Abstract
BackgroundCirculating advanced glycated end-products (AGEs) including pentosidine accumulating in chronic kidney disease (CKD) patients due to retention and increased formation are thought to contribute to cardiovascular disease (CVD). Here we evaluated factors linked to increased plasma pentosidine and its association with mortality in patients with different stages of CKD and undergoing different treatments.MethodsPlasma pentosidine, biomarkers of inflammation, oxidative stress and nutritional status were investigated in CKD 1–2 (n = 37), CKD 3–4 (n = 54), CKD 5 non-dialyzed (CKD5-ND; n = 386), peritoneal dialysis (PD; n = 74) and hemodialysis (HD; n = 195) patients. Factors predicting plasma pentosidine were analysed by multivariate regression analysis and mortality risk was assessed by GENMOD procedure.ResultsPlasma pentosidine levels, which were higher in CKD5-ND, PD and HD groups than in CKD 1–2 group, were significantly lower in PD than in HD patients, and not different between PD patients and CKD5-ND patients. Pentosidine associated inversely with glomerular filtration rate (GFR), and additionally in PD with 8-hydroxy-2‘-deoxyguanosine (8-OHdG), and interleukin 6 (IL-6); in HD with age, IL-6 and body mass index (BMI); in CKD5-ND with age, 8-OHdG, IL-6, high-sensitive C-reactive protein (hsCRP), and soluble vascular cell adhesion protein-1 (sVCAM-1); in CKD 3–4 with 8-OHdG and sVCAM-1; and in CKD 1–2 with age and sVCAM-1. In multivariate analysis, age (one standard deviation, 1-SD higher), malnutrition (subjective global assessment, SGA), oxidative stress (8-OHdG, 1-SD higher), and belonging to CKD5-ND, HD and PD cohorts associated with 1-SD higher pentosidine. In GENMOD, 1-SD higher pentosidine independently predicted all-cause mortality (relative risk, RR = 1.04; 95% confidence interval, CI, 1.01–1.08, p = 0.01) and CVD mortality (RR = 1.03; 95% CI, 1.01–1.06, p = 0.03) after adjusting for all confounders.ConclusionsPlasma pentosidine is markedly elevated in CKD and associates with low GFR, oxidative stress and inflammation, and is an independent predictor of mortality in CKD patients.
Highlights
In patients with chronic kidney disease (CKD), the decline of renal function associates with increasing mortality, mainly due to cardiovascular disease (CVD), especially when glomerular filtration rate (GFR) falls below 60 ml/min
The grant from Baxter Healthcare Corporation was a general grant to Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, to support research activities at Karolinska Institutet to promote the Circulating advanced glycated end-products (AGEs) including pentosidine accumulating in chronic kidney disease (CKD) patients due to retention and increased formation are thought to contribute to cardiovascular disease (CVD)
Plasma pentosidine levels, which were higher in CKD 5 non-dialyzed (CKD5-ND), peritoneal dialysis (PD) and HD groups than in CKD 1–2 group, were significantly lower in PD than in HD patients, and not different between PD patients and CKD5-ND patients
Summary
In patients with chronic kidney disease (CKD), the decline of renal function associates with increasing mortality, mainly due to cardiovascular disease (CVD), especially when glomerular filtration rate (GFR) falls below 60 ml/min. Traditional cardiovascular risk factors such as advanced age, hypertension and diabetes are common, and the prognosis is further worsened —especially in end-stage renal disease (ESRD) patients—by cardiovascular complications linked to novel and uraemia-related risk factors such as inflammation, endothelial dysfunction, oxidative stress, fluid overload and vascular calcification [1, 2]. We measured plasma pentosidine in 746 patients with different stages of CKD and undergoing different dialysis treatments including peritoneal dialysis (PD) and hemodialysis (HD), explored factors potentially linked to an increased level of pentosidine, and analysed the association of pentosidine with cardiovascular and all-cause mortality. Circulating advanced glycated end-products (AGEs) including pentosidine accumulating in chronic kidney disease (CKD) patients due to retention and increased formation are thought to contribute to cardiovascular disease (CVD). We evaluated factors linked to increased plasma pentosidine and its association with mortality in patients with different stages of CKD and undergoing different treatments
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