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Partial characterization of the molecular nature of collagen-linked fluorescence: role of diabetes and end-stage renal disease.

ABSTRACT: Collagen-linked fluorescence at excitation/emission 370/440 nm has widely been used as a marker for advanced glycation in studies of aging, diabetic complications, and end-stage renal disease (ESRD). Diagnostic devices measuring skin autofluorescence at this wavelength revealed an association between fluorescence and cardiovascular morbidity and mortality. We now report the presence of a major fluorophore (LW-1) in human skin collagen which increases with age, diabetes, and ESRD. It has a molecular weight of 623.2Da, a UV maximum at 348 nm, and involves a lysine residue in an aromatic ring. LW-1 could not be synthesized using traditional glycation chemistry suggesting a complex mechanism of formation, perhaps related to hypoxia since elevated levels were also found in nondiabetic individuals with chronic lung disease.

SUBMITTER: Sell DR

PROVIDER: S-EPMC2812593 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Partial characterization of the molecular nature of collagen-linked fluorescence: role of diabetes and end-stage renal disease.

Sell David R DR Nemet Ina I Monnier Vincent M VM

Archives of biochemistry and biophysics 20091030 2

Collagen-linked fluorescence at excitation/emission 370/440 nm has widely been used as a marker for advanced glycation in studies of aging, diabetic complications, and end-stage renal disease (ESRD). Diagnostic devices measuring skin autofluorescence at this wavelength revealed an association between fluorescence and cardiovascular morbidity and mortality. We now report the presence of a major fluorophore (LW-1) in human skin collagen which increases with age, diabetes, and ESRD. It has a molecu ...[more]

PMID: 19879855

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Fast renal decline to end-stage renal disease: an unrecognized feature of nephropathy in diabetes.

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Circulating proteins linked to apoptosis processes and fast development of end stage kidney disease in diabetes.

Project description:Background: Many circulating proteins are associated with risk of ESKD but their source and the biological pathways/disease processes they represent are unclear. Methods: Using OLINK proteomics platform, concentrations of 455 proteins were measured in plasma specimens obtained at baseline from 399 individuals with diabetes. Results: Elevated concentrations of 46 circulating proteins were associated (p <10-5) with development of ESKD (n=149) during 7-15 years of follow-up. Twenty of these proteins enriched apoptosis/TNF receptors signaling pathways. A subset (5-7), summarized as an apoptosis score, together with clinical variables accurately predicted risk of ESKD. Expression of genes encoding the 46 proteins in peripheral white blood cells showed no difference between cells from individuals who did or did not develop ESKD. In contrast, plasma concentration of many of the 46 proteins differed by this outcome. In snRNA-seq analysis of kidney biopsies, the majority of genes encoding for the 20 apoptosis/TNF receptors proteins were overexpressed in injured versus healthy proximal tubule cells. Expression of these 20 genes also correlated with the overall index of apoptosis in these cells. Conclusion: Elevated levels of circulating proteins flagging apoptotic processes/TNF receptors signaling pathways, and likely originating from injured/apoptotic proximal tubular cells, preceded the development of ESKD.

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Pre-End-Stage Renal Disease Hemoglobin Variability Predicts Post-End-Stage Renal Disease Mortality in Patients Transitioning to Dialysis.

Project description:BACKGROUND:Hemoglobin variability (Hb-var) has been associated with increased mortality both in non-dialysis dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD) patients. However, the impact of Hb-var in advanced NDD-CKD on outcomes after dialysis initiation remains unknown. METHODS:Among 11,872 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 through September 2011, we assessed Hb-var calculated from the residual SD of at least 3 Hb values during the last 6 months before dialysis initiation (prelude period) using within-subject linear regression models, and stratified into quartiles. Outcomes included post-transition all-cause, cardiovascular, and infection-related mortality, assessed in Cox proportional hazards models and adjusted for demographics, comorbidities, length of hospitalization, medications, estimated glomerular filtration rate (eGFR), type of vascular access, Hb parameters (baseline Hb [i.e., intercept] and change in Hb [i.e., slope]), and number of Hb measurements. RESULTS:Higher prelude Hb-var was associated with use of iron and antiplatelet agents, tunneled dialysis catheter use, higher levels of baseline Hb, change in Hb, eGFR, and serum ferritin. After multivariable adjustment, higher prelude Hb-var was associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality (adjusted hazard ratios [95% CI] for the highest [vs. lowest] quartile of Hb-var, 1.10 [1.02-1.19], 1.28 [0.93-1.75], and 0.93 [0.79-1.10], respectively). CONCLUSIONS:High pre-ESRD Hb-var is associated with higher mortality, particularly from infectious causes rather than cardiovascular causes. Further research is required to clarify the underlying mechanisms and true causal nature of the observed association.

| S-EPMC5707124 | biostudies-literature

The Impact of Diabetes Mellitus on Vascular Biomarkers in Patients with End-Stage Renal Disease.

Project description:Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD) and an important risk factor for cardiovascular (CV) disease. We investigated the impact of DM on subclinical CV damage by comprehensive screening protocol in ESRD patients.Echocardiography, coronary computed tomography angiogram, 24-h ambulatory blood pressure monitoring, and central blood pressure with pulse wave velocity (PWV) were performed in 91 ESRD patients from the Cardiovascular and Metabolic disease Etiology Research Center-HIgh risk cohort.The DM group (n=38) had higher systolic blood pressure than the non-DM group (n=53), however, other clinical CV risk factors were not different between two groups. Central aortic systolic pressure (148.7±29.8 mm Hg vs. 133.7±27.0 mm Hg, p= 0.014), PWV (12.1±2.7 m/s vs. 9.4±2.1 m/s, p<0.001), and early mitral inflow to early mitral annulus velocity (16.7±6.4 vs. 13.7±5.9, p=0.026) were higher in the DM group. Although the prevalence of coronary artery disease (CAD) was not different between the DM and the non-DM group (95% vs. 84.4%, p=0.471), the severity of CAD was higher in the DM group (p=0.01). In multivariate regression analysis, DM was an independent determinant for central systolic pressure (p=0.011), PWV (p<0.001) and the prevalence of CAD (p=0.046).Diabetic ESRD patients have higher central systolic pressure and more advanced arteriosclerosis than the non-DM control group. These findings suggest that screening for subclinical CV damage may be helpful for diabetic ESRD patients.

| S-EPMC5122655 | biostudies-literature

Short adult height increases the risk of end-stage renal disease in type 2 diabetes.

Project description:ObjectiveAlthough short adult height has been associated with an increasing variety of diseases and all-cause death, no reliable data exist on the association between adult height and end-stage renal disease (ESRD) in diabetic patients. We investigated the relationship between short adult height, development of ESRD, and mortality in type 2 diabetes mellitus (DM).MethodsThis nationwide population-based cohort study analyzed clinical data from a total of 2,621,907 subjects aged ≥30 years with type 2 DM between January 1, 2009 and December 31, 2012, using the National Health Insurance Database in Korea.ResultsDuring a 6.9-year follow-up period, 220,457 subjects (8.4%) died, and 28,704 subjects (1.1%) started dialysis. Short adult height significantly increased the incidence of ESRD and all-cause mortality in the overall cohort analysis. In multivariable Cox models, hazard ratios (HR) for the development of ESRD comparing the highest and lowest quartiles of adult height were 0.86 (95% CI 0.83-0.89). All-cause mortality also decreased with the highest height compared to patients with the lowest height, after fully adjusting for confounding variables (HR 0.79, 95% CI 0.78-0.81). Adult height had an inverse relationship to newly diagnosed ESRD (male: HR 0.86, 95% CI 0.83-0.90, female: HR 0.84, 95% CI 0.79-0.90) and all-cause mortality (male: HR 0.81, 95% CI 0.79-0.82, female: HR 0.80, 95% CI 0.78-0.82).ConclusionsShort adult height is strongly associated with the increased risk of ESRD development and all-cause mortality in type 2 DM.

| S-EPMC7583136 | biostudies-literature

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