Advanced Glycation End Products in End-Stage Renal Disease and Their Removal

Schinzel, Reinhard; Münch, Gerald; Heidland, A.; Šebeková, Katarína

doi:10.1159/000045934

Cited by 54 publications

(42 citation statements)

References 42 publications

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“…It has been recognized that AGEs accumulated in organisms in an age-dependent manner. N e -carboxymethyl-lysine (CML) and pentosidine, two major AGEs, were found in several tissues, like kidney, bone, eye, skeletal muscle, cartilage, arterial wall, or brain, and shown to be correlated to the risk of adverse aging-related outcomes (5)(6)(7)(8)(9)(10). Because AGE formation is cumulative and irreversible, glycoxidation particularly affects extracellular matrix (ECM) proteins because of their long biological life.…”

mentioning

confidence: 99%

Protein carbamylation is a hallmark of aging

Gorisse

Piètrement

Vuiblet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

164

125

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Aging is a progressive process determined by genetic and acquired factors. Among the latter are the chemical reactions referred to as nonenzymatic posttranslational modifications (NEPTMs), such as glycoxidation, which are responsible for protein molecular aging. Carbamylation is a more recently described NEPTM that is caused by the nonenzymatic binding of isocyanate derived from urea dissociation or myeloperoxidase-mediated catabolism of thiocyanate to free amino groups of proteins. This modification is considered an adverse reaction, because it induces alterations of protein and cell properties. It has been shown that carbamylated proteins increase in plasma and tissues during chronic kidney disease and are associated with deleterious clinical outcomes, but nothing is known to date about tissue protein carbamylation during aging. To address this issue, we evaluated homocitrulline rate, the most characteristic carbamylation-derived product (CDP), over time in skin of mammalian species with different life expectancies. Our results show that carbamylation occurs throughout the whole lifespan and leads to tissue accumulation of carbamylated proteins. Because of their remarkably long half-life, matrix proteins, like type I collagen and elastin, are preferential targets. Interestingly, the accumulation rate of CDPs is inversely correlated with longevity, suggesting the occurrence of still unidentified protective mechanisms. In addition, homocitrulline accumulates more intensely than carboxymethyl-lysine, one of the major advanced glycation end products, suggesting the prominent role of carbamylation over glycoxidation reactions in age-related tissue alterations. Thus, protein carbamylation may be considered a hallmark of aging in mammalian species that may significantly contribute in the structural and functional tissue damages encountered during aging.

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mentioning

confidence: 99%

Protein carbamylation is a hallmark of aging

Gorisse

Piètrement

Vuiblet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

164

125

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“…Treatment with ramipril did not influence the levels of CMLFone of the most prominent AGEs 31 Fbut resulted in a mild decline of fluorescent AGEs. This effect could not be attributed to merely seasonal variations, since the comparison of these data collected after the 2-month period in patients on conventional treatment (diuretics and/or b-blockers) did not show significant changes (Table 1).…”

Section: Effect Of Ramiprilmentioning

confidence: 80%

Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products

Šebeková

Gazdíková

Syrova³

et al. 2003

J Hum Hypertens

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“…However, because glycation of uromodulin in the urine of patients with DKD impairs its ability to form high molecular weight polymers or matrix-like structures, glcUMOD may contribute to this increased susceptibility to UTIs in patients with DKD. High molecular weight uromodulin polymers may bind pathogenic bacteria and prevent their adherence to glycoproteins and glycolipids on luminal plasma membranes, thus reducing or preventing UTIs [18], which are common in patients with Type 2 DM [52]. Bates et al [53] revealed that UMOD serves as a soluble receptor for type 1 fimbriated E. coli and helps eliminate bacteria from the urinary tract, and showed that UMOD protein knockout mice are more prone to urinary tract infection.…”

Section: Discussionmentioning

confidence: 99%

“…Serum and tissue AGE concentrations are markedly elevated in patients with ESRD, and are twice as high in patients with ESRD and DM [17]. The kidney is one of the major sites for AGE accumulation and AGE-associated damage [18]. Most AGEs are removed and filtered across the glomerular membrane and reabsorbed or catabolized in the renal proximal tubules, while the rest are excreted in the urine [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Urinary glycated uromodulin in diabetic kidney disease

et al. 2017

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Advanced glycation end-products (AGEs) form during oxidative stress, which is increased in diabetes mellitus (DM). Uromodulin is a protein with a renal protective effect, and may be subject to glycation. The implications of uromodulin glycation and AGEs in the urine are not understood. Here, immunoprecipitation and liquid chromatography-mass spectrometry identified glycated uromodulin (glcUMOD) in the urine of 62.5% of patients with diabetic kidney disease (DKD), 20.0% of patients with non-diabetic chronic kidney disease (CKD), and no DM patients with normal renal function or healthy control participants; a finding replicated in a larger cohort of 84 patients with CKD in a case-control study (35 with DM, 49 without). Uromodulin forms high molecular weight polymers that associate with microvesicles and exosomes. Differential centrifugation identified uromodulin in the supernatant, microvesicles, and exosomes of the urine of healthy participants, but only in the supernatant of samples from patients with DKD, suggesting that glycation influences uromodulin function. Finally, the diagnostic and prognostic utility of measuring urinary glcUMOD concentration was examined. Urinary glcUMOD concentration was substantially higher in DKD patients than non-diabetic CKD patients. Urinary glcUMOD concentration predicted DKD status, particularly in patients with CKD stages 1-3a aged <65 years and with urine glcUMOD concentration 9,000 arbitrary units (AU). Urinary uromodulin is apparently glycated in DKD and forms AGEs, and glcUMOD may serve as a biomarker for DKD.

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Advanced Glycation End Products in End-Stage Renal Disease and Their Removal

Cited by 54 publications

References 42 publications

Protein carbamylation is a hallmark of aging

Protein carbamylation is a hallmark of aging

Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products

Urinary glycated uromodulin in diabetic kidney disease

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