Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

Abstract

Background and objectives Novel markers may help to improve risk prediction in CKD. One potential candidate is tissue advanced glycation end product accumulation, a marker of cumulative metabolic stress, which can be assessed by a simple noninvasive measurement of skin autofluorescence. Skin autofluorescence correlates with higher risk of cardiovascular events and mortality in people with diabetes or people requiring RRT, but its role in earlier CKD has not been studied.Design, setting, participants, & measurements A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling for biochemistry, and measurement of skin autofluorescence. Kaplan-Meier plots and multivariate Cox proportional hazards models were used to investigate associations between skin autofluorescence (categorical in quartiles) and all-cause mortality.Results In total, 1707 participants had skin autofluorescence measured; 170 (10%) participants died after a median of 3.6 years of follow-up. The most common cause of death was cardiovascular disease (41%). Higher skin autofluorescence was associated significantly with poorer survival (all-cause mortality, P,0.001) on KaplanMeier analysis. Univariate and age/sex-adjusted Cox proportional hazards models showed that the highest quartile of skin autofluorescence was associated with all-cause mortality (hazard ratio, 2.64; 95% confidence interval, 1.71 to 4.08; P,0.001 and hazard ratio, 1.84; 95% confidence interval, 1.18 to 2.86; P=0.003, respectively, compared with the lowest quartile). This association was not maintained after additional adjustment to include cardiovascular disease, diabetes, smoking, body mass index, eGFR, albuminuria, and hemoglobin.Conclusions Skin autofluorescence was not independently associated with all-cause mortality in this study. Additional research is needed to clarify whether it has a role in risk prediction in CKD.

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%.…”

“…Heterogeneity was modified from not important to moderate after removing data from Meerwaldt et al (I 2 =43.5%)32 and Fraser et al (I 2 =43.6%)27 for cardiovascular mortality. In addition, heterogeneity was modified from substantial to moderate only after removing data from Siriopol et al (I 2 =47.0%) 34…”