Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure

Makita, Zenji; Bucala, Richard; Rayfield, Elliot J.; Fuh, Hubert; Manogue, Kirk R.; Cerami, Anthony; Viassara, H.; Friedman, Eli A.; Kaufman, Allen; Korbet, Stephen M.; Barth, Robert H.; Winston, Jonathan

doi:10.1016/s0140-6736(94)92935-1

Cited by 360 publications

(226 citation statements)

References 15 publications

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“…In the present study, we observed increased CML clearance in the AVE7688 group, indicating that enhanced excretion may contribute to the reduction of plasma and tissue levels of CML. Moreover, this effect may be of clinical relevance, particularly when the endogenous and/or exogenous supply of AGEs is increased and glomerular filtration is impaired, such as in advanced stages of diabetic nephropathy [34,35]. The clearance of CML may be influenced by changes in renal filtration, secretion, and reabsorption [36].…”

Section: Discussionmentioning

confidence: 99%

Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition

Wihler¹,

Schäfer²,

Schmid³

et al. 2005

Diabetologia

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Aims/hypothesis: Renal accumulation of AGEs may contribute to the progression of diabetic nephropathy. We evaluated the effect of ramipril (a pure ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidase) on renal accumulation of the advanced glycation end-product (AGE) 3-deoxyglucosone-imidazolone, carboxymethyllysine (CML) and pentosidine, and on clearance of CML in type 2 diabetes. Methods: Male Zucker diabetic fatty rats (ZDF, Gmi-fa/fa) rats were treated from age 10 to 37 weeks with ramipril (1 mg·kg −1 ·day −1 ), AVE7688 (45 mg·kg −1 ·day −1 ) or without drug. Ramipril and AVE7688 reduced albuminuria by 30 and 90%, respectively. Results: ZDF rats showed increased renal accumulation of the AGE subtypes 3-deoxyglucosone-imidazolone, pentosidine and CML by about 40, 55 and 55%, respectively compared with heterozygous, non-diabetic control animals at the age of 37 weeks. AVE7688 but not ramipril attenuated the renal accumulation of 3-deoxyglucosone-imidazolone, pentosidine and CML and improved CML clearance in ZDF rats. During glycation reactions in vitro, AVE7688 also demonstrated potent chelating activity and inhibited metal-catalysed formation of pentosidine and CML. Conclusions/interpretation: Improved AGE clearance and direct inhibition of AGE formation by chelation may contribute to reduced accumulation of renal AGEs and to the nephroprotective effects of vasopeptidase inhibition in type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition

Wihler¹,

Schäfer²,

Schmid³

et al. 2005

Diabetologia

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“…Advanced glycation endproduct-peptides hi the human circulation may represent a hitherto unrecognised class of reactive and potentially toxic substances which can exacerbate renal and extrarenal vascular pathology and render these patients sensitive to accelerated atherosclerosis. Elimination of these circulating low molecular mass advanced glycation endproducts by the kidney is impaired in patients with end-stage renal disease and this function is inadequately performed by the current types of dialysis membranes (6,25). Hence a rapid and sensitive assay for the determination of advanced glycation endproducts in serum might be valuable for assessing cardiovascular risks and for monitoring the efficacy of advanced glycation endproduct removal procedures (by dialysis or adsorption), or for testing novel pharmacological approaches for inhibition of their formation.…”

Section: Discussionmentioning

confidence: 99%

Determination of Advanced Glycation End Products in Serum by Fluorescence Spectroscopy and Competitive ELISA

Münch

Keis²,

Weßels³

et al. 1997

Clinical Chemistry and Laboratory Medicine

194

191

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Summary: Recent studies suggest that advanced glycation endproducts play an important role in cardiovascular complications of ageing, diabetes and end-stage renal failure. Since highly elevated levels of advanced glycation endproducts are present in serum of patients on maintenance haemodialysis, an accurate and rapid assay for their determination would be useful. This would be particularly valuable for monitoring the removal of advanced glycation endproducts by novel dialysis membranes, as well as the effect of new drugs for the inhibition of their formation.Measurement of advanced glycation endproducts in serum was performed by two competitive ELISAs, using a monoclonal antibody directed against imidazolone, an advanced glycation endproduct formed by the reaction of arginine with 3-deoxyglucosone, and a polyclonal antibody directed against keyhole limpet haemocyanin-advanced glycation endproduct, as well as by quantitative fluorescence spectroscopy.Each of the assays showed significant differences between the controls and the maintenance haemodialysis patients. Advanced glycation endproduct levels determined by each of the ELISAs correlated with total and protein-bound fluorescence, but not with each other, suggesting a variable distribution of advanced glycation endproducts on serum proteins among the maintenance haemodialysis patients.

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“…30 Second, in diabetic subjects, vascular lesions are related not only to the numerous metabolic anomalies linked to this pathological condition 31 but also to the induction of tissue damage via slow, irreversible changes in extracellular molecules due to hyperglycemia, particularly covalent modifications and the resulting advanced glycation end products. 37 Third, homocysteine has also been shown to enhance smooth muscle cell proliferation and even alter elastic tissue. 38,39 Finally, ET is enhanced not only in the circulation but also mostly in terms of its expression in the arterial wall, 40 with potential consequences on vascular smooth muscle proliferation.…”

Section: Discussionmentioning

confidence: 99%

Influence of Biochemical Alterations on Arterial Stiffness in Patients With End-stage Renal Disease

Blacher

Demuth

Guérin

et al. 1998

ATVB

190

115

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Abstract-The incremental elastic modulus of the common carotid and radial arteries is increased in patients with end-stage renal disease (ESRD), independently of blood pressure, wall stress, and the presence of atherosclerotic alterations. Whether biochemical factors may be involved in the arterial changes and related to renal dysfunction remain largely ignored. To assess this question, we measured aortic (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial) pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in comparison with 57 control subjects similar in age, sex ratio, and mean blood pressure. We evaluated arterial blood presure by sphygmomanometry, aortic calcifications and cardiac mass by echography, and routine biochemical parameters, total plasma homocysteine, and plasma endothelin levels by standard techniques. In the population of patients with ESRD, on the basis of multiple stepwise regression analysis, aortic PWV was positively and independently correlated with systolic blood pressure (PϽ.0001), age (PϽ.0001), prevalence of aortic calcification (Pϭ.0004), and the prevalence of diabetes mellitus (Pϭ.0043). Upper-limb PWV was influenced exclusively by mean blood pressure (PϽ.0001). Lower-limb PWV was positively and independently correlated with plasma total homocysteine (Pϭ.0004) and plasma endothelin (Pϭ.0187) only. At any vascular site, PWV was not independently correlated with tobacco consumption; plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was independently correlated with cardiac mass (Pϭ.0022). This study provides evidence that in ESRD patients, the stiffness of the arterial wall and cardiac mass are strongly influenced by biochemical factors related to the kidney alterations and are independent of age and blood pressure level. Increased plasma endothelin and homocysteine may be specifically involved in the vascular damage of lower limbs. (Arterioscler Thromb Vasc Biol. 1998;18:535-541.)

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Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure

Cited by 360 publications

References 15 publications

Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition

Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition

Determination of Advanced Glycation End Products in Serum by Fluorescence Spectroscopy and Competitive ELISA

Influence of Biochemical Alterations on Arterial Stiffness in Patients With End-stage Renal Disease

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