin AF is also independently associated with cardiovascular and all-cause mortality in hemodialysis patients (20,21). Potential for reversibility of AGE accumulation has been observed in patients moving from dialysis to renal transplant (22).…”