Advanced glycation end products (AGEs) estimated by skin autofluorescence are related with cardiovascular risk in renal transplant

Abstract

BackgroundAdvanced glycation end products (AGEs) accumulation, a measure of cumulative metabolic stress, constitute a novel pathogenic mechanism involved in aging, diabetes, cardiovascular (CVD) and chronic kidney disease (CKD). Despite removal of uremic toxins and AGEs after a successful renal transplant (RT), CVD remains the leading cause of mortality. We hypothesized that AGEs measurement by Skin Autofluorescence (SAF) might be useful even after a successful RT and thus reflect the high cardiovascular risk burden of these patients.Methods189 stable RT (61% men, aged 56±13.0 years), CKD stages 1–4 and >12 months since RT were enrolled. Variables collected comprised comorbid history, medication use, smoking habit, routine biochemistry, subclinical atheromatosis by ankle-brachial-index (ABI) and allograft resistivity index (RI), 24-h ABPM, anthropometry and handgrip strength. AGEs were measured by SAF and expressed in arbitrary units (AU). Vascular age was estimated by Koetsier´s formula (SAF-0.83/0.024) and expected 10-years cardiovascular death risk was calculated with the REGICOR score.ResultsMean SAF was 3.00±0.83 AU and estimated vascular age 90±34.7 years (30 years above biological age). SAF was higher among men (3.10±0.91 vs 2.81±0.66), diabetic nephropathy (3.49±0.75 vs 2.96±0.83) and steroid users (3.14±0.86 vs 2.71±0.69). We observed a positive correlation of SAF with night-systolic blood pressure (r = 0.25, p = 0.001), parathormone (r = 0.20, p<0.01), phosphate (r = 0.28, p<0.001) and negative with hemoglobin (r = -0.29, p<0.001), CKD-EPI (r = -0.32, p<0.001), albumin (r = -0.17, p<0.05), and dynamometry (r = -0.20, p<0.01). Subclinical vascular atheromatosis (ABI and RI) as well as the REGICOR scale (r = 0.35 p<0.001) were also correlated with SAF. In multivariable analysis age, gender, steroid use, serum phosphate and handgrip strength remained independently associated with SAF.ConclusionsSAF levels are elevated in RT patients and correlate with CVD risk. Besides age and male sex, our results suggest that phosphate overload, steroid use and nutritional status are important factors linking to AGEs accumulation.

Circulating Advanced Glycation Endproducts and Long-Term Risk of Cardiovascular Mortality in Kidney Transplant Recipients

“…Furthermore, our analyses relied on data from direct and specific measurements of two major circulating AGEs. Of note, previous evidence has also been limited to the use of skin autofluorescence readings (10)(11)(12)(13). It is critical to take into account that the current understanding of AGEs a The coefficients of the indirect ab path and the total ab+c' path are standardized for the SD of the potential mediators, circulating CML and CEL concentrations and cardiovascular mortality.…”

“…In patients with ESKD, clinical studies have shown the adverse cardiovascular and survival effects of AGEs (10,11). In kidney transplant recipients, the hypothesis that AGEs play a role in the pathogenesis of cardiovascular disease may be supported by evidence that connects indirect and nonspecific measurements of AGEs with risk factors of cardiovascular disease (12,13). A strong body of evidence on the general theory of circulating AGE pathology supports its pivotal role in the initiation and progression of cardiovascular disease, which, in turn, is the leading individual cause of premature mortality after a successful kidney transplantation.…”

Role of the Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Prognostic Factor for Mortality in Hemodialysis and Peritoneal Dialysis Patients

“…The putative role of membrane RAGE activation and sRAGE circulating levels in cardiovascular complications of CKD patients are still very controversial. Previous studies indicated that AGEs levels are higher in CKD patients and, by interacting with membrane RAGE, they may activate intracellular signaling pathways that lead to oxidative stress, inflammation, vascular stiffness, atherosclerosis, tissue remodeling, and fibrosis [ 39 – 41 ]. Blockage of RAGE has been suggested as one potential protective mechanism against AGE-induced cardiovascular complications and sRAGE may just work in this way by linking to AGEs and preventing their interaction with RAGE [ 6 , 40 , 42 ].…”

Association of hemoglobin glycation index and its interaction with obesity /family history of hypertension on hypertension risk: a community-based cross-sectional survey

“…In spontaneously hypertensive rats, the levels of AGEs were shown to be elevated [35]. Meanwhile, AGEs accumulation was shown to be closely related with night-systolic blood pressure, subclinical vascular atheromatosis and expected 10-year cardiovascular death risk in subjects with successful renal transplant [36]. In addition, chronic in ammation was recognized to be involved in the development of hypertension [37].…”