B-CRF : nutritional complications
B- CRF ; dermatological complications
D- Diabetes type 2 with CV complications
Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD
Simon D.S. Fraser*,
Paul J. Roderick*,
Christopher W. McIntyre‡, Richard J. Fluck†,
Natasha J. McIntyre†,
Maarten W. Taal†
Scott Harris*,
+ Author Affiliations
*Academic Unit of Primary Care and Population Sciences, Southampton General Hospital,
Southampton, Hampshire, United Kingdom;
†Department of Renal Medicine, Royal Derby Hospital National Health Service Foundation
Trust, Derby, Derbyshire, United Kingdom; and
‡Department of Nephrology, Division of Medical Sciences and Graduate-Entry Medicine,
University of Nottingham, Nottingham, United Kingdom
Correspondence:
Dr. Simon D.S. Fraser, Academic Unit of Primary Care and Population Sciences, Level C,
South Academic Block, Southampton General Hospital, Tremona Road, Southampton,
Hampshire SO16 6YD, UK. Email: s.fraser@soton.ac.uk
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 Kaplan–Meier 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.
COMMENTS
In the context of CKD, accumulation of advanced glycation end products (AGEs) has been
identified as a novel risk factor for cardiovascular disease (CVD) AGEs are a heterogeneous
group of compounds formed by the reaction of free amino groups on proteins, lipids, and
nucleic acids with reactive carbonyl groups on reducing sugars. They accumulate by
endogenous formation through nonenzymatic reaction over time (the Maillard reaction) or
from reactive carbonyl products generated by oxidative stress (dicarbonyl stress).
Accumulation of AGEs also occurs from exogenous sources, principally food cooked at high
temperature, and AGEs formed by smoking. In addition, AGEs are normally excreted by the
kidneys and therefore, accumulate with decreased renal function.
Serum AGEs are subject to fluctuation and have been shown to be a poor indicator of AGE
accumulation in tissue compared with skin biopsy . Assessment of AGE accumulation in
practice has been simplified by devices that measure skin autofluorescence (AF).
Skin AF was assessed on the left forearm using an AGE Reader device (DiagnOptics,
Groningen, The Netherlands). Three readings were taken, and the average was calculated.
This cohort study of people with CKD has shown that higher levels of skin AF were
associated with all-cause mortality but that this association was lost after adjusting for
established risk factors, including eGFR and albuminuria. Presently skin fluorescence due to
AGEs deposition seems not useful in clinical practice for evaluation of progression of renal
insufficiency. More studies are required for the final evaluation of this technique in patients
with diabetic nephropathy.
Pr. Jacques CHANARD
Professor of Nephrology