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. 2020 Jul 13;17(7):e1003163.
doi: 10.1371/journal.pmed.1003163. eCollection 2020 Jul.

The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study

Adam Shardlow  1 , Natasha J McIntyre  1 , Nitin V Kolhe  2 , Laura B Nellums  3 , Richard J Fluck  2 , Christopher W McIntyre  4   5 , Maarten W Taal  1   2
Affiliations

The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study

Adam Shardlow et al. PLoS Med. .

Abstract

Background: Tissue advanced glycation end product (AGE) accumulation has been proposed as a marker of cumulative metabolic stress that can be assessed noninvasively by measurement of skin autofluorescence (SAF). In persons on haemodialysis, SAF is an independent risk factor for cardiovascular events (CVEs) and all-cause mortality (ACM), but data at earlier stages of chronic kidney disease (CKD) are inconclusive. We investigated SAF as a risk factor for CVEs and ACM in a prospective study of persons with CKD stage 3.

Methods and findings: Participants with estimated glomerular filtration rate (eGFR) 59 to 30 mL/min/1.73 m2 on two consecutive previous blood tests were recruited from 32 primary care practices across Derbyshire, United Kingdom between 2008 and 2010. SAF was measured in participants with CKD stage 3 at baseline, 1, and 5 years using an AGE reader (DiagnOptics). Data on hospital admissions with CVEs (based on international classification of diseases [ICD]-10 coding) and deaths were obtained from NHS Digital. Cox proportional hazards models were used to investigate baseline variables associated with CVEs and ACM. A total of 1,707 of 1,741 participants with SAF readings at baseline were included in this analysis: The mean (± SD) age was 72.9 ± 9.0 years; 1,036 (60.7%) were female, 1,681 (98.5%) were of white ethnicity, and mean (±SD) eGFR was 53.5 ± 11.9 mL/min/1.73 m2. We observed 319 deaths and 590 CVEs during a mean of 6.0 ± 1.5 and 5.1 ± 2.2 years of observation, respectively. Higher baseline SAF was an independent risk factor for CVEs (hazard ratio [HR] 1.12 per SD, 95% CI 1.03-1.22, p = 0.01) and ACM (HR 1.16, 95% CI 1.03-1.30, p = 0.01). Additionally, increase in SAF over 1 year was independently associated with subsequent CVEs (HR 1.11 per SD, 95% CI 1.00-1.22; p = 0.04) and ACM (HR 1.24, 95% CI 1.09-1.41, p = 0.001). We relied on ICD-10 codes to identify hospital admissions with CVEs, and there may therefore have been some misclassification.

Conclusions: We have identified SAF as an independent risk factor for CVE and ACM in persons with early CKD. These findings suggest that interventions to reduce AGE accumulation, such as dietary AGE restriction, may reduce cardiovascular risk in CKD, but this requires testing in prospective randomised trials. Our findings may not be applicable to more ethnically diverse or younger populations.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: MWT is an Academic Editor for PLOS Medicine.

Figures

Fig 1
Fig 1. Flow chart showing the numbers of participants involved at each stage of the study.
CKD. chronic kidney disease; KDIGO, kidney disease improving global outcomes; SAF, skin autofluorescence.
Fig 2
Fig 2. Kaplan–Meier plot showing CVE free survival by tertiles of SAF (dotted line, lowest tertile; dashed line, middle tertile; solid line, highest tertile; log-rank test: chi-square 41.4; p < 0.001).
CVE, cardiovascular event; SAF, skin autofluorescence.
Fig 3
Fig 3. Kaplan–Meier plot showing survival by tertiles of SAF (dotted line, lowest tertile; dashed line, middle tertile; solid line, highest tertile; log-rank test: chi-square 42.5; p < 0.001).
SAF, skin autofluorescence.
See this image and copyright information in PMC

References

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